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Sample records for prevents bacterial translocation

  1. Abdominal radiation causes bacterial translocation

    International Nuclear Information System (INIS)

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-01-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa

  2. Periarrest intestinal bacterial translocation and resuscitation outcome.

    Science.gov (United States)

    Chalkias, Athanasios; Scheetz, Marc H; Gulati, Anil; Xanthos, Theodoros

    2016-02-01

    During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Bacterial translocation and enteral nutrition in humans: an outsider looks in.

    Science.gov (United States)

    Lipman, T O

    1995-01-01

    To assess the literature documenting the existence of bacterial translocation in humans, the effects of enteral nutrition on bacterial translocation in humans, and the hypothesis that enteral nutrition prevents bacterial translocation in humans. Sources included Medline search, references from review articles, and references from animal and human studies. The goal was to include all animal and human studies directly addressing questions of bacterial translocation and nutritional status or nutritional support. An attempt was made to briefly summarize methodology and findings of relevent studies. No general attempt was made to assess quality of individual studies. Bacterial translocation is a well documented phenomenon in animal models. Starvation and malnutrition of themselves do not induce bacterial translocation, but may facilitate translocation in the presence of other systemic insults. Parenteral nutrition and many forms of enteral nutrition may induce and/or facilitate bacterial translocation. Chow and certain fiber sources seem protective. Moderate direct and several lines of indirect evidence support the existence of bacterial translocation in humans. There is no direct evidence and questionable indirect evidence suggesting that enteral nutrition prevents or modifies bacterial translocation in humans. The hypothesis relating enteral nutrition and bacterial translocation in critically ill patients remains attractive, but unproven.

  4. Obstructive jaundice promotes bacterial translocation in humans.

    Science.gov (United States)

    Kuzu, M A; Kale, I T; Cöl, C; Tekeli, A; Tanik, A; Köksoy, C

    1999-01-01

    Significant bacterial translocation was demonstrated following experimental biliary obstruction, however very little is known about the importance and the prevalence of gut-origin sepsis in obstructive jaundice patients. Therefore, the aim of this study was to investigate the concept of gut-origin sepsis in obstructive jaundiced patients and its clinical importance. Twenty-one patients requiring laparotomy for obstructive jaundice (group I) and thirty patients operated on electively mainly for chronic cholecystitis (group II) were studied. Peritoneal swab, mesenteric lymph node, portal venous blood, liver wedge biopsy and bile were sampled for culture immediately after opening the peritoneum. Additionally, peripheral blood samples were taken pre- and post-operatively from all patients. Post-operatively, patients were monitored for infectious complications. The mean serum bilirubin concentration, gamma glutamyl transferase and alkaline phosphatase levels in jaundiced patients before therapeutic intervention were significantly higher than in control patients. Five patients demonstrated bacterial translocation in group I (24%), whereas only one did so in group II (3.5%, p jaundice significantly promotes bacterial translocation in humans, however, its clinical importance has yet to be defined.

  5. Growth hormone reduces mortality and bacterial translocation in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-de-Segura, I.A.; Miguel, E. de [`La Paz` Hospital, Madrid (Spain). Dept. of Experimental Surgery; Prieto, I. [`La Paz` Hospital, Madrid (Spain). Dept. of General and Digestive Surgery; Grande, A.G. [`La Paz` Hospital, Madrid (Spain). Dept. of Oncology Radiotherapy; Garcia, P.; Mendez, J. [`La Paz` Hospital, Madrid (Spain). Dept. of Clinical Biochemistry; Guerra, A. [`La Paz` Hospital, Madrid (Spain). Dept. of Microbiology

    1998-09-01

    Growth hormone stimulates the growth of intestinal mucosa and may reduce the severity of injury caused by radiation. Male Wistar rats underwent abdominal irradiation (12 Gy) and were treated with either human growth hormone (hGH) or saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation, and the ileal mucosal thickness, proliferation, and disaccharidase activity were assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement (29%, p<0.05). Bacterial translocation was also reduced by hGH (p<0.05). Treating irradiated rats with hGH prevented body weight loss (p<0.05). Mucosal thickness increased faster in irradiated hGH-treated animals. The proliferative index showed an increment in hGH-treated animals (p<0.05). Giving hGH to irradiated rats prevented decrease in sucrose activity, and increment in lactase activity. In conclusion, giving hGH to irradiated rats promotes the adaptative process of the intestine and acute radiation-related negative effects, including mortality, bacterial translocation, and weight loss. (orig.)

  6. L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

    Science.gov (United States)

    Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

    2014-02-01

    Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

  7. OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice

    International Nuclear Information System (INIS)

    Nose, Masako; Uzawa, Akiko; Ogyu, Toshiaki; Suzuki, Gen

    2001-01-01

    Acute radiation induces bacterial translocation from the gut, followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterial translocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterial translocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation. (author)

  8. OK-432 reduces mortality and bacterial translocation in irradiated and granulocyte-colony stimulating factor (G-CSF)-treated mice

    Energy Technology Data Exchange (ETDEWEB)

    Nose, Masako; Uzawa, Akiko; Ogyu, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan); Suzuki, Gen

    2001-06-01

    Acute radiation induces bacterial translocation from the gut, followed by systemic infection and sepsis. In order to reduce the mortality after acute whole body irradiation, it is essential to control bacterial translocation. In this study, we established a bacterial translocation assay as a sensitive method to detect minor mucosal injury by radiation. By utilizing this assay, we evaluated the adverse effects, if any, of hematopoietic reagents on the mucosal integrity in the respiratory and gastro-intestinal tracts. Bacterial translocation to the liver and spleen occurred after whole-body irradiation if the dose exceeded 6 Gy. The administration of G-CSF unexpectedly increased the bacterial translocation in 8 Gy-irradiated mice. The pharmaceutical preparation of low-virulent Streptococcus pyogenes, OK-432, significantly reduced the endotoxin levels in peripheral blood without any reduction of bacterial translocation. A combined treatment with G-CSF and OK-432 decreased bacterial translocation and prevented death. This result indicates that the early administration of G-CSF has an adverse effect on bacterial translocation, and that a combined treatment of G-CSF and OK-432 attenuates the adverse effect of G-CSF and improves the survival rate after acute irradiation. (author)

  9. Scintigraphic visualization of bacterial translocation in experimental strangulated intestinal obstruction

    International Nuclear Information System (INIS)

    Galeev, Yu.M.; Popov, M.V.; Salato, O.V.; Lishmanov, Yu.B.; Grigorev, E.G.; Aparcin, K.A.

    2009-01-01

    The purpose of this study was to obtain scintigraphic images depicting translocation of 99m Tc-labelled Escherichia coli bacteria through the intestinal barrier and to quantify this process using methods of nuclear medicine. Thirty male Wistar rats (including 20 rats with modelled strangulated intestinal obstruction and 10 healthy rats) were used for bacterial scintigraphy. 99m Tc-labelled E. coli bacteria ( 99m Ts-E. coli) with an activity of 7.4-11.1 MBq were administered into a section of the small intestine. Scintigraphic visualization of bacterial translocation into organs and tissues of laboratory animals was recorded in dynamic (240 min) and static (15 min) modes. The number of labelled bacteria, which migrated through the intestinal barrier, was quantified by calculating the translocation index (TI). Control indicated no translocation of 99m Ts-E. coli administered into the intestine through the parietes of the small intestine's distal part in healthy animals. Animals with strangulated obstruction demonstrated different migration strength and routes of labelled bacteria from strangulated and superior to strangulation sections of the small intestine. 99m Ts-E. coli migrated from the strangulated loop into the peritoneal cavity later causing systemic bacteraemia through peritoneal resorption. The section of the small intestine, which was superior to the strangulation, demonstrated migration of labelled bacteria first into the portal and then into the systemic circulation. The strangulated section of the small intestine was the main source of bacteria dissemination since the number of labelled bacteria, which migrated from this section significantly, exceeded that of the area superior to the strangulation section of the small intestine (p = 0.0003). Bacterial scintigraphy demonstrated the possibility of visualizing migration routes of labelled bacteria and quantifying their translocation through the intestinal barrier. This approach to study bacterial

  10. Bacterial translocation and intestinal injury in experimental necrotizing enterocolitis model.

    Science.gov (United States)

    Ciftci, I; Ozdemir, M; Aktan, M; Aslan, K

    2012-01-01

    To study the occurrence of bacterial translocation and to assess the impact of breastfeeding on bacterial translocation in the animal model of necrotizing enterocolitis. A total of 20 neonate Sprague-Dawley rats were enrolled in the study. Rats were randomly allocated into either control or study group just after birth. Ten newborn rats in the control group were left with their mother to be breast-fed. In contrary, necrotizing enterocolitis group consisted of neonates that were separated from their mothers, housed in an incubator and were gavaged with a special rodent formula three times daily. Survival rates, weight changes, and morphologic scoring obtained after microscopic evaluation were determined as microbiologic evaluation criteria. All the rats in the control group survived, while 1 (10 %) rat died in the necrotizing enterocolitis group. Mortality rates of the two groups were similar. All the formula-fed animals in the necrotizing enterocolitis group had significant weight loss compared to the breast milk-fed rats in the control group (pmicrorganisms in the bowel pass through the intestinal barrier and reach the liver and the spleen via the hematogenous route. This condition is closely related to the impairment of physiological and functional features of the intestinal barrier and is independent from the degree of intestinal injury. Bacterial translocation should be remembered in cases suspected of necrotizing enterocolitis, and a rapid and effective treatment algorithm should be applied in such circumstances (Tab. 3, Fig. 3, Ref. 21). Full Text in PDF www.elis.sk.

  11. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation.

    Science.gov (United States)

    Andersen, Kirstin; Kesper, Marie Sophie; Marschner, Julian A; Konrad, Lukas; Ryu, Mi; Kumar Vr, Santhosh; Kulkarni, Onkar P; Mulay, Shrikant R; Romoli, Simone; Demleitner, Jana; Schiller, Patrick; Dietrich, Alexander; Müller, Susanna; Gross, Oliver; Ruscheweyh, Hans-Joachim; Huson, Daniel H; Stecher, Bärbel; Anders, Hans-Joachim

    2017-01-01

    CKD associates with systemic inflammation, but the underlying cause is unknown. Here, we investigated the involvement of intestinal microbiota. We report that collagen type 4 α3-deficient mice with Alport syndrome-related progressive CKD displayed systemic inflammation, including increased plasma levels of pentraxin-2 and activated antigen-presenting cells, CD4 and CD8 T cells, and Th17- or IFNγ-producing T cells in the spleen as well as regulatory T cell suppression. CKD-related systemic inflammation in these mice associated with intestinal dysbiosis of proteobacterial blooms, translocation of living bacteria across the intestinal barrier into the liver, and increased serum levels of bacterial endotoxin. Uremia did not affect secretory IgA release into the ileum lumen or mucosal leukocyte subsets. To test for causation between dysbiosis and systemic inflammation in CKD, we eradicated facultative anaerobic microbiota with antibiotics. This eradication prevented bacterial translocation, significantly reduced serum endotoxin levels, and fully reversed all markers of systemic inflammation to the level of nonuremic controls. Therefore, we conclude that uremia associates with intestinal dysbiosis, intestinal barrier dysfunction, and bacterial translocation, which trigger the state of persistent systemic inflammation in CKD. Uremic dysbiosis and intestinal barrier dysfunction may be novel therapeutic targets for intervention to suppress CKD-related systemic inflammation and its consequences. Copyright © 2016 by the American Society of Nephrology.

  12. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  13. High positive end-expiratory pressure levels promote bacterial translocation in experimental pneumonia

    NARCIS (Netherlands)

    Lachmann, Robert A.; van Kaam, Anton H.; Haitsma, Jack J.; Lachmann, Burkhard

    2007-01-01

    A previous study in piglets with experimental pneumonia showed that reducing atelectasis by means of open lung ventilation attenuated bacterial translocation compared to conventional ventilation settings. This study examined the effect of open lung ventilation with higher than necessary positive

  14. Bacterial translocation in rats nonfunctioning diverted distal colon.

    Science.gov (United States)

    Pinto, Francisco Edilson Leite; Brandt, Carlos Teixeira; Medeiros, Aldo da Cunha; de Oliveira, Ariano José Freitas; Jerônimo, Selma Maria; de Brito, Helena Marques Fonseca

    2007-01-01

    To investigate whether the alterations of the diverted colon segment mucosa, evidenced in fecal colitis, would be able to alter Bacterial Translocation (BT). Sixty-two Wistar male rats ranging from 220 to 320 grams of weight, were divided in two groups: A (Colostomy) and B (Control), with 31 animals each one. In group A, all animals underwent end colostomy, one stoma, in ascending colon; and in the 70th POD was injected in five rats, by rectal route diverted segment - 2 ml of a 0.9% saline solution in animals (A1 subgroup); in eight it was inoculated, by rectal route, 2 ml of a solution containing Escherichia coli ATCC 25922 (American Type Culture Collection), in a concentration of 10(8) Colony Forming Unit for milliliters (CFU/ml) - A2 Subgroup; in ten animals the same solution of E. coli was inoculated, in a concentration of 10(11) CFU/ml (A3 Subgroup); and in eight it was collected part of the mucus found in the diverted distal colonic segment for neutral sugars and total proteins dosage (A4 subgroup). The animals from the group B underwent the same procedures of group A, but with differences in the colostomy confection. In rats from subgroups A1, A2, A3, B1, B2, and B3 2 ml of blood were aspirated from the heart, and fragments from mesenteric lymphatic nodule, liver, spleen, lung and kidney taken for microbiological analysis, after their death. This analysis consisted of evidencing the presence of E. coli ATCC 25922 CFU. Mann-Whitney and ANOVA Tests were applied as analytic techniques for association of variables. The occurrence of BT was evidenced only in those animals in which inoculated concentration of E. coli ATCC 25922, reached levels of 10(11)CFU/ml, i.e. in Subgroups A3 and B3, although, being significantly greater (80%) in those animals without colostomy (subgroup B3) when compared to the ones with colostomy (20%) from the subgroup A3 (P subgroup A3, as in B3. Blood culture was considered positive in 60% of the animals from subgroup B3 and in 10% of

  15. Lactobacillus plantarum L9 but not Lactobacillus acidophilus LA reduces tumour necrosis factor induced bacterial translocation in Caco-2 cells.

    Science.gov (United States)

    Wang, B; Chen, J; Wang, S; Zhao, X; Lu, G; Tang, X

    2017-05-30

    Translocation of bacteria across the intestinal barrier is important in the pathogenesis of systemic sepsis and multiple organ dysfunction syndromes. Inflammatory cytokines increase paracellular permeability that allows increased luminal bacteria to translocate across mucosal epithelium and further deteriorate the gut barrier. In order to reduce this risk, the prophylactic use of probiotics has been recently addressed. In this paper, we investigate the protective role toward tumour necrosis factor (TNF)-α induced non-pathogenic Escherichia coli translocation across Caco-2 monolayers of Lactobacillus strains. According to our experimental data, Lactobacillus plantarum L9 and Lactobacillus acidophilus LA have good capacities to adhere to Caco-2 cells. Addition of L. plantarum L9 and L. acidophilus LA to the enterocyte monolayer surface result in significant inhibition of E. coli adhesion and cell internalisation. However, L. plantarum L9 and L. acidophilus LA did not inhibit the growth of the non-pathogenic E. coli B5 after 24 h incubation. Exposure to TNF-α for 6 h caused a dramatic increase in E. coli B5 translocation across Caco-2 cells, which was uncoupled from increases in paracellular permeability. Pretreatment with L. plantarum L9 prevent TNF-α induced transcellular bacterial translocation and IL-8 production in Caco-2 cells. L. plantarum L9 also did not affect the integrity of the monolayers, as indicated by lactate dehydrogenase release, horseradish peroxidase permeability, and transepithelial electrical resistance. L. plantarum L9 showed the potential to protect enterocytes from an acute inflammatory response and therefore could be good potential prophylactic agents in counteracting bacterial translocation.

  16. Effects of subtotal colectomy on bacterial translocation during experimental acute pancreatitis

    NARCIS (Netherlands)

    van Minnen, LP; Nieuwenhuijs, VB; de Bruijn, MT; Verheem, A; Visser, MR; van Dijk, JE; Akkermans, LMA; Gooszen, HG

    Objectives: The colon is considered a major source of bacteria causing infection of pancreatic necrosis in acute pancreatitis (AP). Subtotal colectomy before AP in rats reduces mortality, but its role in affecting small bowel flora, bacterial translocation, and infection of pancreatic necrosis is

  17. Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation.

    Science.gov (United States)

    Ruan, Xiangcai; Shi, Hanping; Xia, Gengfeng; Xiao, Ying; Dong, Jiaxi; Ming, Feiping; Wang, Shenming

    2007-10-01

    The aim of the present study was to determine the effects of peroral encapsulated Bifidobacteria on intestinal microflora, bacterial translocation (BT), plasma endotoxin, and ileal villi injury in a rat model of hemorrhagic shock. Sprague-Dawley rats were fed daily with three different diet supplements: phosphate buffered saline, Bifidobacteria (10(9) colon-forming units/day), or microencapsulated Bifidobacteria (10(9) colony-forming units/day). After 7 d of treatment, rats were anesthetized for hemorrhagic or sham shock. Then a laparotomy was performed to determine microbiological analysis of cecal content, BT to mesenteric lymph nodes, plasma endotoxin, and terminal ileal villous damage. In the hemorrhagic-shock model, rats pretreated with Bifidobacteria showed decreases in total aerobes in cecum, magnitude of total aerobes to BT, levels of plasma endotoxin, and percentage of ileal villous damage when compared with rats treated with phosphate buffered saline. Encapsulated Bifidobacteria induced greater decreases than intact Bifidobacteria in this model, except for no difference in percentage of ileal villous damage between the two groups. In addition, the incidence of BT was decreased in hemorrhagic rats pretreated with Bifidobacteria compared with control. However, the magnitude of total anaerobes and Bifidobacteria BT were similar among hemorrhagic-shocked rats receiving three different supplements. Bifidobacteria can be useful in preventing BT in hemorrhagic-shocked rats, and encapsulated Bifidobacteria can augment this effect further. Peroral administration of Bifidobacteria may be a favorable strategy to prevent sepsis and multiple organ dysfunction syndrome in hemorrhagic shock.

  18. A kinetic Monte Carlo approach to investigate antibiotic translocation through bacterial porins

    International Nuclear Information System (INIS)

    Ceccarelli, Matteo; Ruggerone, Paolo; Vargiu, Attilio V

    2012-01-01

    Many relevant biological processes take place on time scales not reachable by standard all-atom computer simulations. The translocation of antibiotics through non-specific bacterial porins is an example. Microscopic effects compete to determine penetration routes and, consequently, free energy barriers to be overcome. Since bacteria can develop resistance to treatment also by reducing their antibiotic permeability, to understand the microscopic aspects of antibiotic translocation is an important step to rationalize drug design. Here, to investigate the translocation we propose a complete numerical model that combines the diffusion-controlled rate theory and a kinetic Monte Carlo scheme based on both experimental data and microscopically well-founded all-atom simulations. Within our model, an antibiotic translocating through an hour-glass-shaped channel can be described as a molecule moving on a potential of mean force featuring several affinity sites and a high central barrier. The implications of our results for the characterization of antibiotic translocation at in vivo concentrations are discussed. The presence of an affinity site close to the mouth of the channel seems to favor the translocation of antibiotics, the affinity site acting as a particle reservoir. Possible connections between results and the appearance of mutations in clinical strains are also outlined. (paper)

  19. Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats.

    Science.gov (United States)

    Yüksek, Yunus Nadi; Kologlu, Murat; Daglar, Gül; Doganay, Mutlu; Dolapci, Istar; Bilgihan, Ayse; Dolapçi, Mete; Kama, Nuri Aydin

    2004-01-01

    The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.

  20. The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury.

    Science.gov (United States)

    Karabeyoğlu, Melih; Unal, Bülent; Bozkurt, Betül; Dolapçi, Iştar; Bilgihan, Ayşe; Karabeyoğlu, Işil; Cengiz, Omer

    2008-01-01

    Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.

  1. Post-splenectomy infections in chronic schistosomiasis as a consequence of bacterial translocation

    Directory of Open Access Journals (Sweden)

    Kedma de Magalhães Lima

    2015-06-01

    Full Text Available INTRODUCTION : Bacterial translocation is the invasion of indigenous intestinal bacteria through the gut mucosa to normally sterile tissues and internal organs. Schistosomiasis may cause alterations in the immune system and damage to the intestines, portal system and mesenteric lymph nodes. This study investigated bacterial translocation and alterations in the intestinal microbiota and mucosa in schistosomiasis and splenectomized mice. METHODS : Forty female 35-day-old Swiss Webster mice were divided into the following four groups with 10 animals each: schistosomotic (ESF, splenectomized schistosomotic (ESEF, splenectomized (EF and control (CF. Infection was achieved by introduction of 50 Schistosoma mansoni (SLM cercariae through the skin. At 125 days after birth, half of the parasitized and unparasitized mice were subjected to splenectomy. Body weights were recorded for one week after splenectomy; then, the mice were euthanized to study bacterial translocation, microbiota composition and intestinal morphometry. RESULTS : We observed significant reductions in the weight increases in the EF, ESF and ESEF groups. There were increases of at least 1,000 CFU of intestinal microbiota bacteria in these groups compared with the CF. The EF, ESF and ESEF mice showed decreases in the heights and areas of villi and the total villus areas (perimeter. We observed frequent co-infections with various bacterial genera. CONCLUSIONS : The ESEF mice showed a higher degree of sepsis. This finding may be associated with a reduction in the immune response associated with the absence of the spleen and a reduction in nutritional absorption strengthened by both of these factors (Schistosoma infection and splenectomy.

  2. Effect of erythropoietin on intestinal injury and bacterial translocation in neonatal rat model of necrotizing enterocolitis

    Directory of Open Access Journals (Sweden)

    Xiao-qing CHEN

    2012-05-01

    Full Text Available Objective  To observe the influence of erythropoietin (EPO on intestinal histopathological changes and bacterial translocation (BT in neonatal rat model of necrotizing enterocolitis (NEC, and explore the protective effect of EPO against NEC. Methods  Seventy-five three-day-old SD rat pups were randomly divided into three groups (25 in each group: normal control group, NEC model group and EPO intervention group. The rat pups in normal control group were placed together with their mothers and breast fed, receiving no other intervention. NEC model group rats were separated from their mothers, housed in an incubator, and gavaged with rat-milk substitute, then experienced hypoxia (breathing 100% nitrogen gas for 90s and cold stress (4℃ for 10min three times daily for 3 days. EPO intervention group rats were fed with the substitute of rat-milk supplemented with 0.1U/ml of EPO, and they were also given hypoxia and cold stress similar to that of the NEC model group. Blood samples were obtained via cardiac puncture, and 2-cm-length of terminal ileum proximal to the ileocecal valve were obtained from the animals on the 4th day. The histopathological changes in terminal ileum were scored after hematoxylin-eosin (HE staining, and the scores ≥2 were defined as NEC. To determine the incidence of bacterial translocation, 16S rRNA real-time fluorescence quantitative PCR was used to detect the bacterial DNA in blood samples. Results  Compared with the NEC model group, the mean rank-sum rate of the intestinal histopathological score (39.4583 vs 53.8696, NEC incidence [25%(6/24 vs 57%(13/23] and bacterial translocation rate [17% (4/24 vs 65%(15/23] in EPO intervention group were significantly lowered (P < 0.05, P < 0.01. Conclusion  Enteral EPO administration is not only effective for reduction of the severity and incidence of NEC, but also for decrease of the bacterial translocation rate in neonatal rat models.

  3. Rifaximin has minor effects on bacterial composition, inflammation and bacterial translocation in cirrhosis

    DEFF Research Database (Denmark)

    Kimer, Nina; Pedersen, Julie S.; Tavenier, Juliette

    2018-01-01

    .4), and MELD score 12 (±3.9). Patients received rifaximin 550 mg BD (n=36) or placebo BD (n=18). Blood and faecal (n=15) sampling were conducted at baseline and after four weeks. Bacterial DNA in blood was determined by real-time qPCR 16S rRNA gene quantification. Bacterial composition in faeces was analysed......: Four weeks of treatment with rifaximin had no impact on the inflammatory state and only minor effects on BT and intestinal bacterial composition in stable, decompensated cirrhosis (NCT01769040)....

  4. Protection against increased intestinal permeability and bacterial translocation induced by intestinal obstruction in mice treated with viable and heat-killed Saccharomyces boulardii.

    Science.gov (United States)

    Generoso, Simone V; Viana, Mirelle L; Santos, Rosana G; Arantes, Rosa M E; Martins, Flaviano S; Nicoli, Jacques R; Machado, José A N; Correia, Maria Isabel T D; Cardoso, Valbert N

    2011-06-01

    There are substantial evidences suggesting that probiotics can protect the gastrointestinal tract against inflammatory or infectious episodes. The effects of oral treatment with viable or heat-killed cells of Saccharomyces boulardii (Sb) on bacterial translocation, intestinal permeability, histological aspect of the ileum, and some immunological parameters were evaluated in a murine intestinal obstruction (IO) model. Bacterial translocation and intestinal permeability in the IO group were significantly higher when compared to a Sham group (p viable and heat-killed S. boulardii prevented these increases, and the data obtained for IO + Sb and IO + heat-killed Sb groups were similar to those observed in the Sham group (p > 0.05). Histological analysis showed preservation of the ileum mucosa in mice that received both forms of the yeast when compared to the lesions observed in the IO group. The levels of serum interleukin (IL)-10 and intestinal secretory immunoglobulin A (sIgA) were higher in the animals that received both yeast treatments when compared to those from IO and Sham groups. Oral treatment with viable or heat-killed cells of S. boulardii maintained intestinal integrity and modulated the immune system in a murine IO model, preventing bacterial translocation and intestinal lesions.

  5. Effects of different recruitment maneuvers on bacterial translocation and ventilator- induced lung injury.

    Science.gov (United States)

    Ergin Özcan, Perihan; Akıncı, Özkan İbrahim; Edipoğlu, İpek; Şentürk, Evren; Baylan, Sevil; Cağatay, Atahan Arif; Türköz, Kemal H; Esen, Figen; Telci, Lütfi; Çakar, Nahit

    2016-03-01

    Investigated in the present study were the effects of various recruitment maneuvers (RMs) using the same inflation pressure-time product on bacterial translocation from lung to blood, and ventilator-induced lung injury (VILI). Tracheotomy was performed on anesthetized rats, and ventilation was initiated using pressure-controlled mode. Subsequently, Pseudomonas aeruginosa was inoculated through the tracheotomy tube and ventilated for 30 minutes before rats were randomly separated into 4 groups. Group 1 underwent sustained inflation (SI), Group 2 underwent low-pressure SI, Group 3 underwent modified sigh, and Group 4 was a control group. Blood cultures were taken at baseline, 15 minutes after randomization (after each RM for the first hour), and finally at 75 minutes after the last RM. The rats were euthanized and the lungs were extirpated. The left lung was taken for measurement of wet:dry weight ratio, and the right lung was used for pathologic evaluation. Positive blood cultures were found to be higher in Group 3 at early study periods. Total pathological scores were also higher in Group 3. Higher severity of ventilator-induced lung injury occurred in the modified sigh group, evidenced by bacterial translocation and results of histopathological evaluation.

  6. Combined Effects of Tauroursodeoxycholic Acid and Glutamine on Bacterial Translocation in Obstructive Jaundiced Rats

    Directory of Open Access Journals (Sweden)

    Ahmet Rahmi Hatipoğlu

    2013-12-01

    Full Text Available Background: Bacterial Translocation is believed to be an important factor on mortality and morbidity in Obstructive Jaundiced. Aims: We investigated the probable or estimated positive effects of tauroursodeoxycholic acid, which has antibacterial and regulatory effects on intestinal flora, together with glutamine on BT in an experimental obstructive jaundiced rat model. Study Design: Animal experimentation. Methods: Forty adult, male, Sprague Dawley rats were used in this study. Animals were randomised and divided into five groups of eight each: sham (Sh; control (common bile duct ligation, CBDL; and supplementation groups administered tauroursodeoxycholic acid (CBDL+T, glutamine (CBDL+G, or tauroursodeoxycholic acid plus glutamine (CBDL+TG. Blood and liver, spleen, MLN, and ileal samples were taken via laparotomy under sterile conditions for investigation of bacterial translocation and intestinal mucosal integrity and hepatic function tests on the tenth postoperative day. Results: There were statistically significant differences in BT rates in all samples except the spleen of the CBDL+TG group compared with the CBDL group (p=0.041, p=0.026, and p=0.041, respectively. Conclusion: It is essential to protect hepatic functions besides maintaining intestinal mucosal integrity in the active struggle against BT occurring in obstructive jaundice. The positive effect on intestinal mucosal integrity can be increased if glutamine is used with tauroursodeoxycholic acid, which also has hepatoprotective and immunomodulatory features.

  7. Assessment of intestinal permeability and bacterial translocation employing nuclear methods in murine mucositis

    Energy Technology Data Exchange (ETDEWEB)

    Pessoa, Rafaela M.; Takenaka, Isabella K.T.M.; Barros, Patricia A.V.; Moura, Livia P.; Contarini, Sara M.L.; Amorim, Juliana M.; Castilho, Raquel O.; Leite, Camila M.A.; Cardoso, Valbert N.; Diniz, Simone Odilia F. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Mg (Brazil)

    2017-07-01

    Full text: Introduction: Mucositis affects approximately 80% of patients who receive chemotherapy combinations. The lesions are painful, restrict food intake and make patients more susceptible to systemic infections. Some agents and strategies are being studied for controlling mucositis, none of them is used in clinical practice. In Minas Gerais, many studies have addressed the popular use of the plant Arrabidaea chica in the form of tea, to treat intestinal cramps and diarrhea, the main symptoms of mucositis. Objective: To evaluate the potential of Arrabidaea chica extract in the management of the integrity of the intestinal mucosa, using the experimental model of gut mucositis induced by 5-Fluorouracila (5-FU). Methods: The UFMG Ethics Committee for Animal Experimentation (CETEA/UFMG) approved this study (nº 411/2015). Male BALB/c mice between 6-8 weeks of age were randomly divided into four groups (n=9) as follows: 1. Control (CTL) - oral administration of saline solution (10 days); 2. A. chica (AC) - oral administration of A. chica extract (10 days); 3. Mucositis (MUC) - underwent mucositis (5-FU) (10 days); 4. Mucositis + A. chica (MUC+ AC) - underwent mucositis and received oral administration of A. chica extract (10 days). At the 7{sup th} day, mice in the MUC and MUC + AC groups received an intraperitoneal (IP) injection containing 300 mg/kg 5-FU, whereas the animals of the CTL and AC groups received a saline IP injection. After 72 hours (10{sup th} experimental day), intestinal permeability was determined by measuring the radioactivity diffusion in the blood after oral administration of diethylenetriaminepentaacetic acid (DTPA) labelled with technetium-99m ({sup 99m}Tc) and bacterial translocation was determined by measuring the radioactivity diffusion in the blood after oral administration of E. coli labelled with technetium-99m ({sup 99m}Tc). After 4 hours, the mice were euthanized and assessed for intestinal permeability, bacterial translocation and

  8. Rye affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in Turkey poults.

    Directory of Open Access Journals (Sweden)

    Guillermo Tellez

    Full Text Available Previously, we have reported that rye significantly increased both viscosity and Clostridium perfringens proliferation when compared with corn in an in vitro digestive model. Two independent trials were conducted to evaluate the effect of rye as a source of energy on bacterial translocation, intestinal viscosity, gut microbiota composition, and bone mineralization, when compared with corn in turkey poults. In each experiment, day-of-hatch, turkey poults were randomly assigned to either a corn or a rye diet (n = 0 /group. At 10 d of age, in both experiments, 12 birds/group were given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d. After 2.5 h of oral gavage, blood and liver samples were collected to evaluate the passage of FITC-d and bacterial translocation (BT respectively. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with a rye diet showed increased (p<0.05 intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that turkey poults fed with rye had increased the number of total lactic acid bacteria (LAB in all three sections of the gastrointestinal tract evaluated when compared to turkey poults fed with corn. Turkey poults fed with rye also had significantly higher coliforms in duodenum and ileum but not in the ceca, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in turkey poults fed with rye when compared with corn fed turkey poults. In conclusion, rye evoked mucosal damage in turkey poults that increased intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition and bone mineralization. Studies to evaluate dietary inclusion of selected Direct-Fed Microbial (DFM candidates that produce exogenous enzymes in rye fed

  9. In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

    Science.gov (United States)

    Maes, Michael; Ringel, Karl; Kubera, Marta; Anderson, George; Morris, Gerwyn; Galecki, Piotr; Geffard, Michel

    2013-09-05

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is accompanied by activation of immuno-inflammatory pathways, increased bacterial translocation and autoimmune responses to serotonin (5-HT). Inflammation is known to damage 5-HT neurons while bacterial translocation may drive autoimmune responses. This study has been carried out to examine the autoimmune responses to 5-HT in ME/CFS in relation to inflammation and bacterial translocation. We examined 5-HT antibodies in 117 patients with ME/CFS (diagnosed according to the centers for disease control and prevention criteria, CDC) as compared with 43 patients suffering from chronic fatigue (CF) but not fulfilling the CDC criteria and 35 normal controls. Plasma interleukin-1 (IL-1), tumor necrosis factor (TNF)α, neopterin and the IgA responses to Gram-negative bacteria were measured. Severity of physio-somatic symptoms was measured using the fibromyalgia and chronic fatigue syndrome rating scale (FF scale). The incidence of positive autoimmune activity against 5-HT was significantly higher (pimmune disorder. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Comprehensive postmortem analyses of intestinal microbiota changes and bacterial translocation in human flora associated mice.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available BACKGROUND: Postmortem microbiological examinations are performed in forensic and medical pathology for defining uncertain causes of deaths and for screening of deceased tissue donors. Interpretation of bacteriological data, however, is hampered by false-positive results due to agonal spread of microorganisms, postmortem bacterial translocation, and environmental contamination. METHODOLOGY/PRINCIPAL FINDINGS: We performed a kinetic survey of naturally occurring postmortem gut flora changes in the small and large intestines of conventional and gnotobiotic mice associated with a human microbiota (hfa applying cultural and molecular methods. Sacrificed mice were kept under ambient conditions for up to 72 hours postmortem. Intestinal microbiota changes were most pronounced in the ileal lumen where enterobacteria and enterococci increased by 3-5 orders of magnitude in conventional and hfa mice. Interestingly, comparable intestinal overgrowth was shown in acute and chronic intestinal inflammation in mice and men. In hfa mice, ileal overgrowth with enterococci and enterobacteria started 3 and 24 hours postmortem, respectively. Strikingly, intestinal bacteria translocated to extra-intestinal compartments such as mesenteric lymphnodes, spleen, liver, kidney, and cardiac blood as early as 5 min after death. Furthermore, intestinal tissue destruction was characterized by increased numbers of apoptotic cells and neutrophils within 3 hours postmortem, whereas counts of proliferative cells as well as T- and B-lymphocytes and regulatory T-cells decreased between 3 and 12 hours postmortem. CONCLUSIONS/SIGNIFICANCE: We conclude that kinetics of ileal overgrowth with enterobacteria and enterococci in hfa mice can be used as an indicator for compromized intestinal functionality and for more precisely defining the time point of death under defined ambient conditions. The rapid translocation of intestinal bacteria starting within a few minutes after death will help

  11. Assessment of bacterial translocation in obstructive jaundice using Tc-99m Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Diniz, Simone Odilia Fernandes; Nelson, David Lee [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia]. E-mail: simone@farmacia.ufmg.br; Barbosa, Alfredo Jose Afonso; Araujo, Ivana Durval; Machado, Leonardo Augusto da Silva [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Medicina; Bernardo Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Dept. de Biofisica e Biometria

    2005-10-15

    In obstructive jaundice, the passage of bacteria and endotoxins through the intestine wall to reach the systemic circulation is associated with septicemia, renal failure and pulmonary dysfunction. The aim of this work was to investigate bacterial translocation utilizing {sup 99m} Tc-E.coli in an experimental model of obstructive jaundice. The levels of bilirubin in rats that were subjected to ligature of the bile duct were significantly increased when compared to control animals (p < 0.001). The biodistribution results did not show any translocation of {sup 99m} Tc-E.coli to the mesenteric lymphatic nodules, liver, spleen or lungs of the rats that suffered ligature of the bile duct (p > 0.05). The evaluation of the intestinal permeability using 'per os' administration of {sup 99m} Tc-DTPA showed 1.61 {+-} 0.57% and 1.39 {+-} 0.72% of radioactivity in the urine of the control and jaundice animals, respectively. The histological analysis of the distal wall of the ileum showed that the covering epithelium and the crypt were morphologically preserved in both groups. The seven-day period after the ligature of the bile duct may not have been long enough to promote modifications in intestinal wall to occur so as to permit the passage of Tc-99m E.coli. (author)

  12. Reduction of intestinal mucosal immune function in heat-stressed rats and bacterial translocation.

    Science.gov (United States)

    Liu, Xiaoxi; Li, Huanrong; Lu, An; Zhong, Yougang; Hou, Xiaolin; Wang, Ning; Jia, Dan; Zan, Junlan; Zhao, Hong; Xu, Jianqin; Liu, Fenghua

    2012-01-01

    The aim of this study was to further understand the effects and mechanism of heat stress on the intestinal mucosal immune system of the rat, including changes in the intestinal mucosal barrier and immune function and their effects on bacterial translocation. Sprague Dawley (SD) rats were randomly divided into control and heat-stress groups. Both groups were housed in a 25°C environment of 60% relative humidity. The heat-stress group was subjected to 40°C for 2 h daily over 3 days. Compared with the control group villi length in the small intestines of the heat-stress group was shortened. Jejunal mucosa were seriously damaged and the number of goblet cells in the epithelia of the duodenum and jejunum was significantly reduced. Electron microscopy revealed intestinal mucosal disorder, a large number of exudates of inflammatory fibrous material, fuzzy tight junction structure between epithelial cells, and cell gap increases in the heat-stress group. Transcription of IFN-γ, IL-2, IL-4, and IL-10, was significantly reduced, as was that of the intestinal mucosal immune-related proteins TLR2, TLR4, and IgA. The number of CD3(+) T cells and CD3(+)CD4(+)CD8(-) T cells in the mesenteric lymph nodes (MLNs) was significantly lower, while the number of CD3(+)CD4(-)CD8(+) T cells was significantly increased. The bacteria isolated from the MLNs were Escherichia coli. Heat stress damages rat intestinal mechanical and mucosal immune barriers, and reduces immune function of the intestinal mucosa and mesenteric lymphoid tissues, leading to bacterial translocation.

  13. [A case of probable bacterial translocation-associated sepsis in healthy adult].

    Science.gov (United States)

    Ohosone, Yasuo; Obana, Mitsuo; Koido, Norihiko; Akizuki, Satoshi; Matsuoka, Yasuo; Kobayashi, Yoshio

    2004-03-01

    We report a patient with bacterial translocation-associated sepsis who was healthy and did not have any related-background. The 57-year-old male had been well until 16 hours before admission, when nausea and vomiting gradually developed and increased in intensity. In the morning of May 22, 2002, he had shaking chills, temperature of 38.6 degrees C and watery diarrhea, and was admitted to Kawasaki Municipal Hospital. On admission, temperature was 40.7 degrees C but otherwise physical examination revealed no particular abnormality. Laboratory data showed total white blood cells of 28,400/microliter, platelet count of 130,000/microliter, creatinine of 2.0 mg/dl and C-reactive protein of 7.5 mg/dl. 1 g of cefmetazole was administered every eight hours. In the early morning of May 23, he suddenly went into shock. At that time, laboratory findings revealed total white blood cells of 33,700/microliter, platelet count of 65,000/microliter, C-reactive protein of 24.9 mg/dl, creatinine of 5.6 mg/dl and serum potassium concentration of 5.7 mEq/l. Gram positive cocci and gram negative rods were isolated from blood culture obtained on admission. Cefmetazole was changed to 1.5 g/day of imipenem/cilastatin sodium and 600 mg/day of clindamycin. In addition, hemodialysis and endotoxin removal with an adsorbent column using polymyxin B were performed. Bacteria detected in the blood on admission were identified as Klebsiela oxytoca and Enterococcus faecium. Imipenem/cilastatin sodium and clindamycin were continued for 13 days. The patient recovered fully and was discharged on June 11. This case suggests that bacterial translocation-associated sepsis might occur even in a hitherto healthy adult.

  14. The normal bacterial flora prevents GI disease

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. The normal bacterial flora prevents GI disease. Inhibits pathogenic enteric bacteria. Decrease luminal pH; Secrete bacteriocidal proteins; Colonization resistance; Block epithelial binding – induce MUC2. Improves epithelial and mucosal barrier integrity. Produce ...

  15. The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Wadowsky, R M; DePudyt, L; Rowe, M I

    1991-04-01

    In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

  16. Giardia duodenalis induces paracellular bacterial translocation and causes postinfectious visceral hypersensitivity

    Science.gov (United States)

    Halliez, Marie C. M.; Motta, Jean-Paul; Feener, Troy D.; Guérin, Gaetan; LeGoff, Laetitia; François, Arnaud; Colasse, Elodie; Favennec, Loic; Gargala, Gilles; Lapointe, Tamia K.; Altier, Christophe

    2016-01-01

    Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis. At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field. PMID:26744469

  17. Assessment of bacterial translocation in obstructive jaundice using Tc-99m Escherichia coli

    International Nuclear Information System (INIS)

    Diniz, Simone Odilia Fernandes; Nelson, David Lee; Barbosa, Alfredo Jose Afonso; Araujo, Ivana Durval; Machado, Leonardo Augusto da Silva; Bernardo Filho, Mario

    2005-01-01

    In obstructive jaundice, the passage of bacteria and endotoxins through the intestine wall to reach the systemic circulation is associated with septicemia, renal failure and pulmonary dysfunction. The aim of this work was to investigate bacterial translocation utilizing 99m Tc-E.coli in an experimental model of obstructive jaundice. The levels of bilirubin in rats that were subjected to ligature of the bile duct were significantly increased when compared to control animals (p 99m Tc-E.coli to the mesenteric lymphatic nodules, liver, spleen or lungs of the rats that suffered ligature of the bile duct (p > 0.05). The evaluation of the intestinal permeability using 'per os' administration of 99m Tc-DTPA showed 1.61 ± 0.57% and 1.39 ± 0.72% of radioactivity in the urine of the control and jaundice animals, respectively. The histological analysis of the distal wall of the ileum showed that the covering epithelium and the crypt were morphologically preserved in both groups. The seven-day period after the ligature of the bile duct may not have been long enough to promote modifications in intestinal wall to occur so as to permit the passage of Tc-99m E.coli. (author)

  18. Three-dimensional structure of the bacterial protein-translocation complex SecYEG.

    Science.gov (United States)

    Breyton, Cécile; Haase, Winfried; Rapoport, Tom A; Kühlbrandt, Werner; Collinson, Ian

    2002-08-08

    Transport and membrane integration of polypeptides is carried out by specific protein complexes in the membranes of all living cells. The Sec transport path provides an essential and ubiquitous route for protein translocation. In the bacterial cytoplasmic membrane, the channel is formed by oligomers of a heterotrimeric membrane protein complex consisting of subunits SecY, SecE and SecG. In the endoplasmic reticulum membrane, the channel is formed from the related Sec61 complex. Here we report the structure of the Escherichia coli SecYEG assembly at an in-plane resolution of 8 A. The three-dimensional map, calculated from two-dimensional SecYEG crystals, reveals a sandwich of two membranes interacting through the extensive cytoplasmic domains. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15 transmembrane helices. In the centre of the dimer we observe a 16 x 25 A cavity closed on the periplasmic side by two highly tilted transmembrane helices. This may represent the closed state of the protein-conducting channel.

  19. Conformation of protein secreted across bacterial outer membranes: a study of enterotoxin translocation from Vibrio cholerae

    International Nuclear Information System (INIS)

    Hirst, T.R.; Holmgren, J.

    1987-01-01

    The secretion of enterotoxin by Vibrio cholerae is punctuated by the transient entry of the toxin subunits into the periplasm. In this paper, the authors show that the subunits oligomerize into an assembled holotoxin within the periplasm prior to their secretion across the outer membrane. The rate of toxin assembly was studied by pulse-labeling cells with [ 35 S]-methionine and then monitoring the turnover of radiolabeled subunits as they assembled within the periplasm. The subunits entered the periplasm as monomers and assembled into oligomers with a half-time of ≅ 1 min. Since assembly was a rapid event compared to the rate of toxin efflux from the periplasm, which had a half-time of ≅ 13 min, they conclude that all of the subunits that pass through the periplasm assemble before they traverse the outer membrane. The average concentration of subunit monomers and assembled holotoxin within the periplasm was calculated to be ≅ 20 and ≅ 260 μg/ml, respectively. This indicates that the periplasm is a suitably concentrated milieu where spontaneous toxin assembly can occur. These findings suggest that protein movement across bacterial outer membranes, in apparent contrast to export across other biological membranes, involves translocation of polypeptides that have already folded into tertiary and even quaternary conformations

  20. The soluble mannose receptor is released from the liver in cirrhotic patients, but is not associated with bacterial translocation

    DEFF Research Database (Denmark)

    Laursen, Tea L; Rødgaard-Hansen, Sidsel; Møller, Holger J

    2017-01-01

    for transjugular intrahepatic portosystemic shunt insertion as a result of refractory ascites (n=17), acute (n=3), or recurrent variceal bleeding (n=8). We analysed plasma from the portal and hepatic veins for bacterial DNA and soluble mannose receptor with qPCR and ELISA. RESULTS: The median soluble mannose...... correlated with the portal pressure prior to transjugular intrahepatic portosystemic shunt insertion (r=.52, Pvariceal bleeding compared...... levels in patients with acute variceal bleeding indicating the soluble mannose receptor as a marker of complications of cirrhosis, but not bacterial translocation....

  1. Use of molecular typing to investigate bacterial translocation from the intestinal tract of chlorpyrifos-exposed rats.

    Science.gov (United States)

    Joly Condette, Claire; Elion Dzon, Bertin; Hamdad, Farida; Biendo, Maurice; Bach, Véronique; Khorsi-Cauet, Hafida

    2016-01-01

    Human are confronted on a daily basis with contaminant pesticide residues in food, water and other components of the environment. Although the digestive system is the first organ to come into contact with food contaminants, very few data are available on the impact of low-dose pesticide exposure during the in utero and postnatal periods on intestinal bacterial translocation (BT). Previous studies have revealed that chlorpyrifos (CPF) exposure is associated with intestinal dysbiosis and the contamination of sterile organs. Here, molecular typing was used to investigate intestinal bacterial translocation in rats exposed to chlorpyrifos in utero and during lactation. The translocated bacteria were profiled, and CPF tolerance and antibiotic resistance traits were determined. A total of 72 intestinal segments and extra-intestinal organs were obtained from 14 CPF-exposed rats. The samples were cultured to isolate bacterial strains that had tolerated treatment with 1 or 5 mg CPF/kg bodyweight/day in vivo. Strains were identified using matrix-assisted laser desorption/ionization (MALDI) Biotyper. The disk diffusion method was used to determine the antibiotic susceptibility. The isolates were genotyped with PCR assays for the enterobacterial repetitive intergenic consensus sequence and random amplification polymorphic DNA. Bacterial translocation was confirmed for 7 of the 31 strains (22.6 %) isolated from extra-intestinal sites. Overall, the most prevalent bacteria were Staphylococcus aureus ( 55.5 % of the 72 intestinal and extra-intestinal isolates), Enterococcus faecalis (27.7 %) and Bacillus cereus (9.8 %). 5 % of the S. aureus isolates displayed methicillin resistance. Seventy two strains were identified phenotypically, and seven translocated strains (mainly S. aureus ) were identified by genotyping. Genotypically confirmed translocation was mainly observed found in pesticide-exposed groups (6 out of 7). BT from the intestinal tract colonized normally sterile

  2. INTESTINAL BACTERIAL TRANSLOCATION IN EXPERIMENTALLY BURNED MICE WITH WOUNDS COLONIZED BY PSEUDOMONAS-AERUGINOSA

    NARCIS (Netherlands)

    MANSON, WL; COENEN, JMFH; KLASEN, HJ; HORWITZ, EH

    1992-01-01

    Translocation of micro-organisms from the gastrointestinal tract may play a role in the pathogenesis of septic complications in severely burned patients. We therefore investigated the influence of burn wound infection with Pseudomonas aeruginosa on translocation in experimentally burned mice. The P.

  3. Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

    OpenAIRE

    Qing Zeng; Xiaolong He; Santhosh Puthiyakunnon; Hansen Xiao; Zelong Gong; Swapna Boddu; Lecheng Chen; Huiwen Tian; Huiwen Tian; Sheng-He Huang; Sheng-He Huang; Hong Cao

    2017-01-01

    Escherichia coli (E. coli) K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS) has a preventive role against neonatal E. coli K1 bacteremia and men...

  4. Detergent disruption of bacterial inner membranes and recovery of protein translocation activity

    International Nuclear Information System (INIS)

    Cunningham, K.; Wickner, W.T.

    1989-01-01

    Isolation of the integral membrane components of protein translocation requires methods for fractionation and functional reconstitution. The authors treated inner-membrane vesicles of Escherichia coli with mixtures of octyl β-D-glucoside, phospholipids, and an integral membrane carrier protein under conditions that extract most of the membrane proteins into micellar solution. Upon dialysis, proteoliposomes were reconstituted that supported translocation of radiochemically pure [ 35 S]pro-OmpA (the precursor of outer membrane protein A). Translocation into these proteoliposomes required ATP hydrolysis and membrane proteins, indicating that the reaction is that of the inner membrane. The suspension of membranes in detergent was separated into supernatant and pellet fractions by ultracentrifugation. After reconstitution, translocation activity was observed in both fractions, but processing by leader peptidase of translocated pro-OmpA to OmpA was not detectable in the reconstituted pellet fraction. Processing activity was restored by addition of pure leader peptidase as long as this enzyme was added before detergent removal, indicating that the translocation activity is not associated with detergent-resistant membrane vesicles. These results show that protein translocation activity can be recovered from detergent-disrupted membrane vesicles, providing a first step towards the goal of isolating the solubilized components

  5. Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

    Science.gov (United States)

    Mandorfer, M; Schwabl, P; Paternostro, R; Pomej, K; Bauer, D; Thaler, J; Ay, C; Quehenberger, P; Fritzer-Szekeres, M; Peck-Radosavljevic, M; Trauner, M; Reiberger, T; Ferlitsch, A

    2018-04-01

    Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P protein [CRP; ρ = 0.249; P protein C ratio; ρ = 0.507; P model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis. © 2018 John Wiley & Sons Ltd.

  6. Assessment of bacterial translocation in obstructive jaundice using Tc-99m Escherichia coli

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    Simone Odília Fernandes Diniz

    2005-10-01

    Full Text Available In obstructive jaundice, the passage of bacteria and endotoxins through the intestine wall to reach the systemic circulation is associated with septicemia, renal failure and pulmonary dysfunction. The aim of this work was to investigate bacterial translocation utilizing 99mTc-E.coli in an experimental model of obstructive jaundice. The levels of bilirubin in rats that were subjected to ligature of the bile duct were significantly increased when compared to control animals (p 0.05. The evaluation of the intestinal permeability using "per os" administration of 99mTc-DTPA showed 1.61 ± 0.57% and 1.39 ± 0.72% of radioactivity in the urine of the control and jaundice animals, respectively. The histological analysis of the distal wall of the ileum showed that the covering epithelium and the crypt were morphologically preserved in both groups. The seven-day period after the ligature of the bile duct may not have been long enough to promote modifications in intestinal wall to occur so as to permit the passage of Tc-99m E.coli.Na icterícia obstrutiva, a passagem de bactérias e endotoxinas através da parede intestinal alcançando a circulação sistêmica está associada com septicemia, falência renal e disfunção pulmonar. A proposta deste trabalho foi investigar a translocação bacteriana, empregando a Tc-99m E.coli, em um modelo experimental de icterícia obstrutiva. Os níveis de bilirrubina nos ratos que sofreram a ligadura do ducto biliar estavam significativamente aumentados quando comparados com os valores dos animais controles (p0,05. A avaliação da permeabilidade intestinal usando a administração "per os" de 99mTc-DTPA mostrou um percentual de eliminação deste radiofármaco na urina de 1,61±0,57 e 1,39±0,72 para os animais controles e ictéricos, respectivamente. A análise histológica da parede distal do íleo mostrou que tanto o epitélio de revestimento quanto as criptas apresentaram morfologicamente conservados em ambos os

  7. Structural and functional characterization of the bacterial translocation inhibitor GE82832.

    Science.gov (United States)

    Brandi, Letizia; Maffioli, Sonia; Donadio, Stefano; Quaglia, Fabio; Sette, Marco; Milón, Pohl; Gualerzi, Claudio O; Fabbretti, Attilio

    2012-09-21

    The structure of GE82832, a translocation inhibitor produced by a soil microorganism, is shown to be highly related to that of dityromycin, a bicyclodecadepsipeptide antibiotic discovered long ago whose characterization had never been pursued beyond its structural elucidation. GE82832 and dityromycin were shown to interfere with both aminoacyl-tRNA and mRNA movement and with the Pi release occurring after ribosome- and EF-G-dependent GTP hydrolysis. These findings and the unusual ribosomal localization of GE82832/dityromycin near protein S13 suggest that the mechanism of inhibition entails an interference with the rotation of the 30S subunit "head" which accompanies the ribosome-unlocking step of translocation. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Role of a Bacillus subtilis Direct-Fed Microbial on Digesta Viscosity, Bacterial Translocation, and Bone Mineralization in Turkey Poults Fed with a Rye-Based Diet.

    Science.gov (United States)

    Latorre, Juan D; Hernandez-Velasco, Xochitl; Kogut, Michael H; Vicente, Jose L; Wolfenden, Ross; Wolfenden, Amanda; Hargis, Billy M; Kuttappan, Vivek A; Tellez, Guillermo

    2014-01-01

    Rye contains high concentrations of non-starch polysaccharides (NSPs), leading to reduced digestibility. Since poultry have little or no endogenous enzymes capable of hydrolyzing these NSP, exogenous carbohydrases as feed additives are used in an attempt to reduce the anti-nutritional effects of these polysaccharides. Previously, an in vitro study conducted in our laboratory showed that inclusion of certain Bacillus direct-fed microbial (DFM) candidates that produce exogenous phytase, lipase, protease, cellulase, and xylanase in high-NSP diets significantly reduced both digesta viscosity and Clostridium perfringens proliferation. In the present study, rye-based turkey starter diets with or without Bacillus-DFM were administered ad libitum to day-of-hatch turkey poults in two independent experiments. In both experiments, day-of-hatch turkey poults were randomly assigned to either a control diet (CON) or a DFM treated diet (n = 25 birds/group). At 10 days-of-age, all turkey poults from experiments 1 and 2 were weighted and 12 turkey poults/group were randomly selected and humanely killed. Liver samples were aseptically collected to evaluate bacterial translocation, and intestinal digesta samples were individually collected to evaluate viscosity. Additionally, in experiment 2 both tibias were removed for assessment of bone parameters. In both experiments, the treated group showed a reduction in the total number of coliforms in the liver and a reduced digesta viscosity when compared to the CON group (P content, calcium content, and phosphorus content when compared with CON turkey poults. In summary, turkey poults fed with a rye-based diet without DFM showed an increase in bacterial translocation and digesta viscosity, accompanied by a reduction in bone mineralization; however, these adverse effects can be prevented by the inclusion of selected a Bacillus-DFM candidate in high-NSP diets.

  9. Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition and bone mineralization in broiler chickens

    Directory of Open Access Journals (Sweden)

    Guillermo eTellez

    2014-09-01

    Full Text Available Two independent trials were conducted to evaluate the utilization of rye as energy source on bacterial translocation, intestinal viscosity, gut integrity, gut microbiota composition, and bone mineralization, when compared with a traditional cereal (corn in broiler chickens. In each experiment, day-of-hatch, broiler chickens were randomly assigned to either a corn or a rye diet (n = 20 chickens/group. At 10d of age, in both experiments, 12 chickens/group were randomly selected, and given an oral gavage dose of fluorescein isothiocyanate dextran (FITC-d. After 2.5 h of oral gavage, blood samples were collected to determine the passage of FITC-d. The liver was collected from each bird to evaluate bacterial translocation (BT. Duodenum, ileum and cecum gut sections were collected to evaluate intestinal viscosity and to enumerate gut microbiota. Tibias were collected for observation of bone parameters. Broilers fed with rye showed increased (p < 0.05 intestinal viscosity, BT, and serum FITC-d. Bacterial enumeration revealed that chickens fed with rye had increased the number of total lactic acid bacteria (LAB in all three sections of the gastrointestinal tract evaluated when compared to chickens fed with corn. Chickens fed with rye also had significantly higher coliforms in duodenum and ileum, whereas the total number of anaerobes increased only in duodenum. A significant reduction in bone strength and bone mineralization was observed in chickens fed with rye when compared with corn fed chickens. In conclusion, rye evoked mucosal damage in chickens that alter the intestinal viscosity, increased leakage through the intestinal tract, and altered the microbiota composition as well as bone mineralization. Studies to evaluate dietary inclusion of selected DFM candidates that produce exogenous enzymes in rye fed chickens are currently being evaluated.

  10. Bacterial translocation and cardiovascular complications of cirrhosis. Authors' response to letter

    DEFF Research Database (Denmark)

    Møller, Søren; Henriksen, Jens Henrik

    2008-01-01

    dysfunction have been somewhat unpredictable.3-5 In two conditions, however, a direct relationship between bacterial infection and increased mortality have been proved, namely infections in relation to bleeding from oesophageal varices and spontaneous bacterial peritonitis.6-8 In both of these complications...

  11. Probiotic Mixture Golden Bifido Prevents Neonatal Escherichia coli K1 Translocation via Enhancing Intestinal Defense

    Directory of Open Access Journals (Sweden)

    Qing Zeng

    2017-09-01

    Full Text Available Escherichia coli (E. coli K1 sepsis and meningitis is a severe infection characterized by high mortality in neonates. Successful colonization and translocation across the intestinal mucosa have been regarded as the critical steps for E. coli K1 sepsis and meningitis. We recently reported that the probiotic mixture, Golden Bifido (containing live Lactobacillus bulgaricus, Bifidobacterium, and Streptococcus thermophilus, LBS has a preventive role against neonatal E. coli K1 bacteremia and meningitis. However, the interaction between the neonatal gut barrier, probiotics and E. coli K1 is still not elucidated. The present study aims to investigate how LBS exerts its protective effects on neonatal gut barrier during E. coli K1 infection. The beneficial effects of LBS were explored in vitro and in vivo using human colon carcinoma cell lines HT-29 and rat model of neonatal E. coli K1 infection, respectively. Our results showed that stimulation with E. coli K1 was able to cause intestinal barrier dysfunction, which were reflected by E. coli K1-induced intestinal damage and apoptosis of intestinal epithelial cells, reduction of mucin, immunoglobulin A (IgA and tight junction proteins expression, as well as increase in intestinal permeability, all these changes facilitate E. coli K1 intestinal translocation. However, these changes were alleviated when HT-29 cells were treated with LBS before E. coli K1 infection. Furthermore, we found that LBS-treated neonatal rats (without E. coli K1 infection have showed higher production of mucin, ZO-1, IgA, Ki67 in intestinal mucosa as well as lower intestinal permeability than that of non-treated rats, indicating that LBS could accelerate the development of neonatal intestinal defense. Taken together, our results suggest that enhancement of the neonatal intestinal defense to fight against E. coli K1 translocation could be the potential mechanism to elucidate how LBS confers a protective effect against neonatal E

  12. Bartonella henselae: subversion of vascular endothelial cell functions by translocated bacterial effector proteins.

    Science.gov (United States)

    Pulliainen, Arto Tapio; Dehio, Christoph

    2009-03-01

    Bartonella henselae (Bh) is a worldwide distributed zoonotic pathogen. Depending on the immune status of the infected individual this bacterium can cause a wide spectrum of clinical manifestations, ranging from cat scratch disease (CSD) to bacillary angiomatosis (BA) and bacillary peliosis (BP). BA and BP are characterized by tumor-like lesions at the skin or in the inner organs, respectively. These structures display pathological sprouting of capillaries with enlarged and hyperproliferated vascular endothelial cells (ECs) that are frequently found in close association with bacteria. Here we review the cellular changes observed upon Bh infection of ECs in vitro and outline the role of the VirB type IV secretion system (T4SS) and its translocated effector proteins in the modulation of EC signalling cascades. The current model how this virulence system could contribute to the vasoproliferative activity of Bh is described.

  13. Saccharomyces cerevisiae strain UFMG 905 protects against bacterial translocation, preserves gut barrier integrity and stimulates the immune system in a murine intestinal obstruction model.

    Science.gov (United States)

    Generoso, Simone V; Viana, Mirelle; Santos, Rosana; Martins, Flaviano S; Machado, José A N; Arantes, Rosa M E; Nicoli, Jacques R; Correia, Maria I T D; Cardoso, Valbert N

    2010-06-01

    Probiotic is a preparation containing microorganisms that confers beneficial effect to the host. This work assessed whether oral treatment with viable or heat-killed yeast Saccharomyces cerevisiae strain UFMG 905 prevents bacterial translocation (BT), intestinal barrier integrity, and stimulates the immunity, in a murine intestinal obstruction (IO) model. Four groups of mice were used: mice undergoing only laparotomy (CTL), undergoing intestinal obstruction (IO) and undergoing intestinal obstruction after previous treatment with viable or heat-killed yeast. BT, determined as uptake of (99m)Tc-E. coli in blood, mesenteric lymph nodes, liver, spleen and lungs, was significantly higher in IO group than in CTL group. Treatments with both yeasts reduced BT in blood and all organs investigated. The treatment with both yeasts also reduced intestinal permeability as determined by blood uptake of (99m)Tc-DTPA. Immunological data demonstrated that both treatments were able to significantly increase IL-10 levels, but only viable yeast had the same effect on sIgA levels. Intestinal lesions were more severe in IO group when compared to CTL and yeasts groups. Concluding, both viable and heat-killed cells of yeast prevent BT, probably by immunomodulation and by maintaining gut barrier integrity. Only the stimulation of IgA production seems to depend on the yeast viability.

  14. Portal versus systemic drainage of small bowel allografts: comparative assessment of survival, function, rejection, and bacterial translocation.

    Science.gov (United States)

    Berney, Thierry; Kato, Tomoaki; Nishida, Seigo; Tector, A Joseph; Mittal, Naveen K; Madariaga, Juan; Nery, Jose R; Cantwell, G Patricia; Ruiz, Philip; Tzakis, Andreas G

    2002-12-01

    Portal venous drainage of small bowel grafts is theoretically more physiologic than systemic drainage, but is technically more demanding. Comparisons in animal models have not demonstrated a clear advantage of one technique over the other, but clinical data are lacking. Clinical records of 36 patients who underwent 37 small bowel transplantation procedures from January 1995 to August 2001 were reviewed. Portal drainage was performed in 19 patients (PD group). Systemic drainage was performed in 18 patients (SD group). Median followup was 531 days. PD and SD patients had similar ICU stays (median 7 versus 9 days) and endotracheal intubation durations (median 3 versus 5 days). All current survivors, with the exception of one patient in each group, are independent from parenteral nutrition. Liver function tests were similar in both groups. There was a twofold increase in tacrolimus dosage in the PD group to achieve similar trough levels indicating a "first-pass" hepatic clearance effect. Cumulative incidence of acute rejection episodes and OKT3-requiring rejection episodes were similar in both groups. To the contrary, a lower incidence of gram-negative rods of Enterococcus sp. in blood or bronchoalveolar lavage suggested that the clearance of translocated intestinal bacteria was more efficient in the PD group. Graft and patient survival rates were similar in both groups. Systemic venous drainage of small bowel transplants is a dependable technique, associated with similar results as portal venous drainage, in terms of overall mortality, morbidity, rejection, function, and patient and graft survival. But attention should be paid to an impaired clearance of intestinal bacterial translocation after systemic drainage.

  15. The Bordetella Secreted Regulator BspR Is Translocated into the Nucleus of Host Cells via Its N-Terminal Moiety: Evaluation of Bacterial Effector Translocation by the Escherichia coli Type III Secretion System.

    Directory of Open Access Journals (Sweden)

    Akio Abe

    Full Text Available Bordetella bronchiseptica is genetically related to B. pertussis and B. parapertussis, which cause respiratory tract infections in humans. These pathogens possess a large number of virulence factors, including the type III secretion system (T3SS, which is required for the delivery of effectors into the host cells. In a previous study, we identified a transcriptional regulator, BspR, that is involved in the regulation of the T3SS-related genes in response to iron-starved conditions. A unique feature of BspR is that this regulator is secreted into the extracellular milieu via the T3SS. To further characterize the role of BspR in extracellular localization, we constructed various truncated derivatives of BspR and investigated their translocation into the host cells using conventional translocation assays. In this study, the effector translocation was evaluated by the T3SS of enteropathogenic E. coli (EPEC, since the exogenous expression of BspR triggers severe repression of the Bordetella T3SS expression. The results of the translocation assays using the EPEC T3SS showed that the N-terminal 150 amino acid (aa residues of BspR are sufficient for translocation into the host cells in a T3SS-dependent manner. In addition, exogenous expression of BspR in HeLa cells demonstrated that the N-terminal 100 aa residues are involved in the nuclear localization. In contrast, the N-terminal 54 aa residues are sufficient for the extracellular secretion into the bacterial culture supernatant via the EPEC T3SS. Thus, BspR is not only a transcriptional regulator in bacteria cytosol, but also functions as an effector that translocates into the nuclei of infected host cells.

  16. The Bordetella Secreted Regulator BspR Is Translocated into the Nucleus of Host Cells via Its N-Terminal Moiety: Evaluation of Bacterial Effector Translocation by the Escherichia coli Type III Secretion System.

    Science.gov (United States)

    Abe, Akio; Nishimura, Ryutaro; Tanaka, Naomichi; Kurushima, Jun; Kuwae, Asaomi

    2015-01-01

    Bordetella bronchiseptica is genetically related to B. pertussis and B. parapertussis, which cause respiratory tract infections in humans. These pathogens possess a large number of virulence factors, including the type III secretion system (T3SS), which is required for the delivery of effectors into the host cells. In a previous study, we identified a transcriptional regulator, BspR, that is involved in the regulation of the T3SS-related genes in response to iron-starved conditions. A unique feature of BspR is that this regulator is secreted into the extracellular milieu via the T3SS. To further characterize the role of BspR in extracellular localization, we constructed various truncated derivatives of BspR and investigated their translocation into the host cells using conventional translocation assays. In this study, the effector translocation was evaluated by the T3SS of enteropathogenic E. coli (EPEC), since the exogenous expression of BspR triggers severe repression of the Bordetella T3SS expression. The results of the translocation assays using the EPEC T3SS showed that the N-terminal 150 amino acid (aa) residues of BspR are sufficient for translocation into the host cells in a T3SS-dependent manner. In addition, exogenous expression of BspR in HeLa cells demonstrated that the N-terminal 100 aa residues are involved in the nuclear localization. In contrast, the N-terminal 54 aa residues are sufficient for the extracellular secretion into the bacterial culture supernatant via the EPEC T3SS. Thus, BspR is not only a transcriptional regulator in bacteria cytosol, but also functions as an effector that translocates into the nuclei of infected host cells.

  17. Interleukin-10 inhibits osteoclastogenesis by reducing NFATc1 expression and preventing its translocation to the nucleus

    Directory of Open Access Journals (Sweden)

    Fox Simon W

    2007-01-01

    Full Text Available Abstract Background IL-10 has a potent inhibitory effect on osteoclastogenesis. In vitro and in vivo studies confirm the importance of this cytokine in bone metabolism, for instance IL-10-deficient mice develop the hallmarks of osteoporosis. Although it is known that IL-10 directly inhibits osteoclastogenesis at an early stage, preventing differentiation of osteoclast progenitors to preosteoclasts, the precise mechanism of its action is not yet clear. Several major pathways regulate osteoclastogenesis, with key signalling genes such as p38, TRAF6, NF-κB and NFATc1 well established as playing vital roles. We have looked at gene expression in eleven of these genes using real-time quantitative PCR on RNA extracted from RANKL-treated RAW264.7 monocytes. Results There was no downregulation by IL-10 of DAP12, FcγRIIB, c-jun, RANK, TRAF6, p38, NF-κB, Gab2, Pim-1, or c-Fos at the mRNA level. However, we found that IL-10 significantly reduces RANKL-induced NFATc1 expression. NFATc1 is transcribed from two alternative promoters in Mus musculus and, interestingly, only the variant transcribed from promoter P1 and beginning with exon 1 was downregulated by IL-10 (isoform 1. In addition, immunofluorescence studies showed that IL-10 reduces NFATc1 levels in RANKL-treated precursors and suppresses nuclear translocation. The inhibitory effect of IL-10 on tartrate-resistant acid phosphatase-positive cell number and NFATc1 mRNA expression was reversed by the protein kinase C agonist phorbol myristate acetate, providing evidence that interleukin-10 disrupts NFATc1 activity through its effect on Ca2+ mobilisation. Conclusion IL-10 acts directly on mononuclear precursors to inhibit NFATc1 expression and nuclear translocation, and we provide evidence that the mechanism may involve disruption of Ca2+ mobilisation. We detected downregulation only of the NFATc1 isoform 1 transcribed from promoter P1. This is the first report indicating that one of the ways in which

  18. Effect of adenine on bacterial translocation using technetium-99m labeled E. coli in an intestinal obstruction model in rats

    International Nuclear Information System (INIS)

    Ugur Oflaz; Fatma Yurt Lambrecht; Osman Yilmaz; Cetin Pekcetin

    2013-01-01

    This study aims to investigate effects of adenine on bacterial translocation (BT) using 99m Tc-labeled E. coli in an intestinal obstruction rat model. In the study twenty-one rats were used. The rats were divided into three groups according to different feeding patterns. The control group (CG) was fed with a standard chow diet for 7 days. Group A1 and group A2 were fed with adenine supplemented chow diet for 7 days. At the end of the feeding period, after all groups was submitted intestinal obstruction. 99m Tc-E. coli was injected into the rats' terminal ileum under anesthetic. The rats were sacrificed under aseptic conditions at 24th h after the surgery. The uptake of 99m Tc-E. coli was determined in organs such as the liver, mesenteric lymph nodes, spleen and ileum. Group A1 and group A2 results show that the uptake of 99m Tc-E. coli decreased in the blood and organs comparing to the CG. As a result, it was observed that adenine reduced the level of BT when compared with CG. The beneficial effect of adenine on BT in intestinal obstruction was observed. However, further studies are needed to more clearly assess how this benefit can be achieved. (author)

  19. Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

    Science.gov (United States)

    Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

    2016-11-01

    Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

  20. Finding of widespread viral and bacterial revolution dsDNA translocation motors distinct from rotation motors by channel chirality and size.

    Science.gov (United States)

    De-Donatis, Gian Marco; Zhao, Zhengyi; Wang, Shaoying; Huang, Lisa P; Schwartz, Chad; Tsodikov, Oleg V; Zhang, Hui; Haque, Farzin; Guo, Peixuan

    2014-01-01

    Double-stranded DNA translocation is ubiquitous in living systems. Cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging and cell entry all involve biomotor-driven dsDNA translocation. Previously, biomotors have been primarily classified into linear and rotational motors. We recently discovered a third class of dsDNA translocation motors in Phi29 utilizing revolution mechanism without rotation. Analogically, the Earth rotates around its own axis every 24 hours, but revolves around the Sun every 365 days. Single-channel DNA translocation conductance assay combined with structure inspections of motor channels on bacteriophages P22, SPP1, HK97, T7, T4, Phi29, and other dsDNA translocation motors such as bacterial FtsK and eukaryotic mimiviruses or vaccinia viruses showed that revolution motor is widespread. The force generation mechanism for revolution motors is elucidated. Revolution motors can be differentiated from rotation motors by their channel size and chirality. Crystal structure inspection revealed that revolution motors commonly exhibit channel diameters larger than 3 nm, while rotation motors that rotate around one of the two separated DNA strands feature a diameter smaller than 2 nm. Phi29 revolution motor translocated double- and tetra-stranded DNA that occupied 32% and 64% of the narrowest channel cross-section, respectively, evidencing that revolution motors exhibit channel diameters significantly wider than the dsDNA. Left-handed oriented channels found in revolution motors drive the right-handed dsDNA via anti-chiral interaction, while right-handed channels observed in rotation motors drive the right-handed dsDNA via parallel threads. Tethering both the motor and the dsDNA distal-end of the revolution motor does not block DNA packaging, indicating that no rotation is required for motors of dsDNA phages, while a small-angle left-handed twist of dsDNA that is

  1. Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention.

    Science.gov (United States)

    Mount, Hillary R; Boyle, Sean D

    2017-09-01

    The etiologies of meningitis range in severity from benign and self-limited to life-threatening with potentially severe morbidity. Bacterial meningitis is a medical emergency that requires prompt recognition and treatment. Mortality remains high despite the introduction of vaccinations for common pathogens that have reduced the incidence of meningitis worldwide. Aseptic meningitis is the most common form of meningitis with an annual incidence of 7.6 per 100,000 adults. Most cases of aseptic meningitis are viral and require supportive care. Viral meningitis is generally self-limited with a good prognosis. Examination maneuvers such as Kernig sign or Brudzinski sign may not be useful to differentiate bacterial from aseptic meningitis because of variable sensitivity and specificity. Because clinical findings are also unreliable, the diagnosis relies on the examination of cerebrospinal fluid obtained from lumbar puncture. Delayed initiation of antibiotics can worsen mortality. Treatment should be started promptly in cases where transfer, imaging, or lumbar puncture may slow a definitive diagnosis. Empiric antibiotics should be directed toward the most likely pathogens and should be adjusted by patient age and risk factors. Dexamethasone should be administered to children and adults with suspected bacterial meningitis before or at the time of initiation of antibiotics. Vaccination against the most common pathogens that cause bacterial meningitis is recommended. Chemoprophylaxis of close contacts is helpful in preventing additional infections.

  2. The uptake, distribution and translocation of 86Rb in alfalfa plants susceptible and resistant to the bacterial wilt and the effect of Corynebacterium insidiosum upon these processes

    International Nuclear Information System (INIS)

    Hanker, I.; Kudelova, A.

    1981-01-01

    Alfalfa (Medicago sativa L.) plants susceptible (S) and resistant (R) to bacterial wilt were fed via roots with a nutrient solution labelled with 86 Rb + , at different times after inoculation with Corynebacterium insidiosum (McCull.) H.L. Jens. The infection did not affect 86 Rb + uptake per plant in the course of a 14-day-period following inoculation; however, it affected its distribution differently in the S- and the R-plants. 86 Rb + uptake significantly decreased due to the infection in the S-plants on the day 49 after inoculation (a 4-h-exposure to 86 Rb + ), with the ions more slowly translocated to the shoots in diseased S-plants than in diseased R-plants. Likely factors causing these effects and their relationship to alfalfa resistance to bacterial wilt are discussed. (author)

  3. Translocação bacteriana para o rim na icterícia obstrutiva experimental Bacterial translocation to kidney in obstructive experimental jaundice

    Directory of Open Access Journals (Sweden)

    Aldo da Cunha Medeiros

    1997-06-01

    Full Text Available Estudo com o objetivo de verificar a possibilidade de ocorrência de translocação bacteriana para os rins de ratos, após ligadura de colédoco. Foram utilizados 29 ratos Wistar com peso médio de 171 ± 12,6g. Os animais foram divididos aleatoriamente em grupo I (n=14 e grupo II (n=15. Com técnica asséptica, nos ratos no grupo I foi feita ligadura de colédoco com fio de seda nº 3 zeros e no grupo II foi simulada a ligadura com a simples manipulação do colédoco com pinça de Adson ("sham operation". No 7º dia pós-operatório os animais foram sacrificados e ressecados os rins para exame histopatológico (coloração H.E. e microbiológico (meios agar sangue e agar MacConkey. Houve crescimento bacteriano de Klebsiela sp em 28,5% dos casos no grupo I e foram observadas alterações histopatológicas significativas no mesmo grupo. As diferenças foram estatisticamente significantes quando foram comparados os 2 grupos (pExperimental study in order to determine if obstructive jaundice promotes basterial translocation from the gastrointestinal tract to the kidney in rats. We used 29 Wistar male rats weighing 171±12,6g. They were ramdomly separated in goup I (n=14 and group II (n=15 and operated with asseptic technic. The group I underwent common bile ducts ligature with number 000 silk suture, and in group II (control the common bile ducts were manipulated with Adson forceps, as a sham operation. On 7th postoperative day the rats were killed with an overdose of anesthesic and had their kidneys resected. Portions of each kidney were harvested for quantitation of bacterial translocation and histopatologic examination. The incidance of bacterial translocation was 28,5% (Klebsiella sp in group I and 0% in group II (p<0,05. Intersticial edema, nephrosis and tubular degeneration were observed in group I and the histology was normal in group II. The authors conclude that obstructive ajundice promotes bacterial translocation to the kidney

  4. A small molecule inhibits Akt through direct binding to Akt and preventing Akt membrane translocation.

    Science.gov (United States)

    Kim, Donghwa; Sun, Mei; He, Lili; Zhou, Qing-Hua; Chen, Jun; Sun, Xia-Meng; Bepler, Gerold; Sebti, Said M; Cheng, Jin Q

    2010-03-12

    The Akt pathway is frequently hyperactivated in human cancer and functions as a cardinal nodal point for transducing extracellular and intracellular oncogenic signals and, thus, presents an exciting target for molecular therapeutics. Here we report the identification of a small molecule Akt/protein kinase B inhibitor, API-1. Although API-1 is neither an ATP competitor nor substrate mimetic, it binds to pleckstrin homology domain of Akt and blocks Akt membrane translocation. Furthermore, API-1 treatment of cancer cells results in inhibition of the kinase activities and phosphorylation levels of the three members of the Akt family. In contrast, API-1 had no effects on the activities of the upstream Akt activators, phosphatidylinositol 3-kinase, phosphatidylinositol-dependent kinase-1, and mTORC2. Notably, the kinase activity and phosphorylation (e.g. Thr(P)(308) and Ser(P)(473)) levels of constitutively active Akt, including a naturally occurring mutant AKT1-E17K, were inhibited by API-1. API-1 is selective for Akt and does not inhibit the activation of protein kinase C, serum and glucocorticoid-inducible kinase, protein kinase A, STAT3, ERK1/2, or JNK. The inhibition of Akt by API-1 resulted in induction of cell growth arrest and apoptosis selectively in human cancer cells that harbor constitutively activated Akt. Furthermore, API-1 inhibited tumor growth in nude mice of human cancer cells in which Akt is elevated but not of those cancer cells in which it is not. These data indicate that API-1 directly inhibits Akt through binding to the Akt pleckstrin homology domain and blocking Akt membrane translocation and that API-1 has anti-tumor activity in vitro and in vivo and could be a potential anti-cancer agent for patients whose tumors express hyperactivated Akt.

  5. Ofloxacin and Penicillin G Combination Therapy in Prevention of Bacterial Translocation and Animal Mortality after Irradiation,

    Science.gov (United States)

    1991-08-01

    best with sepsis (4). The livers were aseptically removed and homogenized immediately. The liver specimens were swabbed onto blood and MacCon...Balews, W. Hanuder, and J. H. Shadomy ciprofloxacin, norfloxacin and nalidixic acid. Eur. J. Clin. (ed.). 1985. Manual of clinical microbiology. 4th ed...of the intestinal tract by norfloxacin in comparison of pefloxacin. ciprofloxacin and ofloxacin. Radiat. human voluntzers and in gnotobiotic mice

  6. Absence of phosphatidylcholine in bacterial membranes facilitates translocation of Sec-dependent β-lactamase AmpC from cytoplasm to periplasm in two Pseudomonas strains.

    Science.gov (United States)

    Liu, Xin; Sun, Yufang; Cao, Fang; Xiong, Min; Yang, Sheng; Li, Yang; Yu, Xuejing; Li, Yadong; Wang, Xingguo

    2017-05-01

    Phosphatidylcholine (PC) is a rare membrane lipid in bacteria but crucial for virulence of various plant and animal pathogens. The pcs- mutant lacking PC in bacterial membranes of Pseudomonas syringae pv. syringae van Hall 1336 displayed more ampicillin resistance. Ampicillin susceptibility tests gave an IC50 (half maximal inhibitory concentration) of 52 mg/ml for Pseudomonas syringae pv. syringae van Hall 1336, 53 mg/ml for the complemented strain 1336 RM (pcs-/+) and 90 mg/ml for the 1336 pcs- mutant. Activity assay of β-lactamase in periplasmic extracts gave 0.050 U/mg for the 1336 wild type, 0.052 U/mg for the 1336RM (pcs-/+), 0.086 U/mg for the 1336 pcs- mutant. Analysis by western blotting showed that the content of AmpC enzyme was markedly different in periplasmic extracts between the wild-type and pcs- mutant strains. Reverse transcriptase PCR also showed that the presence or absence of PC in bacterial membranes did not affect the transcription of ampC gene. The phenotype of the pcs- mutant was able to be recovered to the wild type by introducing a wild-type pcs gene into the pcs- mutant. Similar results were also obtained from the soil-dwelling bacterium Pseudomonas sp. 593. Our results demonstrate that the absence of PC in bacterial membranes facilitates the translocation of Sec-dependent β-lactamase AmpC from cytoplasm to periplasm, and the enhanced ampicillin-resistance in the pcs- strains mainly comes from effective translocation of AmpC via Sec-pathway. Copyright © 2016. Published by Elsevier Ltd.

  7. Preventing Bacterial Infections using Metal Oxides Nanocoatings on Bone Implant

    Science.gov (United States)

    Duceac, L. D.; Straticiuc, S.; Hanganu, E.; Stafie, L.; Calin, G.; Gavrilescu, S. L.

    2017-06-01

    Nowadays bone implant removal is caused by infection that occurs around it possibly acquired after surgery or during hospitalization. The purpose of this study was to reveal some metal oxides applied as coatings on bone implant thus limiting the usual antibiotics-resistant bacteria colonization. Therefore ZnO, TiO2 and CuO were synthesized and structurally and morphologically analized in order to use them as an alternative antimicrobial agents deposited on bone implant. XRD, SEM, and FTIR characterization techniques were used to identify structure and texture of these nanoscaled metal oxides. These metal oxides nanocoatings on implant surface play a big role in preventing bacterial infection and reducing surgical complications.

  8. A case of reversible posterior leukoencephalopathy syndrome which developed during chemoradiotherapy for head and neck cancer. The involvement of bacterial translocation was considered

    International Nuclear Information System (INIS)

    Tachibana, Shinya; Terao, Hajime; Sanbe, Takeyuki; Katsuno, Masahiro; Takemura, Hideki

    2007-01-01

    Combination therapy such as chemotherapy and radiotherapy is often chosen, depending on the case, for head and neck cancer in view of the preservation of potency. However, on the other hand, it is necessary to note the onset of therapeutic side effects. The patient was a 35-year-old woman. During chemoradiotherapy for mesopharyngeal carcinoma, she suddenly developed shock and multiple organ failure, requiring intensive treatment. She also developed reversible central nerve symptoms during the course. The involvement of bacterial translocation was thought to be the cause of shock, and the reversible central nerve symptoms were considered to be a pathological condition, known as reversible posterior leukoencephalopathy syndrome. We discuss these conditions on the basis of the clinical features, and the process that led to diagnosis in this case. (author)

  9. Nanosized Selenium: A Novel Platform Technology to Prevent Bacterial Infections

    Science.gov (United States)

    Wang, Qi

    As an important category of bacterial infections, healthcare-associated infections (HAIs) are considered an increasing threat to the safety and health of patients worldwide. HAIs lead to extended hospital stays, contribute to increased medical costs, and are a significant cause of morbidity and mortality. In the United States, infections encountered in the hospital or a health care facility affect more than 1.7 million patients, cost 35.7 billion to 45 billion, and contribute to 88,000 deaths in hospitals annually. The most conventional and widely accepted method to fight against bacterial infections is using antibiotics. However, because of the widespread and sometimes inappropriate use of antibiotics, many strains of bacteria have rapidly developed antibiotic resistance. Those new, stronger bacteria pose serious, worldwide threats to public health and welfare. In 2014, the World Health Organization (WHO) reported antibiotic resistance as a global serious threat that is no longer a prediction for the future but is now reality. It has the potential to affect anyone, of any age, in any country. The most effective strategy to prevent antibiotic resistance is minimizing the use of antibiotics. In recent years, nanomaterials have been investigated as one of the potential substitutes of antibiotics. As a result of their vastly increased ratio of surface area to volume, nanomaterials will likely exert a stronger interaction with bacteria which may affect bacterial growth and propagation. A major concern of most existing antibacterial nanomaterials, like silver nanoparticles, is their potential toxicity. But selenium is a non-metallic material and a required nutrition for the human body, which is recommended by the FDA at a 53 to 60 μg daily intake. Nanosized selenium is considered to be healthier and less toxic compared with many metal-based nanomaterials due to the generation of reactive oxygen species from metals, especially heavy metals. Therefore, the objectives of

  10. Evaluation of a Bacillus direct-fed microbial candidate on digesta viscosity, bacterial translocation, microbiota composition and bone mineralisation in broiler chickens fed on a rye-based diet.

    Science.gov (United States)

    Latorre, J D; Hernandez-Velasco, X; Bielke, L R; Vicente, J L; Wolfenden, R; Menconi, A; Hargis, B M; Tellez, G

    2015-01-01

    1. The effects of the dietary inclusion of a Bacillus-based direct-fed microbial (DFM) candidate on digesta viscosity, bacterial translocation, microbiota composition and bone mineralisation were evaluated in broilers consuming rye-based diets. 2. In the present study, control mash rye-based diets (CON) or Bacillus-DFM supplemented diets (TRT) were administered ad libitum to male broilers in three independent experiments. 3. In Experiments 1 and 2 (n = 25/group), liver samples were taken to evaluate bacterial translocation, digesta samples were used for viscosity measurements and the intestinal microbial flora was evaluated from different intestinal sections to enumerate total recovered gram-negative bacteria (TGB), lactic acid bacteria (LAB) and anaerobic bacteria (TAB). Additionally, both tibias were removed for assessment of bone quality. 4. In Experiment 3, each experimental group had 8 replicates of 20 chickens (n = 160/group). Weekly, body weight (BW), feed intake (FI) and feed conversion ratio (FCR) were evaluated. At d 28-of-age, samples were taken to determine bacterial translocation, digesta viscosity and bone quality characteristics. 5. In all experiments, consumption of Bacillus-DFM reduced bacterial translocation to the liver and digesta viscosity. Additionally, DFM supplementation improved BW, bone quality measurements and FCR. Moreover, chickens fed on the Bacillus-DFM diet in Experiments 1 and 2 showed a significant reduction in the number of gram-negative and anaerobic bacteria in the duodenal content compared to control. 6. In summary, chickens fed on a rye-based diet without DFM inclusion showed an increase in bacterial translocation and digesta viscosity, accompanied by reduced performance and bone quality variables relative to the Bacillus-DFM candidate group. Hence, incorporation into the feed of a selected DFM ameliorated the adverse anti-nutritional effects related to utilisation of rye-based diets in broilers chickens.

  11. Bacterial interference for prevention of urinary tract infection: an overview.

    Science.gov (United States)

    Darouiche, R O; Hull, R A

    2000-01-01

    Urinary tract infection (UTI) is the most common infection in patients with spinal cord injury (SCI) and is a major cause of morbidity and mortality in this population. The bladders of patients with SCI, particularly those with indwelling bladder catheters, can become colonized by a variety of organisms, including those that may, and others that may not, cause symptoms of infection. The latter group of bacteria, so-called benign colonizers, are often left untreated because they may provide some protection against symptomatic infection with more pathogenic bacteria. In recent years, deliberate urogenital tract colonization with benign bacterial strains was studied with the objective of offering some protection against invasion by uropathogenic strains. When well-characterized strains of Lactobacillus sp. were used to colonize the vagina of women prone to frequent UTI, a moderate reduction in the rate of recurrent UTI was observed. In other studies, a non-pathogenic prototype of Escherichia coli (strain 83,972) causing asymptomatic bacteriuria was used for deliberate bladder colonization. These preliminary observations encourage the examination of the safety and preventive efficacy of this approach in human subjects.

  12. Soluble CD163 and soluble mannose receptor predict survival and decompensation in patients with liver cirrhosis, and correlate with gut permeability and bacterial translocation

    DEFF Research Database (Denmark)

    Rainer, F; Horvath, A; Sandahl, T D

    2017-01-01

    BACKGROUND: Activated hepatic macrophages play a key role in inflammation and fibrosis progression in chronic liver disease. AIM: To assess the prognostic value of soluble (s)CD163 and mannose receptor (sMR) in cirrhotic patients and explore associations with markers of intestinal permeability...... (lactulose-mannitol ratio, diamine oxidase), bacterial translocation (endotoxin, lipopolysaccharide-binding protein) and markers of systemic immune activation (interleukin-6, interleukin-8, sCD14). METHODS: We prospectively investigated 101 cirrhotic patients (Child-Pugh class A: n = 72, Child-Pugh classes B.......3, Child-Pugh class A = 4.2, Child-Pugh classes B and C = 8.4 mg/L; sMR in healthy controls = 15.8, Child-Pugh class A = 36.5, Child-Pugh classes B and C = 66.3 μg/dL). A total of 21 patients died during the observation period. Patients with sCD163 levels above 5.9 mg/L showed significantly reduced...

  13. Exploitation of eukaryotic ubiquitin signaling pathways by effectors translocated by bacterial type III and type IV secretion systems.

    Directory of Open Access Journals (Sweden)

    Aurélie Angot

    2007-01-01

    Full Text Available The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome to destroy earmarked proteins, but depending on the polyubiquitin chain topology, it can also result in new protein properties. Both ubiquitin-orchestrated protein degradation and modification have also been shown to be essential for the host's immune response to pathogens. Many animal and plant pathogenic bacteria utilize type III and/or type IV secretion systems to inject effector proteins into host cells, where they subvert host signaling cascades as part of their infection strategy. Recent progress in the determination of effector function has taught us that playing with the host's ubiquitination system seems a general tactic among bacteria. Here, we discuss how bacteria exploit this system to control the timing of their effectors' action by programming them for degradation, to block specific intermediates in mammalian or plant innate immunity, or to target host proteins for degradation by mimicking specific ubiquitin/proteasome system components. In addition to analyzing the effectors that have been described in the literature, we screened publicly available bacterial genomes for mimicry of ubiquitin proteasome system subunits and detected several new putative effectors. Our understanding of the intimate interplay between pathogens and their host's ubiquitin proteasome system is just beginning. This exciting research field will aid in better understanding this interplay, and may also provide new insights into eukaryotic ubiquitination processes.

  14. FOXP2 promotes the nuclear translocation of POT1, but FOXP2(R553H), mutation related to speech-language disorder, partially prevents it

    International Nuclear Information System (INIS)

    Tanabe, Yuko; Fujita, Eriko; Momoi, Takashi

    2011-01-01

    Highlights: → We isolated protection of telomeres 1 (POT1) as a FOXP2-associated protein by a yeast two-hybrid. → FOXP2 associated and co-localized with POT1 in the nuclei. → FOXP2(R553H) also co-localized with POT1 in both the cytoplasm and nuclei. → FOXP2(R553H) partially prevented the nuclear translocation of POT1. → FOXP2(R553H) mutation may be associated with the pathogenesis of speech-language disorder. -- Abstract: FOXP2 is a forkhead box-containing transcription factor with several recognizable sequence motifs. However, little is known about the FOXP2-associated proteins except for C-terminal binding protein (CtBP). In the present study, we attempted to isolate the FOXP2-associated protein with a yeast two-hybrid system using the C-terminal region, including the forkhead domain, as a bait probe, and identified protection of telomeres 1 (POT1) as a FOXP2-associated protein. Immunoprecipitation assay confirmed the association with FOXP2 and POT1. POT1 alone localized in the cytoplasm but co-localized with FOXP2 and the forkhead domain of FOXP2 in nuclei. However, both FOXP2 with mutated nuclear localization signals and (R553H) mutated forkhead, which is associated with speech-language disorder, prevented the nuclear translocation of POT1. These results suggest that FOXP2 is a binding partner for the nuclear translocation of POT1. As loss of POT1 function induces the cell arrest, the impaired nuclear translocation of POT1 in the developing neuronal cells may be associated with the pathogenesis of speech-language disorder with FOXP2(R553H) mutation.

  15. Atrofia mucosa/translocação bacteriana na sepse experimental em ratos Wistar Mucosal atrophy/bacterial translocation in experimental sepsis in Wistar rats

    Directory of Open Access Journals (Sweden)

    Armando José d'Acampora

    2004-10-01

    Full Text Available OBJETIVO: Avalizar a relação entre lesão mucosa e translocação bacteriana. MÉTODO: Utilizou-se 50 ratos distribuídos em 5 grupos: 1.Controle: injeção de inóculo padrão de Pseudomonas aeruginosa, 2.Dreno: injeção do inóculo padrão e drenagem da cavidade abdominal, após 6 horas, 3.Lavado: injeção do inóculo padrão e lavagem da cavidade abdominal, após 6 horas, 4.Lavado + dreno: injeção do inóculo padrão e após 6 horas, drenagem e lavagem da cavidade, 5.Normal: avaliação histológica da parede intestinal normal. Após o óbito, realizou-se hemocultura e cultura peritoneal. Realizou-se medida da espessura total da parede do jejuno e da camada mucosa em vilosidades seccionadas de forma longitudinal. RESULTADOS: Na hemocultura, houve crescimento de Pseudomonas aeruginosa e Escherichia coli em 90% e 52,5% dos animais. Na cultura peritoneal, houve crescimento de P. aeruginosa, E. coli e Klebsiella sp em 87,5%, 85% e 5% dos animais. Quanto a altura da camada mucosa e da parede intestinal, não houve alteração estatisticamente significativa entre os 5 grupos. CONCLUSÃO: A sepse aguda não causou alteração na camada mucosa do intestino delgado e a translocação ocorrida não pode ser considerada como decorrente de uma lesão da mucosa intestinal.PURPOSE: Observe the relation between small intestine's mucosal injury and bacterial translocation. METHODS: 50 adult female rats were distributed in 5 groups: 1. Control: intraperitoneal injection of Pseudomonas aeruginosa, 2. Drainage: intraperitoneal injection of P. aeruginosa and drainage of the abdominal cavity, after 6 hours, 3. Washed: intraperitoneal injection of P. aeruginosa and washing of the abdominal cavity, after 6 hours, 4. Washed + drainage: intraperitoneal injection of P. aeruginosa plus drainage and washing of the cavity, after 6 hours, 5. Normal: evaluation of the normal intestinal wall. After death, blood and peritoneal cultures were performed. Fragments of

  16. Surface zwitterionization: Effective method for preventing oral bacterial biofilm formation on hydroxyapatite surfaces

    Science.gov (United States)

    Lee, Myoungjin; Kim, Heejin; Seo, Jiae; Kang, Minji; Kang, Sunah; Jang, Joomyung; Lee, Yan; Seo, Ji-Hun

    2018-01-01

    In this study, we conducted surface zwitterionization of hydroxyapatite (HA) surfaces by immersing them in the zwitterionic polymer solutions to provide anti-bacterial properties to the HA surface. Three different monomers containing various zwitterionic groups, i.e., phosphorylcholine (PC), sulfobetaine (SB), and carboxybetaine (CB), were copolymerized with the methacrylic monomer containing a Ca2+-binding moiety, using the free radical polymerization method. As a control, functionalization of the copolymer containing the Ca2+-binding moiety was synthesized using a hydroxy group. The stable immobilization of the zwitterionic functional groups was confirmed by water contact angle analysis and X-ray photoelectron spectroscopy (XPS) measurement conducted after the sonication process. The zwitterionized HA surface showed significantly decreased protein adsorption, whereas the hydroxyl group-coated HA surface showed limited efficacy. The anti-bacterial adhesion property was confirmed by conducting Streptococcus mutans (S. mutans) adhesion tests for 6 h and 24 h. When furanone C-30, a representative anti-quorum sensing molecule for S. mutans, was used, only a small amount of bacteria adhered after 6 h and the population did not increase after 24 h. In contrast, zwitterionized HA surfaces showed almost no bacterial adhesion after 6 h and the effect was retained for 24 h, resulting in the lowest level of oral bacterial adhesion. These results confirm that surface zwitterionization is a promising method to effectively prevent oral bacterial adhesion on HA-based materials.

  17. CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection.

    Science.gov (United States)

    Bikard, David; Hatoum-Aslan, Asma; Mucida, Daniel; Marraffini, Luciano A

    2012-08-16

    Pathogenic bacterial strains emerge largely due to transfer of virulence and antimicrobial resistance genes between bacteria, a process known as horizontal gene transfer (HGT). Clustered, regularly interspaced, short palindromic repeat (CRISPR) loci of bacteria and archaea encode a sequence-specific defense mechanism against bacteriophages and constitute a programmable barrier to HGT. However, the impact of CRISPRs on the emergence of virulence is unknown. We programmed the human pathogen Streptococcus pneumoniae with CRISPR sequences that target capsule genes, an essential pneumococcal virulence factor, and show that CRISPR interference can prevent transformation of nonencapsulated, avirulent pneumococci into capsulated, virulent strains during infection in mice. Further, at low frequencies bacteria can lose CRISPR function, acquire capsule genes, and mount a successful infection. These results demonstrate that CRISPR interference can prevent the emergence of virulence in vivo and that strong selective pressure for virulence or antibiotic resistance can lead to CRISPR loss in bacterial pathogens. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Bacterial translocation in rats nonfunctioning diverted distal colon Translocação bacteriana no coto colônico distal desfuncionalizado de ratos

    Directory of Open Access Journals (Sweden)

    Francisco Edilson Leite Pinto Júnior

    2007-06-01

    Full Text Available PURPOSE: To investigate whether the alterations of the diverted colon segment mucosa, evidenced in fecal colitis, would be able to alter Bacterial Translocation (BT. METHODS: Sixty-two Wistar male rats ranging from 220 to 320 grams of weight, were divided in two groups: A (Colostomy and B (Control, with 31 animals each one. In group A, all animals underwent end colostomy, one stoma, in ascending colon; and in the 70th POD was injected in five rats, by rectal route diverted segment - 2ml of a 0.9% saline solution in animals (A1 subgroup; in eight it was inoculated, by rectal route, 2ml of a solution containing Escherichia coli ATCC 25922 (American Type Culture Collection, in a concentration of 10(8 Colony Forming Unit for milliliters (CFU/ml - A2 Subgroup; in ten animals the same solution of E. coli was inoculated, in a concentration of 10(11 CFU/ml (A3 Subgroup; and in eight it was collected part of the mucus found in the diverted distal colonic segment for neutral sugars and total proteins dosage (A4 subgroup. The animals from the group B underwent the same procedures of group A, but with differences in the colostomy confection. In rats from subgroups A1, A2, A3, B1, B2, and B3 2ml of blood were aspirated from the heart, and fragments from mesenteric lymphatic nodule, liver, spleen, lung and kidney taken for microbiological analysis, after their death. This analysis consisted of evidencing the presence of E. coli ATCC 25922 CFU. Mann-Whitney and ANOVA Tests were applied as analytic techniques for association of variables. RESULTS: The occurrence of BT was evidenced only in those animals in which inoculated concentration of E. coli ATCC 25922, reached levels of 10(11CFU/ml, i.e. in Subgroups A3 and B3, although, being significantly greater (80% in those animals without colostomy (subgroup B3 when compared to the ones with colostomy (20% from the subgroup A3 (P OBJETIVO: Investigar se as alterações do cólon desfuncionalizado, evidenciadas na

  19. Sphingosine Prevents Bacterial Adherence to Endotracheal Tubes: A Novel Mechanism to Prevent Ventilator-Associated Pneumonia

    Science.gov (United States)

    2016-06-21

    rinsed in 100 mL HEPES/saline (H/S) (132 mM NaCl [sodium chloride], 20 mM HEPES [ pH 7.4], 5 mM KCl [potassium chloride], 1 mM CaCl2 [calcium chloride...kinase reaction was initiated by addition of 0.004 units sphingosine kinase in 50 mM HEPES ( pH 7.4), 250 mM NaCl, 30 mM MgCl2, 1 µM adenosine...adhere to the surface prior to biofilm formation. The source of the bacterial inoculant (i.e., oral secretions, gastric reflux, inhaled droplets, etc

  20. Phytochemicals prevent mitochondrial membrane permeabilization and protect SH-SY5Y cells against apoptosis induced by PK11195, a ligand for outer membrane translocator protein.

    Science.gov (United States)

    Wu, Yuqiu; Shamoto-Nagai, Masayo; Maruyama, Wakako; Osawa, Toshihiko; Naoi, Makoto

    2017-01-01

    Epidemiological studies present the beneficial effects of dietary habits on prevention of aging-associated decline of brain function. Phytochemicals, the second metabolites of food, protect neuronal cells from cell death in cellular models of neurodegenerative disorders, and the neuroprotective activity has been ascribed to the anti-oxidant and anti-inflammatory functions. In this paper, the cellular mechanism of neuroprotection by phytochemicals was investigated, using the cellular model of mitochondrial apoptosis induced by PK11195, a ligand of outer membrane translocator protein, in SH-SY5Y cells. PK11195 induced mitochondrial membrane permeabilization with rapid transit production of superoxide (superoxide flashes) and calcium release from mitochondria, and activated apoptosis signal pathway. Study on the structure-activity relationship of astaxanthin, ferulic acid derivatives, and sesame lignans revealed that these phytochemicals inhibited mitochondrial membrane permeabilization and protected cells from apoptosis. Ferulic acid derivatives and sesame lignans inhibited or enhanced the mitochondrial pore formation and cell death by PK11195 according to their amphiphilic properties, not directly depending on the antioxidant activity. Regulation of pore formation at mitochondrial membrane is discussed as a novel mechanism behind neuroprotective activity of phytochemicals in aging and age-associated neurodegenerative disorders, and also behind dual functions of phytochemicals in neuronal and cancer cells.

  1. [Spontaneous bacterial peritonitis].

    Science.gov (United States)

    Strauss, Edna; Caly, Wanda Regina

    2003-01-01

    Spontaneous bacterial peritonitis occurs in 30% of patients with ascites due to cirrhosis leading to high morbidity and mortality rates. The pathogenesis of spontaneous bacterial peritonitis is related to altered host defenses observed in end-stage liver disease, overgrowth of microorganisms, and bacterial translocation from the intestinal lumen to mesenteric lymph nodes. Clinical manifestations vary from severe to slight or absent, demanding analysis of the ascitic fluid. The diagnosis is confirmed by a number of neutrophils over 250/mm3 associated or not to bacterial growth in culture of an ascites sample. Enterobacteriae prevail and Escherichia coli has been the most frequent bacterium reported. Mortality rates decreased markedly in the last two decades due to early diagnosis and prompt antibiotic treatment. Third generation intravenous cephalosporins are effective in 70% to 95% of the cases. Recurrence of spontaneous bacterial peritonitis is common and can be prevented by the continuous use of oral norfloxacin. The development of bacterial resistance demands the search for new options in the prophylaxis of spontaneous bacterial peritonitis; probiotics are a promising new approach, but deserve further evaluation. Short-term antibiotic prophylaxis is recommended for patients with cirrhosis and ascites shortly after an acute episode of gastrointestinal bleeding.

  2. How nanotechnology-enabled concepts could contribute to the prevention, diagnosis and therapy of bacterial infections.

    Science.gov (United States)

    Herrmann, Inge K

    2015-05-29

    This viewpoint summarizes a selection of nanotechnology-based key concepts relevant to critical care medicine. It focuses on novel approaches for a trigger-dependent release of antimicrobial substances from degradable nano-sized carriers, the ultra-sensitive detection of analytes in body fluid samples by plasmonic and fluorescent nanoparticles, and the rapid removal of pathogens from whole blood using magnetic nanoparticles. The concepts presented here could significantly contribute to the prevention, diagnosis and therapy of bacterial infections in future and it is now our turn to bring them from the bench to the bedside.

  3. Stainless steel modified with poly(ethylene glycol) can prevent protein adsorption but not bacterial adhesion

    DEFF Research Database (Denmark)

    Wei, Jiang; Bagge, Dorthe; Gram, Lone

    2003-01-01

    The surface of AISI 316 grade stainless steel (SS) was modified with a layer of poly(ethylene glycol) (PEG) (molecular weight 5000) with the aim of preventing protein adsorption and bacterial adhesion. Model SS substrates were first modified to introduce a very high density of reactive amine groups....... The chemical composition and uniformity of the surfaces were determined using X-ray photoelectron spectroscopy (XPS) and time-of-flight static secondary ion mass spectrometry (ToF-SSIMS) in the imaging mode. The effects of PEI concentration and different substrate pre-cleaning methods on the structure...

  4. Streptococcus pyogenes translocates across an epithelial barrier.

    Science.gov (United States)

    Sumitomo, Tomoko

    2017-01-01

    Streptococcus pyogenes is a β-hemolytic organism responsible for a wide variety of human diseases that commonly occur as self-limiting purulent diseases of the pharynx and skin. Although the occurrence of invasive infections by S. pyogenes is rare, mortality rates remain high even with progressive medical therapy. As a prerequisite for causing the severe invasive disease, S. pyogenes must invade underlying sterile tissues by translocating across the epithelial barrier. In this study, streptolysin S and SpeB were identified as the novel factors that facilitate bacterial translocation via degradation of intercellular junctions. Furthermore, we found that S. pyogenes exploits host plasminogen for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. Here, I would like to show our study on bacterial translocation across the epithelial barrier through paracellular route.

  5. Real-time qPCR improves meningitis pathogen detection in invasive bacterial-vaccine preventable disease surveillance in Fiji

    OpenAIRE

    Dunne, Eileen M.; Mantanitobua, Silivia; Singh, Shalini P.; Reyburn, Rita; Tuivaga, Evelyn; Rafai, Eric; Tikoduadua, Lisi; Porter, Barbara; Satzke, Catherine; Strachan, Janet E.; Fox, Kimberly K.; Jenkins, Kylie M.; Jenney, Adam; Baro, Silo; Mulholland, E. Kim

    2016-01-01

    As part of the World Health Organization Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance in Suva, Fiji, cerebrospinal fluid (CSF) samples from suspected meningitis patients of all ages were examined by traditional methods (culture, Gram stain, and latex agglutination for bacterial antigen) and qPCR for Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Of 266 samples tested, pathogens were identified in 47 (17.7%). S. pneumoniae was the most co...

  6. ADN bacteriano en pacientes con cirrosis y ascitis estéril: Papel como marcador de translocación bacteriana y herramienta pronóstica Bacterial DNA in patients with cirrhosis ans sterile ascites: Its role as a marker of bacterial translocation and prognosis tool

    Directory of Open Access Journals (Sweden)

    J. M. González-Navajas

    2007-10-01

    Full Text Available Durante la última década hemos presenciado un aumento de la cantidad de datos relativos a la presencia de translocación bacteriana en los modelos experimentales de cirrosis. Sin embargo, los estudios clínicos se han visto limitados por la falta de métodos no invasivos para estudiar dicho fenómeno. En los últimos años, las investigaciones realizadas en nuestro laboratorio se han centrado en la detección del ADN bacteriano en el suero y el líquido ascítico de los pacientes con cirrosis y ascitis estéril, y en las implicaciones clínicas que ello conlleva. Al principio, gracias a un método basado en la reacción en cadena de la polimerasa (PCR y el secuenciamiento automatizado de nucleótidos, pudimos detectar e identificar la presencia de fragmentos de ADN bacteriano en dichos pacientes con ascitis no neutrocítica y con cultivo negativo. Desde entonces hemos acumulado una serie de datos que indican que la presencia de ADN bacteriano podría desempeñar un papel importante no sólo como marcador de translocación bacteriana, sino también como factor pronóstico a corto plazo. Expondremos aquí el pasado, el presente y el futuro de esta línea de investigación.During the last decade, we have witnessed an increase in the amount of data related with the presence of bacterial translocation in experimental models of cirrhosis. However, clinical studies have been limited by the lack of non-invasive methods to study this phenomenon. Over the past years, the research developed in our laboratory has been focused on the detection of bacterial DNA in serum and ascitic fluid of patients with cirrhosis and sterile ascites, the clinical and immunological implications of such finding. Initially, by means of a polymerase chain reaction (PCR-based method and automated nucleotide sequencing, we were able to detect and identify the presence of fragments of bacterial DNA in the mentioned patients with culture-negative, non-neutrocytic ascites. Since

  7. Deep Sequencing of RNA from Blood and Oral Swab Samples Reveals the Presence of Nucleic Acid from a Number of Pathogens in Patients with Acute Ebola Virus Disease and Is Consistent with Bacterial Translocation across the Gut.

    Science.gov (United States)

    Carroll, Miles W; Haldenby, Sam; Rickett, Natasha Y; Pályi, Bernadett; Garcia-Dorival, Isabel; Liu, Xuan; Barker, Gary; Bore, Joseph Akoi; Koundouno, Fara Raymond; Williamson, E Diane; Laws, Thomas R; Kerber, Romy; Sissoko, Daouda; Magyar, Nóra; Di Caro, Antonino; Biava, Mirella; Fletcher, Tom E; Sprecher, Armand; Ng, Lisa F P; Rénia, Laurent; Magassouba, N'faly; Günther, Stephan; Wölfel, Roman; Stoecker, Kilian; Matthews, David A; Hiscox, Julian A

    2017-01-01

    treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium , particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium . However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.

  8. Studies on the Use of Plant Extracts for the Prevention of Bacterial ...

    African Journals Online (AJOL)

    The various extracts and standard drugs reduced bacterial attachment on the catheters in the order: ciprofloxacin > Psidium guajava > Aloe vera > gentamicin > Gongronema latifolium > untreated sections. Carica papaya, Ocimum gratisimum and Vernonia amygdalina potentiated bacterial attachment. Furthermore, the ...

  9. Perinatal asphyxia leads to PARP-1 overactivity, p65 translocation, IL-1β and TNF-α overexpression, and apoptotic-like cell death in mesencephalon of neonatal rats: prevention by systemic neonatal nicotinamide administration.

    Science.gov (United States)

    Neira-Peña, T; Rojas-Mancilla, E; Munoz-Vio, V; Perez, R; Gutierrez-Hernandez, M; Bustamante, D; Morales, P; Hermoso, M A; Gebicke-Haerter, P; Herrera-Marschitz, M

    2015-05-01

    Perinatal asphyxia (PA) is a leading cause of neuronal damage in newborns, resulting in long-term neurological and cognitive deficits, in part due to impairment of mesostriatal and mesolimbic neurocircuitries. The insult can be as severe as to menace the integrity of the genome, triggering the overactivation of sentinel proteins, including poly (ADP-ribose) polymerase-1 (PARP-1). PARP-1 overactivation implies increased energy demands, worsening the metabolic failure and depleting further NAD(+) availability. Using a global PA rat model, we report here evidence that hypoxia increases PARP-1 activity, triggering a signalling cascade leading to nuclear translocation of the NF-κB subunit p65, modulating the expression of IL-1β and TNF-α, pro-inflammatory molecules, increasing apoptotic-like cell death in mesencephalon of neonate rats, monitored with Western blots, qPCR, TUNEL and ELISA. PARP-1 activity increased immediately after PA, reaching a maximum 1-8 h after the insult, while activation of the NF-κB signalling pathway was observed 8 h after the insult, with a >twofold increase of p65 nuclear translocation. IL-1β and TNF-α mRNA levels were increased 24 h after the insult, together with a >twofold increase in apoptotic-like cell death. A single dose of the PARP-1 inhibitor nicotinamide (0.8 mmol/kg, i.p.), 1 h post delivery, prevented the effect of PA on PARP-1 activity, p65 translocation, pro-inflammatory cytokine expression and apoptotic-like cell death. The present study demonstrates that PA leads to PARP-1 overactivation, increasing the expression of pro-inflammatory cytokines and cell death in mesencephalon, effects prevented by systemic neonatal nicotinamide administration, supporting the idea that PARP-1 inhibition represents a therapeutic target against the effects of PA.

  10. [Spontaneous bacterial peritonitis in liver cirrhosis: optimization issues of prevention and treatment].

    Science.gov (United States)

    Vinnitskaia, E V; Drozdov, V N; Petyrakov, A V; Sil'vestrova, S Iu; Brezgin, A G

    2012-01-01

    Research of features of a current of a spontaneous bacterial peritonitis (SBP) allows to allocate close interrelation between SBP, system inflammatory reaction and a sepsis to consider SBP, as one of stages in evolution of the difficult infectious process caused, as a rule, by resident flora, developing at patients with decompensated liver cirrhosis (LC), which demands timely preventive maintenance and adequate antibacterial therapy. In the present work therapy and preventive maintenance SBP questions are considered. In article the extensive review of the data of the literature and own supervision by efficiency of treatment SBP also is presented. For the purpose of optimization of pharmacotherapy of the sick LC, the complicated ascites, had been conducted pharmacokinetics research ciprofloxacin (CPF) according to dynamics of its maintenance in blood serum (BS) and ascitic fluid (AF) depending on presence and ascites size. Materials and methods. Researches are spent 18 sick decompensated liver cirrhosis (a class B and C on Ch-P), without signs SBP after unitary reception of 500 mg CPF per os on an empty stomach. All patients have been divided on two groups: I gr. (n = 10) with the expressed, intense ascites (> 10 1) and II gr. (n = 8) with the moderate, small ascites. Definition CPF in BS also was already carried out by a method of a highly effective liquid chromatography. On the basis of the received data for each patient counted the semidelucing period (T1/2), the area under pharmacokinetic curve (curve concentration - time) - (AUC), volume of distribution of a preparation (Avd), factor AUC(AF)\\MIC (size of the relation of the area under pharmacokinetic curve to its minimum inhibitive concentration). Results of research have shown that concentration levels (C) (CPF in BS and AF for the given concrete patient are at one level, showing thus distinctions in dynamic behavior. Average value AUC(AF)\\MIC (MIC - minimum inhibitive concentration) at patients II gr. has

  11. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis

    OpenAIRE

    Giorgio Gugliotta; Gloria Calagna; Giorgio Adile; Salvatore Polito; Salvatore Saitta; Patrizia Speciale; Stefano Palomba; Antonino Perino; Roberta Granese; Biagio Adile

    2015-01-01

    Objective: Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. Materials and methods: This was a retrospective...

  12. Haloarchaeal Protein Translocation via the Twin Arginine Translocation Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Pohlschroder Mechthild

    2009-02-03

    Protein transport across hydrophobic membranes that partition cellular compartments is essential in all cells. The twin arginine translocation (Tat) pathway transports proteins across the prokaryotic cytoplasmic membranes. Distinct from the universally conserved Sec pathway, which secretes unfolded proteins, the Tat machinery is unique in that it secretes proteins in a folded conformation, making it an attractive pathway for the transport and secretion of heterologously expressed proteins that are Sec-incompatible. During the past 7 years, the DOE-supported project has focused on the characterization of the diversity of bacterial and archaeal Tat substrates as well as on the characterization of the Tat pathway of a model archaeon, Haloferax volcanii, a member of the haloarchaea. We have demonstrated that H. volcanii uses this pathway to transport most of its secretome.

  13. Preventing bacterial growth on implanted device with an interfacial metallic film and penetrating X-rays.

    Science.gov (United States)

    An, Jincui; Sun, An; Qiao, Yong; Zhang, Peipei; Su, Ming

    2015-02-01

    Device-related infections have been a big problem for a long time. This paper describes a new method to inhibit bacterial growth on implanted device with tissue-penetrating X-ray radiation, where a thin metallic film deposited on the device is used as a radio-sensitizing film for bacterial inhibition. At a given dose of X-ray, the bacterial viability decreases as the thickness of metal film (bismuth) increases. The bacterial viability decreases with X-ray dose increases. At X-ray dose of 2.5 Gy, 98% of bacteria on 10 nm thick bismuth film are killed; while it is only 25% of bacteria are killed on the bare petri dish. The same dose of X-ray kills 8% fibroblast cells that are within a short distance from bismuth film (4 mm). These results suggest that penetrating X-rays can kill bacteria on bismuth thin film deposited on surface of implant device efficiently.

  14. Drug resistance of bacterial dental biofilm and the potential use of natural compounds as alternative for prevention and treatment.

    Science.gov (United States)

    Kouidhi, Bochra; Al Qurashi, Yasir Mohammed A; Chaieb, Kamel

    2015-03-01

    Oral diseases, such as dental caries and periodontal disease are directly linked with the ability of bacteria to form biofilm. The development of dental caries involves acidogenic and aciduric Gram-positive bacteria colonizing the supragingival biofilm (Streptococcus, Lactobacillus and Actinomycetes). Periodontal diseases have been linked to anaerobic Gram-negative bacteria forming a subgingival plaque (Porphyromonas gingivalis, Actinobacillus, Prevotella and Fusobacterium). Cells embedded in biofilm are up to 1000-fold more resistant to antibiotics compared to their planctonic ones. Several mechanisms have been proposed to explain biofilms drug resistance. Given the increased bacterial resistance to antibiotics currently used in dentistry, a great importance is given to natural compounds for the prevention of oral bacterial growth, adhesion and colonization. Over the past decade, interest in drugs derived from medicinal plants has markedly increased. It has been well documented that medicinal plants and natural compounds confer considerable antibacterial activity against various microorganisms including cariogenic and periodontal pathogens. This paper provides a review of the literature focusing on the studies on (i) biofilm in the oral cavity, (ii) drug resistance of bacterial biofilm and (iii) the potential use of plant extracts, essential oils and natural compounds as biofilm preventive agents in dentistry, involving their origin and their mechanism of biofilm inhibition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Is intravesical instillation of hyaluronic acid and chondroitin sulfate useful in preventing recurrent bacterial cystitis? A multicenter case control analysis.

    Science.gov (United States)

    Gugliotta, Giorgio; Calagna, Gloria; Adile, Giorgio; Polito, Salvatore; Saitta, Salvatore; Speciale, Patrizia; Palomba, Stefano; Perino, Antonino; Granese, Roberta; Adile, Biagio

    2015-10-01

    Urinary tract infections (UTIs) are common in the female population and, over a lifetime, about half of women have at least one episode of UTI requiring antibiotic therapy. The aim of the current study was to compare two different strategies for preventing recurrent bacterial cystitis: intravesical instillation of hyaluronic acid (HA) plus chondroitin sulfate (CS), and antibiotic prophylaxis with sulfamethoxazole plus trimethoprim. This was a retrospective review of two different cohorts of women affected by recurrent bacterial cystitis. Cases (experimental group) were women who received intravesical instillations of a sterile solution of high concentration of HA + CS in 50 mL water with calcium chloride every week during the 1(st) month and then once monthly for 4 months. The control group included women who received traditional therapy for recurrent cystitis based on daily antibiotic prophylaxis using sulfamethoxazole 200 mg plus trimethoprim 40 mg for 6 weeks. Ninety-eight and 76 patients were treated with experimental and control treatments, respectively. At 12 months after treatment, 69 and 109 UTIs were detected in the experimental and control groups, respectively. The proportion of patients free from UTIs was significantly higher in the experimental than in the control group (36.7% vs. 21.0%; p = 0.03). Experimental treatment was well tolerated and none of the patients stopped it. The intravesical instillation of HA + CS is more effective than long-term antibiotic prophylaxis for preventing recurrent bacterial cystitis. Copyright © 2015. Published by Elsevier B.V.

  16. Prevention of oral bacterial flora transmission by using mouth-to-mask ventilation during CPR.

    Science.gov (United States)

    Cydulka, R K; Connor, P J; Myers, T F; Pavza, G; Parker, M

    1991-01-01

    The Emergency Cardiac Care Committee of the American Heart Association has recently recommended utilizing protective barrier precautions during CPR (1,2). We assessed 17 mask and faceshield resuscitation devices for adequacy of barrier protection. Eight of the devices were faceshields (CPR Microshield, Hygenic, MedCare Mask, Resusci, Samaritan, Sealeasy, Portex); 8 were mask devices (Laerdal, Dyna Med, MTM Emergency Lung Ventilator, MTM Emergency Resuscitator, Res-Q-Flo, Rightway Mouth-to-Mask Resuscitation, Trufit), and one of the devices did not meet the criteria for either faceshield or mask (Lifesaver). All masks were disinfected, applied to the investigator's face as directed by the manufacturers' instructions, and then cultured for oral aerobic bacterial flora on the rescuer side. No mask devices cultured positive for oral aerobic bacterial flora, while 6 of 8 faceshield devices cultured positive for oral aerobic bacterial flora (P less than 0.007). The CPR Microshield and the Portex faceshield were the only devices that did not develop a positive culture. We conclude that all ventilation devices with a one-way valve, except the Sealeasy device, provide adequate barrier type protection from oral aerobic bacterial flora when simulating mouth-to-barrier type protection when performing mouth-to-mouth ventilation.

  17. Simulations of Polymer Translocation

    Science.gov (United States)

    Vocks, H.

    2008-07-01

    Transport of molecules across membranes is an essential mechanism for life processes. These molecules are often long, and the pores in the membranes are too narrow for the molecules to pass through as a single unit. In such circumstances, the molecules have to squeeze -- i.e., translocate -- themselves through the pores. DNA, RNA and proteins are such naturally occuring long molecules in a variety of biological processes. Understandably, the process of translocation has been an active topic of current research: not only because it is a cornerstone of many biological processes, but also due to its relevance for practical applications. Translocation is a complicated process in living organisms -- the presence of chaperone molecules, pH, chemical potential gradients, and assisting molecular motors strongly influence its dynamics. Consequently, the translocation process has been empirically studied in great variety in biological literature. Study of translocation as a biophysical process is more recent. Herein, the polymer is simplified to a sequentially connected string of N monomers as it passes through a narrow pore on a membrane. The quantities of interest are the typical time scale for the polymer to leave a confining cell (the ``escape of a polymer from a vesicle'' time scale), and the typical time scale the polymer spends in the pore (the ``dwell'' time scale) as a function of N and other parameters like membrane thickness, membrane adsorption, electrochemical potential gradient, etc. Our research is focused on computer simulations of translocation. Since our main interest is in the scaling properties, we use a highly simplified description of the translocation process. The polymer is described as a self-avoiding walk on a lattice, and its dynamics consists of single-monomer jumps from one lattice site to another neighboring one. Since we have a very efficient program to simulate such polymer dynamics, which we decribe in Chapter 2, we can perform long

  18. Problem-elephant translocation: translocating the problem and the elephant?

    Directory of Open Access Journals (Sweden)

    Prithiviraj Fernando

    Full Text Available Human-elephant conflict (HEC threatens the survival of endangered Asian elephants (Elephas maximus. Translocating "problem-elephants" is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: "homers" returned to the capture site, "wanderers" ranged widely, and "settlers" established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals.

  19. Oncogene Translocations and NHL

    Science.gov (United States)

    A colloboration with several large population-based cohorts to determine whether the prevalence or level of t14;18 is associated with risk of NHL and to investigate the clonal relationship between translocation-bearing cells and subsequent tumors

  20. Sutures coated with antiseptic pomade to prevent bacterial colonization: a randomized clinical trial.

    Science.gov (United States)

    Cruz, Fernando; Leite, Fabiola; Cruz, Gustavo; Cruz, Silvia; Reis, Juarez; Pierce, Matthew; Cruz, Mauro

    2013-08-01

    The aim of this study was to assess if an antiseptic pomade could reduce the bacterial colonization on multifilament sutures. A randomized clinical trial was conducted with 40 volunteer patients of both sexes aged 18-70, randomly separated into experimental (n = 20) and control (n = 20) groups. The experimental group received pomade-coated sutures (iodoform + calendula) and the control group uncoated sutures. Two millimeters of the suture was harvested from each patient from the 1st to the 15th postoperative day. The bacteria that had adhered to them were cultured. The number of colony-forming units per milliliter (CFU/mL) was determined and the groups were compared using the Mann-Whitney statistical test (P antiseptic pomade was effective in reducing bacterial colonization on silk braided sutures. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Nanocomposited coatings produced by laser-assisted process to prevent silicone hydogels from protein fouling and bacterial contamination

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Guobang; Chen, Yi; Zhang, Jin, E-mail: jzhang@eng.uwo.ca

    2016-01-01

    Graphical abstract: Nanocomposited-coating was deposited on silicone hydrogel by using the matrix-assisted pulsed laser evaporation (MAPLE) process. The ZnO–PEG nanocomposited coating reduces over 50% protein absorption on silicone hydrogel, and can inhibit the bacterial growth efficiently. - Highlights: • We developed a nanocomposited coating to prevent silicone hydrogel from biofouling. • Matrix-assisted pulsed laser evaporation can deposit inorganic–organic nanomaterials. • The designed nanocomposited coating reduces protein absorption by over 50%. • The designed nanocomposited coating shows significant antimicrobial efficiency. - Abstract: Zinc oxide (ZnO) nanoparticles incorporating with polyethylene glycol (PEG) were deposited together on the surface of silicone hydrogel through matrix-assisted pulsed laser evaporation (MAPLE). In this process, frozen nanocomposites (ZnO–PEG) in isopropanol were irradiated under a pulsed Nd:YAG laser at 532 nm for 1 h. Our results indicate that the MAPLE process is able to maintain the chemical backbone of polymer and prevent the nanocomposite coating from contamination. The ZnO–PEG nanocomposited coating reduces over 50% protein absorption on silicone hydrogel. The cytotoxicity study shows that the ZnO–PEG nanocomposites deposited on silicone hydrogels do not impose the toxic effect on mouse NIH/3T3 cells. In addition, MAPLE-deposited ZnO–PEG nanocomposites can inhibit the bacterial growth significantly.

  2. Perioperative management for the prevention of bacterial infection in cardiac implantable electronic device placement

    Directory of Open Access Journals (Sweden)

    Katsuhiko Imai

    2016-08-01

    Full Text Available Cardiac implantable electronic devices (CIEDs have become important in the treatment of cardiac disease and placement rates increased significantly in the last decade. However, despite the use of appropriate antimicrobial prophylaxis, CIED infection rates are increasing disproportionately to the implantation rate. CIED infection often requires explantation of all hardware, and at times results in death. Surgical site infection (SSI is the most common cause of CIED infection as a pocket infection. The best method of combating CIED infection is prevention. Prevention of CIED infections comprises three phases: before, during, and after device implantation. The most critical factors in the prevention of SSIs are detailed operative techniques including the practice of proper technique by the surgeon and surgical team.

  3. Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures

    NARCIS (Netherlands)

    R.P.L. Louwen (Rogier); E.E.S. Nieuwenhuis (Edward); L. van Marrewijk (Leonie); D. Horst-Kreft (Deborah); L.F. de Ruiter (Lilian); A.P. Heikema (Astrid); W.J.B. van Wamel (Willem); J.A. Wagenaar (Jaap); H.P. Endtz (Hubert); J.N. Samsom (Janneke); P. van Baarlen (Peter); A.S. Akhmanova (Anna); A.F. van Belkum (Alex)

    2012-01-01

    textabstractTranslocation across intestinal epithelial cells is an established pathogenic feature of the zoonotic bacterial species Campylobacter jejuni. The number of C. jejuni virulence factors known to be involved in translocation is limited. In the present study, we investigated whether

  4. Co-trimoxazole alone for prevention of bacterial infection in patients with acute leukaemia.

    Science.gov (United States)

    Starke, I D; Donnelly, P; Catovsky, D; Darrell, J; Johnson, S A; Goldman, J M; Galton, D A

    1982-01-02

    43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

  5. Prevention of Bacterial Biofilm Formation on Soft Contact Lenses Using Natural Compounds.

    Science.gov (United States)

    El-Ganiny, Amira M; Shaker, Ghada H; Aboelazm, Abeer A; El-Dash, Heba A

    2017-12-01

    In eye care field, contact lenses (CL) have a great impact on improving vision, but their use can be limited by ocular infection. CL- associated infections can be reduced by good attention to CL storage case practice. CL-care solutions should be able to control microbial growth on CL. The aim of the study was to evaluate and compare the efficacy of CL-care solutions (found in Egyptian market) with some natural compounds in removal and inhibition of bacterial biofilm formed on soft CL. Clinical isolates were recovered from patients having conjunctivitis from Benha University Hospital and identified microbiologically. Quantification of biofilm was done using microtiter plate assay. Three multipurpose CL-care solutions were examined for their ability to remove and inhibit biofilm. Also four natural extracts having antibacterial activity and are safe on eye were tested for their anti-biofilm activity. The major bacterial isolates from eye infections were Pseudomonas aeruginosa (36%) and Staphylococcus spp. (37.8%). Only 33.3% of isolates showed ability to produce weak to moderate biofilm. The tested multi-purpose CL-care solutions showed moderate ability to remove preformed biofilm. Among the tested natural compounds, Calendula officinalis and Buddleja salviifolia extracts showed an excellent efficacy in inhibition of biofilm and also removal of preformed biofilm. This study demonstrated that isolates from infected eye and CL-cases showed weak to moderate biofilm formation. Calendula officinalis and Buddleja salviifolia extracts showed excellent effect on inhibition and removal of biofilm, these extracts could be added into CL-care solutions which could markedly reduce eye-infections during CL-wear.

  6. Non-return valves do not prevent backflow and bacterial contamination of intravenous infusions

    NARCIS (Netherlands)

    Ellger, B.; Kiski, D.; Diem, E.; van den Heuvel, I.; Freise, H.; Van Aken, H.; Hinder, F.; Friedrich, A. W.

    Non-return valves (NRVs) are designed to avoid backflow of infusion fluid against the designated direction of flow (DDF) when more than one infusion is delivered via one venous access. We tested in vitro whether NRVs reliably prevent flow against the DDF at clinically relevant low flow rates. Since

  7. Rasagiline prevents apoptosis induced by PK11195, a ligand of the outer membrane translocator protein (18 kDa), in SH-SY5Y cells through suppression of cytochrome c release from mitochondria.

    Science.gov (United States)

    Naoi, Makoto; Maruyama, Wakako; Yi, Hong

    2013-11-01

    Rasagiline protects neuronal cells from cell death caused by various lines of insults. Its neuroprotective function is due to suppression of mitochondrial apoptosis signaling and induction of neuroprotective genes, including Bcl-2 and neurotrophic factors. Rasagiline inhibits the mitochondrial membrane permeabilization, an initial stage in apoptosis, but the mechanism has been elusive. In this paper, it was investigated how rasagiline regulates mitochondrial death cascade in apoptosis induced in SH-SY5Y cells by PK11195, a ligand of the outer membrane translocator protein of 18 kDa. Rasagiline prevented release of cytochrome c (Cyt-c), and the following caspase 3 activation, ATP depletion and apoptosis, but did not inhibit the mitochondrial membrane potential collapse, in contrast to Bcl-2 overexpression. Rasagiline stabilized the mitochondrial contact site and suppressed Cyt-c release into cytoplasm, which should be the critical point for the regulation of apoptosis. Monoamine oxidase was not associated with anti-apoptotic activity of rasagiline in PK11195-induced apoptosis.

  8. Intestinal translocation of clinical isolates of vancomycin-resistant Enterococcus faecalis and ESBL-producing Escherichia coli in a rat model of bacterial colonization and liver ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Karin M van der Heijden

    Full Text Available The objectives of this study were to develop a rat model of gastrointestinal colonization with vancomycin-resistant Enterococcus faecalis (VRE and extended-spectrum beta-lactamase (ESBL-producing E. coli and to evaluate intestinal translocation to blood and tissues after total and partial hepatic ischemia. Methods - We developed a model of rat colonization with VRE and ESBL-E coli. Then we studied four groups of colonized rats: Group I (with hepatic pedicle occlusion causing complete liver ischemia and intestinal stasis; Group II (with partial liver ischemia without intestinal stasis; Group III (surgical manipulation without hepatic ischemia or intestinal stasis; Group IV (anesthetized without surgical manipulation. After sacrifice, portal and systemic blood, large intestine, small intestine, spleen, liver, lungs, and cervical and mesenteric lymph nodes were cultured. Endotoxin concentrations in portal and systemic blood were determined. Results - The best inocula were: VRE: 2.4×10(10 cfu and ESBL-E. coli: 1.12×10(10 cfu. The best results occurred 24 hours after inoculation and antibiotic doses of 750 µg/mL of water for vancomycin and 2.1 mg/mL for ceftriaxone. There was a significantly higher proportion of positive cultures for ESBL-E. coli in the lungs in Groups I, II and III when compared with Group IV (67%; 60%; 75% and 13%, respectively; p:0.04. VRE growth was more frequent in mesenteric lymph nodes for Groups I (67% and III (38% than for Groups II (13% and IV (none (p:0.002. LPS was significantly higher in systemic blood of Group I (9.761 ± 13.804 EU/mL-p:0.01. No differences for endotoxin occurred in portal blood. Conclusion -We developed a model of rats colonized with resistant bacteria useful to study intestinal translocation. Translocation occurred in surgical procedures with and without hepatic ischemia-reperfusion and probably occurred via the bloodstream. Translocation was probably lymphatic in the ischemia-reperfusion groups

  9. Meningitis Outbreak Caused by Vaccine-Preventable Bacterial Pathogens - Northern Ghana, 2016.

    Science.gov (United States)

    Aku, Fortress Y; Lessa, Fernanda C; Asiedu-Bekoe, Franklin; Balagumyetime, Phoebe; Ofosu, Winfred; Farrar, Jennifer; Ouattara, Mahamoudou; Vuong, Jeni T; Issah, Kofi; Opare, Joseph; Ohene, Sally-Ann; Okot, Charles; Kenu, Ernest; Ameme, Donne K; Opare, David; Abdul-Karim, Abass

    2017-08-04

    Bacterial meningitis is a severe, acute infection of the fluid surrounding the brain and spinal cord that can rapidly lead to death. Even with recommended antibiotic treatment, up to 25% of infected persons in Africa might experience neurologic sequelae (1). Three regions in northern Ghana (Upper East, Northern, and Upper West), located in the sub-Saharan "meningitis belt" that extends from Senegal to Ethiopia, experienced periodic outbreaks of meningitis before introduction of serogroup A meningococcal conjugate vaccine (MenAfriVac) in 2012 (2,3). During December 9, 2015-February 16, 2016, a total of 432 suspected meningitis cases were reported to health authorities in these three regions. The Ghana Ministry of Health, with assistance from CDC and other partners, tested cerebrospinal fluid (CSF) specimens from 286 patients. In the first 4 weeks of the outbreak, a high percentage of cases were caused by Streptococcus pneumoniae; followed by an increase in cases caused by Neisseria meningitidis, predominantly serogroup W. These data facilitated Ghana's request to the International Coordinating Group* for meningococcal polysaccharide ACW vaccine, which was delivered to persons in the most affected districts. Rapid identification of the etiologic agent causing meningitis outbreaks is critical to inform targeted public health and clinical interventions, including vaccination, clinical management, and contact precautions.

  10. Streptomyces lunalinharesii 235 prevents the formation of a sulfate-reducing bacterial biofilm

    Directory of Open Access Journals (Sweden)

    Juliana Pacheco da Rosa

    Full Text Available ABSTRACT Streptomyces lunalinharesii strain 235 produces an antimicrobial substance that is active against sulfate reducing bacteria, the major bacterial group responsible for biofilm formation and biocorrosion in petroleum reservoirs. The use of this antimicrobial substance for sulfate reducing bacteria control is therefore a promising alternative to chemical biocides. In this study the antimicrobial substance did not interfere with the biofilm stability, but the sulfate reducing bacteria biofilm formation was six-fold smaller in carbon steel coupons treated with the antimicrobial substance when compared to the untreated control. A reduction in the most probable number counts of planktonic cells of sulfate reducing bacteria was observed after treatments with the sub-minimal inhibitory concentration, minimal inhibitory concentration, and supra-minimal inhibitory concentration of the antimicrobial substance. Additionally, when the treated coupons were analyzed by scanning electron microscopy, the biofilm formation was found to be substantially reduced when the supra-minimal inhibitory concentration of the antimicrobial substance was used. The coupons used for the biofilm formation had a small weight loss after antimicrobial substance treatment, but corrosion damage was not observed by scanning electron microscopy. The absence of the dsrA gene fragment in the scraped cell suspension after treatment with the supra-minimal inhibitory concentration of the antimicrobial substance suggests that Desulfovibrio alaskensis was not able to adhere to the coupons. This is the first report on an antimicrobial substance produced by Streptomyces active against sulfate reducing bacteria biofilm formation. The application of antimicrobial substance as a potential biocide for sulfate reducing bacteria growth control could be of great interest to the petroleum industry.

  11. Antibacterial activity of Thymoquinone, an active principle of Nigella sativa and its potency to prevent bacterial biofilm formation

    Directory of Open Access Journals (Sweden)

    Bakhrouf Amina

    2011-04-01

    Full Text Available Abstract Background Thymoquinone is an active principle of Nigella sativa seed known as "Habbah Al-Sauda" in Arabic countries and "Sinouj" in Tunisia. Bacterial biofilms tend to exhibit significant tolerance to antimicrobials drugs during infections. Methods The antibacterial activity of Thymoquinone (TQ and its biofilm inhibition potencies were investigated on 11 human pathogenic bacteria. The growth and development of the biofilm were assessed using the crystal violet (CV and the 2, 3-bis [2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide (XTT reduction assay. Results TQ exhibited a significant bactericidal activity against the majority of the tested bacteria (MICs values ranged from 8 to 32 μg/ml especially Gram positive cocci (Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510. Crystal violet assay demonstrated that the minimum biofilm inhibition concentration (BIC50 was reached with 22 and 60 μg/ml for Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis CIP 106510 respectively. In addition our data revealed that cells oxidative activity was influenced by TQ supplementation. In the same way, TQ prevented cell adhesion to glass slides surface. Conclusion The ability of TQ to prevent biofilm formation warrants further investigation to explore its use as bioactive substances with antibiofilm potential.

  12. The Role of Antimicrobial Peptides in Preventing Multidrug-Resistant Bacterial Infections and Biofilm Formation

    Directory of Open Access Journals (Sweden)

    Kyung-Soo Hahm

    2011-09-01

    Full Text Available Over the last decade, decreasing effectiveness of conventional antimicrobial-drugs has caused serious problems due to the rapid emergence of multidrug-resistant pathogens. Furthermore, biofilms, which are microbial communities that cause serious chronic infections and dental plaque, form environments that enhance antimicrobial resistance. As a result, there is a continuous search to overcome or control such problems, which has resulted in antimicrobial peptides being considered as an alternative to conventional drugs. Antimicrobial peptides are ancient host defense effector molecules in living organisms. These peptides have been identified in diverse organisms and synthetically developed by using peptidomimic techniques. This review was conducted to demonstrate the mode of action by which antimicrobial peptides combat multidrug-resistant bacteria and prevent biofilm formation and to introduce clinical uses of these compounds for chronic disease, medical devices, and oral health. In addition, combinations of antimicrobial peptides and conventional drugs were considered due to their synergetic effects and low cost for therapeutic treatment.

  13. Prolonging the duration of preventing bacterial adhesion of nanosilver-containing polymer films through hydrophobicity.

    Science.gov (United States)

    Yin, Bing; Liu, Tao; Yin, Yansheng

    2012-12-11

    A superhydrophobic coating composed of silver nanoparticles was developed on copper from fluorinated multilayered polyelectrolyte films to examine its performance in preventing microbial adhesion. Antibacterial and antibiofouling experiments for this novel coating were conducted with SRB. From the disk diffusion tests (for 48 h), it was found that, compared to the traditional coating composed of nanosilver, this novel coating significantly improved antibacterial performance and long-term effectiveness. The oxidation states of the immobilized silver in polyelectrolyte multilayer films were investigated with X-ray photoelectron spectroscopy (XPS), and the stability of the immobilized silver was evaluated through a leaching test. It was found that if silver was exposed to aqueous environments some ionic silver species would be produced and released. The ion release kinetics showed that the duration of sustained release of antibacterial Ag ions from the novel coatings was prolonged, which was why they had more long-term antibacterial performance.

  14. Regulator of Calcineurin 1 Gene Isoform 4, Down-regulated in Hepatocellular Carcinoma, Prevents Proliferation, Migration, and Invasive Activity of Cancer Cells and Metastasis of Orthotopic Tumors by Inhibiting Nuclear Translocation of NFAT1.

    Science.gov (United States)

    Jin, Haojie; Wang, Cun; Jin, Guangzhi; Ruan, Haoyu; Gu, Dishui; Wei, Lin; Wang, Hui; Wang, Ning; Arunachalam, Einthavy; Zhang, Yurong; Deng, Xuan; Yang, Chen; Xiong, Yi; Feng, Hugang; Yao, Ming; Fang, Jingyuan; Gu, Jianren; Cong, Wenming; Qin, Wenxin

    2017-09-01

    xenograft tumors, with fewer metastases and blood vessels, than control HCC cells. In HCC cells, RCAN1.4 inhibited expression of insulin-like growth factor 1 and vascular endothelial growth factor A by reducing calcineurin activity and blocking nuclear translocation of nuclear factor of activated T cells (NFAT1). HCC cells incubated with the calcineurin inhibitor cyclosporin A had decreased nuclear level of NFAT1. HCC cells had hypermethylation of a CpG island in the 5' regulatory region of RCAN1.4, which reduced its expression. RCAN1.4 is down-regulated in HCC tissues, compared with non-tumor liver tissues. RCAN1.4 prevents cell proliferation, migration, and invasion in vitro; overexpressed RCAN1.4 in HCC cells prevents growth, angiogenesis, and metastases of xenograft tumors by inhibiting calcineurin activity and nuclear translocation of NFAT1. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Bacterial translocation in an experimental intestinal obstruction model: C-reactive protein reliability? Translocação bacteriana no modelo experimental de obstrução intestinal: A proteína C-reativa é confiável?

    Directory of Open Access Journals (Sweden)

    Saleh Ibrahim El-Awady

    2009-04-01

    Full Text Available BACKGROUND: Bacterial translocation occurs in preseptic conditions such as intestinal obstruction through unclear mechanism. The C-reactive protein is an acute phase reactant and a marker of ischemia. METHODS: 45 albino male rats were divided into 3 groups each 15 rats. GI control, GII simple intestinal-obstruction and GIII strangulated obstruction. Outcome measures were: (1 Bacteriologic count and typing for intestinal contents, intestinal wall, liver, mesenteric lymph nodes and blood (cardiac and portal (2 Histopathologic: mucosal injury score, inflammatory cell infiltrate in the wall, MLN, liver, (3 Biochemical: serum CRP, IL-10, mucosal stress pattern (glutathione peroxidase-malonyldialdhyde tissue levels. RESULTS: (1 Intestinal obstruction associates with BT precursors (Bact-overgrowth, mucosal-acidosis, immuno-incomptence, (2 Bacterial translocation (frequency and density was found higher in strangulated I.O, that was mainly enteric (aerobic and anaerobic and mostly E.coli, (3 The pathogen commonality supports the gut origin hypothesis but the systemic inflammatory response goes with the cytokine generating one. (4 The CRP median values for GI, II, III were 0.5, 6.9, 8.5 mg/L, for BT +ve 8 mg/L and 0.75 mg/L for BT -ve rats. CONCLUSION: Bacterial translocation occurs bi-directional (systemic-portal in intestinal obstruction and the resultant inflammatory response pathogenesis is mostly 3 hit model. The CRP is a non selective marker of suspected I.O cases. However, it is a reliable marker of BT, BT density and vascular compromise during I.O.OBJETIVO: Translocação bacteriana ocorre em condições pré-sépticas como na obstrução intestinal por mecanismo não esclarecido. A proteína C-reativa é um marcador de ischemia em fase aguda. A proposição é investigar os possíveis efeitos da obstrução intestinal no equilíbrio ecológico microbiano. MÉTODOS: 45 ratos machos albinos foram distribuídos em três grupos de 15 ratos. GI

  16. Agrobacterium infection : translocation of virulence proteins and role of VirF in host cells

    NARCIS (Netherlands)

    Jurado Jácome, Esmeralda

    2011-01-01

    The VirB/D4 Type four secretion system (T4SS) is a bacterial multiprotein complex that spans the bacterial envelope, which mediates the translocation of T-DNA and effector virulence proteins into recipient cell. My research revealed that the Agrobacterium VirE3 and VirD2 proteins are effector

  17. Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

    Directory of Open Access Journals (Sweden)

    Mombo-Ngoma Ghyslain

    2010-10-01

    Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

  18. Multicenter randomized controlled trial of bacterial interference for prevention of urinary tract infection in patients with neurogenic bladder.

    Science.gov (United States)

    Darouiche, Rabih O; Green, Bruce G; Donovan, William H; Chen, David; Schwartz, Michael; Merritt, John; Mendez, Michelle; Hull, Richard A

    2011-08-01

    To compare the effectiveness of bacterial interference versus placebo in preventing urinary tract infection (UTI). The main outcome measure was the numbers of episodes of UTI/patient-year. Randomization was computer generated, with allocation concealment by visibly indistinguishable products distributed from a core facility. The healthcare providers and those assessing the outcomes were unaware of the group allocation. Adult patients (n = 65) with neurogenic bladder after spinal cord injury and a history of recurrent UTI were randomized in a 3:1 ratio to receive either Escherichia coli HU2117 or sterile saline. Urine cultures were obtained weekly during the first month and then monthly for 1 year. The patients were evaluable if they remained colonized with E. coli HU2117 for >4 weeks (experimental group). The trial is closed to follow-up. Of the 59 patients who received bladder inoculations, 27 were evaluable (17 in the experimental group and 10 in the placebo group). The 2 study groups had comparable clinical characteristics. Of 17 patients colonized with E. coli HU2117 and the 10 control patients, 5 (29%, 95% confidence interval 0.11-0.56) and 7 (70%, 95% confidence interval 0.35-0.92) developed >1 episode of UTI (P = .049; 1-sided Fisher's exact test), respectively. The average number of episodes of UTI/patient-year was also lower (P = .02, Wilcoxon rank sum test) in the experimental (0.50) than in the control group (1.68). E. coli HU2117 did not cause symptomatic UTI. Bladder colonization with E. coli HU2117 safely reduces the risk of symptomatic UTI in patients with spinal cord injury. Effective, but less complex, methods for achieving bladder colonization with E. coli HU2117 are under investigation. Published by Elsevier Inc.

  19. Valproic acid mitigates the inflammatory response and prevents acute respiratory distress syndrome in a murine model of Escherichia coli pneumonia at the expense of bacterial clearance.

    Science.gov (United States)

    Kasotakis, George; Galvan, Manuel; King, Elizabeth; Sarkar, Beda; Stucchi, Arthur; Mizgerd, Joseph P; Burke, Peter A; Remick, Daniel

    2017-04-01

    Histone deacetylase inhibitors (HDACI) are members of a family of epigenetic modifying agents with broad anti-inflammatory properties. These anti-inflammatory properties may have important therapeutic implications in acute respiratory distress syndrome (ARDS). However, administration of HDACI may create an immunosuppressive environment conducive to bacterial growth. Accordingly, the aim of the current study is to investigate the effect of HDACI valproic acid (VPA) on host inflammatory response and bacterial burden in a murine model of Escherichia coli pneumonia-induced ARDS. ARDS was induced in male C57BL6 mice (n = 24) by endotracheal instillation of 3 × 10 E. coli. VPA (250 mg/kg) was administered 30 minutes after E. coli instillation in the intervention group. Blood samples were collected at 3 and 6 hours, and animals were sacrificed at 6 hours. Bronchoalveolar lavage (BAL) was performed, and tissue specimens were harvested. Cytokine levels were measured in blood and BAL, and so was transalveolar protein transit. Cell counts and colony forming units were quantified in BAL fluid. VPA reduced neutrophil influx into the lungs and local tissue destruction through decreased myeloperoxidase activity. It also ameliorated the pulmonary and systemic inflammatory response. This led to greater bacterial proliferation in the pulmonary parenchyma. Administration of VPA in a clinically relevant bacterial model of murine ARDS mitigates the host inflammatory response, essentially preventing ARDS, but creates an immunosuppressive environment that favors bacterial overgrowth.

  20. Bovine Immunoglobulin/Protein Isolate Binds Pro-Inflammatory Bacterial Compounds and Prevents Immune Activation in an Intestinal Co-Culture Model

    Science.gov (United States)

    Detzel, Christopher J.; Horgan, Alan; Henderson, Abigail L.; Petschow, Bryon W.; Warner, Christopher D.; Maas, Kenneth J.; Weaver, Eric M.

    2015-01-01

    Intestinal barrier dysfunction is associated with chronic gastrointestinal tract inflammation and diseases such as IBD and IBS. Serum-derived bovine immunoglobulin/protein isolate (SBI) is a specially formulated protein preparation (>90%) for oral administration. The composition of SBI is greater than 60% immunoglobulin including contributions from IgG, IgA, and IgM. Immunoglobulin within the lumen of the gut has been recognized to have anti-inflammatory properties and is involved in maintaining gut homeostasis. The binding of common intestinal antigens (LPS and Lipid A) and the ligand Pam3CSK4, by IgG, IgA, and IgM in SBI was shown using a modified ELISA technique. Each of these antigens stimulated IL-8 and TNF-α cytokine production by THP-1 monocytes. Immune exclusion occurred as SBI (≤50 mg/mL) bound free antigen in a dose dependent manner that inhibited cytokine production by THP-1 monocytes in response to 10 ng/mL LPS or 200 ng/mL Lipid A. Conversely, Pam3CSK4 stimulation of THP-1 monocytes was unaffected by SBI/antigen binding. A co-culture model of the intestinal epithelium consisted of a C2BBe1 monolayer separating an apical compartment from a basal compartment containing THP-1 monocytes. The C2BBe1 monolayer was permeabilized with dimethyl palmitoyl ammonio propanesulfonate (PPS) to simulate a damaged epithelial barrier. Results indicate that Pam3CSK4 was able to translocate across the PPS-damaged C2BBe1 monolayer. However, binding of Pam3CSK4 by immunoglobulins in SBI prevented Pam3CSK4 translocation across the damaged C2BBe1 barrier. These results demonstrated steric exclusion of antigen by SBI which prevented apical to basal translocation of antigen due to changes in the physical properties of Pam3CSK4, most likely as a result of immunoglobulin binding. This study demonstrates that immunoglobulins in SBI can reduce antigen-associated inflammation through immune and steric exclusion mechanisms and furthers the mechanistic understanding of how SBI

  1. The anti-translocation and anti-inflammatory effect of cinnamon oil in mice with TNBS induced colitis

    Czech Academy of Sciences Publication Activity Database

    Bujňáková, D.; Juhás, Štefan; Faix, Š.

    2013-01-01

    Roč. 68, č. 5 (2013), s. 1000-1003 ISSN 0006-3088 Institutional support: RVO:67985904 Keywords : bacterial translocation * E. coli * colitis * cinnamon oil Subject RIV: CE - Biochemistry Impact factor: 0.696, year: 2013

  2. EspZ of enteropathogenic and enterohemorrhagic Escherichia coli regulates type III secretion system protein translocation.

    Science.gov (United States)

    Berger, Cedric N; Crepin, Valerie F; Baruch, Kobi; Mousnier, Aurelie; Rosenshine, Ilan; Frankel, Gad

    2012-01-01

    Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal "translocation stop" activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation. Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are important diarrheal pathogens responsible for significant morbidity and mortality in developing countries and the developed world, respectively. The virulence strategy of EPEC and EHEC revolves around a conserved type III secretion system (T3SS), which translocates bacterial proteins known as effectors directly into host cells. Previous studies have shown that when cells are infected in two

  3. Unraveling the relationship between microbial translocation and systemic immune activation in HIV infection

    Science.gov (United States)

    Shan, Liang; Siliciano, Robert F.

    2014-01-01

    Chronic immune activation is a key factor in HIV-1 disease progression. The translocation of microbial products from the intestinal lumen into the systemic circulation occurs during HIV-1 infection and is associated closely with immune activation; however, it has not been determined conclusively whether microbial translocation drives immune activation or occurs as a consequence of HIV-1 infection. In an important study in this issue of the JCI, Kristoff and colleagues describe the role of microbial translocation in producing immune activation in an animal model of HIV-1 infection, SIV infection of pigtailed macaques. Blocking translocation of intestinal bacterial LPS into the circulation dramatically reduced T cell activation and proliferation, production of proinflammatory cytokines, and plasma SIV RNA levels. This study directly demonstrates that microbial translocation promotes the systemic immune activation associated with HIV-1/SIV infection. PMID:24837427

  4. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

    2014-01-01

    impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching......Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...

  5. Prevention of intravenous bacterial injection from health care provider hands: the importance of catheter design and handling.

    Science.gov (United States)

    Loftus, Randy W; Patel, Hetal M; Huysman, Bridget C; Kispert, David P; Koff, Matthew D; Gallagher, John D; Jensen, Jens T; Rowlands, John; Reddy, Sundara; Dodds, Thomas M; Yeager, Mark P; Ruoff, Kathryn L; Surgenor, Stephen D; Brown, Jeremiah R

    2012-11-01

    Device-related bloodstream infections are associated with a significant increase in patient morbidity and mortality in multiple health care settings. Recently, intraoperative bacterial contamination of conventional open-lumen 3-way stopcock sets has been shown to be associated with increased patient mortality. Intraoperative use of disinfectable, needleless closed catheter devices (DNCCs) may reduce the risk of bacterial injection as compared to conventional open-lumen devices due to an intrinsic barrier to bacterial entry associated with valve design and/or the capacity for surface disinfection. However, the relative benefit of DNCC valve design (intrinsic barrier capacity) as compared to surface disinfection in attenuation of bacterial injection in the clinical environment is untested and entirely unknown. The primary aim of the current study was to investigate the relative efficacy of a novel disinfectable stopcock, the Ultraport zero, with and without disinfection in attenuating intraoperative injection of potential bacterial pathogens as compared to a conventional open-lumen stopcock intravascular device. The secondary aims were to identify risk factors for bacterial injection and to estimate the quantity of bacterial organisms injected during catheter handling. Four hundred sixty-eight operating room environments were randomized by a computer generated list to 1 of 3 device-injection schemes: (1) injection of the Ultraport zero stopcock with hub disinfection before injection, (2) injection of the Ultraport zero stopcock without prior hub disinfection, and (3) injection of the conventional open-lumen stopcock closed with sterile caps according to usual practice. After induction of general anesthesia, the primary anesthesia provider caring for patients in each operating room environment was asked to perform a series of 5 injections of sterile saline through the assigned device into an ex vivo catheter system. The primary outcome was the incidence of bacterial

  6. ESX-1-mediated translocation to the cytosol controls virulence of mycobacteria

    KAUST Repository

    Houben, Diane

    2012-05-08

    Mycobacterium species, including Mycobacterium tuberculosis and Mycobacterium leprae, are among the most potent human bacterial pathogens. The discovery of cytosolic mycobacteria challenged the paradigm that these pathogens exclusively localize within the phagosome of host cells. As yet the biological relevance of mycobacterial translocation to the cytosol remained unclear. In this current study we used electron microscopy techniques to establish a clear link between translocation and mycobacterial virulence. Pathogenic, patient-derived mycobacteria species were found to translocate to the cytosol, while non-pathogenic species did not. We were further able to link cytosolic translocation with pathogenicity by introducing the ESX-1 (type VII) secretion system into the non-virulent, exclusively phagolysosomal Mycobacterium bovis BCG. Furthermore, we show that translocation is dependent on the C-terminus of the early-secreted antigen ESAT-6. The C-terminal truncation of ESAT-6 was shown to result in attenuation in mice, again linking translocation to virulence. Together, these data demonstrate the molecular mechanism facilitating translocation of mycobacteria. The ability to translocate from the phagolysosome to the cytosol is with this study proven to be biologically significant as it determines mycobacterial virulence. © 2012 Blackwell Publishing Ltd.

  7. The efficacy of different anti-microbial metals at preventing the formation of, and eradicating bacterial biofilms of pathogenic indicator strains.

    Science.gov (United States)

    Gugala, Natalie; Lemire, Joe A; Turner, Raymond J

    2017-06-01

    The emergence of multidrug-resistant pathogens and the prevalence of biofilm-related infections have generated a demand for alternative anti-microbial therapies. Metals have not been explored in adequate detail for their capacity to combat infectious disease. Metal compounds can now be found in textiles, medical devices and disinfectants-yet, we know little about their efficacy against specific pathogens. To help fill this knowledge gap, we report on the anti-microbial and antibiofilm activity of seven metals: silver, copper, titanium, gallium, nickel, aluminum and zinc against three bacterial strains, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. To evaluate the capacity of metal ions to prevent the growth of, and eradicate biofilms and planktonic cells, bacterial cultures were inoculated in the Calgary Biofilm Device (minimal biofilm eradication concentration) in the presence of the metal salts. Copper, gallium and titanium were capable of preventing planktonic and biofilm growth, and eradicating established biofilms of all tested strains. Further, we observed that the efficacies of the other tested metal salts displayed variable efficacy against the tested strains. Further, contrary to the enhanced resistance anticipated from bacterial biofilms, particular metal salts were observed to be more effective against biofilm communities versus planktonic cells. In this study, we have demonstrated that the identity of the bacterial strain must be considered before treatment with a particular metal ion. Consequent to the use of metal ions as anti-microbial agents to fight multidrug-resistant and biofilm-related infections increases, we must aim for more selective deployment in a given infectious setting.

  8. Translocation of Helicobacter pylori CagA into Gastric Epithelial Cells by Type IV Secretion

    Science.gov (United States)

    Odenbreit, Stefan; Püls, Jürgen; Sedlmaier, Bettina; Gerland, Elke; Fischer, Wolfgang; Haas, Rainer

    2000-02-01

    The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA+) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

  9. Another reptile translocation to a national park

    Directory of Open Access Journals (Sweden)

    W.R. Branch

    1990-10-01

    Full Text Available On 4 May 1988 a sub-adult (50 mm snout-vent length, 42 mm tail Jones' girdled lizard Cordylus tropidosternum jonesi was collected in a pile of wood being off-loaded at the new restcamp in the Karoo National Park, Beaufort West. The wood had been transported by lorry from the Kruger National Park. The specimen is deposited in the herpetological collection of the Port Elizabeth Museum (PEM R 4584. Jones' girdled lizard is a small, arboreal cordylid that shelters under tree bark and in hollow logs. It is common and widely-distributed in the Kruger National Park (Pienaar, Haacke & Jacobsen 1983, The Reptiles of the Kruger National Park, 3rd edition. Pretoria: National Parks Board and adjacent lowveld, being replaced in northern Zimbabwe and East Africa by the nominate race. Hewitt & Power (1913, Transactions of the Royal Society of South Africa 3: 147-176, 1913 reported a similar translocation of the species to Kimberley in association with timber brought to the diamond mining camps. One of us noted recently the ease and danger of the unwitting spread of commensal reptile species into conservation areas (Branch 1978, Koedoe 30: 165, and this is confirmed by this additional example. We recommend that should similar shipments of wood be considered essential, then they be fumigated to prevent the translocation of other alien organisms that may potentially have more dangerous consequences.

  10. [Epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients : Update 2017 of the interdisciplinary AWMF S3 guideline].

    Science.gov (United States)

    Kranz, J; Schmidt, S; Lebert, C; Schneidewind, L; Vahlensieck, W; Sester, U; Fünfstück, R; Helbig, S; Hofmann, W; Hummers, E; Kunze, M; Kniehl, E; Naber, K; Mandraka, F; Mündner-Hensen, B; Schmiemann, G; Wagenlehner, F M E

    2017-06-01

    Update of the 2010 published evidence-based S3 guideline on epidemiology, diagnostics, therapy and management of uncomplicated, bacterial, outpatient-acquired urinary tract infections in adult patients. The guideline contains current evidence for the rational use of antimicrobial substances, avoidance of inappropriate use of certain antibiotic classes and development of resistance. The update was created under the leadership of the German Association of Urology (DGU). A systematic literature search was conducted for the period 01 January 2008 to 31 December 2015. International guidelines have also been taken into account. Evidence level and risk of bias were used for quality review. Updated information on bacterial susceptibility, success, collateral damage and safety of first- and second-line antibiotics was given. For the treatment of uncomplicated cystitis the first line antibiotics are fosfomycin trometamol, nitrofurantoin, nitroxoline, pivmecillinam, trimethoprim (with consideration of the local resistance rates). Fluoroquinolones and cephalosporins should not be used as first choice antibiotics. In the case of uncomplicated pyelonephritis of mild to moderate forms, preferably cefpodoxime, ceftibuten, ciprofloxacin or levofloxacin should be used as oral antibiotics. The updated German S3 guideline provides comprehensive evidence- and consensus-based recommendations on epidemiology, diagnostics, therapy, prevention and management of uncomplicated bacterial outpatient acquired urinary tract infections in adult patients. Antibiotic stewardship aspects have significantly influenced the therapeutic recommendations. A broad implementation in all clinical practice settings is necessary to ensure a foresighted antibiotic policy and thus t improve clinical care.

  11. Prevention of bacterial and fungal infections in acute leukemia patients: a new and potent combination of oral norfloxacin and amphotericin B.

    Science.gov (United States)

    Yamada, T; Dan, K; Nomura, T

    1993-09-01

    The effect of a combination regimen using norfloxacin (NFLX) and amphotericin B (AMPH-B) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a randomized, controlled trial was studied. One hundred and six consecutive, evaluable patients were randomly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily, or amphotericin B only. A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group (34.6% vs 56.9%; P combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy.

  12. Prevention

    Science.gov (United States)

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  13. Maternal and early onset neonatal bacterial sepsis: burden and strategies for prevention in sub-Saharan Africa.

    Science.gov (United States)

    Seale, Anna C; Mwaniki, Michael; Newton, Charles R J C; Berkley, James A

    2009-07-01

    Maternal and child health are high priorities for international development. Through a Review of published work, we show substantial gaps in current knowledge on incidence (cases per live births), aetiology, and risk factors for both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa. Although existing published data suggest that sepsis causes about 10% of all maternal deaths and 26% of neonatal deaths, these are likely to be considerable underestimates because of methodological limitations. Successful intervention strategies in resource-rich settings and early studies in sub-Saharan Africa suggest that the burden of maternal and early onset neonatal bacterial sepsis could be reduced through simple interventions, including antiseptic and antibiotic treatment. An effective way to expedite evidence to guide interventions and determine the incidence, aetiology, and risk factors for sepsis in sub-Saharan Africa would be through a multiarmed factorial intervention trial aimed at reducing both maternal and early onset neonatal bacterial sepsis in sub-Saharan Africa.

  14. [Dermohypodermitis and gut translocation Escherichia coli septicemia in a newborn infant].

    Science.gov (United States)

    Gouache, E; Chantier, E; Hubert, N; Rivière, M-F

    2013-01-01

    The burden of neonatal bacterial infections continues. They remain a significant cause of death and morbidity, despite recommendations for prevention. The epidemiology of these infections has changed. Currently the two most causative pathogens for early-onset neonatal sepsis and for late-onset sepsis in term infants are Group B streptococci (GBS) and Escherichia coli. E. coli's role is increasingly important since the widespread use of intrapartum antibiotic prophylaxis. In late-onset infections, one of the suggested pathophysiological mechanisms is microbial translocation in the gut secondary to digestive colonization, particularly when E. coli is isolated in blood cultures. This can occur either before or after birth. Bacterial sepsis can be associated with various non-specific peripheral manifestations involving skin and soft tissues. We report the case of a full-term, 26-day-old newborn admitted to the hospital for fever. She presented with dermohypodermitis of the left trunk and was diagnosed with E. coli septicemia. She was discharged in good condition after appropriate intravenous antibiotic therapy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Prevention of bacterial infections in the newborn by pre-delivery administration of azithromycin: Study protocol of a randomized efficacy trial.

    Science.gov (United States)

    Roca, Anna; Oluwalana, Claire; Camara, Bully; Bojang, Abdoulie; Burr, Sarah; Davis, Timothy M E; Bailey, Robin; Kampmann, Beate; Mueller, Jenny; Bottomley, Christian; D'Alessandro, Umberto

    2015-11-19

    Neonatal deaths, estimated at approximately 4 million annually, now account for almost 40% of global mortality in children aged under-five. Bacterial sepsis is a leading cause of neonatal mortality. Assuming the mother is the main source for bacterial transmission to newborns, the primary objective of the trial is to determine the impact of one oral dose of azithromycin, given to women in labour, on the newborn's bacterial carriage in the nasopharynx. Secondary objectives include the impact of the intervention on bacterial colonization in the baby and the mother during the first month of life. This is a Phase III, double -blind, placebo controlled randomized clinical trial in which 830 women in labour were randomized to either a single dose of 2 g oral azithromycin or placebo (ratio 1:1). The trial included pregnant women in labour aged 18 to 45 years attending study health centres in the Western Gambia. A post-natal check of the mother and baby was conducted at the health centre by study clinicians before discharge and 8-10 days after delivery. Home follow up visits were conducted daily during the first week and then weekly until week 8 after delivery. Vaginal swabs and breast milk samples were collected from the mothers, and the pathogens Streptococcus pneumoniae, Group B Streptococcus (GBS) and Staphylococcus aureus were isolated from the study samples. For bacterial isolates, susceptibility pattern to azithromycin was determined using disk diffusion and E-test. Eye swabs were collected from newborns with eye discharge during the follow up period, and Chlamydial infection was assessed using molecular methods. This is a proof-of-concept study to assess the impact of antibiotic preventive treatment of women during labour on bacterial infections in the newborn. If the trial confirms this hypothesis, the next step will be to assess the impact of this intervention on neonatal sepsis. The proposed intervention should be easily implementable in developing countries

  16. Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity.

    Science.gov (United States)

    Mesén-Ramírez, Paolo; Reinsch, Ferdinand; Blancke Soares, Alexandra; Bergmann, Bärbel; Ullrich, Ann-Katrin; Tenzer, Stefan; Spielmann, Tobias

    2016-05-01

    Protein export is central for the survival and virulence of intracellular P. falciparum blood stage parasites. To reach the host cell, exported proteins cross the parasite plasma membrane (PPM) and the parasite-enclosing parasitophorous vacuole membrane (PVM), a process that requires unfolding, suggestive of protein translocation. Components of a proposed translocon at the PVM termed PTEX are essential in this phase of export but translocation activity has not been shown for the complex and questions have been raised about its proposed membrane pore component EXP2 for which no functional data is available in P. falciparum. It is also unclear how PTEX mediates trafficking of both, soluble as well as transmembrane proteins. Taking advantage of conditionally foldable domains, we here dissected the translocation events in the parasite periphery, showing that two successive translocation steps are needed for the export of transmembrane proteins, one at the PPM and one at the PVM. Our data provide evidence that, depending on the length of the C-terminus of the exported substrate, these steps occur by transient interaction of the PPM and PVM translocon, similar to the situation for protein transport across the mitochondrial membranes. Remarkably, we obtained constructs of exported proteins that remained arrested in the process of being translocated across the PVM. This clogged the translocation pore, prevented the export of all types of exported proteins and, as a result, inhibited parasite growth. The substrates stuck in translocation were found in a complex with the proposed PTEX membrane pore component EXP2, suggesting a role of this protein in translocation. These data for the first time provide evidence for EXP2 to be part of a translocating entity, suggesting that PTEX has translocation activity and provide a mechanistic framework for the transport of soluble as well as transmembrane proteins from the parasite boundary into the host cell.

  17. Markovian description of unbiased polymer translocation

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil); Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, UnED Angra dos Reis, Angra dos Reis, 23953-030, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil)

    2012-10-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  18. Markovian description of unbiased polymer translocation

    International Nuclear Information System (INIS)

    Mondaini, Felipe; Moriconi, L.

    2012-01-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  19. Dynamics of polymer translocation through kinked nanopores.

    Science.gov (United States)

    Wang, Junfang; Wang, Yilin; Luo, Kaifu

    2015-02-28

    Polymer translocation through nanopore has potential technological applications for DNA sequencing, where one challenge problem is to slow down translocation speed. Inspired by experimental findings that kinked nanopores exhibit a large reduction in translocation velocity compared with their straight counterparts, we investigate the dynamics of polymer translocation through kinked nanopores in two dimensions under an applied external field. With increasing the tortuosity of an array of nanopores, our analytical results show that the translocation probability decreases. Langevin dynamics simulation results support this prediction and further indicate that with increasing the tortuosity, translocation time shows a slow increase followed by a rapid increase after a critical tortuosity. This behavior demonstrates that kinked nanopores can effectively reduce translocation speed. These results are interpreted by the roles of the tortuosity for decreasing the effective nanopore diameter, increasing effective nanopore length, and greatly increasing the DNA-pore friction.

  20. The E Block motif is associated with Legionella pneumophila translocated substrates.

    Science.gov (United States)

    Huang, Li; Boyd, Dana; Amyot, Whitney M; Hempstead, Andrew D; Luo, Zhao-Qing; O'Connor, Tamara J; Chen, Cui; Machner, Matthias; Montminy, Timothy; Isberg, Ralph R

    2011-02-01

    Legionella pneumophila promotes intracellular growth by moving bacterial proteins across membranes via the Icm/Dot system. A strategy was devised to identify large numbers of Icm/Dot translocated proteins, and the resulting pool was used to identify common motifs that operate as recognition signals. The 3' end of the sidC gene, which encodes a known translocated substrate, was replaced with DNA encoding 200 codons from the 3' end of 442 potential substrate-encoding genes. The resulting hybrid proteins were then tested in a high throughput assay, in which translocated SidC antigen was detected by indirect immunofluorescence. Among translocated substrates, regions of 6-8 residues called E Blocks were identified that were rich in glutamates. Analysis of SidM/DrrA revealed that loss of three Glu residues, arrayed in a triangle on an α-helical surface, totally eliminated translocation of a reporter protein. Based on this result, a second strategy was employed to identify Icm/Dot substrates having carboxyl terminal glutamates. From the fusion assay and the bioinformatic queries, carboxyl terminal sequences from 49 previously unidentified proteins were shown to promote translocation into target cells. These studies indicate that by analysing subsets of translocated substrates, patterns can be found that allow predictions of important motifs recognized by Icm/Dot. © 2010 Blackwell Publishing Ltd.

  1. Reducing atelectasis attenuates bacterial growth and translocation in experimental pneumonia

    NARCIS (Netherlands)

    van Kaam, Anton H.; Lachmann, Robert A.; Herting, Egbert; de Jaegere, Anne; van Iwaarden, Freek; Noorduyn, L. Arnold; Kok, Joke H.; Haitsma, Jack J.; Lachmann, Burkhard

    2004-01-01

    Besides being one of the mechanisms responsible for ventilator-induced lung injury, atelectasis also seems to aggravate the course of experimental pneumonia. In this study, we examined the effect of reducing the degree of atelectasis by natural modified surfactant and/or open lung ventilation on

  2. Preventively enteral application of immunoglobulin enriched colostrums milk can modulate postoperative inflammatory response

    Science.gov (United States)

    2013-01-01

    Several studies demonstrated acute inflammatory response following traumatic injury. Inflammatory response during surgical interventions was verified by a significant increase of endotoxin plasma levels and a decrease of the endotoxin neutralizing capacity (ENC). However, the incidence of elevated endotoxin levels was significantly higher (89%) than detected bacterial translocation (35%). Thus parts or products of Gram-negative bacteria seem to translocate more easily into the blood circulation than whole bacteria. Along with the bacterial translocation, the inflammatory response correlated directly with the severity of the surgical intervention. In comparison after major and minor surgery Interleukin-6 (IL-6) and C-reactive protein (CRP) was also significantly different. Similar effects in mediator release were shown during endovascular stent graft placement and open surgery in infrarenal aortic aneurysm. Open surgery demonstrated a significant stronger endotoxin translocation and a decrease of ENC. Strategies to prevent translocation seem to be sensible. Colostrum is the first milk produced by the mammary glands within the first days after birth. It contains a complex system of immune factors and has a long history of use in traditional medicine. Placebo-controlled studies verified that prophylactic oral application of immunoglobulin-enriched colostrum milk preparation diminishes perioperative endotoxemia, prevents reduction of ENC and reduces postoperative CRP-levels, suggesting a stabilization of the gut barrier. This effect may be caused by immunoglobulin transportation by the neonatal receptor FcRn of the mucosal epithelium. In conclusion, there is an association of perioperative endotoxemia and the subsequent increase in mediators of the acute phase reaction in surgical patients. A prophylactic oral application of colostrum milk is likely to stabilize the gut barrier i.e. reduces the influx of lipopolysaccharides arising from Gram-negative bacterial

  3. Vacuum plasma sprayed coatings using ionic silver doped hydroxyapatite powder to prevent bacterial infection of bone implants.

    Science.gov (United States)

    Guimond-Lischer, Stefanie; Ren, Qun; Braissant, Olivier; Gruner, Philipp; Wampfler, Bruno; Maniura-Weber, Katharina

    2016-03-10

    Fast and efficient osseointegration of implants into bone is of crucial importance for their clinical success; a process that can be enhanced by coating the implant surface with hydroxyapatite (HA) using the vacuum plasma spray technology (VPS). However, bacterial infections, especially the biofilm formation on implant surfaces after a surgery, represent a serious complication. With ever-increasing numbers of antibiotic-resistant bacteria, there is great interest in silver (Ag) as an alternative to classical antibiotics due to its broad activity against Gram-positive and Gram-negative bacterial strains. In the present study, silver ions were introduced into HA spray powder by ion exchange and the HA-Ag powder was applied onto titanium samples by VPS. The Ag-containing surfaces were evaluated for the kinetics of the silver release, its antibacterial effect against Staphylococcus aureus as well as Escherichia coli, and possible cytotoxicity against human bone cells. The HA-Ag coatings with different concentrations of Ag displayed mechanical and compositional properties that fulfill the regulatory requirements. Evaluation of the Ag release kinetic showed a high release rate in the first 24 h followed by a decreasing release rate over the four subsequent days. The HA-Ag coatings showed no cytotoxicity to primary human bone cells while exhibiting antibacterial activity to E. coli and S. aureus.

  4. Zoonotic bacterial meningitis in human adults

    NARCIS (Netherlands)

    van Samkar, Anusha; Brouwer, Matthijs C.; van der Ende, Arie; van de Beek, Diederik

    2016-01-01

    To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by

  5. Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin.

    Science.gov (United States)

    Prince, Lynne R; Bianchi, Stephen M; Vaughan, Kathryn M; Bewley, Martin A; Marriott, Helen M; Walmsley, Sarah R; Taylor, Graham W; Buttle, David J; Sabroe, Ian; Dockrell, David H; Whyte, Moira K B

    2008-03-01

    Neutrophils undergo rapid constitutive apoptosis that is accelerated following bacterial ingestion as part of effective immunity, but is also accelerated by bacterial exotoxins as a mechanism of immune evasion. The paradigm of pathogen-driven neutrophil apoptosis is exemplified by the Pseudomonas aeruginosa toxic metabolite, pyocyanin. We previously showed pyocyanin dramatically accelerates neutrophil apoptosis both in vitro and in vivo, impairs host defenses, and favors bacterial persistence. In this study, we investigated the mechanisms of pyocyanin-induced neutrophil apoptosis. Pyocyanin induced early lysosomal dysfunction, shown by altered lysosomal pH, within 15 min of exposure. Lysosomal disruption was followed by mitochondrial membrane permeabilization, caspase activation, and destabilization of Mcl-1. Pharmacological inhibitors of a lysosomal protease, cathepsin D (CTSD), abrogated pyocyanin-induced apoptosis, and translocation of CTSD to the cytosol followed pyocyanin treatment and lysosomal disruption. A stable analog of cAMP (dibutyryl cAMP) impeded the translocation of CTSD and prevented the destabilization of Mcl-1 by pyocyanin. Thus, pyocyanin activated a coordinated series of events dependent upon lysosomal dysfunction and protease release, the first description of a bacterial toxin using a lysosomal cell death pathway. This may be a pathological pathway of cell death to which neutrophils are particularly susceptible, and could be therapeutically targeted to limit neutrophil death and preserve host responses.

  6. Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins*

    Science.gov (United States)

    Job, Viviana; Matteï, Pierre-Jean; Lemaire, David; Attree, Ina; Dessen, Andréa

    2010-01-01

    The type III secretion system (T3SS) is a complex nanomachine employed by many Gram-negative pathogens, including the nosocomial agent Pseudomonas aeruginosa, to inject toxins directly into the cytoplasm of eukaryotic cells. A key component of all T3SS is the translocon, a proteinaceous channel that is inserted into the target membrane, which allows passage of toxins into target cells. In most bacterial species, two distinct membrane proteins (the “translocators”) are involved in translocon formation, whereas in the bacterial cytoplasm, however, they remain associated to a common chaperone. To date, the strategy employed by a single chaperone to recognize two distinct translocators is unknown. Here, we report the crystal structure of a complex between the Pseudomonas translocator chaperone PcrH and a short region from the minor translocator PopD. PcrH displays a 7-helical tetratricopeptide repeat fold that harbors the PopD peptide within its concave region, originally believed to be involved in recognition of the major translocator, PopB. Point mutations introduced into the PcrH-interacting region of PopD impede translocator-chaperone recognition in vitro and lead to impairment of bacterial cytotoxicity toward macrophages in vivo. These results indicate that T3SS translocator chaperones form binary complexes with their partner molecules, and the stability of their interaction regions must be strictly maintained to guarantee bacterial infectivity. The PcrH-PopD complex displays homologs among a number of pathogenic strains and could represent a novel, potential target for antibiotic development. PMID:20385547

  7. Awareness of need and actual use of prophylaxis: lack of patient compliance in the prevention of bacterial endocarditis

    NARCIS (Netherlands)

    van der Meer, J. T.; van Wijk, W.; Thompson, J.; Valkenburg, H. A.; Michel, M. F.

    1992-01-01

    Antibiotics are given before some medical and dental procedures to patients with congenital or acquired heart disease to prevent endocarditis. The majority of practitioners and patients are aware of the need for this prophylaxis, although in practice prophylaxis is administered infrequently. It is

  8. Novel insights in preventing Gram-negative bacterial infection in cirrhotic patients: review on the effects of GM-CSF in maintaining homeostasis of the immune system.

    Science.gov (United States)

    Xu, Dong; Zhao, Manzhi; Song, Yuhu; Song, Jianxin; Huang, Yuancheng; Wang, Junshuai

    2015-01-01

    Cirrhotic patients with dysfunctional and/or low numbers of leukocytes are often infected with bacteria, especially Gram-negative bacteria, which is characterized by producing lipopolysaccharide (LPS). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a pleiotropic cytokine that influences the production, maturation, function, and survival of various immune cells. In this paper, we reviewed not only Toll-like receptors 4 (TLR4) signaling pathway and its immunological effect, but also the specific stimulating function and autocrine performance of GM-CSF on hematopoietic cells, as well as the recent discovery of innate response activator-B cells in protection against microbial sepsis and the direct LPS-TLR4 signaling on hematopoiesis. Thus we concluded that GM-CSF might play important roles in preventing Gram-negative bacterial infections in cirrhotic patients through maintaining immune system functions and homeostasis.

  9. Confirmation of translocated gastrointestinal bacteria in a neonatal model.

    Science.gov (United States)

    Moy, J; Lee, D J; Harmon, C M; Drongowski, R A; Coran, A G

    1999-11-01

    The hypothesis that enteric bacteria translocate from the gastrointestinal (GI) tract to extraintestinal sites has been extensively studied. However, definitive evidence that spontaneous bacterial translocation and dissemination from the GI tract to extraintestinal sites occur in a neonatal model has been lacking. The aim of this study was to confirm this phenomenon by tracking enterally administered, plasmid-labeled bacteria to extraintestinal sites. Escherichia coli 07:K1 (E. coli K1) with and without a nontransferable, ampicillin resistance plasmid (pGEM-7) were used in this study. Newborn New Zealand white rabbit pups were separated into three treatment groups: transformed E. coli K1 (E. coli K1 + pGEM-7, n = 20), nontransformed E. coli K1 (n = 12), and control pups (no bacteria, n = 7). Pups were enterally fed 10% Formulac solution supplemented with a suspension of bacteria respective to their group. After the pups fed twice daily for 2 days, representative tissue specimens from the small bowel (SB), mesenteric lymph nodes (MLNs), spleen (SPL), and liver (LIV) were aseptically harvested and tested for culture growth in ampicillin-supplemented medium. Positive growths of plasmid-induced ampicillin-resistant bacteria were detected in tissue specimens harvested from rabbits fed transformed E. coli K1, but were not detected in the other groups. This experiment demonstrated conclusively that transformed E. coli K1 fed to healthy rabbit pups spontaneously translocated from the intestinal lumen and subsequently disseminated to the mesenteric lymph nodes, spleen, and liver. Copyright 1999 Academic Press.

  10. Prevention

    Science.gov (United States)

    ... Contact Aging & Health A to Z Find a Geriatrics Healthcare Professional Medications & Older Adults Making Your Wishes ... Prevention Hearing Loss Heart Attack High Blood Pressure Nutrition Osteoporosis Shingles Skin Cancer Related News Quitting Smoking, ...

  11. Balanced Reciprocal Translocations Detected at Amniocentesis

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2010-12-01

    Conclusion: Balanced reciprocal translocations detected at amniocentesis may be associated with fetal anomalies in cases of concomitant aneuploidy, de novo X-autosome translocation or de novo CCR. Genetic counseling of a de novo simple reciprocal translocation at amniocentesis remains difficult because approximately one-fourth of the parents opt for termination of the pregnancy, and detailed ultrasonography and array comparative genomic hybridization are helpful for parental counseling under such circumstances.

  12. Translocations affecting human immunoglobulin heavy chain locus

    Directory of Open Access Journals (Sweden)

    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  13. Surface display of proteins by Gram-negative bacterial autotransporters

    Directory of Open Access Journals (Sweden)

    Mourez Michael

    2006-06-01

    Full Text Available Abstract Expressing proteins of interest as fusions to proteins of the bacterial envelope is a powerful technique with many biotechnological and medical applications. Autotransporters have recently emerged as a good tool for bacterial surface display. These proteins are composed of an N-terminal signal peptide, followed by a passenger domain and a translocator domain that mediates the outer membrane translocation of the passenger. The natural passenger domain of autotransporters can be replaced by heterologous proteins that become displayed at the bacterial surface by the translocator domain. The simplicity and versatility of this system has made it very attractive and it has been used to display functional enzymes, vaccine antigens as well as polypeptides libraries. The recent advances in the study of the translocation mechanism of autotransporters have raised several controversial issues with implications for their use as display systems. These issues include the requirement for the displayed polypeptides to remain in a translocation-competent state in the periplasm, the requirement for specific signal sequences and "autochaperone" domains, and the influence of the genetic background of the expression host strain. It is therefore important to better understand the mechanism of translocation of autotransporters in order to employ them to their full potential. This review will focus on the recent advances in the study of the translocation mechanism of autotransporters and describe practical considerations regarding their use for bacterial surface display.

  14. Enteropathogenic Escherichia coli translocate Tir and form an intimin-Tir intimate attachment to red blood cell membranes.

    Science.gov (United States)

    Shaw, Robert K; Daniell, Sarah; Frankel, Gad; Knutton, Stuart

    2002-05-01

    Type III secretion allows bacteria to inject effector proteins into host cells. In enteropathogenic Escherichia coli (EPEC) the type III secreted protein, Tir, is translocated to the host-cell plasma membrane where it functions as a receptor for the bacterial adhesin intimin, leading to intimate bacterial attachment and "attaching and effacing" (A/E) lesion formation. To study EPEC type III secretion the interaction of EPEC with monolayers of red blood cells (RBCs) has been exploited and in a recent study [Shaw, R. K., Daniell, S., Ebel, F., Frankel, G. & Knutton, S. (2001 ). Cell Microbiol 3, 213-222] it was shown that EPEC induced haemolysis of RBCs and translocation of EspD, a putative pore-forming type III secreted protein in the RBC membrane. Here it is demonstrated that EPEC are able to translocate and correctly insert Tir into the RBC membrane and produce an intimin-Tir intimate bacterial attachment, identical to that seen in A/E lesions. Following translocation Tir did not undergo any change in apparent molecular mass or become tyrosine-phosphorylated and there was no focusing of RBC cytoskeletal actin beneath intimately adherent bacteria, and no pedestal formation. This study, employing an RBC model of infection, has demonstrated that Tir translocation can be separated from host-cell-mediated Tir modifications; the data show that the EPEC type III protein translocation apparatus is sufficient to deliver and correctly insert Tir into host-cell membranes independent of eukaryotic cell functions.

  15. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  16. A descriptive study on prevalence of bacterial pathogens in diabetic ulcer and Interventional component for the prevention of foot ulcers

    Directory of Open Access Journals (Sweden)

    Jerlin Priya, Rajamanickam Rajkumar, Bakthasingh

    2014-11-01

    Full Text Available Diabetes is considered to have reached epidemic proportions worldwide. The most distressing complication of diabetes is foot ulcer and is the major cause of lower limb amputation. Hence, they require a prolonged hospital stay to combat more serious complications like gangrene and lower limb amputation. Early detection and prompt treatment help in alleviating the ulceration. Methods: The present study was conducted among 50 diabetes patients. Study subjects were selected using non probability purposive sampling technique. Pus samples were collected by using sterile swabs in a sterile manner from the ulcerated area. The wounds are washed vigorously with normal saline solution before collection of specimen. The specimens were transported immediately to the laboratory for culture. The clinical specimens were first screened microscopically by Gram’s stain, and then cultured on blood agar (aerobically and an aerobically, MacConkey agar and Robertson cooked meat broth for 48 hours at 37°C in 5-10 percent CO2 and bacteria’s were isolated. Results: The socio demographic profile of the present study reveals that males were predominant among the study population. Type II diabetes was more common, majority of study subjects are suffering from diabetes for more than 5 years and are treated with oral hypoglycemic drugs. The wound size was ≤ 2cms in majority of study subjects. The bacteriological profile of diabetic ulcer reveals that a majority of 23 (46% had growth of Staphylococcus aureus and 19 (38% had growth of klebsiella and a minimum of 6 (12% and 2 (4% had grown of Pseudomonas and Staphylococcus albus. Conclusion: Early detection of these bacterial pathogens helps to minimize the disease progress.

  17. A New, Potent, and Placenta-Permeable Macrolide Antibiotic, Solithromycin, for the Prevention and Treatment of Bacterial Infections in Pregnancy.

    Science.gov (United States)

    Keelan, Jeffrey A; Payne, Matthew S; Kemp, Matthew W; Ireland, Demelza J; Newnham, John P

    2016-01-01

    Intrauterine infection-inflammation is a major cause of early preterm birth and subsequent neonatal mortality and acute or long-term morbidity. Antibiotics can be administered in pregnancy to prevent preterm birth either prophylactically to women at high risk for preterm delivery, or to women with diagnosed intrauterine infection, prelabor rupture of membranes, or in suspected preterm labor. The therapeutic goals of each of these scenarios are different, with different pharmacological considerations, although effective antimicrobial therapy is an essential requirement. An ideal antibiotic for these clinical indications would be (a) one that is easily administered and orally bioactive, (b) has a favorable adverse effect profile (devoid of reproductive toxicity or teratogenicity), (c) is effective against the wide range of microorganisms known to be commonly associated with intra-amniotic infection, (d) provides effective antimicrobial protection within both the fetal and amniotic compartments after maternal delivery, (e) has anti-inflammatory properties, and (f) is effective against antibiotic-resistant microorganisms. Here, we review the evidence from clinical, animal, and ex vivo/in vitro studies that demonstrate that a new macrolide-derived antibiotic - solithromycin - has all of these properties and, hence, may be an ideal antibiotic for the treatment and prevention of intrauterine infection--related pregnancy complications. While this evidence is extremely encouraging, it is still preliminary. A number of key studies need to be completed before solithromycin's true potential for use in pregnancy can be ascertained.

  18. A new, potent and placenta-permeable macrolide antibiotic, solithromycin, for the prevention and treatment of bacterial infections in pregnancy

    Directory of Open Access Journals (Sweden)

    Jeffrey A Keelan

    2016-04-01

    Full Text Available Intrauterine infection-inflammation is a major cause of early preterm birth and subsequent neonatal morbidity and acute or long-term mortality. Antibiotics can be administered in pregnancy to prevent preterm birth either prophylactically to women at high risk for preterm delivery, or to women with diagnosed intrauterine infection, prelabour rupture of membranes, or in suspected preterm labour. The therapeutic goals of each of these scenarios are different, with different pharmacological considerations, although effective antimicrobial therapy is an essential requirement. An ideal antibiotic for these clinical indications would be a one that is easily administered and orally bioactive, b has a favourable adverse effect profile (devoid of reproductive toxicity or teratogenicity, c is effective against the wide range of microorganisms known to be commonly associated with intra-amniotic infection, d provides effective antimicrobial protection within both the fetal and amniotic compartments after maternal delivery, e has anti-inflammatory properties, and f is effective against antibiotic resistant microorganisms. Here we review the evidence from clinical, animal and ex-vivo/in-vitro studies that demonstrates that a new macrolide-derived antibiotic - solithromycin - has all of these properties and hence may be an ideal antibiotic for the treatment and prevention of intrauterine infection-related pregnancy complications. While this evidence is extremely encouraging, it is still preliminary. A number of key studies need to be completed before solithromycin’s true potential for use in pregnancy can be ascertained.

  19. Bacterial Keratitis

    Science.gov (United States)

    ... Español Eye Health / Eye Health A-Z Bacterial Keratitis Sections What Is Bacterial Keratitis? Bacterial Keratitis Symptoms ... Lens Care Bacterial Keratitis Treatment What Is Bacterial Keratitis? Leer en Español: ¿Qué Es la Queratitis Bacteriana? ...

  20. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    Supplementary figure 1. (a–i) Putative novel genes created by the breakpoints. Translocation chromosomes are shown with the translocated segment indicated in red and the untranslocated segments in black or blue. Purple arrows indicate whether the chromosome is a donor (arrow pointing up) or a recipient (arrow ...

  1. Nuclear translocation and retention of growth hormone

    DEFF Research Database (Denmark)

    Mertani, Hichem C; Raccurt, Mireille; Abbate, Aude

    2003-01-01

    We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by us...

  2. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    †Dedicated to the memory of our colleague T Bhavani Prasanna. Abbreviations used: Dp, duplication; Df, deficiency; ITs, insertional translocations; LG, lineage group; OR, Oak Ridge; ORFs, open reading frames; PCR, polymerase chain reaction; QTs, quasiterminal translocations; RIP, repeat-induced point mutation.

  3. Protein malnutrition and metronidazole induced intestinal bacterial ...

    African Journals Online (AJOL)

    This study was designed to assess the effects of protein malnutrition (PM) associated with antibiotic on growth weight, cecal bacterial overgrowth and enterobacteria translocation. Eighteen Gnotobiotic young Wistar rats (135 ± 2.35 g) were treated orally with antibiotic and submitted to dietary restriction based on maize diet ...

  4. Recent Advances and Understanding of Using Probiotic-Based Interventions to Restore Homeostasis of the Microbiome for the Prevention/Therapy of Bacterial Diseases.

    Science.gov (United States)

    Suchodolski, Jan S; Jergens, Albert E

    2016-04-01

    The importance of the microbiome in health and disease has galvanized interest in using manipulations of the gastrointestinal ecosystem to prevent and/or combat gut bacterial infections and to restore mucosal homeostasis in patients with generalized microbial imbalances (i.e., dysbiosis), including the human inflammatory bowel diseases, Crohn's disease, and ulcerative colitis. Probiotics, prebiotics, or their combination use (i.e., synbiotics) are one mechanism for modifying the microbiota and exerting direct and indirect effects on the host immune responses and metabolomics profiles. These beneficial effects are transferred through various pathways, including the production of antimicrobial peptides, promoting the growth of beneficial microbes and enhancing immunomodulatory functions via various metabolites. While probiotic therapy has been used empirically for decades with mixed success, the recent advances in molecular and mass spectrophotometric techniques for the characterization of the complexity and diversity of the intestinal microbiome has aided in better understanding of host-microbe interactions. It is important to better understand the functional properties of the microbiome, because it is now clear that the microbiota secretes many metabolites that have a direct impact on host immune responses. This information will improve selection of the most appropriate probiotic strains that selectively target intestinal disease processes.

  5. Prevention of infectious complications in surgical patients: potential role of probiotics

    NARCIS (Netherlands)

    Besselink, Marc G. H.; Timmerman, Harro M.; van Minnen, L. Paul; Akkermans, Louis M. A.; Gooszen, Hein G.

    2005-01-01

    Infectious complications in surgical patients often originate from the intestinal microflora. In the critically ill patient, small bowel motility is disturbed, leading to bacterial overgrowth and subsequent bacterial translocation due to dysfunction of the gut mucosal barrier. The optimal

  6. Immune activation is associated with increased gut microbial translocation in treatment-naive, HIV-infected children in a resource-limited setting.

    Science.gov (United States)

    Pilakka-Kanthikeel, Sudheesh; Kris, Arheart; Selvaraj, Anbalagan; Swaminathan, Soumya; Pahwa, Savita

    2014-05-01

    Gut damage resulting in microbial translocation (MT) is considered a major cause of immune activation (IA) in HIV infection, but data in children are limited, particularly in the absence of antiretroviral therapy. Sixty perinatally HIV-infected, antiretroviral therapy-naive children, aged 2-12 years, were evaluated for plasma levels of lipopolysaccharide, DNA sequences encoding bacterial 16 second ribosomal DNA (16S rDNA) and soluble CD14 concurrently with markers of CD4 and CD8 T-cell IA and immune exhaustion (IE), CD4 counts, and plasma viral load. At study entry, participants were classified into immune categories (ICs): IC1 (CD4% > 25), IC2 (CD4% 15-25), and IC3 (CD4% natural history cohort of HIV-infected children not on therapy, MT was more pronounced in the most severely immunocompromised patients and was associated with IA. Strategies to reduce MT may help to reduce IA and prevent CD4 depletion.

  7. DNA nanopore translocation in glutamate solutions

    NARCIS (Netherlands)

    Plesa, C.; Van Loo, N.; Dekker, C.

    2015-01-01

    Nanopore experiments have traditionally been carried out with chloride-based solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an alternative, and study the viscosity, conductivity, and nanopore translocation characteristics of potassium-, sodium-, and lithium-glutamate

  8. Carbon and nitrogen translocation between seagrass ramets

    NARCIS (Netherlands)

    Marbà, N.; Hemminga, M.A.; Mateo, M.A.; Duarte, C.M.; Maas, Y.E.M.; Terrados, J.; Gacia, E.

    2002-01-01

    The spatial scale and the magnitude of carbon and nitrogen translocation was examined in 5 tropical (Cymodocea serrulata, Halophila stipulacea, Halodule uninervis, Thalassodendron ciliatum, Thalassia hemprichii) and 3 temperate (Cymodocea nodosa, Posidonia oceanica, Zostera noltii) seagrass species

  9. Decatransin, a new natural product inhibiting protein translocation at the Sec61/SecYEG translocon

    Science.gov (United States)

    Junne, Tina; Wong, Joanne; Studer, Christian; Aust, Thomas; Bauer, Benedikt W.; Beibel, Martin; Bhullar, Bhupinder; Bruccoleri, Robert; Eichenberger, Jürg; Estoppey, David; Hartmann, Nicole; Knapp, Britta; Krastel, Philipp; Melin, Nicolas; Oakeley, Edward J.; Oberer, Lukas; Riedl, Ralph; Roma, Guglielmo; Schuierer, Sven; Petersen, Frank; Tallarico, John A.; Rapoport, Tom A.; Spiess, Martin; Hoepfner, Dominic

    2015-01-01

    ABSTRACT A new cyclic decadepsipeptide was isolated from Chaetosphaeria tulasneorum with potent bioactivity on mammalian and yeast cells. Chemogenomic profiling in S. cerevisiae indicated that the Sec61 translocon complex, the machinery for protein translocation and membrane insertion at the endoplasmic reticulum, is the target. The profiles were similar to those of cyclic heptadepsipeptides of a distinct chemotype (including HUN-7293 and cotransin) that had previously been shown to inhibit cotranslational translocation at the mammalian Sec61 translocon. Unbiased, genome-wide mutagenesis followed by full-genome sequencing in both fungal and mammalian cells identified dominant mutations in Sec61p (yeast) or Sec61α1 (mammals) that conferred resistance. Most, but not all, of these mutations affected inhibition by both chemotypes, despite an absence of structural similarity. Biochemical analysis confirmed inhibition of protein translocation into the endoplasmic reticulum of both co- and post-translationally translocated substrates by both chemotypes, demonstrating a mechanism independent of a translating ribosome. Most interestingly, both chemotypes were found to also inhibit SecYEG, the bacterial Sec61 translocon homolog. We suggest ‘decatransin’ as the name for this new decadepsipeptide translocation inhibitor. PMID:25616894

  10. Unraveling the Dynamics of Ribosome Translocation

    Science.gov (United States)

    Chen, Jin; Tsai, Albert; O’Leary, Seán E.; Petrov, Alexey; Puglisi, Joseph D.

    2013-01-01

    Translocation is one of the key events in translation, requiring large-scale conformational changes in the ribosome, movements of two transfer RNAs (tRNAs) across a distance of more than 20 Å, and the coupled movement of the messenger RNA (mRNA) by one codon, completing one cycle of peptide-chain elongation. Translocation is catalyzed by elongation factor G (EF-G in bacteria), which hydrolyzes GTP in the process. However, how the conformational rearrangements of the ribosome actually drive the movements of the tRNAs and how EF-G GTP hydrolysis plays a role in this process are still unclear. Fluorescence methods, both single-molecule and bulk, have provided a dynamic view of translocation, allowing us to follow the different conformational changes of the ribosome in real-time. The application of electron microscopy has revealed new conformational intermediates during translocation and important structural rearrangements in the ribosome that drive tRNA movement, while computational approaches have added quantitative views of the translational pathway. These recent advances shed light on the process of translocation, providing insight on how to resolve the different descriptions of translocation in the current literature. PMID:23142574

  11. Curcumin attenuates insulin resistance in hepatocytes by inducing Nrf2 nuclear translocation.

    Science.gov (United States)

    Zhao, Shu-Guang; Li, Qiang; Liu, Zhen-Xiong; Wang, Jing-Jie; Wang, Xv-Xia; Qin, Ming; Wen, Qin-Sheng

    2011-01-01

    NF-E2-Related Factor-2 (Nrf2) is a transcription factor that plays a crucial role in the cellular protection against oxidative stress. Curcumin has been reported to induce Nrf2 nuclear translocation and upregulate the expression of numerous reactive oxygen species (ROS) detoxifying and antioxidant genes in hepatocytes. This study was designed to investigate whether curcumin-induced Nrf2 nuclear translocation could reduce ROS-mediated insulin resistance in cultured LO2 hepatocytes. Human LO2 hepatocytes were incubated with curcumine and glucose oxidase (GO) in the presence/absence of wortmannin (a phosphatidyinositol 3-kinase (PI3K) inhibitor), oxidative stress, cellular damage, Nrf2 nuclear translocation and insulin resistance were measured. GO exposure significantly increased intracellular ROS, glutathione (GSH) depletion, malondialdehyde (MDA) formation, and increased activities of cellular lactate dehydrogenase (LDH) and aspartate amino transferase (AST), as well as causing insulin resistance. Curcumin pretreatment significantly attenuated these disturbances in intracellular ROS, liver enzyme activity and significantly antagonized the lipid peroxidation, GSH depletion and insulin resistance induced by GO in LO2 hepatocytes. These effects paralleled Nrf2 nuclear translocation induced by curcumin. Wortmannin partially blocked curcumin-induced Nrf2 nuclear translocation. In addition, wortmannin prevented curcumin-induced improvements in intracellular ROS, MDA formation, GSH depletion, liver enzyme activity and insulin resistance in cultured LO2 hepatocytes. These findings suggest that curcumin could reduce ROS-mediated insulin resistance in hepatocytes, at least in part through nuclear translocation of Nrf2.

  12. Expansion of syndromic vaccine preventable disease surveillance to include bacterial meningitis and Japanese encephalitis: evaluation of adapting polio and measles laboratory networks in Bangladesh, China and India, 2007-2008.

    Science.gov (United States)

    Cavallaro, Kathleen F; Sandhu, Hardeep S; Hyde, Terri B; Johnson, Barbara W; Fischer, Marc; Mayer, Leonard W; Clark, Thomas A; Pallansch, Mark A; Yin, Zundong; Zuo, Shuyan; Hadler, Stephen C; Diorditsa, Serguey; Hasan, A S M Mainul; Bose, Anindya S; Dietz, Vance

    2015-02-25

    Surveillance for acute flaccid paralysis with laboratory confirmation has been a key strategy in the global polio eradication initiative, and the laboratory platform established for polio testing has been expanded in many countries to include surveillance for cases of febrile rash illness to identify measles and rubella cases. Vaccine-preventable disease surveillance is essential to detect outbreaks, define disease burden, guide vaccination strategies and assess immunization impact. Vaccines now exist to prevent Japanese encephalitis (JE) and some etiologies of bacterial meningitis. We evaluated the feasibility of expanding polio-measles surveillance and laboratory networks to detect bacterial meningitis and JE, using surveillance for acute meningitis-encephalitis syndrome in Bangladesh and China and acute encephalitis syndrome in India. We developed nine syndromic surveillance performance indicators based on international surveillance guidelines and calculated scores using supervisory visit reports, annual reports, and case-based surveillance data. Scores, variable by country and targeted disease, were highest for the presence of national guidelines, sustainability, training, availability of JE laboratory resources, and effectiveness of using polio-measles networks for JE surveillance. Scores for effectiveness of building on polio-measles networks for bacterial meningitis surveillance and specimen referral were the lowest, because of differences in specimens and techniques. Polio-measles surveillance and laboratory networks provided useful infrastructure for establishing syndromic surveillance and building capacity for JE diagnosis, but were less applicable for bacterial meningitis. Laboratory-supported surveillance for vaccine-preventable bacterial diseases will require substantial technical and financial support to enhance local diagnostic capacity. Published by Elsevier Ltd.

  13. Molecular studies of free and translocation trisomy

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Lefort, G. [Univ. of Zuerich (Switzerland)] [and others

    1994-09-01

    Twenty cases of trisomy 13 were examined with molecular markers to determine the origin of the extra chromosome. Six cases had translocation trisomy: two de novo rob(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;13q)r(13). Eighteen of nineteen informative patients were consistant with a maternal origin of the extra chromosome. Lack of a third allele at any locus in any of the three t(13q;13q) cases indicate that all were most likely isochromosomes of post-meiotic origin. In addition, two free trisomy cases were compatible with a somatic origin. Two mosaic free trisomy-13 cases, however, were both consistent with a maternal meiotic origin. The patient with a paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13;14) carrier and most trisomies are maternal in origin, this result should not be surprising; however it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. One balanced (non-trisomic) case with a non-mosaic 45,-13,-13,+t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologs, as has been found for all homologous Robertsonian translocations so far investigated. It is therefore also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. We cannot therefore infer anything about the origin of the chromosomes 13 and 14 involved in the two cases with de novo t(13q;14q) plus a maternally derived trisomy 13.

  14. Bacterial meningitis

    NARCIS (Netherlands)

    Roos, Karen L.; van de Beek, Diederik

    2010-01-01

    Bacterial meningitis is a neurological emergency. Empiric antimicrobial and adjunctive therapy should be initiated as soon as a single set of blood cultures has been obtained. Clinical signs suggestive of bacterial meningitis include fever, headache, meningismus, vomiting, photophobia, and an

  15. Translocation pathways for inhaled asbestos fibers

    Directory of Open Access Journals (Sweden)

    Mantegazza F

    2008-01-01

    Full Text Available Abstract We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption and hydraulic (interstitial pressure is subatmospheric pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation. Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow and in the liver (reflecting high microvascular permeability while it is relatively low in the brain (due to low permeability of blood-brain barrier. Ultrafine fibers (length

  16. Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies

    Science.gov (United States)

    Morrison, Charles S.; Chen, Pai-Lien; Kwok, Cynthia; McCormack, Sheena; McGrath, Nuala; Watson-Jones, Deborah; Gottlieb, Sami L.

    2018-01-01

    Background Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. Methods and findings We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993–2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15–24-year-old than 25–49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15–24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15–24-year-olds was 4.6% (95% CI

  17. Prevalence of sexually transmitted infections and bacterial vaginosis among women in sub-Saharan Africa: An individual participant data meta-analysis of 18 HIV prevention studies.

    Science.gov (United States)

    Torrone, Elizabeth A; Morrison, Charles S; Chen, Pai-Lien; Kwok, Cynthia; Francis, Suzanna C; Hayes, Richard J; Looker, Katharine J; McCormack, Sheena; McGrath, Nuala; van de Wijgert, Janneke H H M; Watson-Jones, Deborah; Low, Nicola; Gottlieb, Sami L

    2018-02-01

    Estimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type. We analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ≥1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa

  18. Effects of nucleotides and nucleotide analogue inhibitors of HIV-1 reverse transcriptase in a ratchet model of polymerase translocation.

    Science.gov (United States)

    Götte, Matthias

    2006-01-01

    A single cycle of nucleotide incorporation by the reverse transcriptase of the human immunodeficiency virus type 1 (HIV-1 RT) involves the initial binding of an incoming nucleotide, a conformational change that traps the substrate, the formation of a new phosphodiester bond, the release of pyrophosphate (PPi), and ultimately polymerase translocation, which clears the nucleotide binding site. This article reviews different mechanistic models for polymerase translocation with emphasis placed on HIV-1 RT. Structure-function analyses of stalled complexes of HIV-1 RT provide strong evidence to suggest that the enzyme can oscillate between pre- and post-translocational states. Nucleotide hydrolysis is not required for the movement of the polymerase in a stalled configuration; thermal energy is sufficient to allow random bidirectional sliding. The next complementary nucleotide, following the incorporated chain-terminator, acts like a pawl of a ratchet that traps the enzyme in the post-translocation state and prevents the reverse movement. Quantitative footprinting experiments have shown that the concentration of the templated nucleotide required to shift the translocational equilibrium forward depends crucially on the structure of the 3'end of the primer. Changes in the relative population of pre- and post-translocation complexes can influence rates of excision of incorporated NRTIs, which, in turn, affects drug susceptibility. The concept of a ratchet model of HIV-1 RT translocation and its implications for drug action and resistance, and the discovery and development of novel antiviral compounds is discussed.

  19. Non-equilibrium effects in chaperone-assisted translocation of a stiff polymer

    Science.gov (United States)

    Haji Abdolvahab, Rouhollah

    2018-01-01

    Chaperone-assisted biopolymer translocation is the main model proposed for translocation in vivo. A dynamical Monte Carlo method is used to simulate the translocation of a stiff homopolymer through a nanopore driven by chaperones. Chaperones are proteins that bind to the polymer near the wall and prevent its backsliding through Cis side. The important parameters include binding energy, size and the local concentration of the chaperones. The profile of these local concentrations, build up the chaperones distribution. Here we investigate the effects of binding energy, size and the exponential distribution of chaperones in their equilibration in each step of the polymer translocation needed for stable translocation time. The simulation results show that in case of chaperones with the size of a monomer (λ = 1) and/or positive effective binding energy and/or uniform distribution, the chaperones binding equilibration rate/frequency is less than 5 times per monomer. However, in some special cases in the exponential distribution of chaperones with size λ > 1 and negative effective binding energy the equilibration rate will diverge to more than 20 times per monomer. We show that this non-equilibrium effect results in supper diffusion, seen before. Moreover, we confirm the equilibration process theoretically.

  20. Case Report: Extrauterine Translocated Contraceptive Device: A ...

    African Journals Online (AJOL)

    The most common presenting symptom was inability to feel the device's string (in three patients). Four of the patients presented within one month of the insertion. Three of the five translocated intraperitoneal devices were recovered by laparotomy and the forth by laparoscopy. The fifth patient, pregnant, defaulted with the ...

  1. 11C-methionine translocation in barley

    International Nuclear Information System (INIS)

    Nakanishi, Hiromi; Bughio, Naimatullah; Shigeta Ishioka, Noriko

    2000-01-01

    11 C-methionine was supplied to barley plants through a single leaf or via the roots and real time 11 C movement was monitored using a PETIS (positron emitting tracer imaging system). In Fe-deficient plants, 11 C-methionine was translocated from the tip of the absorbing leaf to the discrimination center' at the basal part of the shoot and then retranslocated to all the chlorotic leaves, while a negligible amount was retranslocated to the roots. In Fe-sufficient plants, methionine was translocated from the absorbing leaf to the discrimination center and then only to the newest leaf on the main shoot. A negligible amount was also retranslocated to the roots. Although, in Fe-sufficient plants, methionine translocation was observed from absorbing roots to shoots, in Fe-deficient plants, only a little amount was translocated from roots to shoots. In conclusion, methionine from the upper portion of a plant is not used as a precursor of mugineic acid under Fe-deficiency conditions. (author)

  2. Familial cryptic translocation in Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  3. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    generating translocations; ... are summarized in table 1. 2.3 Overview of the method used to define the breakpoint junction sequences .... showed linkage with the nucleolus organizer region (NOR) in LG VL but not to markers on LG VL or LG V ...

  4. Bacterial Proteasomes.

    Science.gov (United States)

    Jastrab, Jordan B; Darwin, K Heran

    2015-01-01

    Interest in bacterial proteasomes was sparked by the discovery that proteasomal degradation is required for the pathogenesis of Mycobacterium tuberculosis, one of the world's deadliest pathogens. Although bacterial proteasomes are structurally similar to their eukaryotic and archaeal homologs, there are key differences in their mechanisms of assembly, activation, and substrate targeting for degradation. In this article, we compare and contrast bacterial proteasomes with their archaeal and eukaryotic counterparts, and we discuss recent advances in our understanding of how bacterial proteasomes function to influence microbial physiology.

  5. Effector protein translocation by the Coxiella burnetii Dot/Icm type IV secretion system requires endocytic maturation of the pathogen-occupied vacuole.

    Directory of Open Access Journals (Sweden)

    Hayley J Newton

    Full Text Available The human pathogen Coxiella burnetii encodes a type IV secretion system called Dot/Icm that is essential for intracellular replication. The Dot/Icm system delivers bacterial effector proteins into the host cytosol during infection. The effector proteins delivered by C. burnetii are predicted to have important functions during infection, but when these proteins are needed during infection has not been clearly defined. Here, we use a reporter system consisting of fusion proteins that have a β-lactamase enzyme (BlaM fused to C. burnetii effector proteins to study protein translocation by the Dot/Icm system. Translocation of BlaM fused to the effector proteins CBU0077, CBU1823 and CBU1524 was not detected until 8-hours after infection of HeLa cells, which are permissive for C. burnetii replication. Translocation of these effector fusion proteins by the Dot/Icm system required acidification of the Coxiella-containing vacuole. Silencing of the host genes encoding the membrane transport regulators Rab5 or Rab7 interfered with effector translocation, which indicates that effectors are not translocated until bacteria traffic to a late endocytic compartment in the host cell. Similar requirements for effector translocation were discerned in bone marrow macrophages derived from C57BL/6 mice, which are primary cells that restrict the intracellular replication of C. burnetii. In addition to requiring endocytic maturation of the vacuole for Dot/Icm-mediated translocation of effectors, bacterial transcription was required for this process. Thus, translocation of effector proteins by the C. burnetii Dot/Icm system occurs after acidification of the CCV and maturation of this specialized organelle to a late endocytic compartment. This indicates that creation of the specialized vacuole in which C. burnetii replicates represents a two-stage process mediated initially by host factors that regulate endocytic maturation and then by bacterial effectors delivered into

  6. Bacterial adhesion

    NARCIS (Netherlands)

    Loosdrecht, van M.C.M.

    1988-01-01

    As mentioned in the introduction of this thesis bacterial adhesion has been studied from a variety of (mostly practice oriented) starting points. This has resulted in a range of widely divergent approaches. In order to elucidate general principles in bacterial adhesion phenomena, we felt it

  7. Retrospective observational study to investigate Sinerga, a multifactorial nutritional product, and bacterial extracts in the prevention of recurrent respiratory infections in children.

    Science.gov (United States)

    Nigro, A; Nicastro, A; Trodella, R

    2014-01-01

    In this retrospective observational clinical study, 167 children, aged 3 to 7 years, of both sexes, with a clinical history of recurrent respiratory infections, administered with bacterial extracts of first and second generation or Sinerga a nutritional product containing palmitoylethanolamide, bovine colostrum, phenylethylamine and the new generation of probiotic kluyveromyces FM B0399, were observed. The goal of the study was to compare the supplementation with Sinerga with the supplementation with bacterial extracts, for the effect on the frequency of episodes of respiratory infection that had resulted in a prescription for antibiotics. The study focused retrospectively on the months from March 2013 to November 2012. The results showed a greater reduction in the frequency of respiratory infections with antibiotic therapy in the group of children supplemented with Sinerga than in the group treated with bacterial extracts. In particular, it was observed that 49.3% of the children supplemented with Sinerga, against 5% of those supplemented with extracts, had no infectious episodes requiring the administration of an antibiotic. 100% of subjects supplemented with Sinerga have had no more than two episodes of respiratory infection, while this condition, in the cohort treated with bacterial extracts, was observed in only 51% of cases.

  8. Mesenteric microcirculatory dysfunctions and translocation of indigenous bacteria in a rat model of strangulated small bowel obstruction

    Directory of Open Access Journals (Sweden)

    Fernando Luiz Zanoni

    2009-01-01

    Full Text Available PRUPOSE: Bacterial translocation has been shown to occur in critically ill patients after extensive trauma, shock, sepsis, or thermal injury. The present study investigates mesenteric microcirculatory dysfunctions, the bacterial translocation phenomenon, and hemodynamic/metabolic disturbances in a rat model of intestinal obstruction and ischemia. METHODS: Anesthetized (pentobarbital 50 mg/kg, i.p. male Wistar rats (250-350 g were submitted to intestinal obstruction or laparotomy without intestinal obstruction (Sham and were evaluated 24 hours later. Bacterial translocation was assessed by bacterial culture of the mesenteric lymph nodes (MLN, liver, spleen, and blood. Leukocyte-endothelial interactions in the mesenteric microcirculation were assessed by intravital microscopy, and P-selectin and intercellular adhesion molecule (ICAM-1 expressions were quantified by immunohistochemistry. Hematocrit, blood gases, lactate, glucose, white blood cells, serum urea, creatinine, bilirubin, and hepatic enzymes were measured. RESULTS: About 86% of intestinal obstruction rats presented positive cultures for E. coli in samples of the mesenteric lymph nodes, liver, and spleen, and 57% had positive hemocultures. In comparison to the Sham rats, intestinal obstruction induced neutrophilia and increased the number of rolling (~2-fold, adherent (~5-fold, and migrated leukocytes (~11-fold; this increase was accompanied by an increased expression of P-selectin (~2-fold and intercellular adhesion molecule-1 (~2-fold in the mesenteric microcirculation. Intestinal obstruction rats exhibited decreased PaCO2, alkalosis, hyperlactatemia, and hyperglycemia, and increased blood potassium, hepatic enzyme activity, serum urea, creatinine, and bilirubin. A high mortality rate was observed after intestinal obstruction (83% at 72 h vs. 0% in Sham rats. CONCLUSION: Intestinal obstruction and ischemia in rats is a relevant model for the in vivo study of mesenteric microcirculatory

  9. Bacterial meningitis in infants.

    Science.gov (United States)

    Ku, Lawrence C; Boggess, Kim A; Cohen-Wolkowiez, Michael

    2015-03-01

    Neonatal bacterial meningitis is uncommon but devastating. Morbidity among survivors remains high. The types and distribution of pathogens are related to gestational age, postnatal age, and geographic region. Confirming the diagnosis is difficult. Clinical signs are often subtle, lumbar punctures are frequently deferred, and cerebrospinal fluid (CSF) cultures can be compromised by prior antibiotic exposure. Infants with bacterial meningitis can have negative blood cultures and normal CSF parameters. Promising tests such as the polymerase chain reaction require further study. Prompt treatment with antibiotics is essential. Clinical trials investigating a vaccine for preventing neonatal Group B Streptococcus infections are ongoing. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Carbon nanotubes as anti-bacterial agents.

    Science.gov (United States)

    Mocan, Teodora; Matea, Cristian T; Pop, Teodora; Mosteanu, Ofelia; Buzoianu, Anca Dana; Suciu, Soimita; Puia, Cosmin; Zdrehus, Claudiu; Iancu, Cornel; Mocan, Lucian

    2017-10-01

    Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

  11. Binding mode analysis of a major T3SS translocator protein PopB with its chaperone PcrH from Pseudomonas aeruginosa.

    Science.gov (United States)

    Banerjee, Anindyajit; Dey, Supratim; Chakraborty, Abhijit; Datta, Aohona; Basu, Abhishek; Chakrabarti, Saikat; Datta, Saumen

    2014-12-01

    Pseudomonas aeruginosa, a Gram-negative pathogen uses a specialized set of Type III secretion system (T3SS) translocator proteins to establish virulence in the host cell. An understanding of the factors that govern translocation by the translocator protein-chaperone complex is thus of immense importance. In this work, experimental and computational techniques were used to probe into the structure of the major translocator protein PopB from P. aeruginosa and to identify the important regions involved in functioning of the translocator protein. This study reveals that the binding sites of the common chaperone PcrH, needed for maintenance of the translocator PopB within the bacterial cytoplasm, which are primarily localized within the N-terminal domain. However, disordered and flexible residues located both at the N- and C-terminal domains are also observed to be involved in association with the chaperone. This intrinsic disorderliness of the terminal domains is conserved for all the major T3SS translocator proteins and is functionally important to maintain the intrinsically disordered state of the translocators. Our experimental and computational analyses suggest that a "disorder-to-order" transition of PopB protein might take place upon PcrH binding. The long helical coiled-coil part of PopB protein perhaps helps in pore formation while the flexible apical region is involved in chaperone interaction. Thus, our computational model of translocator protein PopB and its binding analyses provide crucial functional insights into the T3SS translocation mechanism. © 2014 Wiley Periodicals, Inc.

  12. Hepatosplenic schistosomiasis is characterised by high blood markers of translocation, inflammation and fibrosis.

    Science.gov (United States)

    Sinkala, Edford; Kapulu, Melissa C; Besa, Ellen; Zyambo, Kanekwa; Chisoso, Ng'andu J; Foster, Graham R; Kelly, Paul

    2016-01-01

    Cirrhosis is the main cause of portal hypertension worldwide but schistosomiasis dominates in much of the tropics. The seroprevalence of Schistosoma mansoni is up to 77% in endemic parts of Zambia. Morbidity is attributed to portal hypertension causing variceal bleeding which can be fatal. Bacterial translocation is associated with portal hypertension in cirrhosis but this is almost unexplored in hepatosplenic schistosomiasis. Liver biopsy is usually used to assess fibrosis although it is invasive and prone to sampling error. We aimed to investigate translocation, fibrosis and inflammatory makers in a case-control study of schistosomiasis at the University Teaching Hospital, Lusaka, Zambia. Patients had oesophageal varices, but were negative for human immunodeficiency virus, hepatitis B and C viruses. Plasma lipopolysaccharide binding protein was used as a marker of translocation while hyaluronan and laminin measured liver fibrosis. Inflammatory markers were measured in blood. Controls were patients with non-specific abdominal pain who had normal endoscopy. Median (interquartile range) lipopolysaccharide binding protein was elevated in patients [44.3 ng/ml (35.7, 57.1)] compared to controls [30.7 ng/ml (30.4, 35.5), P < 0.0001]. Hyaluronan was higher in patients [111.6 ng/ml (39.1, 240.3)] compared to controls [21.0 ng/ml (12.4, 37.6), P < 0.0001] and so was laminin [2.2 μg/ml (1.0, 3.7)] compared to controls [0.9 μg/ml (0.7, 1.2), P = 0.0015]. Inflammatory markers, except C-reactive protein, were elevated in patients. These data suggest that the bacterial translocation contributes to systemic inflammation in hepatosplenic schistosomiasis. Elevated fibrotic markers suggest they may be useful in diagnosing and monitoring periportal fibrosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Differential effects of antiretrovirals on microbial translocation and gut microbiota composition of HIV-infected patients.

    Science.gov (United States)

    Villanueva-Millán, María J; Pérez-Matute, Patricia; Recio-Fernández, Emma; Lezana Rosales, José M; Oteo, José A

    2017-03-09

    Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long-term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV-infected patients. We carried out a cross-sectional study of 45 HIV-infected patients on cART, classified as nucleoside reverse transcriptase inhibitors (NRTIs)+ protease inhibitors (PIs) (n = 15), NRTIs+ non-nucleoside reverse transcriptase inhibitors (NNRTIs) (n = 22), and NRTIs+ integrase strand transfer inhibitors (INSTIs) (n = 8). Untreated HIV-infected patients (n = 5) and non-infected volunteers (n = 21) were also included. Soluble markers of bacterial translocation and inflammation were measured and gut microbiota composition was analysed using 16S rDNA pyrosequencing (Illumina MiSeq). The NRTIs+INSTIs regimen was associated with levels of systemic inflammation that were similar to uninfected controls. The reduction in faecal bacterial diversity induced by HIV infection was also restored by this regimen. HIV infection was more closely related to changes in lower taxonomic units and diversity rather than at the phylum level. The NRTIs+PIs regimen showed the highest reduction in bacterial species, whereas NRTIs+INSTIs induced a minor loss of bacterial species and a significant increase in others. Our study demonstrated that INSTI-based ART was associated with levels of systemic inflammation and microbial diversity similar to that of uninfected controls. The role of INSTIs other than raltegravir needs to be further investigated. Patients on the NRTIs+PIs regimen presented the highest reduction in bacterial species compared with other antiretrovirals and naive patients

  14. Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

    Science.gov (United States)

    Ruano-Gallego, David; Álvarez, Beatriz; Fernández, Luis Ángel

    2015-09-18

    Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these "molecular syringes" for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells.

  15. Financial costs of large carnivore translocations--accounting for conservation.

    Science.gov (United States)

    Weise, Florian J; Stratford, Ken J; van Vuuren, Rudolf J

    2014-01-01

    Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  16. Financial costs of large carnivore translocations--accounting for conservation.

    Directory of Open Access Journals (Sweden)

    Florian J Weise

    Full Text Available Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars. Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23, and $2,108 per leopard (n = 6. One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%, followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4% of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown with a strong species bias. Four leopards (66.7% were successfully translocated but only eight of the 20 cheetahs (40.0% with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  17. Effects of metronidazole and probiotics oligosaccharide on bacterial ...

    African Journals Online (AJOL)

    The present study aims to evaluate the effects of metronidazole, probiotics oligosaccharide on indigenous microflora and bacterial translocation (BT) in protein malnourished rats. Thirty male Wistar rats were divided into three groups: protein malnourished rats PM (group1, n = 10) were fed with maize only, protein ...

  18. Bacterial Vaginosis

    Science.gov (United States)

    ... Archive STDs Home Page Bacterial Vaginosis (BV) Chlamydia Gonorrhea Genital Herpes Hepatitis HIV/AIDS & STDs Human Papillomavirus ( ... of getting other STDs, such as chlamydia and gonorrhea . These bacteria can sometimes cause pelvic inflammatory disease ( ...

  19. Translocation of bacteria from the gut to the eggs triggers maternal transgenerational immune priming in Tribolium castaneum.

    Science.gov (United States)

    Knorr, Eileen; Schmidtberg, Henrike; Arslan, Derya; Bingsohn, Linda; Vilcinskas, Andreas

    2015-12-01

    Invertebrates can be primed to enhance their protection against pathogens they have encountered before. This enhanced immunity can be passed maternally or paternally to the offspring and is known as transgenerational immune priming. We challenged larvae of the red flour beetle Tribolium castaneum by feeding them on diets supplemented with Escherichia coli, Micrococcus luteus or Pseudomonas entomophila, thus mimicking natural exposure to pathogens. The oral uptake of bacteria induced immunity-related genes in the offspring, but did not affect the methylation status of the egg DNA. However, we observed the translocation of bacteria or bacterial fragments from the gut to the developing eggs via the female reproductive system. Such translocating microbial elicitors are postulated to trigger bacterial strain-specific immune responses in the offspring and provide an alternative mechanistic explanation for maternal transgenerational immune priming in coleopteran insects. © 2015 The Authors.

  20. Bacterial Dissemination to the Brain in Sepsis.

    Science.gov (United States)

    Singer, Benjamin H; Dickson, Robert P; Denstaedt, Scott J; Newstead, Michael W; Kim, Kwi; Falkowski, Nicole R; Erb-Downward, John R; Schmidt, Thomas M; Huffnagle, Gary B; Standiford, Theodore J

    2018-03-15

    Sepsis causes brain dysfunction and neuroinflammation. It is unknown whether neuroinflammation in sepsis is initiated by dissemination of bacteria to the brain and sustained by persistent infection, or whether neuroinflammation is a sterile process resulting solely from circulating inflammatory mediators. To determine if gut bacteria translocate to the brain during sepsis, and are associated with neuroinflammation. Murine sepsis was induced using cecal ligation and puncture, and sepsis survivor mice were compared with sham and unoperated control animals. Brain tissue of patients who died of sepsis was compared with patients who died of noninfectious causes. Bacterial taxa were characterized by 16S ribosomal RNA gene sequencing in both murine and human brain specimens; compared among sepsis and nonsepsis groups; and correlated with levels of S100A8, a marker of neuroinflammation using permutational multivariate ANOVA. Viable gut-associated bacteria were enriched in the brains of mice 5 days after surviving abdominal sepsis (P < 0.01), and undetectable by 14 days. The community structure of brain-associated bacteria correlated with severity of neuroinflammation (P < 0.001). Furthermore, bacterial taxa detected in brains of humans who die of sepsis were distinct from those who died of noninfectious causes (P < 0.001) and correlated with S100A8/A9 expression (P < 0.05). Although bacterial translocation is associated with acute neuroinflammation in murine sepsis, bacterial translocation did not result in chronic cerebral infection. Postmortem analysis of patients who die of sepsis suggests a role for bacteria in acute brain dysfunction in sepsis. Further work is needed to determine if modifying gut-associated bacterial communities modulates brain dysfunction after sepsis.

  1. Measurement of background translocation frequencies in individuals with clones

    Energy Technology Data Exchange (ETDEWEB)

    Wade, Marcelle J. [California State Univ. (CalState), Hayward, CA (United States)

    1996-08-01

    In the leukemia case the unseparated B and T lymphocytes had a high translocation frequency even after 0.0014, respectively. After purging all clones from the data, the translocation frequencies for Bio 8 and Bio 23 were 0.00750.0014 and 0.0073 metaphases were scored for chromosomal aberrations,, specifically reciprocal translocations, using fluorescence in situ hybridization (FISH). Metaphase spreads were used from two healthy, unexposed individuals (not exposed to radiation, chemotherapy or radiotherapy) and one early B- precursor acute lymphocytic leukemia (ALL) patient (metaphase spreads from both separated T lymphocytes and unseparated B and T lymphocytes were scored). All three individuals had an abnormally high translocation frequency. The high translocation frequencies resulted from clonal expansion of specific translocated chromosomes. I show in this thesis that by purging (discounting or removing) clones from the data of unexposed individuals, one can obtain true background translocation frequencies. In two cases, Bio 8 and Bio 23, the measured translocation frequency for chromosomes 1, 2 and 4 was 0.0124 purging all of the clones from the data. This high translocation frequency may be due to a low frequency of some clones and may not be recognized. The separated T lymphocytes had a higher translocation frequency than expected.

  2. SepD/SepL-dependent secretion signals of the type III secretion system translocator proteins in enteropathogenic Escherichia coli.

    Science.gov (United States)

    Deng, Wanyin; Yu, Hong B; Li, Yuling; Finlay, B Brett

    2015-04-01

    The type III protein secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE) is essential for the pathogenesis of attaching/effacing bacterial pathogens, including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. These pathogens use the T3SS to sequentially secrete three categories of proteins: the T3SS needle and inner rod protein components; the EspA, EspB, and EspD translocators; and many LEE- and non-LEE-encoded effectors. SepD and SepL are essential for translocator secretion, and mutations in either lead to hypersecretion of effectors. However, how SepD and SepL control translocator secretion and secretion hierarchy between translocators and effectors is poorly understood. In this report, we show that the secreted T3SS components, the translocators, and both LEE- and non-LEE-encoded effectors all carry N-terminal type III secretion and translocation signals. These signals all behave like those of the effectors and are sufficient for mediating type III secretion and translocation by wild-type EPEC and hypersecretion by the sepD and sepL mutants. Our results extended previous observations and suggest that the secretion hierarchy of the different substrates is determined by a signal other than the N-terminal secretion signal. We identified a domain located immediately downstream of the N-terminal secretion signal in the translocator EspB that is required for SepD/SepL-dependent secretion. We further demonstrated that this EspB domain confers SepD/SepL- and CesAB-dependent secretion on the secretion signal of effector EspZ. Our results thus suggest that SepD and SepL control and regulate secretion hierarchy between translocators and effectors by recognizing translocator-specific export signals. Many bacterial pathogens use a syringe-like protein secretion apparatus, termed the type III protein secretion system (T3SS), to secrete and inject numerous proteins directly into the host cells to

  3. Prevent Pneumonia

    Centers for Disease Control (CDC) Podcasts

    2015-08-06

    CDC’s Matthew Westercamp explains what pneumonia is, its symptoms, and how to prevent it.  Created: 8/6/2015 by National Center for Immunization and Respiratory Diseases (NCIRD), Division of Bacterial Diseases (DBD), Respiratory Diseases Branch (RDB).   Date Released: 8/6/2015.

  4. RNAi drives nonreciprocal translocations at eroding chromosome ends to establish telomere-free linear chromosomes.

    Science.gov (United States)

    Begnis, Martina; Apte, Manasi S; Masuda, Hirohisa; Jain, Devanshi; Wheeler, David Lee; Cooper, Julia Promisel

    2018-04-13

    The identification of telomerase-negative HAATI (heterochromatin amplification-mediated and telomerase-independent) cells, in which telomeres are superseded by nontelomeric heterochromatin tracts, challenged the idea that canonical telomeres are essential for chromosome linearity and raised crucial questions as to how such tracts translocate to eroding chromosome ends and confer end protection. Here we show that HAATI arises when telomere loss triggers a newly recognized illegitimate translocation pathway that requires RNAi factors. While RNAi is necessary for the translocation events that mobilize ribosomal DNA (rDNA) tracts to all chromosome ends (forming "HAATI rDNA " chromosomes), it is dispensable for HAATI rDNA maintenance. Surprisingly, Dicer (Dcr1) plays a separate, RNAi-independent role in preventing formation of the rare HAATI subtype in which a different repetitive element (the subtelomeric element) replaces telomeres. Using genetics and fusions between shelterin components and rDNA-binding proteins, we mapped the mechanism by which rDNA loci engage crucial end protection factors-despite the absence of telomere repeats-and secure end protection. Sequence analysis of HAATI rDNA genomes allowed us to propose RNA and DNA polymerase template-switching models for the mechanism of RNAi-triggered rDNA translocations. Collectively, our results reveal unforeseen roles for noncoding RNAs (ncRNAs) in assembling a telomere-free chromosome end protection device. © 2018 Begnis et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Bartonella henselae trimeric autotransporter adhesin BadA expression interferes with effector translocation by the VirB/D4 type IV secretion system.

    Science.gov (United States)

    Lu, Yun-Yueh; Franz, Bettina; Truttmann, Matthias C; Riess, Tanja; Gay-Fraret, Jérémie; Faustmann, Marco; Kempf, Volkhard A J; Dehio, Christoph

    2013-05-01

    The Gram-negative, zoonotic pathogen Bartonella henselae is the aetiological agent of cat scratch disease, bacillary angiomatosis and peliosis hepatis in humans. Two pathogenicity factors of B. henselae - each displaying multiple functions in host cell interaction - have been characterized in greater detail: the trimeric autotransporter Bartonella adhesin A (BadA) and the type IV secretion system VirB/D4 (VirB/D4 T4SS). BadA mediates, e.g. binding to fibronectin (Fn), adherence to endothelial cells (ECs) and secretion of vascular endothelial growth factor (VEGF). VirB/D4 translocates several Bartonella effector proteins (Beps) into the cytoplasm of infected ECs, resulting, e.g. in uptake of bacterial aggregates via the invasome structure, inhibition of apoptosis and activation of a proangiogenic phenotype. Despite this knowledge of the individual activities of BadA or VirB/D4 it is unknown whether these major virulence factors affect each other in their specific activities. In this study, expression and function of BadA and VirB/D4 were analysed in a variety of clinical B. henselae isolates. Data revealed that most isolates have lost expression of either BadA or VirB/D4 during in vitro passages. However, the phenotypic effects of coexpression of both virulence factors was studied in one clinical isolate that was found to stably coexpress BadA and VirB/D4, as well as by ectopic expression of BadA in a strain expressing VirB/D4 but not BadA. BadA, which forms a dense layer on the bacterial surface, negatively affected VirB/D4-dependent Bep translocation and invasome formation by likely preventing close contact between the bacterial cell envelope and the host cell membrane. In contrast, BadA-dependent Fn binding, adhesion to ECs and VEGF secretion were not affected by a functional VirB/D4 T4SS. The obtained data imply that the essential virulence factors BadA and VirB/D4 are likely differentially expressed during different stages of the infection cycle of

  6. Cytolethal distending toxin (CDT): a bacterial weapon to control host cell proliferation?

    Science.gov (United States)

    De Rycke, J; Oswald, E

    2001-09-25

    Cytolethal distending toxins (CDT) constitute a family of genetically related bacterial protein toxins able to stop the proliferation of numerous cell lines. This effect is due to their ability to trigger in target cells a signaling pathway that normally prevents the transition between the G2 and the M phase of the cell cycle. Produced by several unrelated Gram-negative mucosa-associated bacterial species, CDTs are determined by a cluster of three adjacent genes (cdtA, cdtB, cdtC) encoding proteins whose respective role is not yet fully elucidated. The CDT-B protein presents sequence homology to several mammalian and bacterial phosphodiesterases, such as DNase I. The putative nuclease activity of CDT-B, together with the activation by CDT of a G2 cell cycle checkpoint, strongly suggests that CDT induces an as yet uncharacterized DNA alteration. However, the effective entry of CDT into cells and subsequent translocation into the nucleus have not yet been demonstrated by direct methods. The relationship between the potential DNA-damaging properties of this original family of toxins and their role as putative virulence factors is discussed.

  7. Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei

    Directory of Open Access Journals (Sweden)

    Sara H. G. Sinclair

    2015-02-01

    Full Text Available Obligate intracellular bacteria have an arsenal of proteins that alter host cells to establish and maintain a hospitable environment for replication. Anaplasma phagocytophilum secrets Ankyrin A (AnkA, via a type IV secretion system, which translocates to the nucleus of its host cell, human neutrophils. A. phagocytophilum-infected neutrophils have dramatically altered phenotypes in part explained by AnkA-induced transcriptional alterations. However, it is unlikely that AnkA is the sole effector to account for infection-induced transcriptional changes. We developed a simple method combining bioinformatics and iTRAQ protein profiling to identify potential bacterial-derived nuclear-translocated proteins that could impact transcriptional programming in host cells. This approach identified 50 A. phagocytophilum candidate genes or proteins. The encoding genes were cloned to create GFP fusion protein-expressing clones that were transfected into HEK-293T cells. We confirmed nuclear translocation of six proteins: APH_0062, RplE, Hup, APH_0382, APH_0385, and APH_0455. Of the six, APH_0455 was identified as a type IV secretion substrate and is now under investigation as a potential nucleomodulin. Additionally, application of this approach to other obligate intracellular bacteria such as Mycobacterium tuberculosis, Chlamydia trachomatis and other intracellular bacteria identified multiple candidate genes to be investigated.

  8. Systematic Identification of Intracellular-Translocated Candidate Effectors in Edwardsiella piscicida

    Directory of Open Access Journals (Sweden)

    Lingzhi Zhang

    2018-02-01

    Full Text Available Many bacterial pathogens inject effectors directly into host cells to target a variety of host cellular processes and promote bacterial dissemination and survival. Identifying the bacterial effectors and elucidating their functions are central to understanding the molecular pathogenesis of these pathogens. Edwardsiella piscicida is a pathogen with a wide host range, and very few of its effectors have been identified to date. Here, based on the genes significantly regulated by macrophage infection, we identified 25 intracellular translocation-positive candidate effectors, including all five previously reported effectors, namely EseG, EseJ, EseH, EseK, and EvpP. A subsequent secretion analysis revealed diverse secretion patterns for the 25 effector candidates, suggesting that multiple transport pathways were involved in the internalization of these candidate effectors. Further, we identified two novel type VI secretion system (T6SS putative effectors and three outer membrane vesicles (OMV-dependent putative effectors among the candidate effectors described above, and further analyzed their contribution to bacterial virulence in a zebrafish model. This work demonstrates an effective approach for screening bacterial effectors and expands the effectors repertoire in E. piscicida.

  9. BACTERIAL CONSORTIUM

    Directory of Open Access Journals (Sweden)

    Payel Sarkar

    2013-01-01

    Full Text Available Petroleum aromatic hydrocarbons like benzen e, toluene, ethyl benzene and xylene, together known as BTEX, has almost the same chemical structure. These aromatic hydrocarbons are released as pollutants in th e environment. This work was taken up to develop a solvent tolerant bacterial cons ortium that could degrade BTEX compounds as they all share a common chemical structure. We have isolated almost 60 different types of bacterial strains from different petroleum contaminated sites. Of these 60 bacterial strains almost 20 microorganisms were screene d on the basis of capability to tolerate high concentration of BTEX. Ten differe nt consortia were prepared and the compatibility of the bacterial strains within the consortia was checked by gram staining and BTEX tolerance level. Four successful mi crobial consortia were selected in which all the bacterial strains concomitantly grew in presence of high concentration of BTEX (10% of toluene, 10% of benzene 5% ethyl benzene and 1% xylene. Consortium #2 showed the highest growth rate in pr esence of BTEX. Degradation of BTEX by consortium #2 was monitored for 5 days by gradual decrease in the volume of the solvents. The maximum reduction observed wa s 85% in 5 days. Gas chromatography results also reveal that could completely degrade benzene and ethyl benzene within 48 hours. Almost 90% degradation of toluene and xylene in 48 hours was exhibited by consortium #2. It could also tolerate and degrade many industrial solvents such as chloroform, DMSO, acetonitrile having a wide range of log P values (0.03–3.1. Degradation of aromatic hydrocarbon like BTEX by a solvent tolerant bacterial consortium is greatly significant as it could degrade high concentration of pollutants compared to a bacterium and also reduces the time span of degradation.

  10. Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining.

    OpenAIRE

    Yu, Xin; Gabriel, Abram

    2004-01-01

    Reciprocal translocations are common in cancer cells, but their creation is poorly understood. We have developed an assay system in Saccharomyces cerevisiae to study reciprocal translocation formation in the absence of homology. We induce two specific double-strand breaks (DSBs) simultaneously on separate chromosomes with HO endonuclease and analyze the subsequent chromosomal rearrangements among surviving cells. Under these conditions, reciprocal translocations via nonhomologous end joining ...

  11. Metallic oxide nanoparticle translocation across the human bronchial epithelial barrier.

    Science.gov (United States)

    George, Isabelle; Naudin, Grégoire; Boland, Sonja; Mornet, Stéphane; Contremoulins, Vincent; Beugnon, Karine; Martinon, Laurent; Lambert, Olivier; Baeza-Squiban, Armelle

    2015-03-14

    Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to quantify the translocation of different metallic NPs across human bronchial epithelial cells and to determine the factors influencing this translocation. Calu-3 cells forming a tight epithelial barrier when grown on a porous membrane in a two compartment chamber were exposed to fluorescently labelled NPs to quantify the NP translocation. NP translocation and uptake by cells were also studied by confocal and transmission electron microscopy. Translocation was characterized according to NP size (16, 50, or 100 nm), surface charge (negative or positive SiO2), composition (SiO2 or TiO2), presence of proteins or phospholipids and in an inflammatory context. Our results showed that NPs can translocate through the Calu-3 monolayer whatever their composition (SiO2 or TiO2), but this translocation was increased for the smallest and negatively charged NPs. Translocation was not associated with an alteration of the integrity of the epithelial monolayer, suggesting a transcytosis of the internalized NPs. By modifying the NP corona, the ability of NPs to cross the epithelial barrier differed depending on their intrinsic properties, making positively charged NPs more prone to translocate. NP translocation can be amplified by using agents known to open tight junctions and to allow paracellular passage. NP translocation was also modulated when mimicking an inflammatory context frequently found in the lungs, altering the epithelial integrity and inducing transient tight junction opening. This in vitro evaluation of NP translocation could be extended to other inhaled NPs to predict their biodistribution.

  12. Engineered fluorescent proteins illuminate the bacterial periplasm

    Directory of Open Access Journals (Sweden)

    Thorben Dammeyer

    2012-10-01

    Full Text Available The bacterial periplasm is of special interest whenever cell factories are designed and engineered. Recombinantely produced proteins are targeted to the periplasmic space of Gram negative bacteria to take advantage of the authentic N-termini, disulfide bridge formation and easy accessibility for purification with less contaminating cellular proteins. The oxidizing environment of the periplasm promotes disulfide bridge formation - a prerequisite for proper folding of many proteins into their active conformation. In contrast, the most popular reporter protein in all of cell biology, Green Fluorescent Protein (GFP, remains inactive if translocated to the periplasmic space prior to folding. Here, the self-catalyzed chromophore maturation is blocked by formation of covalent oligomers via interchain disulfide bonds in the oxidizing environment. However, different protein engineering approaches addressing folding and stability of GFP resulted in improved proteins with enhanced folding properties. Recent studies describe GFP variants that are not only active if translocated in their folded form via the twin-arginine translocation (Tat pathway, but actively fold in the periplasm following general secretory pathway (Sec and signal recognition particle (SRP mediated secretion. This mini-review highlights the progress that enables new insights into bacterial export and periplasmic protein organization, as well as new biotechnological applications combining the advantages of the periplasmic production and the Aequorea-based fluorescent reporter proteins.

  13. Engineered fluorescent proteins illuminate the bacterial periplasm.

    Science.gov (United States)

    Dammeyer, Thorben; Tinnefeld, Philip

    2012-01-01

    The bacterial periplasm is of special interest whenever cell factories are designed and engineered. Recombinantely produced proteins are targeted to the periplasmic space of Gram negative bacteria to take advantage of the authentic N-termini, disulfide bridge formation and easy accessibility for purification with less contaminating cellular proteins. The oxidizing environment of the periplasm promotes disulfide bridge formation - a prerequisite for proper folding of many proteins into their active conformation. In contrast, the most popular reporter protein in all of cell biology, Green Fluorescent Protein (GFP), remains inactive if translocated to the periplasmic space prior to folding. Here, the self-catalyzed chromophore maturation is blocked by formation of covalent oligomers via interchain disulfide bonds in the oxidizing environment. However, different protein engineering approaches addressing folding and stability of GFP resulted in improved proteins with enhanced folding properties. Recent studies describe GFP variants that are not only active if translocated in their folded form via the twin-arginine translocation (Tat) pathway, but actively fold in the periplasm following general secretory pathway (Sec) and signal recognition particle (SRP) mediated secretion. This mini-review highlights the progress that enables new insights into bacterial export and periplasmic protein organization, as well as new biotechnological applications combining the advantages of the periplasmic production and the Aequorea-based fluorescent reporter proteins.

  14. ENGINEERED FLUORESCENT PROTEINS ILLUMINATE THE BACTERIAL PERIPLASM

    Directory of Open Access Journals (Sweden)

    Thorben Dammeyer

    2012-10-01

    Full Text Available The bacterial periplasm is of special interest whenever cell factories are designed and engineered. Recombinantely produced proteins are targeted to the periplasmic space of Gram negative bacteria to take advantage of the authentic N-termini, disulfide bridge formation and easy accessibility for purification with less contaminating cellular proteins. The oxidizing environment of the periplasm promotes disulfide bridge formation – a prerequisite for proper folding of many proteins into their active conformation. In contrast, the most popular reporter protein in all of cell biology, Green Fluorescent Protein (GFP, remains inactive if translocated to the periplasmic space prior to folding. Here, the self-catalyzed chromophore maturation is blocked by formation of covalent oligomers via interchain disulfide bonds in the oxidizing environment. However, different protein engineering approaches addressing folding and stability of GFP resulted in improved proteins with enhanced folding properties. Recent studies describe GFP variants that are not only active if translocated in their folded form via the twin-arginine translocation (Tat pathway, but actively fold in the periplasm following general secretory pathway (Sec and signal recognition particle (SRP mediated secretion. This mini-review highlights the progress that enables new insights into bacterial export and periplasmic protein organization, as well as new biotechnological applications combining the advantages of the periplasmic production and the Aequorea-based fluorescent reporter proteins.

  15. DNA Translocation in Nanometer Thick Silicon Nanopores.

    Science.gov (United States)

    Rodríguez-Manzo, Julio A; Puster, Matthew; Nicolaï, Adrien; Meunier, Vincent; Drndić, Marija

    2015-06-23

    Solid-state nanopores are single-molecule sensors that detect changes in ionic conductance (ΔG) when individual molecules pass through them. Producing high signal-to-noise ratio for the measurement of molecular structure in applications such as DNA sequencing requires low noise and large ΔG. The latter is achieved by reducing the nanopore diameter and membrane thickness. While the minimum diameter is limited by the molecule size, the membrane thickness is constrained by material properties. We use molecular dynamics simulations to determine the theoretical thickness limit of amorphous Si membranes to be ∼1 nm, and we designed an electron-irradiation-based thinning method to reach that limit and drill nanopores in the thinned regions. Double-stranded DNA translocations through these nanopores (down to 1.4 nm in thickness and 2.5 nm in diameter) provide the intrinsic ionic conductance detection limit in Si-based nanopores. In this regime, where the access resistance is comparable to the nanopore resistance, we observe the appearance of two conductance levels during molecule translocation. Considering the overall performance of Si-based nanopores, our work highlights their potential as a leading material for sequencing applications.

  16. Longing Itineraries: Building the Translocal Community

    Directory of Open Access Journals (Sweden)

    Gustavo López Angel

    2017-06-01

    Full Text Available Migration has reshaped social practices, the sense of belonging has been rethought, and the membership is renegotiated and contended; this is why strategies for their sustainability have been generated. The translocal community operates through multilocated relationships that reveal the ways in which migrants are adapting to the new demands of the community. We emphasize the emotional impulse of nostalgia as one of the vehicles of sustainability for the community. The community is redefined and understood in a set of socio-cultural relationships its members generate, and where the locality is not central, but the connection. A new dimension of the social community space is not just the community gathered in a specific place, but also that agreements, commitments, and acknowledgments are exhibited and settled in the cyberspace; this cyberspace gives cohesion and brings a dynamic element to preserve the community, despite the fact that it is even less concrete than the spatial notion of territory. Facebook, YouTube and a blog are the web platforms of the virtual space where "neighbors, compatriots and citizens" (categories of ascription from the migration get together, where there is a reproduction of social practices (even the most ancient and fundamental ones, to give a new dimension to a translocal, multilocated and ciberlocated community.

  17. Chromosomal Translocations: Chicken or Egg? | Center for Cancer Research

    Science.gov (United States)

    Many tumor cells have abnormal chromosomes. Some of these abnormalities are caused by chromosomal translocations, which occur when two chromosomes break and incorrectly rejoin, resulting in an exchange of genetic material. Translocations can activate oncogenes, silence tumor suppressor genes, or result in the creation of completely new fusion gene products. While there is little doubt that chromosomal translocations can contribute to cancer, there is an active "chicken and the egg" discussion about the role translocations and other chromosomal abnormalities play—do they actually cause cancer or merely occur because of other changes within the cancer cell.  

  18. Factors affecting translocation and sclerotial formation in Morchella esculenta

    International Nuclear Information System (INIS)

    Amir, R.; Levanon, D.; Hadar, Y.; Chet, I.

    1995-01-01

    Amir, R., Levanon, D., Hadar, Y., and Chet, I. 1995. Factors affecting translocation and sclerotial formation in Morchella esculenta. Experimental Mycology 19, 61-70. Morchella esculenta was grown on square split plates, forming sclerotia on one side and mycelium on the other. After the fungus ceased to colonize and before sclerotial initials appeared, [ 14 C]3-O-methyl glucose was added to the edge of the plate on the mycelial side. The effect of various activities in the mycelium (source) and sclerotia (sink) on sclerotial formation and translocation were examined using inhibitors and water potential changes of the media. Sodium azide or cycloheximide applied separately to both sides inhibited both sclerotial formation and translocation, showing that processes in the source and sink depend on metabolic activities as well as protein synthesis. The use of nikkomycin inhibited sclerotial formation, without affecting translocation to the sclerotia. Since the hyphal tips swelled and burst, the translocated compounds were lost to the media. In a strain defective in sclerotial formation, used as a control, no translocation took place, showing that there is a connection between sclerotial formation and translocation. Reversal of the water potential gradient between the two media (lower on the mycelial side), reduced the formation of sclerotia and translocation to them. Translocation to Morchella sclerotia takes place via turgor driven mass flow, but is nevertheless affected by activities in both the source and the sink. (author)

  19. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer

    HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method is a Fluore......HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method...

  20. Bacterial Ecology

    DEFF Research Database (Denmark)

    Fenchel, Tom

    2011-01-01

    Bacterial ecology is concerned with the interactions between bacteria and their biological and nonbiological environments and with the role of bacteria in biogeochemical element cycling. Many fundamental properties of bacteria are consequences of their small size. Thus, they can efficiently exploit...

  1. Bacterial meningitis

    NARCIS (Netherlands)

    Heckenberg, Sebastiaan G. B.; Brouwer, Matthijs C.; van de Beek, Diederik

    2014-01-01

    Bacterial meningitis is a neurologic emergency. Vaccination against common pathogens has decreased the burden of disease. Early diagnosis and rapid initiation of empiric antimicrobial and adjunctive therapy are vital. Therapy should be initiated as soon as blood cultures have been obtained,

  2. Bacterial lipases

    NARCIS (Netherlands)

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation,

  3. Bacterial Ecology

    DEFF Research Database (Denmark)

    Fenchel, Tom

    2011-01-01

    , the production and oxidation of methane, nitrate reduction and fixation of atmospheric nitrogen are exclusively carried out by different groups of bacteria. Some bacterial species – ‘extremophiles’ – thrive in extreme environments in which no eukaryotic organisms can survive with respect to temperature, salinity...

  4. Bacterial Vaginosis

    Science.gov (United States)

    ... that coats the walls of the vagina Vaginal discharge with an unpleasant or fishlike odor Vaginal pain or itching Burning during urination Doctors are unsure of the incubation period for bacterial vaginosis. How Is the Diagnosis Made? Your child’s pediatrician can make the diagnosis ...

  5. Bacterial stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Bacterial stress. Physicochemical and chemical parameters: temperature, pressure, pH, salt concentration, oxygen, irradiation. Nutritional depravation: nutrient starvation, water shortage. Toxic compounds: Antibiotics, heavy metals, toxins, mutagens. Interactions with other cells: ...

  6. Conformational Changes of the Clamp of the Protein Translocation ATPase SecA.

    Science.gov (United States)

    Chen, Yu; Bauer, Benedikt W; Rapoport, Tom A; Gumbart, James C

    2015-07-17

    Post-translational protein translocation across the bacterial plasma membrane is mediated by the interplay of the SecA ATPase and the protein-conducting SecY channel. SecA consists of several domains, including two nucleotide-binding domains (NBD1 and NBD2), a polypeptide cross-linking domain (PPXD), a helical scaffold domain (HSD), and a helical wing domain (HWD). PPXD, HSD, and NBD2 form a clamp that positions the polypeptide substrate above the channel so that it can be pushed into the channel by a two-helix finger of the HSD. How the substrate is accommodated in the clamp during translocation is unclear. Here, we report a crystal structure of Thermotoga maritima SecA at 1.9 Å resolution. Structural analysis and free-energy calculations indicate that the new structure represents an intermediate state during the transition of the clamp from an open to a closed conformation. Molecular dynamics simulations show that closure of the clamp occurs in two phases, an initial movement of PPXD, HSD, and HWD as a unit, followed by a movement of PPXD alone toward NBD2. Simulations in the presence of a polypeptide chain show that the substrate associates with the back of the clamp by dynamic hydrogen bonding and that the clamp is laterally closed by a conserved loop of the PPXD. Mutational disruption of clamp opening or closure abolishes protein translocation. These results suggest how conformational changes of SecA allow substrate binding and movement during protein translocation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    reduce or delay bacterial biofilm formation of a range of urinary tract infectious E.coli and Klebsiella isolates. Several other proteinaceous coatings were also found to display anti-adhesive properties, possibly providing a measure for controlling the colonization of implant materials. Several other...... components. These substances may both mediate and stabilize the bacterial biofilm. Finally, several adhesive structures were examined, and a novel physiological biofilm phenotype in E.coli biofilms was characterized, namely cell chain formation. The autotransporter protein, antigen 43, was implicated...

  8. Translocation of cell-penetrating peptides into Candida fungal pathogens.

    Science.gov (United States)

    Gong, Zifan; Karlsson, Amy J

    2017-09-01

    Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

  9. Epidemiology, Diagnosis, and Antimicrobial Treatment of Acute Bacterial Meningitis

    NARCIS (Netherlands)

    Brouwer, Matthijs C.; Tunkel, Allan R.; van de Beek, Diederik

    2010-01-01

    The epidemiology of bacterial meningitis has changed as a result of the widespread use of conjugate vaccines and preventive antimicrobial treatment of pregnant women. Given the significant morbidity and mortality associated with bacterial meningitis, accurate information is necessary regarding the

  10. An Updated View of Translocator Protein (TSPO

    Directory of Open Access Journals (Sweden)

    Nunzio Denora

    2017-12-01

    Full Text Available Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO, first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery. This special issue was programmed with the aim of summarizing the latest findings about the role of TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or therapeutics. A total of 9 papers have been accepted for publication in this issue, in particular, 2 reviews and 7 primary data manuscripts, overall describing the main advances in this field.

  11. Enzymatic evidence for the key role of arginine in nitrogen translocation by arbuscular mycorrhiza fungi

    DEFF Research Database (Denmark)

    Cruz, C.; Egsgaard, Helge; Trujillo, C.

    2007-01-01

    Key enzymes of the urea cycle and N-15-labeling patterns of arginine (Arg) were measured to elucidate the involvement of Arg in nitrogen translocation by arbuscular mycorrhizal (AM) fungi. Mycorrhiza was established between transformed carrot (Daucus carota) roots and Glomus intraradices in two...... weight h(-1). The results highlight the synchronization of the spatially separated reactions involved in the anabolic and catabolic arms of the urea cycle. This synchronization is a prerequisite for Arg to be a key component in nitrogen translocation in the AM mycelium....... was used to follow the dynamics of nitrogen incorporation into and turnover of Arg. Both the absence of external nitrogen and the presence of L- norvaline, an inhibitor of Arg synthesis, prevented the synthesis of Arg in the ERM and resulted in decreased activity of arginase and urease in the AM root...

  12. Adsorption-driven translocation of polymer chain into nanopores

    Science.gov (United States)

    Yang, Shuang; Neimark, Alexander V.

    2012-06-01

    The polymer translocation into nanopores is generally facilitated by external driving forces, such as electric or hydrodynamic fields, to compensate for entropic restrictions imposed by the confinement. We investigate the dynamics of translocation driven by polymer adsorption to the confining walls that is relevant to chromatographic separation of macromolecules. By using the self-consistent field theory, we study the passage of a chain trough a small opening from cis to trans compartments of spherical shape with adsorption potential applied in the trans compartment. The chain transfer is modeled as the Fokker-Plank diffusion along the free energy landscape of the translocation pass represented as a sum of the free energies of cis and trans parts of the chain tethered to the pore opening. We investigate how the chain length, the size of trans compartment, the magnitude of adsorption potential, and the extent of excluded volume interactions affect the translocation time and its distribution. Interplay of these factors brings about a variety of different translocation regimes. We show that excluded volume interactions within a certain range of adsorption potentials can cause a local minimum on the free energy landscape, which is absent for ideal chains. The adsorption potential always leads to the decrease of the free energy barrier, increasing the probability of successful translocation. However, the translocation time depends non-monotonically of the magnitude of adsorption potential. Our calculations predict the existence of the critical magnitude of adsorption potential, which separates favorable and unfavorable regimes of translocation.

  13. Aspirin plus ticlopidine prevented experimental endocarditis due to Enterococcus faecalis and Streptococcus gallolyticus.

    Science.gov (United States)

    Veloso, Tiago Rafael; Oechslin, Frank; Que, Yok-Ai; Moreillon, Philippe; Entenza, José Manuel; Mancini, Stefano

    2015-11-01

    Enterococcus faecalis and Streptococcus gallolyticus cause infective endocarditis (IE), which can originate from the continuous release or translocation of low bacterial numbers into the bloodstream. In this context, IE cannot be prevented with antibiotics. We previously demonstrated that aspirin plus ticlopidine protected rats from IE due to S. gordonii and Staphylococcus aureus. Here we showed that aspirin plus ticlopidine significantly reduced vegetation weight and protected 73 and 64% rats (P faecalis and S. gallolyticus, respectively. These results further support the potential use of aspirin plus ticlopidine for a global prevention of IE in high-risk patients. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Bacterial lipases

    OpenAIRE

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    1994-01-01

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, meaning a sharp increase in lipase activity observed when the substrate starts to form an emulsion, thereby presenting to the enzyme an interfacial area. As a consequence, the kinetics of a lipase rea...

  15. Translocation events in a single-walled carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    He Jin; Lindsay, Stuart [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States); Liu Hao [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 (United States); Pang Pei; Cao Di, E-mail: jinhe@asu.ed [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States)

    2010-11-17

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  16. Translocation events in a single-walled carbon nanotube

    International Nuclear Information System (INIS)

    He Jin; Lindsay, Stuart; Liu Hao; Pang Pei; Cao Di

    2010-01-01

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  17. Multistep Current Signal in Protein Translocation through Graphene Nanopores

    KAUST Repository

    Bonome, Emma Letizia

    2015-05-07

    © 2015 American Chemical Society. In nanopore sensing experiments, the properties of molecules are probed by the variation of ionic currents flowing through the nanopore. In this context, the electronic properties and the single-layer thickness of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two nonequilibrium molecular dynamics methods with a bioinformatic structural analysis. To obtain a qualitative picture of the translocation process and to identify salient features we performed unsupervised structural clustering on translocation conformations. This allowed us to identify some specific and robust translocation intermediates, characterized by significantly different ionic current flows. We found that the ion current strictly anticorrelates with the amount of pore occupancy by thioredoxin residues, providing a putative explanation of the multilevel current scenario observed in recently published translocation experiments.

  18. Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

    Directory of Open Access Journals (Sweden)

    Täuber Martin G

    2003-09-01

    Full Text Available Abstract Background Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S-alpha-(4-hydroxyphenyl-beta-methyl-4-(phenylmethyl-1-piperid inepropanol (RO 25-6981. Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28 or 3.75 mg (150 mg/kg; n = 15 every 3 h or an equal volume of sterile saline (250 μl; n = 40 starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. Results Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P Conclusions Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures.

  19. A Novel Inhibitor Prevents the Peripheral Neuroparalysis of Botulinum Neurotoxins

    Science.gov (United States)

    Azarnia Tehran, Domenico; Zanetti, Giulia; Leka, Oneda; Lista, Florigio; Fillo, Silvia; Binz, Thomas; Shone, Clifford C.; Rossetto, Ornella; Montecucco, Cesare; Paradisi, Cristina; Mattarei, Andrea; Pirazzini, Marco

    2015-01-01

    Botulinum neurotoxins (BoNTs) form a large class of potent and deadly neurotoxins. Given their growing number, it is of paramount importance to discover novel inhibitors targeting common steps of their intoxication process. Recently, EGA was shown to inhibit the action of bacterial toxins and viruses exhibiting a pH-dependent translocation step in mammalian cells, by interfering with their entry route. As BoNTs act in the cytosol of nerve terminals, the entry into an appropriate compartment wherefrom they translocate the catalytic moiety is essential for toxicity. Herein we propose an optimized procedure to synthesize EGA and we show that, in vitro, it prevents the neurotoxicity of different BoNT serotypes by interfering with their trafficking. Furthermore, in mice, EGA mitigates botulism symptoms induced by BoNT/A and significantly decreases the lethality of BoNT/B and BoNT/D. This opens the possibility of using EGA as a lead compound to develop novel inhibitors of botulinum neurotoxins. PMID:26670952

  20. Mechanisms underlying stage-1 TRPL channel translocation in Drosophila photoreceptors.

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

    Full Text Available TRP channels function as key mediators of sensory transduction and other cellular signaling pathways. In Drosophila, TRP and TRPL are the light-activated channels in photoreceptors. While TRP is statically localized in the signaling compartment of the cell (the rhabdomere, TRPL localization is regulated by light. TRPL channels translocate out of the rhabdomere in two distinct stages, returning to the rhabdomere with dark-incubation. Translocation of TRPL channels regulates their availability, and thereby the gain of the signal. Little, however, is known about the mechanisms underlying this trafficking of TRPL channels.We first examine the involvement of de novo protein synthesis in TRPL translocation. We feed flies cycloheximide, verify inhibition of protein synthesis, and test for TRPL translocation in photoreceptors. We find that protein synthesis is not involved in either stage of TRPL translocation out of the rhabdomere, but that re-localization to the rhabdomere from stage-1, but not stage-2, depends on protein synthesis. We also characterize an ex vivo eye preparation that is amenable to biochemical and genetic manipulation. We use this preparation to examine mechanisms of stage-1 TRPL translocation. We find that stage-1 translocation is: induced with ATP depletion, unaltered with perturbation of the actin cytoskeleton or inhibition of endocytosis, and slowed with increased membrane sterol content.Our results indicate that translocation of TRPL out of the rhabdomere is likely due to protein transport, and not degradation/re-synthesis. Re-localization from each stage to the rhabdomere likely involves different strategies. Since TRPL channels can translocate to stage-1 in the absence of ATP, with no major requirement of the cytoskeleton, we suggest that stage-1 translocation involves simple diffusion through the apical membrane, which may be regulated by release of a light-dependent anchor in the rhabdomere.

  1. Probiotics (VSL#3 prevent endothelial dysfunction in rats with portal hypertension: role of the angiotensin system.

    Directory of Open Access Journals (Sweden)

    Sherzad K Rashid

    Full Text Available AIMS: Portal hypertension characterized by generalized vasodilatation with endothelial dysfunction affecting nitric oxide (NO and endothelium-dependent hyperpolarization (EDH has been suggested to involve bacterial translocation and/or the angiotensin system. The possibility that ingestion of probiotics prevents endothelial dysfunction in rats following common bile duct ligation (CBDL was evaluated. METHODS: Rats received either control drinking water or the probiotic VSL#3 solution (50 billion bacteria.kg body wt⁻¹.day⁻¹ for 7 weeks. After 3 weeks, rats underwent surgery with either resection of the common bile duct or sham surgery. The reactivity of mesenteric artery rings was assessed in organ chambers, expression of proteins by immunofluorescence and Western blot analysis, oxidative stress using dihydroethidium, and plasma pro-inflammatory cytokine levels by flow cytometry. RESULTS: Both NO- and EDH-mediated relaxations to acetylcholine were reduced in the CBDL group compared to the sham group, and associated with a reduced expression of Cx37, Cx40, Cx43, IKCa and SKCa and an increased expression of endothelial NO synthase (eNOS. In aortic sections, increased expression of NADPH oxidase subunits, angiotensin converting enzyme, AT1 receptors and angiotensin II, and formation of ROS and peroxynitrite were observed. VSL#3 prevented the deleterious effect of CBDL on EDH-mediated relaxations, vascular expression of connexins, IKCa, SKCa and eNOS, oxidative stress, and the angiotensin system. VSL#3 prevented the CBDL-induced increased plasma TNF-α, IL-1α and MCP-1 levels. CONCLUSIONS: These findings indicate that VSL#3 ingestion prevents endothelial dysfunction in the mesenteric artery of CBDL rats, and this effect is associated with an improved vascular oxidative stress most likely by reducing bacterial translocation and the local angiotensin system.

  2. Minimizing the cost of translocation failure with decision-tree models that predict species' behavioral response in translocation sites.

    Science.gov (United States)

    Ebrahimi, Mehregan; Ebrahimie, Esmaeil; Bull, C Michael

    2015-08-01

    The high number of failures is one reason why translocation is often not recommended. Considering how behavior changes during translocations may improve translocation success. To derive decision-tree models for species' translocation, we used data on the short-term responses of an endangered Australian skink in 5 simulated translocations with different release conditions. We used 4 different decision-tree algorithms (decision tree, decision-tree parallel, decision stump, and random forest) with 4 different criteria (gain ratio, information gain, gini index, and accuracy) to investigate how environmental and behavioral parameters may affect the success of a translocation. We assumed behavioral changes that increased dispersal away from a release site would reduce translocation success. The trees became more complex when we included all behavioral parameters as attributes, but these trees yielded more detailed information about why and how dispersal occurred. According to these complex trees, there were positive associations between some behavioral parameters, such as fight and dispersal, that showed there was a higher chance, for example, of dispersal among lizards that fought than among those that did not fight. Decision trees based on parameters related to release conditions were easier to understand and could be used by managers to make translocation decisions under different circumstances. © 2015 Society for Conservation Biology.

  3. Prevention of Food Poisoning.

    Science.gov (United States)

    Army Quartermaster School, Ft. Lee, VA.

    The programed text provides a single lesson, four-hour, correspondence subcourse on the prevention of food poisoning. It covers the following areas: a definition of food poisoning; chemical food poisoning; biological food poisoning; causes and prevention of trichinosis; six factors controlling bacteria growth; bacterial infection; prevention of…

  4. Blockade of NMDA receptor subtype NR2B prevents seizures but not apoptosis of dentate gyrus neurons in bacterial meningitis in infant rats

    Science.gov (United States)

    Kolarova, Anna; Ringer, Ralph; Täuber, Martin G; Leib, Stephen L

    2003-01-01

    Background Excitotoxic neuronal injury by action of the glutamate receptors of the N-methyl-d-aspartate (NMDA) subtype have been implicated in the pathogenesis of brain damage as a consequence of bacterial meningitis. The most potent and selective blocker of NMDA receptors containing the NR2B subunit is (R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperid inepropanol (RO 25-6981). Here we evaluated the effect of RO 25-6981 on hippocampal neuronal apoptosis in an infant rat model of meningitis due to Streptococcus pneumoniae. Animals were randomized for treatment with RO 25-6981 at a dosage of either 0.375 mg (15 mg/kg; n = 28) or 3.75 mg (150 mg/kg; n = 15) every 3 h or an equal volume of sterile saline (250 μl; n = 40) starting at 12 h after infection. Eighteen hours after infection, animals were assessed clinically and seizures were observed for a period of 2 h. At 24 h after infection animals were sacrificed and brains were examined for apoptotic injury to the dentate granule cell layer of the hippocampus. Results Treatment with RO 25-6981 had no effect on clinical scores, but the incidence of seizures was reduced (P < 0.05 for all RO 25-6981 treated animals combined). The extent of apoptosis was not affected by low or high doses of RO 25-6981. Number of apoptotic cells (median [range]) was 12.76 [3.16–25.3] in animals treated with low dose RO 25-6981 (control animals 13.8 [2.60–31.8]; (P = NS) and 9.8 [1.7–27.3] (controls: 10.5 [2.4–21.75]) in animals treated with high dose RO 25-6981 (P = NS). Conclusions Treatment with a highly selective blocker of NMDA receptors containing the NR2B subunit failed to protect hippocampal neurons from injury in this model of pneumococcal meningitis, while it had some beneficial effect on the incidence of seizures. PMID:13129439

  5. Bacterial mitosis

    DEFF Research Database (Denmark)

    Møller-Jensen, Jakob; Borch, Jonas; Dam, Mette

    2003-01-01

    Bacterial DNA segregation takes place in an active and ordered fashion. In the case of Escherichia coli plasmid R1, the partitioning system (par) separates paired plasmid copies and moves them to opposite cell poles. Here we address the mechanism by which the three components of the R1 par system...... movement is powered by insertional polymerization of ParM. Consistently, we find that segregating plasmids are positioned at the ends of extending ParM filaments. Thus, the process of R1 plasmid segregation in E. coli appears to be mechanistically analogous to the actin-based motility operating...

  6. Does translocation influence physiological stress in the desert tortoise?

    Science.gov (United States)

    Drake, K.K.; Nussear, K.E.; Esque, T.C.; Barber, A.M.; Vittum, K.M.; Medica, P.A.; Tracy, C.R.; Hunter, K.W.

    2012-01-01

    Wildlife translocation is increasingly used to mitigate disturbances to animals or habitat due to human activities, yet little is known about the extent to which translocating animals causes stress. To understand the relationship between physiological stress and translocation, we conducted a multiyear study (2007–2009) using a population of desert tortoises (Gopherus agassizii) near Fort Irwin, California. Blood samples were collected from adult tortoises in three treatment groups (resident, translocated and control) for 1 year prior to and 2 years after translocation. Samples were analyzed by radioimmunoassay for plasma total corticosterone (CORT), a glucocorticoid hormone commonly associated with stress responses in reptiles. CORT values were analyzed in relation to potential covariates (animal sex, date, behavior, treatment, handling time, air temperature, home-range size, precipitation and annual plant production) among seasons and years. CORT values in males were higher than in females, and values for both varied monthly throughout the activity season and among years. Year and sex were strong predictors of CORT, and translocation explained little in terms of CORT. Based on these results, we conclude that translocation does not elicit a physiological stress response in desert tortoises.

  7. Forced Translocation of Polymer through Nanopore: Deterministic Model and Simulations

    Science.gov (United States)

    Wang, Yanqian; Panyukov, Sergey; Liao, Qi; Rubinstein, Michael

    2012-02-01

    We propose a new theoretical model of forced translocation of a polymer chain through a nanopore. We assume that DNA translocation at high fields proceeds too fast for the chain to relax, and thus the chain unravels loop by loop in an almost deterministic way. So the distribution of translocation times of a given monomer is controlled by the initial conformation of the chain (the distribution of its loops). Our model predicts the translocation time of each monomer as an explicit function of initial polymer conformation. We refer to this concept as ``fingerprinting''. The width of the translocation time distribution is determined by the loop distribution in initial conformation as well as by the thermal fluctuations of the polymer chain during the translocation process. We show that the conformational broadening δt of translocation times of m-th monomer δtm^1.5 is stronger than the thermal broadening δtm^1.25 The predictions of our deterministic model were verified by extensive molecular dynamics simulations

  8. Slowing down DNA translocation using magnetic and optical tweezers

    Science.gov (United States)

    Peng, Hongbo; Wu, Shanshan; Ryul Park, Sang; Potter, Andrew; Ling, X. S.

    2006-03-01

    Electric-field driven DNA translocation through nanopores can be exploited for DNA sequencing and other applications. However, the DNA translocation under normal patch-clamp-type measurement is too fast to allow detailed measurements of individual or few nucleotides. We propose a concept to slow down the DNA translocation through the nanopore by using magnetic (or optical) tweezers. The 3' end of a single-strand DNA can be attached to a streptavidin-coated magnetic bead through a single biotin molecule. During DNA translocation, the 5' end of DNA will be electrophoretically drawn through the nanopore to the trans side while the 3' end of DNA stays in the cis side with the magnetic bead. A set of permanent magnets or electric coils can be used to generate a magnetic field gradient large enough to pull the bead, hence the DNA out of the nanopore. The net force on the magnetic bead will determine this back-translocation speed. By carefully tuning the magnetic field gradient and the voltage bias on the nanopore, one can make the back-translocation much slower than the conventional forward-translocation in which case the DNA is driven only by the electric force. We will report our experimental design as well as the preliminary results.

  9. Translocation of threatened plants as a conservation measure in China.

    Science.gov (United States)

    Liu, Hong; Ren, Hai; Liu, Qiang; Wen, XiangYing; Maunder, Michael; Gao, JiangYun

    2015-12-01

    We assessed the current status of plant conservation translocation efforts in China, a topic poorly reported in recent scientific literature. We identified 222 conservation translocation cases involving 154 species, of these 87 were Chinese endemic species and 101 (78%) were listed as threatened on the Chinese Species Red List. We categorized the life form of each species and, when possible, determined for each case the translocation type, propagule source, propagule type, and survival and reproductive parameters. A surprisingly large proportion (26%) of the conservation translocations in China were conservation introductions, largely implemented in response to large-scale habitat destruction caused by the Three-Gorge Dam and another hydropower project. Documentation and management of the translocations varied greatly. Less than half the cases had plant survival records. Statistical analyses showed that survival percentages were significantly correlated with plant life form and the type of planting materials. Thirty percent of the cases had records on whether or not individuals flowered or fruited. Results of information theoretic model selection indicated that plant life form, translocation type, propagule type, propagule source, and time since planting significantly influenced the likelihood of flowering and fruiting on the project level. We suggest that the scientific-based application of species conservation translocations should be promoted as part of a commitment to species recovery management. In addition, we recommend that the common practice of within and out of range introductions in nature reserves to be regulated more carefully due to its potential ecological risks. We recommend the establishment of a national office and database to coordinate conservation translocations in China. Our review effort is timely considering the need for a comprehensive national guideline for the newly announced nation-wide conservation program on species with extremely

  10. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  11. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    International Nuclear Information System (INIS)

    Shimura, Takaya; Higashiyama, Shigeki; Joh, Takashi; Yoshida, Michihiro; Fukuda, Shinji; Ebi, Masahide; Hirata, Yoshikazu; Mizoshita, Tsutomu; Tanida, Satoshi; Kataoka, Hiromi; Kamiya, Takeshi

    2012-01-01

    Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P < 0.01). The growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Both the function of HB-EGF as an EGFR ligand and a novel signal for

  12. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Directory of Open Access Journals (Sweden)

    Shimura Takaya

    2012-05-01

    Full Text Available Abstract Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C, translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF and mutated HB-EGF (HB-EGF-mC, which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 % and in the cytoplasm only in 25 cases (26.0 %. The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P  Conclusions Both the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

  13. Absorption and translocation of phosphorus-32 in guava leaves

    International Nuclear Information System (INIS)

    Natale, William

    1997-01-01

    Phosphorus is easily absorbed by the leaves and translocated. The objective of this work was to evaluate the absorption and translocation of P by guava leaves, with time. When a solution containing 2% MAP and specific activity 0.15 μCi/ml was applied. MAP labelled with 32 P was applied in the 3 rd pair of leaves. These and other leaves, roots and stem were collected separately and analyzed accordingly. The results showed that 20 days after application 12% of the applied P was absorbed by the guava leaves. The translocation of P started immediately after its absorption reaching 20% 2fter 20 days. (author). 19 refs., 4 tabs

  14. Phenylmethimazole Blocks dsRNA-Induced IRF3 Nuclear Translocation and Homodimerization

    Directory of Open Access Journals (Sweden)

    Maria C. Courreges

    2012-10-01

    Full Text Available Previous studies revealed that phenylmethimazole (C10 inhibits IRF3 signaling, preventing dsRNA-induction of type 1 interferon gene expression, production, and downstream signaling. In the present study, we investigated the molecular basis for C10 inhibition of dsRNA-stimulated IRF3 signaling. IRF-3 Trans-AM assays were used to measure C10 effects on dsRNA induction of IRF3 DNA binding. Green fluorescent protein-labeled IRF3 was used to measure C10 effects on dsRNA-induced IRF3 nuclear translocation. Native PAGE, SDS PAGE, and western blotting were used to identify effects of C10 on IRF3 homodimer formation and phosphorylation, respectively. There was a significant impairment of dsRNA-induced IRF3 DNA binding activity in human embryonic kidney and pancreatic cancer cells with C10 treatment. C10 also blocked dsRNA-induced IRF3 nuclear translocation and homodimer formation without blocking serine 396 phosphorylation of IRF3. Together, these results indicate that C10 interferes with IRF3 signaling by blocking dsRNA-induced IRF3 homodimer formation, a prerequisite for nuclear translocation and DNA binding activities.

  15. FtsK translocation on DNA stops at XerCD-dif.

    Science.gov (United States)

    Graham, James E; Sivanathan, Viknesh; Sherratt, David J; Arciszewska, Lidia K

    2010-01-01

    Escherichia coli FtsK is a powerful, fast, double-stranded DNA translocase, which can strip proteins from DNA. FtsK acts in the late stages of chromosome segregation by facilitating sister chromosome unlinking at the division septum. KOPS-guided DNA translocation directs FtsK towards dif, located within the replication terminus region, ter, where FtsK activates XerCD site-specific recombination. Here we show that FtsK translocation stops specifically at XerCD-dif, thereby preventing removal of XerCD from dif and allowing activation of chromosome unlinking by recombination. Stoppage of translocation at XerCD-dif is accompanied by a reduction in FtsK ATPase and is not associated with FtsK dissociation from DNA. Specific stoppage at recombinase-DNA complexes does not require the FtsKgamma regulatory subdomain, which interacts with XerD, and is not dependent on either recombinase-mediated DNA cleavage activity, or the formation of synaptic complexes.

  16. A Protein Rotaxane Controls the Translocation of Proteins Across a ClyA Nanopore.

    Science.gov (United States)

    Biesemans, Annemie; Soskine, Misha; Maglia, Giovanni

    2015-09-09

    Rotaxanes, pseudorotaxanes, and catenanes are supramolecular complexes with potential use in nanomachinery, molecular computing, and single-molecule studies. Here we constructed a protein rotaxane in which a polypeptide thread is encircled by a Cytolysin A (ClyA) nanopore and capped by two protein stoppers. The rotaxane could be switched between two states. At low negative applied potentials (nanopore indefinitely. Under this configuration the rotaxane prevents the diffusion of protein molecules across the lipid bilayer and provides a useful platform for single-molecule analysis. High negative applied potentials (-100 mV) dismantled the interlocked rotaxane system by the forceful translocation of the protein stopper, allowing new proteins to be trapped inside or transported across the nanopore. The observed voltage threshold for the translocation of the protein stopper through the nanopore related well to the biphasic voltage dependence of the residence time measured for the freely diffusing protein stopper. We propose a model in which molecules translocate through a nanopore when the average dwell time decreases with the applied potential.

  17. Nitric oxide induces thioredoxin-1 nuclear translocation: Possible association with the p21Ras survival pathway

    International Nuclear Information System (INIS)

    Arai, Roberto J.; Masutani, H.; Yodoi, J.; Debbas, V.; Laurindo, Francisco R.; Stern, A.; Monteiro, Hugo P.

    2006-01-01

    One of the major redox-regulating molecules with thiol reducing activity is thioredoxin-1 (TRX-1). TRX-1 is a multifunctional protein that exists in the extracellular millieu, cytoplasm, and nucleus, and has a distinct role in each environment. It is well known that TRX-1 promptly migrates to the nuclear compartment in cells exposed to oxidants. However, the intracellular location of TRX-1 in cells exposed to nitrosothiols has not been investigated. Here, we demonstrated that the exposure of HeLa cells to increasing concentrations of the nitrosothiol S-nitroso-N-acetylpenicillamine (SNAP) promoted TRX-1 nuclear accumulation. The SNAP-induced TRX-1 translocation to the nucleus was inhibited by FPTIII, a selective inhibitor of p21Ras. Furthermore, TRX-1 migration was attenuated in cells stably transfected with NO insensitive p21Ras (p21 RasC118S ). Downstream to p21Ras, the MAP Kinases ERK1/2 were activated by SNAP under conditions that promote TRX-1 nuclear translocation. Inhibition of MEK prevented SNAP-stimulated ERK1/2 activation and TRX-1 nuclear migration. In addition, cells treated with p21Ras or MEK inhibitor showed increased susceptibility to cell death induced by SNAP. In conclusion, our observations suggest that the nuclear translocation of TRX-1 is induced by SNAP involving p21Ras survival pathway

  18. HIV enteropathy and aging: gastrointestinal immunity, mucosal epithelial barrier, and microbial translocation.

    Science.gov (United States)

    Wang, Hongyin; Kotler, Donald P

    2014-07-01

    Despite decreases in morbidity and mortality as a result of antiretroviral therapy, gastrointestinal dysfunction remains common in HIV infection. Treated patients are at risk for complications of 'premature' aging, such as cardiovascular disease, osteopenia, neurocognitive decline, malignancies, and frailty. This review summarizes recent observations in this field. Mucosal CD4 lymphocytes, especially Th17 cells, are depleted in acute HIV and simian immune deficiency virus (SIV) infections, although other cell types also are affected. Reconstitution during therapy often is incomplete, especially in mucosa. Mucosal barrier function is affected by both HIV infection and aging and includes paracellular transport via tight junctions and uptake through areas of apoptosis; other factors may affect systemic antigen exposure. The resultant microbial translocation is associated with systemic immune activation in HIV and SIV infections. There is evidence of immune activation and microbial translocation in the elderly. The immune phenotypes of immunosenescence in HIV infection and aging appear similar. There are several targets for intervention; blockage of residual mucosal virus replication, preventing antigen uptake, modulating the microbiome, improving T cell recovery, combining therapies aimed at mucosal integrity, augmenting mucosal immunity, and managing traditional risk factors for premature aging in the general population. Aging may interact with HIV enteropathy to enhance microbial translocation and immune activation.

  19. Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance

    Directory of Open Access Journals (Sweden)

    Giang T. Nguyen

    2017-08-01

    Full Text Available Reactive oxygen species (ROS generated by NADPH oxidase play an important role in antimicrobial host defense and inflammation. Their deficiency in humans results in recurrent and severe bacterial infections, while their unregulated release leads to pathology from excessive inflammation. The release of high concentrations of ROS aids in clearance of invading bacteria. Localization of ROS release to phagosomes containing pathogens limits tissue damage. Host immune cells, like neutrophils, also known as PMNs, will release large amounts of ROS at the site of infection following the activation of surface receptors. The binding of ligands to G-protein-coupled receptors (GPCRs, toll-like receptors, and cytokine receptors can prime PMNs for a more robust response if additional signals are encountered. Meanwhile, activation of Fc and integrin directly induces high levels of ROS production. Additionally, GPCRs that bind to the bacterial-peptide analog fMLP, a neutrophil chemoattractant, can both prime cells and trigger low levels of ROS production. Engagement of these receptors initiates intracellular signaling pathways, resulting in activation of downstream effector proteins, assembly of the NADPH oxidase complex, and ultimately, the production of ROS by this complex. Within PMNs, ROS released by the NADPH oxidase complex can activate granular proteases and induce the formation of neutrophil extracellular traps (NETs. Additionally, ROS can cross the membranes of bacterial pathogens and damage their nucleic acids, proteins, and cell membranes. Consequently, in order to establish infections, bacterial pathogens employ various strategies to prevent restriction by PMN-derived ROS or downstream consequences of ROS production. Some pathogens are able to directly prevent the oxidative burst of phagocytes using secreted effector proteins or toxins that interfere with translocation of the NADPH oxidase complex or signaling pathways needed for its activation

  20. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S

    2014-01-01

    In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene (IG-MYC), as opposed to a non......-immunoglobulin partner gene (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent in situ hybridisation (FISH) with split probes. MYC translocation partner gene was identified by IGH/MYC fusion probes and/or kappa/lambda split probes. Clinical...... data were collected from patient files. MYC translocation was identified in 28/225 patients. IG-MYC translocation partner gene was identified in 12/24 patients. DH translocation was identified in 23/228 patients. IG-MYC translocation partner gene was identified in 9/19 DH patients. Neither MYC-nor DH...

  1. CB2 cannabinoid receptors contribute to bacterial invasion and mortality in polymicrobial sepsis.

    Directory of Open Access Journals (Sweden)

    Balázs Csóka

    2009-07-01

    Full Text Available Sepsis is a major healthcare problem and current estimates suggest that the incidence of sepsis is approximately 750,000 annually. Sepsis is caused by an inability of the immune system to eliminate invading pathogens. It was recently proposed that endogenous mediators produced during sepsis can contribute to the immune dysfunction that is observed in sepsis. Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB(2 receptors on immune cells. Here we examined the role of CB(2 receptors in regulating the host's response to sepsis.The role of CB(2 receptors was studied by subjecting CB(2 receptor wild-type and knockout mice to bacterial sepsis induced by cecal ligation and puncture. We report that CB(2 receptor inactivation by knockout decreases sepsis-induced mortality, and bacterial translocation into the bloodstream of septic animals. Furthermore, CB(2 receptor inactivation decreases kidney and muscle injury, suppresses splenic nuclear factor (NF-kappaB activation, and diminishes the production of IL-10, IL-6 and MIP-2. Finally, CB(2 receptor deficiency prevents apoptosis in lymphoid organs and augments the number of CD11b(+ and CD19(+ cells during CLP.Taken together, our results establish for the first time that CB(2 receptors are important contributors to septic immune dysfunction and mortality, indicating that CB(2 receptors may be therapeutically targeted for the benefit of patients suffering from sepsis.

  2. Silibinin induces apoptosis via calpain-dependent AIF nuclear translocation in U87MG human glioma cell death

    Directory of Open Access Journals (Sweden)

    Kim Yong K

    2011-04-01

    Full Text Available Abstract Background Silibinin, a natural polyphenolic flavonoid, has been reported to induce cell death in various cancer cell types. However, the molecular mechanism is not clearly defined. Our previous study showed that silibinin induces glioma cell death and its effect was effectively prevented by calpain inhibitor. The present study was therefore undertaken to examine the role of calpain in the silibinin-induced glioma cell death. Methods U87MG cells were grown on well tissue culture plates and cell viability was measured by MTT assay. ROS generation and △ψm were estimated using the fluorescence dyes. PKC activation and Bax expression were measured by Western blot analysis. AIF nuclear translocation was determined by Western blot and immunocytochemistry. Results Silibinin induced activation of calpain, which was blocked by EGTA and the calpain inhibitor Z-Leu-Leu-CHO. Silibinin caused ROS generation and its effect was inhibited by calpain inhibitor, the general PKC inhibitor GF 109203X, the specific PKCδ inhibitor rottlerin, and catalase. Silibinin-induce cell death was blocked by calpain inhibitor and PKC inhibitors. Silibinin-induced PKCδ activation and disruption of △ψm were prevented by the calpain inhibitor. Silibinin induced AIF nuclear translocation and its effect was prevented by calpain inhibitor. Transfection of vector expressing microRNA of AIF prevented the silibinin-induced cell death. Conclusions Silibinin induces apoptotic cell death through a calpain-dependent mechanism involving PKC, ROS, and AIF nuclear translocation in U87MG human glioma cells.

  3. A case of posttraumatic splenic translocation into the thorax

    International Nuclear Information System (INIS)

    Sosnowski, P.; Sikorski, L.; Ziemianski, A.

    1993-01-01

    A case of the left diaphragmatic hernia due to blunt thoracic and abdominal trauma is presented. Characteristic radiological signs of splenic translocation into the thorax contributed to quick diagnosis and immediate surgical intervention. (author)

  4. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Science.gov (United States)

    2010-07-01

    ... manifests as balanced reciprocal translocations in progeny descended from parental males treated with... significance desired. (B) (iv) Assignment to groups. Animals shall be randomized and assigned to treatment and...

  5. DNA translocations through solid-state plasmonic nanopores.

    Science.gov (United States)

    Nicoli, Francesca; Verschueren, Daniel; Klein, Misha; Dekker, Cees; Jonsson, Magnus P

    2014-12-10

    Nanopores enable label-free detection and analysis of single biomolecules. Here, we investigate DNA translocations through a novel type of plasmonic nanopore based on a gold bowtie nanoantenna with a solid-state nanopore at the plasmonic hot spot. Plasmonic excitation of the nanopore is found to influence both the sensor signal (nanopore ionic conductance blockade during DNA translocation) and the process that captures DNA into the nanopore, without affecting the duration time of the translocations. Most striking is a strong plasmon-induced enhancement of the rate of DNA translocation events in lithium chloride (LiCl, already 10-fold enhancement at a few mW of laser power). This provides a means to utilize the excellent spatiotemporal resolution of DNA interrogations with nanopores in LiCl buffers, which is known to suffer from low event rates. We propose a mechanism based on plasmon-induced local heating and thermophoresis as explanation of our observations.

  6. DNA-graphene interactions during translocation through nanogaps.

    Directory of Open Access Journals (Sweden)

    Hiral N Patel

    Full Text Available We study how double-stranded DNA translocates through graphene nanogaps. Nanogaps are fabricated with a novel capillary-force induced graphene nanogap formation technique. DNA translocation signatures for nanogaps are qualitatively different from those obtained with circular nanopores, owing to the distinct shape of the gaps discussed here. Translocation time and conductance values vary by ∼ 100%, which we suggest are caused by local gap width variations. We also observe exponentially relaxing current traces. We suggest that slow relaxation of the graphene membrane following DNA translocation may be responsible. We conclude that DNA-graphene interactions are important, and need to be considered for graphene-nanogap based devices. This work further opens up new avenues for direct read of single molecule activitities, and possibly sequencing.

  7. Slowing DNA Translocation in a Nanofluidic Field-Effect Transistor.

    Science.gov (United States)

    Liu, Yifan; Yobas, Levent

    2016-04-26

    Here, we present an experimental demonstration of slowing DNA translocation across a nanochannel by modulating the channel surface charge through an externally applied gate bias. The experiments were performed on a nanofluidic field-effect transistor, which is a monolithic integrated platform featuring a 50 nm-diameter in-plane alumina nanocapillary whose entire length is surrounded by a gate electrode. The field-effect transistor behavior was validated on the gating of ionic conductance and protein transport. The gating of DNA translocation was subsequently studied by measuring discrete current dips associated with single λ-DNA translocation events under a source-to-drain bias of 1 V. The translocation speeds under various gate bias conditions were extracted by fitting event histograms of the measured translocation time to the first passage time distributions obtained from a simple 1D biased diffusion model. A positive gate bias was observed to slow the translocation of single λ-DNA chains markedly; the translocation speed was reduced by an order of magnitude from 18.4 mm/s obtained under a floating gate down to 1.33 mm/s under a positive gate bias of 9 V. Therefore, a dynamic and flexible regulation of the DNA translocation speed, which is vital for single-molecule sequencing, can be achieved on this device by simply tuning the gate bias. The device is realized in a conventional semiconductor microfabrication process without the requirement of advanced lithography, and can be potentially further developed into a compact electronic single-molecule sequencer.

  8. Mechanism of RNA Translocation by a Viral Packaging Motor

    OpenAIRE

    Lisal, Jiri

    2006-01-01

    Molecular motors are proteins that convert chemical energy into mechanical work. The viral packaging ATPase P4 is a hexameric molecular motor that translocates RNA into preformed viral capsids. P4 belongs to the ubiquitous class of hexameric helicases. Although its structure is known, the mechanism of RNA translocation remains elusive. Here we present a detailed kinetic study of nucleotide binding, hydrolysis, and product release by P4. We propose a stochastic-sequential cooperative model to ...

  9. Electrically facilitated translocation of protein through solid nanopore

    OpenAIRE

    Wu, Lingzhi; Liu, Hang; Zhao, Wenyuan; Wang, Lei; Hou, Chuanrong; Liu, Quanjun; Lu, Zuhong

    2014-01-01

    Nanopores have been proven as versatile single-molecule sensors for individual unlabeled biopolymer detection and characterization. In the present work, a relative large nanopore with a diameter of about 60 nm has been used to detect protein translocation driven by a series of applied voltages. Compared with previous studied small nanopores, a distinct profile of protein translocation through a larger nanopore has been characterized. First, a higher threshold voltage is required to drive prot...

  10. Molecular studies of translocations and trisomy involving chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Dutly, F.; Schinzel, A.A. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1996-01-11

    Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13)(p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy. The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy. 30 refs., 1 fig., 2 tabs.

  11. A Mathematical Model of Black Rhino Translocation Strategy

    Directory of Open Access Journals (Sweden)

    Dipo Aldila

    2015-03-01

    Full Text Available A deterministic mathematical model of the black rhino population in South Africa will be discussed. The model is constructed by dividing the black rhino population into multiple patches. The impact of human intervention on different translocation strategies is incorporated into the model. It is shown that, when implemented correctly, translocation can accelerate the growth rate of the total black rhino population. Equilibrium points are shown with their local stability criteria.

  12. Carbon translocation in zooanthaellae-coelenterate symbioses

    International Nuclear Information System (INIS)

    Battey, J.F.

    1985-01-01

    When host and algal triglycerides synthesized in the symbiotic sea anemone Condylactis gigantea during light and dark incubations in 14 C-bicarbonate and 14 C-acetate were deacylated, more then 80% of the radioactivity was found in the fatty acid moiety. In contrast, triglycerides isolated from zooxanthellae and host incubated in 14 C-glycerol in the dark were found to have more then 95% of their radioactivity in the glycerol moiety. During 14 C-glycerol incubations in the light, radioactivity in the fatty acid moiety of zooxanthellae triglyceride fatty acid moiety stayed below 5% during 14 C-glycerol incubations in the light. These results show neither the zooxanthellae nor host can rapidly convert glycerol to fatty acid. Radioactivity from 14 C-glycerol that does eventually appear in host lipid may have been respired to 14 CO 2 then photosynthetically fixed by the zooxanthellae and synthesized into lipid fatty acid. The isolated zooxanthellae of C. gigantea contained 3.62 +/- 0.33 mM glycerol, which was 26x the 0.141 +/- 0.02 mM found in the coelenterate tissue. Aposymbiotic coelenterate tissue contained 0.169 +/- 0.05 mM glycerol. The metabolic inhibitors, sodium cyanide, aminooxyacetic acid and cerulenin were used to try and uncouple the production of glycerol by the zooxanthellae from its utilization by the coelenterate host. 10 -5 M NaCN increased the ratio of cross photosynthesis to respiration in both intact tentacles and isolated zooxanthellae, increased translocation from 17.7 +/- 3.5% of total fixed carbon in controls to 43.5 +/- 5.79%, and doubled the amount of photosynthetically fixed carbon accumulating in the coelenterate host over that in controls

  13. Structure and operation of bacterial tripartite pumps.

    Science.gov (United States)

    Hinchliffe, Philip; Symmons, Martyn F; Hughes, Colin; Koronakis, Vassilis

    2013-01-01

    In bacteria such as Pseudomonas aeruginosa and Escherichia coli, tripartite membrane machineries, or pumps, determine the efflux of small noxious molecules, such as detergents, heavy metals, and antibiotics, and the export of large proteins including toxins. They are therefore influential in bacterial survival, particularly during infections caused by multidrug-resistant pathogens. In these tripartite pumps an inner membrane transporter, typically an ATPase or proton antiporter, binds and translocates export or efflux substrates. In cooperation with a periplasmic adaptor protein it recruits and opens a TolC family cell exit duct, which is anchored in the outer membrane and projects across the periplasmic space between inner and outer membranes. Assembled tripartite pumps thus span the entire bacterial cell envelope. We review the atomic structures of each of the three pump components and discuss how these have allowed high-resolution views of tripartite pump assembly, operation, and possible inhibition.

  14. Direct observation of DNA translocation influenced by electrically gated nanopores

    Science.gov (United States)

    Ando, Genki; Moriya, Hiroki; Tsukahira, Kenta; Yano, Satoshi; Mitsui, Toshiyuki

    2012-02-01

    One of remarkable recent developments in the solid state nanopore based DNA analysis is adding the ability to control electric potential near nanopore as a gate electrode by patterning metal in or on nanopore. In this approach, better control of DNA translocations for example, slowing down the translocation speed might be expected. We have fabricated insulator-metal-insulator nanopores of rather large 100 nm pore in diameter. The 100 nm diameter pores allow us to observe the translocation of lambda-DNA molecules directly by means of fluorescence microscopy without heavy clogging of the DNA molecules into the pores. By controlling ?gate voltage? on metal relative to the cis and trans voltages, the translocation rates of DNA are able to change. Interestingly, applying pulse voltage to the gate metal near 100 ms to reverse the direction of the electric field near the cis side of nanopore reverses the direction of the DNA translocation instantaneously. This in fact provides us a new way to repeat translocation of the same DNA molecule. Furthermore, repeating the pulse tends to clear off the clogged DNA molecules in nanopore. We will present more details of these phenomena caused by the gate voltages.

  15. Cytosolic extract induces Tir translocation and pedestals in EPEC-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Alyson I Swimm

    2008-01-01

    Full Text Available Enteropathogenic Escherichia coli (EPEC are deadly contaminants in water and food, and induce protrusion of actin-filled membranous pedestals beneath themselves upon attachment to intestinal epithelia. Pedestal formation requires clustering of Tir and subsequent recruitment of cellular tyrosine kinases including Abl, Arg, and Etk as well as signaling molecules Nck, N-WASP, and Arp2/3 complex. We have developed a cytosolic extract-based cellular system that recapitulates actin pedestal formation in permeabilized red blood cells (RBC infected with EPEC. RBC support attachment of EPEC and translocation of virulence factors, but not pedestal formation. We show here that extract induces a rapid Ca++-dependent release of Tir from the EPEC Type III secretion system, and that cytoplasmic factor(s present in the extract facilitate translocation of Tir into the RBC plasma membrane. We show that Abl and related kinases in the extract phosphorylate Tir and that actin polymerization can be reconstituted in infected RBC following addition of cytosolic extract. Reconstitution requires the bacterial virulence factors Tir and intimin, and phosphorylation of Tir on tyrosine residue 474 results in the recruitment of Nck, N-WASP, and Arp2/3 complex beneath attached bacteria at sites of actin polymerization. Together these data describe a biochemical system for dissection of host components that mediate Type III secretion and the mechanisms by which complexes of proteins are recruited to discrete sites within the plasma membrane to initiate localized actin polymerization and morphological changes.

  16. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Science.gov (United States)

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  17. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Directory of Open Access Journals (Sweden)

    Mukesh

    Full Text Available The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  18. BACTERIAL PLASMIDS

    Directory of Open Access Journals (Sweden)

    Marina Dinic

    2007-12-01

    Full Text Available Plasmids, extrachromosomal DNA, were identified in bacteria pertaining to family of Enterobacteriacae for the very first time. After that, they were discovered in almost every single observed strain. The structure of plasmids is made of circular double chain DNA molecules which are replicated autonomously in a host cell. Their length may vary from few up to several hundred kilobase (kb. Among the bacteria, plasmids are mostly transferred horizontally by conjugation process. Plasmid replication process can be divided into three stages: initiation, elongation, and termination. The process involves DNA helicase I, DNA gyrase, DNA polymerase III, endonuclease, and ligase.Plasmids contain genes essential for plasmid function and their preservation in a host cell (the beginning and the control of replication. Some of them possess genes whichcontrol plasmid stability. There is a common opinion that plasmids are unnecessary fora growth of bacterial population and their vital functions; thus, in many cases they can be taken up or kicked out with no lethal effects to a plasmid host cell. However,there are numerous biological functions of bacteria related to plasmids. Plasmids identification and classification are based upon their genetic features which are presented permanently in all of them, and these are: abilities to preserve themselves in a host cell and to control a replication process. In this way, plasmids classification among incompatibility groups is performed. The method of replicon typing, which is based on genotype and not on phenotype characteristics, has the same results as in compatibility grouping.

  19. High-speed detection of DNA translocation in nanopipettes

    Science.gov (United States)

    Fraccari, Raquel L.; Ciccarella, Pietro; Bahrami, Azadeh; Carminati, Marco; Ferrari, Giorgio; Albrecht, Tim

    2016-03-01

    We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface. Electronic supplementary information (ESI) available: Gel electrophoresis confirming lengths and purity of DNA samples, comparison between Axopatch 200B and custom-built setup, comprehensive low-noise amplifier characterization, representative I-V curves of nanopipettes used, typical scatter plots of τ vs. peak amplitude for the four LDNA's used, table of most probable τ values, a comparison between different fitting models for the DNA translocation time distribution, further details on the stochastic numerical simulation of the scaling statistics and the derivation of the extended

  20. Mast cells trigger epithelial barrier dysfunction, bacterial translocation and postoperative ileus in a mouse model

    NARCIS (Netherlands)

    Snoek, S. A.; Dhawan, S.; van Bree, S. H.; Cailotto, C.; van Diest, S. A.; Duarte, J. M.; Stanisor, O. I.; Hilbers, F. W.; Nijhuis, L.; Koeman, A.; van den Wijngaard, R. M.; Zuurbier, C. J.; Boeckxstaens, G. E.; de Jonge, W. J.

    2012-01-01

    Background Abdominal surgery involving bowel manipulation commonly results in inflammation of the bowel wall, which leads to impaired intestinal motility and postoperative ileus (POI). Mast cells have shown to play a key role in the pathogenesis of POI in mouse models and human studies. We studied

  1. Modulation of bacterial translocation in mice mediated through lactose and human milk oligosaccharides.

    Science.gov (United States)

    Mielcarek, C; Romond, P C; Romond, M B; Bezirtzoglou, E

    2011-12-01

    Massive resection of the small intestine in infants is imposed to the regulation of several intestinal pathological situations, as intestinal adaptation cannot be relied upon. Many nutritional disturbances are occurring following surgery procedure. In this vein, long-term parenteral feeding is adopt to improve prognosis not always successfully. Clostridia and more specifically Clostridium perfringens, are suspected to participate in the physiopathology of the rising situation. In order to investigate the effect of lactose and human milk neutral oligosaccharides (HMNOs) on Clostridia, germfree mice were inoculated either with enterotoxigenic C.perfringens strain isolated from a patient with NEC, or with a human microbiota harboring C.clostridioforme group(HF). In this vein, different doses of lactose were administrated during 2 weeks in adult mice on an attempt to evaluate the lactase activity. Intake of lactose (70 g/L) and HMNOs (7 g/L) in C.perfringens monoassociated mice induced mortality within a week. In HF mice, no mortality was observed. An increase in Clostridia occurrence was observed in the median ileum after intake of 7 g lactose (p = 0.017). Higher clostridial numbers occurred in caecum following intake of 70 g lactose (p drinking lower lactose concentrations. Finally, bacteremia was more frequent in 70 g lactose/L mice (p milk oligosaccharides could favor clostridial population when reaching the lower intestine. The shortness of the small intestine in infants underwent massive intestinal resection seems to be associated to an incomplete breakdown of lactose. Enteral feeds formulas deprived in lactose would be more suitable in enteral feeding of infants. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. Association of markers of bacterial translocation with immune activation in decompensated cirrhosis

    DEFF Research Database (Denmark)

    Mortensen, Christian; Jensen, Jørgen Skov; Hobolth, Lise

    2014-01-01

    to be a promising surrogate marker for BT, although its clinical relevance has been questioned. MATERIALS AND METHODS: In 38 cirrhotic patients with and without SBP, bDNA in blood and ascites were assessed by 16S rDNA quantitative PCR. Levels of lipopolysaccharide-binding protein in plasma and highly sensitive C......-reactive protein, tumour necrosis factor-α, soluble urokinase plasminogen activating receptor, interleukin-6, interleukin 8, interferon-γ inducible protein-10 and vascular endothelial growth factor in plasma and ascites were measured by multiplex cytokine and ELISA assays. RESULTS: In patients without signs of SBP...... or positive cultures, we found a high frequency of bDNA but low concordance of bDNA between blood and ascites. Markers of inflammation were not significantly different between blood bDNA-positive (22%), ascites bDNA-positive (52%), and bDNA-negative patients. The 16S rDNA PCR failed to show bDNA in two out...

  3. Investigation of the Mechanism That Powers DNA Translocation During Bacterial Natural Transformation

    OpenAIRE

    Foster, Hannah

    2016-01-01

    If deoxyribonucleic acids are the building blocks of life, perhaps the proteins that move, shape, and assemble nucleic acids should be called architects. These proteins come in every size and shape and have vastly different roles and mechanisms, but they share one thing in common: they help determine what life looks like by their interactions with DNA and RNA. Several of these protein architects play integral roles in the spread of genetic material among bacteria in natural transformation, th...

  4. Colonização e translocação bacteriana orofaríngea, gástrica e traqueal em crianças submetidas à ventilação pulmonar mecânica Colonización y translocación bacteriana orofaríngea, gástrica y traqueal en niños sometidos a ventilación pulmonar mecánica Oropharyngeal colonization, and gastric and tracheal bacterial translocation, in children experiencing mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Denise Miyuki Kusahara

    2012-01-01

    .aeruginosa, A. baumanii y S.aureus. La mayoría de los niños (80,0% sufrió translocación orofaríngea durante el internamiento en la UCIP. CONCLUSIÓN: los niños críticamente enfermos pueden representar un grupo de pacientes con riesgo aumentado para la colonización y translocación bacteriana con predominio de la región orofaríngea hacia la tráquea.OBJECTIVE: To describe the pattern of oropharyngeal colonization and bacterial translocation, gastric and tracheal, in children experiencing mechanical ventilation. METHODS: This descriptive study was conducted in a pediatric intensive care unit (PICU. Thirty children were recruited for the study, and 216 serial cultures were analyzed from oropharyngeal, gastric and tracheal secretions. Microbiological characteristics, demographic, clinical and treatment data were evaluated. RESULTS: Among those who participated in the gastric suctioning, there was a predominance of children with chronic diseases, for which antibiotics, sedatives and gastric protectors were used. There was an increase in the number of children colonized by pathogens during hospitalization, and there was a predominance of several species: Enterobacter spp, K.pneumoniae, P. aeruginosa, A. baumannii and S. aureus. The majority of children (80.0% experienced oropharyngeal translocation during hospitalization in the PICU. CONCLUSION: Critically ill children may represent a group of patients at increased risk for colonization and bacterial translocation, predominantly from the oropharyngeal region to the trachea.

  5. Prevention of Infective (Bacterial) Endocarditis: Wallet Card

    Science.gov (United States)

    ... placement of orthodontic brackets; and shedding of deciduous teeth and bleeding from trauma to the lips or oral mucosa. Antibiotic Prophylactic Regimens for Dental Procedures Situation Oral Unable to take oral medication ...

  6. Dissection of Axial-Pore Loop Function during Unfolding and Translocation by a AAA+ Proteolytic Machine

    Directory of Open Access Journals (Sweden)

    Ohad Iosefson

    2015-08-01

    Full Text Available In the axial channels of ClpX and related hexameric AAA+ protein-remodeling rings, the pore-1 loops are thought to play important roles in engaging, mechanically unfolding, and translocating protein substrates. How these loops perform these functions and whether they also prevent substrate dissociation to ensure processive degradation by AAA+ proteases are open questions. Using ClpX pore-1-loop variants, single-molecule force spectroscopy, and ensemble assays, we find that the six pore-1 loops function synchronously to grip and unfold protein substrates during a power stroke but are not important in preventing substrate slipping between power strokes. The importance of grip strength is task dependent. ClpX variants with multiple mutant pore-1 loops translocate substrates as well as the wild-type enzyme against a resisting force but show unfolding defects and a higher frequency of substrate release. These problems are magnified for more mechanically stable target proteins, supporting a threshold model of substrate gripping.

  7. The dynamic behavior of bacterial macrofibers growing with one end prevented from rotating: variation in shaft rotation along the fiber's length, and supercoil movement on a solid surface toward the constrained end

    Directory of Open Access Journals (Sweden)

    Chen Liling

    2003-08-01

    Full Text Available Abstract Background Bacterial macrofibers twist as they grow, writhe, supercoil and wind up into plectonemic structures (helical forms the individual filaments of which cannot be taken apart without unwinding that eventually carry loops at both of their ends. Terminal loops rotate about the axis of a fiber's shaft in contrary directions at increasing rate as the shaft elongates. Theory suggests that rotation rates should vary linearly along the length of a fiber ranging from maxima at the loop ends to zero at an intermediate point. Blocking rotation at one end of a fiber should lead to a single gradient: zero at the blocked end to maximum at the free end. We tested this conclusion by measuring directly the rotation at various distances along fiber length from the blocked end. The movement of supercoils over a solid surface was also measured in tethered macrofibers. Results Macrofibers that hung down from a floating wire inserted through a terminal loop grew vertically and produced small plectonemic structures by supercoiling along their length. Using these as markers for shaft rotation we observed a uniform gradient of initial rotation rates with slopes of 25.6°/min. mm. and 36.2°/min. mm. in two different fibers. Measurements of the distal tip rotation in a third fiber as a function of length showed increases proportional to increases in length with constant of proportionality 79.2 rad/mm. Another fiber tethered to the floor grew horizontally with a length-doubling time of 74 min, made contact periodically with the floor and supercoiled repeatedly. The supercoils moved over the floor toward the tether at approximately 0.06 mm/min, 4 times faster than the fiber growth rate. Over a period of 800 minutes the fiber grew to 23 mm in length and was entirely retracted back to the tether by a process involving 29 supercoils. Conclusions The rate at which growing bacterial macrofibers rotated about the axis of the fiber shaft measured at various

  8. [PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia].

    Science.gov (United States)

    Guerra-Castillo, Francisco Xavier; Ramos-Cervantes, María Teresa; Rosel-Pech, Cecilia; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina

    2016-01-01

    In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

  9. Electrostatics of polymer translocation events in electrolyte solutions.

    Science.gov (United States)

    Buyukdagli, Sahin; Ala-Nissila, T

    2016-07-07

    We develop an analytical theory that accounts for the image and surface charge interactions between a charged dielectric membrane and a DNA molecule translocating through the membrane. Translocation events through neutral carbon-based membranes are driven by a competition between the repulsive DNA-image-charge interactions and the attractive coupling between the DNA segments on the trans and the cis sides of the membrane. The latter effect is induced by the reduction of the coupling by the dielectric membrane. In strong salt solutions where the repulsive image-charge effects dominate the attractive trans-cis coupling, the DNA molecule encounters a translocation barrier of ≈10 kBT. In dilute electrolytes, the trans-cis coupling takes over image-charge forces and the membrane becomes a metastable attraction point that can trap translocating polymers over long time intervals. This mechanism can be used in translocation experiments in order to control DNA motion by tuning the salt concentration of the solution.

  10. A somatic origin of homologous Robertsonian translocations and isochromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. (Univ. of Zurich (Switzerland)); Basaran, S.; Yueksel-Apak, M. (Univ. of Istanbul (Turkey)); Neri, G. (Universita Cattolica, Rome (Italy)); Serville, F. (Hopital d' Enfants Pellegrin, Bordeaux (France)); Balicek, P.; Haluza, R. (Univ. Hospital of Hradeck Kralove, Hradec Kralove (Czech Republic)); Farah, L.M.S. (Escuola Paulista de Medicina, Sao Paulo (Brazil)) (and others)

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  11. Bacterial contamination of blood products.

    Science.gov (United States)

    Palavecino, Elizabeth; Jacobs, Michael; Yomtovian, Roslyn

    2004-11-01

    The occurrence of a septic reaction resulting from bacterial contamination of blood products, particularly with room-temperature stored platelets, is the most common transfusion-associated infectious risk in the United States. Bacterial contamination of blood products was first identified more than 60 years ago; yet, strategies to resolve this problem have proved daunting despite ongoing awareness and increasing concern especially in the last few years. With the recent US Food and Drug Administration (FDA) approval of culture methods for quality control testing of platelet units and the promulgation of accreditation standards by the College of American Pathologists and American Association of Blood Banks to detect bacterially contaminated platelet units and to prevent transfusion of these units, blood banks and transfusion services have finally started to address this problem, in a more standardized manner. Furthermore, as new methods of interdicting, inactivating and detecting bacterially contaminated blood products emerge, it is hoped that the problem of bacterial contamination of blood products will be overcome.

  12. Integration of enteric fever surveillance into the WHO-coordinated Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) platform: A low cost approach to track an increasingly important disease.

    Science.gov (United States)

    Saha, Senjuti; Islam, Maksuda; Uddin, Mohammad J; Saha, Shampa; Das, Rajib C; Baqui, Abdullah H; Santosham, Mathuram; Black, Robert E; Luby, Stephen P; Saha, Samir K

    2017-10-01

    Lack of surveillance systems and accurate data impede evidence-based decisions on treatment and prevention of enteric fever, caused by Salmonella Typhi/Paratyphi. The WHO coordinates a global Invasive Bacterial-Vaccine Preventable Diseases (IB-VPD) surveillance network but does not monitor enteric fever. We evaluated the feasibility and sustainability of integrating enteric fever surveillance into the ongoing IB-VPD platform. The IB-VPD surveillance system uses WHO definitions to enroll 2-59 month children hospitalized with possible pneumonia, sepsis or meningitis. We expanded this surveillance system to additionally capture suspect enteric fever cases during 2012-2016, in two WHO sentinel hospitals of Bangladesh, by adding inclusion criteria of fever ≥102°F for ≥3 days, irrespective of other manifestations. Culture-positive enteric fever cases from in-patient departments (IPD) detected in the hospital laboratories but missed by the expanded surveillance, were also enrolled to assess completion. Costs for this integration were calculated for the additional personnel and resources required. In the IB-VPD surveillance, 5,185 cases were enrolled; 3% (N = 171/5185) were positive for microbiological growth, of which 55% (94/171) were culture-confirmed cases of enteric fever (85 Typhi and 9 Paratyphi A). The added inclusion criteria for enteric fever enrolled an additional 1,699 cases; 22% (358/1699) were positive, of which 85% (349/358) were enteric fever cases (305 Typhi and 44 Paratyphi A). Laboratory surveillance of in-patients of all ages enrolled 311 additional enteric fever cases (263 Typhi and 48 Paratyphi A); 9% (28/311) were 2-59 m and 91% (283/311) >59 m. Altogether, 754 (94+349+311) culture-confirmed enteric fever cases were found, of which 471 were 2-59 m. Of these 471 cases, 94% (443/471) were identified through the hospital surveillances and 6% (28/471) through laboratory results. Twenty-three percent (170/754) of all cases were children surveillance

  13. Bacterial proteases and virulence

    DEFF Research Database (Denmark)

    Frees, Dorte; Brøndsted, Lone; Ingmer, Hanne

    2013-01-01

    with the proteases either encoded within the same polypeptide or on separate subunits. In contrast, substrate recognition by extracellular proteases is less selective and therefore these enzymes are generally expressed as zymogens to prevent premature proteolytic activity that would be detrimental to the cell......Bacterial pathogens rely on proteolysis for variety of purposes during the infection process. In the cytosol, the main proteolytic players are the conserved Clp and Lon proteases that directly contribute to virulence through the timely degradation of virulence regulators and indirectly by providing...... signalling to short-circuit host cell processes. Common to both intra- and extracellular proteases is the tight control of their proteolytic activities. In general, substrate recognition by the intracellular proteases is highly selective which is, in part, attributed to the chaperone activity associated...

  14. Translocation of polymers into crowded media with dynamic attractive nanoparticles.

    Science.gov (United States)

    Cao, Wei-Ping; Ren, Qing-Bao; Luo, Meng-Bo

    2015-07-01

    The translocation of polymers through a small pore into crowded media with dynamic attractive nanoparticles is simulated. Results show that the nanoparticles at the trans side can affect the translocation by influencing the free-energy landscape and the diffusion of polymers. Thus the translocation time τ is dependent on the polymer-nanoparticle attraction strength ɛ and the mobility of nanoparticles V. We observe a power-law relation of τ with V, but the exponent is dependent on ɛ and nanoparticle concentration. In addition, we find that the effect of attractive dynamic nanoparticles on the dynamics of polymers is dependent on the time scale. At a short time scale, subnormal diffusion is observed at strong attraction and the diffusion is slowed down by the dynamic nanoparticles. However, the diffusion of polymers is normal at a long time scale and the diffusion constant increases with the increase in V.

  15. Translocation techniques used to establish pen farmed Alaskan reindeer

    Directory of Open Access Journals (Sweden)

    R. A. Dieterich

    1990-09-01

    Full Text Available Small herds of reindeer (Rangifer tarandus frequently have been needed to be established in fenced holding pens for research or commercial reasons in Alaska and other areas. Native ranges of reindeer in Alaska were not on road systems, and the diet of the native reindeer had to be changed when they were translocated to small pens. Economics of transportation and feeding played an important role in the feasibility of translocation. Gathering and holding of reindeer for shipment, transport methods, adjustment of free-ranging reindeer to confinement, and a new diet were primary considerations to insure survival. Minimal psychologic stress of short duration, thermoregulation, and physical comfort were extremely important in carrying out a successful translocation. Receiving facilities, feed, and personnel were equally important. A minimum of one month was required to adjust reindeer to confinement and diet change.

  16. Role for FimH in Extraintestinal Pathogenic Escherichia coli Invasion and Translocation through the Intestinal Epithelium.

    Science.gov (United States)

    Poole, Nina M; Green, Sabrina I; Rajan, Anubama; Vela, Luz E; Zeng, Xi-Lei; Estes, Mary K; Maresso, Anthony W

    2017-11-01

    The translocation of bacteria across the intestinal epithelium of immunocompromised patients can lead to bacteremia and life-threatening sepsis. Extraintestinal pathogenic Escherichia coli (ExPEC), so named because this pathotype infects tissues distal to the intestinal tract, is a frequent cause of such infections, is often multidrug resistant, and chronically colonizes a sizable portion of the healthy population. Although several virulence factors and their roles in pathogenesis are well described for ExPEC strains that cause urinary tract infections and meningitis, they have not been linked to translocation through intestinal barriers, a fundamentally distant yet important clinical phenomenon. Using untransformed ex situ human intestinal enteroids and transformed Caco-2 cells, we report that ExPEC strain CP9 binds to and invades the intestinal epithelium. ExPEC harboring a deletion of the gene encoding the mannose-binding type 1 pilus tip protein FimH demonstrated reduced binding and invasion compared to strains lacking known E. coli virulence factors. Furthermore, in a murine model of chemotherapy-induced translocation, ExPEC lacking fimH colonized at levels comparable to that of the wild type but demonstrated a statistically significant reduction in translocation to the kidneys, spleen, and lungs. Collectively, this study indicates that FimH is important for ExPEC translocation, suggesting that the type 1 pilus is a therapeutic target for the prevention of this process. Our study also highlights the use of human intestinal enteroids in the study of enteric diseases. Copyright © 2017 American Society for Microbiology.

  17. The action spectrum in chloroplast translocation in multilayer leaf cells

    Directory of Open Access Journals (Sweden)

    Zbigniew Lechowski

    2015-01-01

    Full Text Available By measurement of light transmittance through a leaf as criterion of chloroplast translocation, the action spectrum of Ajuga reptans was established. In the spectrum obtained, a correction was introduced for leaf autoabsorption calculated on the basis of the Beer-Lambert law. The action spectrum has two maxima: at λ= 375 nm and λ= 481 nm. The range above 502 nm has no significant effect on chloroplast translocation. Comparison with other objects examined demonstrated that in multilayer leaf cells riboflavin seems also to be a photoreceptor active in this process.

  18. Free energy evaluation in polymer translocation via Jarzynski equality

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe, E-mail: fmondaini@if.ufrj.br [Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, Petrópolis, 25.620-003, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970, Rio de Janeiro, RJ (Brazil)

    2014-05-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations, which provide free energy estimates for unbiased three-dimensional polymer translocation. We employ the Jarzynski equality in its rigorous setting, to compute the variation of the free energy in single monomer translocation events. In our three-dimensional Langevin simulations, the excluded-volume and van der Waals interactions between beads (monomers and membrane atoms) are modeled through a repulsive Lennard-Jones (LJ) potential and consecutive monomers are subject to the Finite-Extension Nonlinear Elastic (FENE) potential. Analysing data for polymers with different lengths, the free energy profile is noted to have interesting finite-size scaling properties.

  19. Centrifugally driven microfluidic disc for detection of chromosomal translocations

    DEFF Research Database (Denmark)

    Brøgger, Anna Line; Kwasny, Dorota; Bosco, Filippo G.

    2012-01-01

    and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control...... and detection chambers. The burst frequencies of the two capillary burst microvalves are separated by 180 rpm enabling precise control of hybridization in each of the chambers. The DNA probes targeting a translocation are immobilized directly on PMMA by a UV-activated procedure, which is compatible...

  20. Role of non-equilibrium conformations on driven polymer translocation.

    Science.gov (United States)

    Katkar, H H; Muthukumar, M

    2018-01-14

    One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/N K , is longer than the relaxation time τ 0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations. We have studied the role of initial conformations of a polyelectrolyte chain (which were artificially generated with a flow field) on the kinetics of its translocation across a nanopore under the action of an externally applied transmembrane voltage V (in the absence of the initial flow field). Stretched (out-of-equilibrium) polyelectrolyte chain conformations are deliberately and systematically generated and used as initial conformations in translocation simulations. Independent simulations are performed to study the relaxation behavior of these stretched chains, and a comparison is made between the relaxation time scale and the mean translocation time (⟨τ⟩). For such artificially stretched initial states, ⟨τ⟩/N K equilibrium approximation. Nevertheless, we observe a scaling of ⟨τ⟩ ∼ 1/V over the entire range of chain stretching studied, in agreement with the predictions of the Fokker-Planck model. On the other hand, for realistic situations where the initial artificially imposed flow field is absent, a comparison of experimental data reported in the literature with the theory of polyelectrolyte dynamics reveals that the Zimm relaxation time (τ Zimm ) is shorter than the mean translocation time for several polymers including single stranded DNA (ssDNA), double stranded DNA (dsDNA), and synthetic polymers. Even when these data are rescaled

  1. "Understanding Adam" multiple reciprocal translocations: complex case presentation.

    Science.gov (United States)

    Linder, Carie E; Lu, Xianglan; Kim, Young Mi; Li, Shibo; Pineda, Jose

    2009-01-01

    This article presents a case review of a newborn diagnosed with a complex chromosomal rearrangement, as demonstrated through a painted chromosomal analysis. This infant presented with multiple dysmorphology including cutis aplasia, multiple ocular malformations, bilateral cleft lip and palate, and postnatal hydrocephaly. A chromosomal analysis revealed multiple-ways, balanced translocation involving chromosomes 3, 4, 6, 8, and 9. This case study provides a unique opportunity to, in retrospect, trace each malformation exploring the pathophysiology, etiology, and correlating origin with chromosomal variation. Careful review of this case, enhanced by the visually augmented representation of each translocation, will increase understanding of chromosomal anomalies and their implications in embryological development and clinical presentation.

  2. BipC, a Predicted Burkholderia pseudomallei Type 3 Secretion System Translocator Protein with Actin Binding Activity

    Directory of Open Access Journals (Sweden)

    Charles W. Vander Broek

    2017-07-01

    Full Text Available Burkholderia pseudomallei is an intracellular bacterial pathogen and the causative agent of melioidosis, a severe disease of humans and animals. Like other clinically important Gram-negative bacteria, fundamental to B. pseudomallei pathogenesis is the Bsa Type III Secretion System. The Bsa system injects bacterial effector proteins into the cytoplasm of target host cells subverting cellular pathways for the benefit of the bacteria. It is required for invasion of non-phagocytic host cells, escape from the endocytic compartment into the host cell cytoplasm, and for virulence in murine models of melioidosis. We have recently described the repertoire of effector proteins secreted by the B. pseudomallei Bsa system, however the functions of many of these effector proteins remain an enigma. One such protein is BipC, a homolog of the translocator/effector proteins SipC and IpaC from Salmonella spp. and Shigella flexneri respectively. SipC and IpaC each have separate and distinct roles acting both as translocators, involved in creating a pore in the eukaryotic cell membrane through which effector proteins can transit, and as effectors by interacting with and polymerizing host cell actin. In this study, pull-down assays demonstrate an interaction between BipC and actin. Furthermore, we show that BipC directly interacts with actin, preferentially with actin polymers (F-actin and has the ability to polymerize actin in a similar manner as that described for SipC. Yet unlike SipC, BipC does not stabilize F-actin filaments, indicating a functionally distinct interaction with actin. Expression of Myc-tagged BipC in HeLa cells induces the formation of pseudopodia similar to that seen for IpaC. This study explores the effector function of BipC and reveals that actin interaction is conserved within the BipC/SipC/IpaC family of translocator/effector proteins.

  3. Cytosolic Access of Intracellular Bacterial Pathogens: The Shigella Paradigm.

    Science.gov (United States)

    Mellouk, Nora; Enninga, Jost

    2016-01-01

    Shigella is a Gram-negative bacterial pathogen, which causes bacillary dysentery in humans. A crucial step of Shigella infection is its invasion of epithelial cells. Using a type III secretion system, Shigella injects several bacterial effectors ultimately leading to bacterial internalization within a vacuole. Then, Shigella escapes rapidly from the vacuole, it replicates within the cytosol and spreads from cell-to-cell. The molecular mechanism of vacuolar rupture used by Shigella has been studied in some detail during the recent years and new paradigms are emerging about the underlying molecular events. For decades, bacterial effector proteins were portrayed as main actors inducing vacuolar rupture. This includes the effector/translocators IpaB and IpaC. More recently, this has been challenged and an implication of the host cell in the process of vacuolar rupture has been put forward. This includes the bacterial subversion of host trafficking regulators, such as the Rab GTPase Rab11. The involvement of the host in determining bacterial vacuolar integrity has also been found for other bacterial pathogens, particularly for Salmonella. Here, we will discuss our current view of host factor and pathogen effector implications during Shigella vacuolar rupture and the steps leading to it.

  4. Cytosolic access of intracellular bacterial pathogens: the Shigella paradigm

    Directory of Open Access Journals (Sweden)

    Nora eMellouk

    2016-04-01

    Full Text Available Shigella is a Gram-negative bacterial pathogen, which causes bacillary dysentery in humans. A crucial step of Shigella infection is its invasion of epithelial cells. Using a type III secretion system, Shigella injects several bacterial effectors ultimately leading to bacterial internalization within a vacuole. Then, Shigella escapes rapidly from the vacuole, it replicates within the cytosol and spreads from cell-to-cell. The molecular mechanism of vacuolar rupture used by Shigella has been studied in some detail during the recent years and new paradigms are emerging about the underlying molecular events. For decades, bacterial effector proteins were portrayed as main actors inducing vacuolar rupture. This includes the effector/translocators IpaB and IpaC. More recently, this has been challenged and an implication of the host cell in the process of vacuolar rupture has been put forward. This includes the bacterial subversion of host trafficking regulators, such as the Rab GTPase Rab11. The involvement of the host in determining bacterial vacuolar integrity has also been found for other bacterial pathogens, particularly for Salmonella. Here, we will discuss our current view of host factor and pathogen effector implications during Shigella vacuolar rupture and the steps leading to it.

  5. Bacterial leaching of uranium ores - a review

    International Nuclear Information System (INIS)

    Lowson, R.T.

    1975-11-01

    The bacterial leaching of uranium ores involves the bacterially catalysed oxidation of associated pyrite to sulphuric acid and Fe 3+ by autotrophic bacteria and the leaching of the uranium by the resulting acidic, oxidising solution. Industrial application has been limited to Thiobacillus thiooxidans and Thiobacillus ferrooxidans at pH 2 to 3, and examples of these are described. The bacterial catalysis can be improved with nutrients or prevented with poisons. The kinetics of leaching are controlled by the bed depth, particle size, percolation rate, mineralogy and temperature. Current work is aimed at quantitatively defining the parameters controlling the kinetics and extending the method to alkaline conditions with other autotrophic bacteria. (author)

  6. DNA translocating through a carbon nanotube can increase ionic current

    International Nuclear Information System (INIS)

    Park, Jae Hyun; Krstić, Predrag S; He Jin; Gyarfas, Brett; Lindsay, Stuart

    2012-01-01

    Translocation of DNA through a narrow, single-walled carbon nanotube can be accompanied by large increases in ion current, recently observed in contrast to the ion current blockade. We use molecular dynamics simulations to show that large electro-osmotic flow can be turned into a large net current via ion-selective filtering by a DNA molecule inside the carbon nanotube. (paper)

  7. Selective bowel decontamination results in gram-positive translocation.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Rowe, M I

    1990-05-01

    Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

  8. The human minisatellite consensus at breakpoints of oncogene translocations

    Energy Technology Data Exchange (ETDEWEB)

    Krowczynska, A.; Krontiris, T.G. (New England Medical Center Hospitals, Boston, MA (United States) Tufts Univ. School of Medicine, Boston, MA (United States)); Rudders, R.A. (New England Medical Center Hospitals, Boston, MA (United States))

    1990-03-11

    A reexamination of human minisatellite (hypervariable) regions following the cloning and sequencing of the new minisatellite, VTR1. 1, revealed that many of these structures possessed a strongly conserved copy of the chi-like octamer, GC(A/T)GG(A/T)GG. In oncogene translocations apparently created by aberrant VDJ recombinase activity, this VTR octamer was often found within a few bases of the breakpoint. Three bcl2 rearrangements which occurred within 2 bp of one another were located precisely adjacent to this consensus; it defined the 5{prime} border of that oncogene's major breakpoint cluster. Several c-myc translocations also occurred within 2 bp of this sequence. While the appearance of a chi-like element in polymorphic minisatellite sequences is consistent with a role promoting either recombination or replication slippage, the existence of such elements at sites of somatic translocations suggests chi function in site-specific recombination, perhaps as a subsidiary recognition signal in immunoglobulin gene rearrangement. The authors discuss the implications of these observations for mechanisms by which oncogene translocations and minisatellite sequences are generated.

  9. Resource Control: A Translocation Of The Scramble For Africa ...

    African Journals Online (AJOL)

    Adopting a theoretical framework successfully adapted from the biological and medical sciences, namely; translocation analysis, the paper traces the ancestry of the present resource control problem to the scramble, first, and then, the use of fiscal and revenue allocation commissions during the colonial era, and the ...

  10. Evaluation of cadmium bioaccumulation and translocation by Hopea ...

    African Journals Online (AJOL)

    parisa

    2012-04-10

    Apr 10, 2012 ... species selected as phytoremediator, three indicators were used namely, bioconcentration factor (BCF, the metal concentration ratio of plant roots to soil), translocation factor (TF, the metal concentration ratio of plant shoots to ... centration of Cd in soil ranges from 0.01 to 2.0 mg kg-1; however, in urban and ...

  11. Concentration Polarization in Translocation of DNA through Nanopores and Nanochannels

    NARCIS (Netherlands)

    Das, S.; Dubsky, P.; van den Berg, Albert; Eijkel, Jan C.T.

    2012-01-01

    In this Letter we provide a theory to show that high-field electrokinetic translocation of DNA through nanopores or nanochannels causes large transient variations of the ionic concentrations in front and at the back of the DNA due to concentration polarization (CP). The CP causes strong local

  12. Introduction: translocal development, development corridors and development chains.

    NARCIS (Netherlands)

    Zoomers, E.B.; Westen, A.C.M. van

    2011-01-01

    This paper offers an introduction to this Special Issue of International Development Planning Review. It uses the concepts of translocal development, development corridors and development chains to secure a better grasp of what development means in the context of globalisation and how ‘local

  13. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  14. Black Rhino Translocations within Africa | Knight | Africa Insight

    African Journals Online (AJOL)

    The responsibility for the conservation of the critically endangered Black Rhinoceros, Diceros bicornis, lies within Africa. This species is managed at the subspecies level and we document nine international translocation case studies involving South Africa since 1962 aimed at re-establishing or boosting populations ...

  15. Bladder calculus resulting from an intravesical translocation of ...

    African Journals Online (AJOL)

    Although perforation of the uterus by an intrauterine contraceptive device (IUCD) is commonly encountered, intravesical translocation and secondary calculus formation is a very rare complication.We report a case of a 60-year old multiparous woman in whom an intrauterine contraceptive Copper-T device inserted 12 years ...

  16. Translocation of radioactive paraquat in some veld grasses | TD ...

    African Journals Online (AJOL)

    In two pot experiments radioactive paraquat was applied to certain important veld grasses (Experiment I-Aristida junciformis, Themeda triandra, Elyonuris argenteus, Andropogon filifolius, Eragrostis curvula; Experiment II-A. junciformis, E. argenteus) to determine the extent of translocation at a young stage of growth with ...

  17. The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

    Directory of Open Access Journals (Sweden)

    Belinda S Hall

    2014-04-01

    Full Text Available Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate

  18. Transcuticular translocation of radionuclides on plant leaf surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Ken-ichi; Watanabe, Tadakazu; Ambe, Shizuko; Yamaguchi, Isamu [Institute of Physical and Chemical Research, Wako, Saitama (Japan)

    1996-12-31

    The cuticle covering all the outermost surfaces of the aerial parts of plants could play a selective role in uptake and translocation of radionuclides from air into plants. In this study, we investigated the transcuticular uptake and translocation behavior via water droplets of various radionuclides in red clover, orchard grass, Japanese radish and mung bean. Ten {mu}l of an aqueous solution of the multitracer generated from Au was applied to the upper surface of the 2nd leaf of the plants at the 5th leaf stage. The plants were then grown for 14 days at 25degC and 70% RH under illumination of artificial solar lights. The transcuticular uptake and translocation throughout the plant were periodically assayed by determining the radioactivity in the surface residue, the cuticle layer beneath the applied site, the leaf area outside the applied site, the other aerial parts and the root of the plant, using an HPGe detector. The applied radionuclides were absorbed into, in turn, the cuticle layer beneath the applied site and then translocated through the cuticle to the inner tissue and eventually to the other aerial parts and finally to the roots, of the plant. The distribution and accumulation in the plant seems to depend upon the characteristics of each radionuclide and plant species. Ca{sup *} and Te{sup *} tended to remain on leaf surfaces without being absorbed into the cuticle. On the other hand, Sc{sup *}, Co{sup *}, Zn{sup *}, Se{sup *}, Rb{sup *}, and Eu{sup *} were easily absorbed and translocated to every part of the plant including the root. The other radionuclides such as Be{sup *}, Mn{sup *}, Sr{sup *}, Y{sup *}, Ba{sup *}, Ce{sup *}, Pm{sup *}, Gd{sup *}, Hf{sup *}, Yb{sup *}, Lu{sup *}, Os{sup *}, Ir{sup *}, and Pt{sup *} remained in the region close to the site of their application. The above results possibly indicate the existence of mechanisms common to these plants for selective transcuticular uptake and translocation of radionuclides within plant

  19. Acute Ethanol Intake Induces NAD(PH Oxidase Activation and Rhoa Translocation in Resistance Arteries

    Directory of Open Access Journals (Sweden)

    Janaina A. Simplicio

    Full Text Available Abstract Background: The mechanism underlying the vascular dysfunction induced by ethanol is not totally understood. Identification of biochemical/molecular mechanisms that could explain such effects is warranted. Objective: To investigate whether acute ethanol intake activates the vascular RhoA/Rho kinase pathway in resistance arteries and the role of NAD(PH oxidase-derived reactive oxygen species (ROS on such response. We also evaluated the requirement of p47phox translocation for ethanol-induced NAD(PH oxidase activation. Methods: Male Wistar rats were orally treated with ethanol (1g/kg, p.o. gavage or water (control. Some rats were treated with vitamin C (250 mg/kg, p.o. gavage, 5 days before administration of water or ethanol. The mesenteric arterial bed (MAB was collected 30 min after ethanol administration. Results: Vitamin C prevented ethanol-induced increase in superoxide anion (O2- generation and lipoperoxidation in the MAB. Catalase and superoxide dismutase activities and the reduced glutathione, nitrate and hydrogen peroxide (H2O2 levels were not affected by ethanol. Vitamin C and 4-methylpyrazole prevented the increase on O2- generation induced by ethanol in cultured MAB vascular smooth muscle cells. Ethanol had no effect on phosphorylation levels of protein kinase B (Akt and eNOS (Ser1177 or Thr495 residues or MAB vascular reactivity. Vitamin C prevented ethanol-induced increase in the membrane: cytosol fraction ratio of p47phox and RhoA expression in the rat MAB. Conclusion: Acute ethanol intake induces activation of the RhoA/Rho kinase pathway by a mechanism that involves ROS generation. In resistance arteries, ethanol activates NAD(PH oxidase by inducing p47phox translocation by a redox-sensitive mechanism.

  20. Post-translational Mechanisms of Host Subversion by Bacterial Effectors.

    Science.gov (United States)

    Scott, Nichollas E; Hartland, Elizabeth L

    2017-12-01

    Bacterial effector proteins are a specialized class of secreted proteins that are translocated directly into the host cytoplasm by bacterial pathogens. Effector proteins have diverse activities and targets, and many mediate post-translational modifications of host proteins. Effector proteins offer potential in novel biotechnological and medical applications as enzymes that may modify human proteins. Here, we discuss the mechanisms used by effectors to subvert the human host through blocking, blunting, or subverting immune mechanisms. This capacity allows bacteria to control host cell function to support pathogen survival, replication and dissemination to other hosts. In addition, we highlight that knowledge of effector protein activity may be used to develop chemical inhibitors as a new approach to treat bacterial infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. RNase A does not translocate the alpha-hemolysin pore.

    Directory of Open Access Journals (Sweden)

    Besnik Krasniqi

    Full Text Available The application of nanopore sensing utilizing the α-hemolysin pore to probe proteins at single-molecule resolution has expanded rapidly. In some studies protein translocation through the α-hemolysin has been reported. However, there is no direct evidence, as yet, that proteins can translocate the α-hemolysin pore. The biggest challenge to obtaining direct evidence is the lack of a highly sensitive assay to detect very low numbers of protein molecules. Furthermore, if an activity based assay is applied then the proteins translocating by unfolding should refold back to an active confirmation for the assay technique to work. To overcome these challenges we selected a model enzyme, ribonuclease A, that readily refolds to an active conformation even after unfolding it with denaturants. In addition we have developed a highly sensitive reverse transcription polymerase chain reaction based activity assay for ribonuclease A. Initially, ribonuclease A, a protein with a positive net charge and dimensions larger than the smallest diameter of the pore, was subjected to nanopore analysis under different experimental conditions. Surprisingly, although the protein was added to the cis chamber (grounded and a positive potential was applied, the interaction of ribonuclease A with α-hemolysin pore induced small and large blockade events in the presence and the absence of a reducing and/or denaturing agent. Upon measuring the zeta potential, it was found that the protein undergoes a charge reversal under the experimental conditions used for nanopore sensing. From the investigation of the effect of voltage on the interaction of ribonuclease A with the α-hemolysin pore, it was impossible to conclude if the events observed were translocations. However, upon testing for ribonuclease A activity on the trans chamber it was found that ribonuclease A does not translocate the α-hemolysin pore.

  3. Biosecurity for Translocations: Cirl Bunting (Emberiza cirlus), Fisher's Estuarine Moth (Gortyna borelii lunata), Short-Haired Bumblebee (Bombus subterraneus) and Pool Frog (Pelophylax lessonae) Translocations as Case Studies.

    Science.gov (United States)

    Vaughan-Higgins, R J; Masters, N; Sainsbury, A W

    2017-03-01

    Exposure to parasites in conservation translocations increases the risks to recipient and translocated populations from disease, and therefore there has been interest in implementing biosecurity methods. Using four case examples we described how biosecurity was applied in practical translocation scenarios prior to and during a translocation and also post-release. We implemented biosecurity, including quarantine barriers, at specific points in the translocation pathway where hazards, identified by the disease risk analysis, had the potential to induce disease. Evidence that biosecurity protected translocated and recipient populations, included an absence of mortality associated with high-risk non-native parasites, a reduction in mortality associated with endemic parasites, the absence of high-risk pathogenic parasites, or associated diseases, at the destination; and the apparent absence of diseases in closely related species at the destination site. The biosecurity protocols did not alter the level or duration of translocated species confinement and therefore probably did not act as a stressor. There is a monetary cost involved in biosecurity but the epidemiological evidence suggests that conservation translocation managers should carefully consider its use. Breakdowns in quarantine have occurred in human hospitals despite considerable investment and training for health professionals, and we therefore judge that there is a need for training in the objectives and maintenance of quarantine barriers in conservation translocations. Biosecurity protocols for conservation translocations should be continually updated in response to findings from disease risk analysis and post-release disease surveillance and we recommend further studies to evaluate their effectiveness.

  4. Short communication: Evidence that microbial translocation occurs in HIV-infected children in the United Kingdom.

    Science.gov (United States)

    Fitzgerald, Felicity; Harris, Kathryn; Doyle, Ronan; Alber, Dagmar; Klein, Nigel

    2013-12-01

    Microbial translocation (MT) from the gut is implicated in driving immune activation, increasing morbidity and mortality in HIV. We used bacterial 16S rDNA PCR, Sanger sequencing, and high-throughput sequencing to identify microbial DNA in the bloodstream of HIV-infected children in London, United Kingdom. Blood samples were collected from sequential children attending the HIV clinic at Great Ormond Street Hospital, London. DNA extraction, broad range 16S rDNA PCR, and standard Sanger sequencing were carried out. A subset of positive samples was analyzed by high-throughput sequencing (Roche 454 platform). Of 105 samples collected from sequential children, nine were positive using broad range 16S rDNA PCR (8.6%; 95% CI 4.4-16%). From three amplicons, 16S rDNA sequences were identified as Streptococcus, Propionibacterium acnes, and coagulase-negative Staphylococcus. Four positive samples were analyzed by high-throughput sequencing. In the three samples in which organisms were identified by Sanger sequencing, the same species were identified. Further species, in differing proportions, were identified in all four samples. The identified organisms included known gut orders Bifidobacteriaceae, Lactobacillaceae, Bacteroidales, and Clostridiales. In immunocompetent children of equivalent age, no bacterial DNA was detected in blood using this approach. This is the first study to our knowledge using molecular techniques to identify MT in children in the developed world. Our data indicate that 16S rDNA is detectable in 8.6% of HIV-infected children. Levels of DNA were low and from multiple bacterial species. Further studies are needed to ascertain the importance of MT in HIV-infected children.

  5. Atlas of alien and translocated indigenous aquatic animals in southern Africa

    CSIR Research Space (South Africa)

    De Moor, IJ

    1988-01-01

    Full Text Available This report serves as an introduction to the problem of alien and translocated aquatic animals in southern Africa is given followed by checklists of the different species which have been introduced into or translocated within the subcontinent...

  6. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

    Science.gov (United States)

    2012-01-01

    Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Conclusions Both the function of HB-EGF as an EGFR ligand

  7. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Karin Kaereby; Pedersen, Maria; Trøseid, Marius

    2013-01-01

    Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.......Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals....

  8. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    NARCIS (Netherlands)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. It is generally accepted that, when no chromosomal rearrangements are involved, man

  9. Protein translocation across the endoplasmic reticulum membrane in cold-adapted organisms

    NARCIS (Netherlands)

    Römisch, Karin; Collie, Nicola; Soto, Nelyn; Logue, James; Lindsay, Margaret; Scheper, Wiep; Cheng, Chi-Hing C.

    2003-01-01

    Secretory proteins enter the secretory pathway by translocation across the membrane of the endoplasmic reticulum (ER) via a channel formed primarily by the Sec61 protein. Protein translocation is highly temperature dependent in mesophilic organisms. We asked whether the protein translocation

  10. Translocation as a conservation tool for Agassiz's desert tortoises: Survivorship, reproduction, and movements

    Science.gov (United States)

    K. E. Nussear; C. R. Tracy; P. A. Medica; D. S. Wilson; R. W. Marlow; P. S. Corn

    2012-01-01

    We translocated 120 Agassiz's desert tortoises to 5 sites in Nevada and Utah to evaluate the effects of translocation on tortoise survivorship, reproduction, and habitat use. Translocation sites included several elevations, and extended to sites with vegetation assemblages not typically associated with desert tortoises in order to explore the possibility of moving...

  11. The Use of Double-Monotelodisomics to Identify Translocations in Triticum aestivum

    DEFF Research Database (Denmark)

    Linde-Laursen, Ib; Larsen, J.

    1974-01-01

    By analysing metaphase I of double-monotelodisomic hybrids between two varieties of hexaploid wheat differentiated by reciprocal translocations it is possible to establish reliably the chromosomes involved in each translocation. Also the chromosome parts translocated may be identified. The use...

  12. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Science.gov (United States)

    2010-07-01

    ... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable translocation test in Drosophila measures the induction of chromosomal translocations in germ cells of insects...

  13. Dek-can rearrangement in translocation (6;9)(p23;q34)

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; van der Plas, D. C.; Selleri, L.; Bartram, C. R.; Martiat, P.; Culligan, D.; Padua, R. A.; Hasper-Voogt, K. P.; Hagemeijer, A.

    1992-01-01

    The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated

  14. [Lactobacillus rhamnosus GG conditioned medium prevents E. coli meningitis by inhibiting nuclear factor-κB pathway].

    Science.gov (United States)

    Zeng, Qing; He, Xiao-Long; Xiao, Han-Sheng; DU, Lei; Li, Yu-Jing; Chen, Le-Cheng; Tian, Hui-Wen; Huang, Sheng-He; Cao, Hong

    2017-01-20

    To investigate whether Lactobacillus rhamnosus GG conditioned medium(LGG-CM)has preventive effect against E. coli K1-induced neuropathogenicity in vitro by inhibiting nuclear factor-κB (NF-κB) signaling pathway. An in vitro blood-brain barrier (BBB) model was constructed using human brain microvascular endothelial cells (HBMECs). The effect of LGG-CM on E. coli-actived NF-κB signaling pathway was assayed using Western blotting. Invasion assay and polymorphonuclear leukocyte (PMN) transmigration assay were performed to explore whether LGG-CM could inhibit E. coli invasion and PMN transmigration across the BBB in vitro. The expressions of ZO-1 and CD44 were detected using Western blotting and immunofluorescence. The changes of trans-epithelial electric resistance (TEER) and bacterial translocation were determined to evaluate the BBB permeability. Pre-treament with LGG-CM inhibited E. coli-activated NF-κB signaling pathway in HBMECs and decreased the invasion of E. coli K1 and transmigration of PMN. Western blotting showed that LGG-CM could alleviate E. coli-induced up-regulation of CD44 and down-regulation of ZO-1 expressions in HBMECs. In addition, pre-treatment with LGG-CM alleviated E. coli K1-induced reduction of TEER and suppressed bacterial translocation across the BBB in vitro. LGG-CM can block E. coli-induced activation of NF-κB signaling pathway and thereby prevents E. coli K1-induced neuropathogenicity by decreasing E. coli K1 invasion rates and PMN transmigration.

  15. Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents.

    Science.gov (United States)

    Christmann, M; Kaina, B

    2000-11-17

    Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gene activity. Cells expressing the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT), thus having the ability to repair O(6)-methylguanine, showed no translocation of MutSalpha, whereas inhibition of MGMT by O(6)-benzylguanine provoked the translocation. The results demonstrate that O(6)-methylguanine lesions are involved in triggering nuclear accumulation of MSH2 and MSH6. The finding that treatment of cells with O(6)-methylguanine-generating mutagens results in an increase of MutSalpha and GT binding activity in the nucleus indicates a novel type of genotoxic stress response.

  16. Balanced reciprocal translocation 5,18: a case report

    Directory of Open Access Journals (Sweden)

    Shahram Savad

    2014-05-01

    Conclusion: A balanced reciprocal translocation carrier is phenotypically normal, but during meiosis І, carrier chromosomes cant pair normally and form quadrivalant instead of bivalant that depend on type of their segregation (alternate, adjacent 1, adjacent 2,3:1,4:0, produce gametes that are chromosomally unbalanced which can result in early fetus abortion. Considering the number of abnormal gametes, the most effective way to help couples with this problem seems to be PGD 24sure, since it can identify reciprocal and Robertsonian translocation and allows concurrent screening of all chromosomes for aneuploidy. Another technique that can be compared with PGD 24sure is fluorescence in situ hybridization (FISH, but it has several technical limitations such as it is expensive and complexity, in addition it has only few probes (for chromosomes 21, 13, 18, X, Y so sometimes necessary to create patient specific protocols.

  17. The Social Construction of Guangzhou as a Translocal Trading Place

    Directory of Open Access Journals (Sweden)

    Angelo Gilles

    2015-01-01

    Full Text Available Guangzhou has become a key destination for sub-Saharan African traders. These traders have established multilocal forms of business organisation and, in so doing, have developed diverse practices to overcome geographical, political and cultural boundaries. This paper focuses on these practices, looking at the ways in which the movements, relations and interactions within these organisational formations are produced, transformed and lived. A close ethnographic examination was made of the livelihoods of 33 African traders from 13 sub-Saharan African countries. Through the concept of trans-locality, the organisational formations of these Africans are conceptualised as links between different places on a larger geographical scale; these links then meet on a local scale in the specific place of Guangzhou. Following a relational understanding of spatial constructions in social science, these links are conceptualised as one of the main drivers for the social construction and transformation of the city as a trans-local trading place.

  18. Slowing down DNA translocation by a nanofiber meshed layer

    Science.gov (United States)

    Zhao, Yue; Xie, Wanyi; Tian, Enling; Ren, Yiwei; Zhu, Jifeng; Deng, Yunsheng; He, Shixuan; Liang, Liyuan; Wang, Yunjiao; Zhou, Daming; Wang, Deqiang

    2018-01-01

    Due to the weak interaction between DNA molecules and the inner surface of nanopores, DNA translocation is very fast, just leaving a short current drop without sufficient information to recognise the nucleotide sequence in the strand. In this paper, we propose a nanopore-nanofiber mesh hybridized structure to decelerate DNA translocation speed. Experimental results reveal that due to hydrophobic interaction between the DNA fragments and the nanofibers, the DNA moving speed can be retarded to two orders of magnitude slower. Furthermore, according to theory simulations, the additional fiber layer will reduce the electric field in the channel but elongate the capture region at the pore orifice, which will be helpful for increasing the capture rate and extending the DNA dwelling time in the meanwhile.

  19. A strategy for generation and balancing of autosome: Y chromosome translocations.

    Science.gov (United States)

    Joshi, Sonal S; Cheong, Han; Meller, Victoria H

    2014-01-01

    We describe a method for generation and maintenance of translocations that move large autosomal segments onto the Y chromosome. Using this strategy we produced ( 2;Y) translocations that relocate between 1.5 and 4.8 Mb of the 2nd chromosome.. All translocations were easily balanced over a male-specific lethal 1 (msl-1) mutant chromosome. Both halves of the translocation carry visible markers, as well as P-element ends that enable molecular confirmation. Halves of these translocations can be separated to produce offspring with duplications and with lethal second chromosome deficiencies . Such large deficiencies are otherwise tedious to generate and maintain.

  20. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins...

  1. Two translocations of chromosome 15q associated with dyslexia

    OpenAIRE

    Nopola-Hemmi, J.; Taipale, M.; Haltia, T.; Lehesjoki, A.; Voutilainen, A.; Kere, J.

    2000-01-01

    Developmental dyslexia is characterised by difficulties in learning to read. As reading is a complex cognitive process, multiple genes are expected to contribute to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of molecular studies during recent years, but so far no genes have been identified. However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in previous linkage studies. We have identified two families with balanced translocations involvi...

  2. A nanopore-nanofiber mesh biosensor to control DNA translocation

    OpenAIRE

    Squires, Allison; Hersey, Joseph S.; Grinstaff, Mark W.; Meller, Amit

    2013-01-01

    Solid-state nanopores show promise as single-molecule sensors for biomedical applications, but to increase their resolution and efficiency analyte molecules must remain longer in the nanopore sensing volume. Here we demonstrate a novel, facile, and customizable nanopore sensor modification that reduces double stranded DNA translocation velocity by two orders of magnitude or more via interactions outside the nanopore. This is achieved by electrospinning a copolymer nanofiber mesh (NFM) directl...

  3. "Translocal Express" juba täna! / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-

    2009-01-01

    27. märtsil algab Kumu Kunstimuuseumis "Public Preparation'i" ("Avalik ettevalmistus") sarja rahvusvaheline seminar "Translocal Express. Golden Age" ("Translokaalne ekspress. Kuldaeg"), kus on kõne all ajalookirjutamise ja kollektiivse mälu roll praegu domineerivas natsionalistlikus diskursuses ja selle käsitlemine kaasaegses kunstis. Seminaril on lähtutud eelkõige kunstnike Martin Krenni (Viin) ja Kristina Normani teoste tutvustamisest

  4. International study of factors affecting human chromosome translocations

    Czech Academy of Sciences Publication Activity Database

    Sigurdson, A.J.; Ha, M.; Hauptmann, M.; Bhatti, P.; Šrám, Radim; Beskid, Olena; Tawn, E.J.; Whitehouse, C.A.; Lindholm, C.; Nakano, M.; Kodama, Y.; Nakamura, N.; Vorobtsova, I.; Oestreicher, U.; Stephan, G.; Yong, L.C.; Bauchinger, M.; Schmid, E.; Chung, H.W.; Darroudi, F.; Roy, L.; Voisin, P.; Barquinero, J.F.; Livingston, G.; Blakey, D.; Hayata, I.; Zhang, W.; Wang, Ch.; Benett, L.M.; Littlefield, L.G.; Edwards, A.A.; Kleinerman, R.A.; Tucker, J.D.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 112-121 ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SI/340/2/00; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosome translocations * FISH * Background frequency Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.363, year: 2008

  5. Particles translocate from the vagina to the oviducts and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Hall, A.S.; Weller, R.E.; Lepel, E.A.; Schirmer, R.E.

    1985-03-01

    To investigate whether particles deposited in the vagina translocate to the oviducts, 0.3 ml of a 4% bone black suspension was deposited in the posterior vaginal fornix of each of five cynomolgus monkeys (Macaca fascicularis) during their mid-menstrual cycle. Simultaneously, each animal received 10 units of oxytocin by intramuscular injection. The oviducts of three animals were removed 1 hr after administration of the bone black, while those of the remaining two animals were removed 72 hr after dosing. The removed oviducts were flushed with Hank's solution and then with collagenase solution. The solutions were collected in clean vials and filtered. The filters were examined for bone black particles by light microscopy, as were filters through which solution blanks (negative controls) had been passed. Particles resembling bone black were found on all filters. There were no appreciable differences in the number or shape of these particles between the solution-blank filters and the oviduct-flush filters. The particles on both the solution-blank filters and on the oviduct-flush filters probably originated from environmental contamination by ubiquitous carbon particles. While these results suggested that no translocation took place, translocation could not be ruled out with certainty in the absence of quantitative analyses. A more definitive pilot study was then conducted with two dosed monkeys and one control, using talc labelled by neutron activation to circumvent the problem of environmental contamination. Gamma-Ray analysis of tissue and peritoneal lavage samples for the radionuclides /sup 46/Sc, /sup 59/Fe and /sup 60/Co indicated that no measurable quantities (i.e. greater than 0.5 micrograms) of talc translocated from the deposition site in the vagina to the uterine cavity and beyond.

  6. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  7. Growth factor deprivation induces cytosolic translocation of SIRT1

    Science.gov (United States)

    Meng, Chengbo; Xing, Da; Wu, Shengnan; Huang, Lei

    2010-02-01

    Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.

  8. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  9. Nanowire-nanopore transistor sensor for DNA detection during translocation

    Science.gov (United States)

    Xie, Ping; Xiong, Qihua; Fang, Ying; Qing, Quan; Lieber, Charles

    2011-03-01

    Nanopore sequencing, as a promising low cost, high throughput sequencing technique, has been proposed more than a decade ago. Due to the incompatibility between small ionic current signal and fast translocation speed and the technical difficulties on large scale integration of nanopore for direct ionic current sequencing, alternative methods rely on integrated DNA sensors have been proposed, such as using capacitive coupling or tunnelling current etc. But none of them have been experimentally demonstrated yet. Here we show that for the first time an amplified sensor signal has been experimentally recorded from a nanowire-nanopore field effect transistor sensor during DNA translocation. Independent multi-channel recording was also demonstrated for the first time. Our results suggest that the signal is from highly localized potential change caused by DNA translocation in none-balanced buffer condition. Given this method may produce larger signal for smaller nanopores, we hope our experiment can be a starting point for a new generation of nanopore sequencing devices with larger signal, higher bandwidth and large-scale multiplexing capability and finally realize the ultimate goal of low cost high throughput sequencing.

  10. Molecular diagnosis of sarcomas: chromosomal translocations in sarcomas.

    Science.gov (United States)

    Lazar, Alexander; Abruzzo, Lynne V; Pollock, Raphael E; Lee, Sangkyou; Czerniak, Bogdan

    2006-08-01

    Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis. To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas. This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas. In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and molecular biologic methods are being increasingly utilized and relied on in sarcoma pathology. These methods include chromosomal karyotyping, fluorescence in-situ hybridization, spectral karyotyping, and polymerase chain reaction- based methods for demonstrating specific chromosomal translocations and fusion genes. Understanding the basis of these methods and their application is critical to better provide accurate and validated specific diagnoses of sarcomas.

  11. Twin-arginine-dependent translocation of folded proteins

    Science.gov (United States)

    Fröbel, Julia; Rose, Patrick; Müller, Matthias

    2012-01-01

    Twin-arginine translocation (Tat) denotes a protein transport pathway in bacteria, archaea and plant chloroplasts, which is specific for precursor proteins harbouring a characteristic twin-arginine pair in their signal sequences. Many Tat substrates receive cofactors and fold prior to translocation. For a subset of them, proofreading chaperones coordinate maturation and membrane-targeting. Tat translocases comprise two kinds of membrane proteins, a hexahelical TatC-type protein and one or two members of the single-spanning TatA protein family, called TatA and TatB. TatC- and TatA-type proteins form homo- and hetero-oligomeric complexes. The subunits of TatABC translocases are predominantly recovered from two separate complexes, a TatBC complex that might contain some TatA, and a homomeric TatA complex. TatB and TatC coordinately recognize twin-arginine signal peptides and accommodate them in membrane-embedded binding pockets. Advanced binding of the signal sequence to the Tat translocase requires the proton-motive force (PMF) across the membranes and might involve a first recruitment of TatA. When targeted in this manner, folded twin-arginine precursors induce homo-oligomerization of TatB and TatA. Ultimately, this leads to the formation of a transmembrane protein conduit that possibly consists of a pore-like TatA structure. The translocation step again is dependent on the PMF. PMID:22411976

  12. Single-strand DNA molecule translocation through nanoelectrode gaps

    International Nuclear Information System (INIS)

    Zhao Xiongce; Payne, Christina M; Cummings, Peter T; Lee, James W

    2007-01-01

    Molecular dynamics simulations were performed to investigate the translocation of single-strand DNA through nanoscale electrode gaps under the action of a constant driving force. The application behind this theoretical study is a proposal to use nanoelectrodes as a screening gap as part of a rapid genomic sequencing device. Preliminary results from a series of simulations using various gap widths and driving forces suggest that the narrowest electrode gap that a single-strand DNA can pass is ∼1.5 nm. The minimum force required to initiate the translocation within nanoseconds is ∼0.3 nN. Simulations using DNA segments of various lengths indicate that the minimum initiation force is insensitive to the length of DNA. However, the average threading velocity of DNA varies appreciably from short to long DNA segments. We attribute such variation to the different nature of drag force experienced by the short and long DNA segments in the environment. It is found that DNA molecules deform significantly to fit in the shape of the nanogap during the translocation

  13. Zoonotic bacterial meningitis in human adults.

    Science.gov (United States)

    van Samkar, Anusha; Brouwer, Matthijs C; van der Ende, Arie; van de Beek, Diederik

    2016-09-13

    To describe the epidemiology, etiology, clinical characteristics, treatment, outcome, and prevention of zoonotic bacterial meningitis in human adults. We identified 16 zoonotic bacteria causing meningitis in adults. Zoonotic bacterial meningitis is uncommon compared to bacterial meningitis caused by human pathogens, and the incidence has a strong regional distribution. Zoonotic bacterial meningitis is mainly associated with animal contact, consumption of animal products, and an immunocompromised state of the patient. In a high proportion of zoonotic bacterial meningitis cases, CSF analysis showed only a mildly elevated leukocyte count. The recommended antibiotic therapy differs per pathogen, and the overall mortality is low. Zoonotic bacterial meningitis is uncommon but is associated with specific complications. The suspicion should be raised in patients with bacterial meningitis who have recreational or professional contact with animals and in patients living in regions endemic for specific zoonotic pathogens. An immunocompromised state is associated with a worse prognosis. Identification of risk factors and underlying disease is necessary to improve treatment. © 2016 American Academy of Neurology.

  14. Forces involved in bacterial adhesion to hydrophilic and hydrophobic surfaces

    NARCIS (Netherlands)

    Boks, N.P.; Norde, W.; Meil, H.C.; Busscher, H.J.

    2008-01-01

    Using a parallel-plate flow chamber, the hydrodynamic shear forces to prevent bacterial adhesion (F-prev) and to detach adhering bacteria (F-det) were evaluated for hydrophilic glass, hydrophobic, dimethyldichlorosilane (DDS)-coated glass and six different bacterial strains, in order to test the

  15. Forces involved in bacterial adhesion to hydrophilic and hydrophobic surfaces

    NARCIS (Netherlands)

    Boks, Niels P.; Norde, Willem; van der Mei, Henny C.; Busscher, Henk J.

    2008-01-01

    Using a parallel-plate flow chamber, the hydrodynamic shear forces to prevent bacterial adhesion (F(prev)) and to detach adhering bacteria (F(det)) were evaluated for hydrophilic glass, hydrophobic, dimethyldichlorosilane (DDS)-coated glass and six different bacterial strains, in order to test the

  16. Centromere structure and function analysis in wheat-rye translocation lines.

    Science.gov (United States)

    Wang, Jing; Liu, Yalin; Su, Handong; Guo, Xianrui; Han, Fangpu

    2017-07-01

    1RS.1BL translocations are centric translocations formed by misdivision and have been used extensively in wheat breeding. However, the role that the centromere plays in the formation of 1RS.1BL translocations is still unclear. Fluorescence in situ hybridization (FISH) was applied to detect the fine structures of the centromeres in 130 1RS.1BL translocation cultivars. Immuno-FISH, chromatin immunoprecipitation (ChIP)-qPCR and RT-PCR were used to investigate the functions of the hybrid centromeres in 1RS.1BL translocations. New 1R translocations with different centromere structures were created by misdivision and pollen irradiation to elucidate the role that the centromere plays in the formation of 1RS.1BL translocations. We found that all of the 1RS.1BL translocations detected contained hybrid centromeres and that wheat-derived CENH3 bound to both the wheat and rye centromeres in the 1RS.1BL translocation chromosomes. Moreover, a rye centromere-specific retrotransposon was actively transcribed in 1RS.1BL translocations. The frequencies of new 1RS hybrid centromere translocations and group-1 chromosome translocations were higher during 1R misdivision. Our study demonstrates the hybrid nature of the centromere in 1RS.1BL translocations. New 1R translocations with different centromere structures were created to help understand the fusion centromere used for wheat breeding and for use as breeding material for the improvement of wheat. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  17. Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation.

    Science.gov (United States)

    Dillon, Stephanie M; Kibbie, Jon; Lee, Eric J; Guo, Kejun; Santiago, Mario L; Austin, Gregory L; Gianella, Sara; Landay, Alan L; Donovan, Andrew M; Frank, Daniel N; McCARTER, Martin D; Wilson, Cara C

    2017-02-20

    Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence microbial translocation and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants. The effect of exogenously added butyrate on gut T-cell activation and HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model. Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo isolated lamina propria mononuclear cells were infected with C-C chemokine receptor type 5-tropic HIV-1Bal, cultured with enteric gram-negative bacteria and a range of butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels measured. Relative abundance of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-uninfected individuals. In HIV-1-infected study participants, R. intestinalis relative abundance inversely correlated with systemic indicators of microbial translocation, immune activation, and vascular inflammation. Exogenous butyrate suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation and HIV-1 infection levels in vitro. Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.

  18. Bacterial Biofilms in Jones Tubes.

    Science.gov (United States)

    Ahn, Eric S; Hauck, Matthew J; Kirk Harris, Jonathan; Robertson, Charles E; Dailey, Roger A

    To investigate the presence and microbiology of bacterial biofilms on Jones tubes (JTs) by direct visualization with scanning electron microscopy and polymerase chain reaction (PCR) of representative JTs, and to correlate these findings with inflammation and/or infection related to the JT. In this study, prospective case series were performed. JTs were recovered from consecutive patients presenting to clinic for routine cleaning or recurrent irritation/infection. Four tubes were processed for scanning electron microscopy alone to visualize evidence of biofilms. Two tubes underwent PCR alone for bacterial quantification. One tube was divided in half and sent for scanning electron microscopy and PCR. Symptoms related to the JTs were recorded at the time of recovery. Seven tubes were obtained. Five underwent SEM, and 3 out of 5 showed evidence of biofilms (60%). Two of the 3 biofilms demonstrated cocci and the third revealed rods. Three tubes underwent PCR. The predominant bacteria identified were Pseudomonadales (39%), Pseudomonas (16%), and Staphylococcus (14%). Three of the 7 patients (43%) reported irritation and discharge at presentation. Two symptomatic patients, whose tubes were imaged only, revealed biofilms. The third symptomatic patient's tube underwent PCR only, showing predominantly Staphylococcus (56%) and Haemophilus (36%) species. Two of the 4 asymptomatic patients also showed biofilms. All symptomatic patients improved rapidly after tube exchange and steroid antibiotic drops. Bacterial biofilms were variably present on JTs, and did not always correlate with patients' symptoms. Nevertheless, routine JT cleaning is recommended to treat and possibly prevent inflammation caused by biofilms.

  19. Polymorphism in Bacterial Flagella Suspensions

    Science.gov (United States)

    Schwenger, Walter J.

    Bacterial flagella are a type of biological polymer studied for its role in bacterial motility and the polymorphic transitions undertaken to facilitate the run and tumble behavior. The naturally rigid, helical shape of flagella gives rise to novel colloidal dynamics and material properties. This thesis studies methods in which the shape of bacterial flagella can be controlled using in vitro methods and the changes the shape of the flagella have on both single particle dynamics and bulk material properties. We observe individual flagellum in both the dilute and semidilute regimes to observe the effects of solvent condition on the shape of the filament as well as the effect the filament morphology has on reptation through a network of flagella. In addition, we present rheological measurements showing how the shape of filaments effects the bulk material properties of flagellar suspensions. We find that the individual particle dynamics in suspensions of flagella can vary with geometry from needing to reptate linearly via rotation for helical filaments to the prevention of long range diffusion for block copolymer filaments. Similarly, for bulk material properties of flagella suspensions, helical geometries show a dramatic enhancement in elasticity over straight filaments while block copolymers form an elastic gel without the aid of crosslinking agents.

  20. Bacterial Carriers for Glioblastoma Therapy

    Directory of Open Access Journals (Sweden)

    Nalini Mehta

    2017-03-01

    Full Text Available Treatment of aggressive glioblastoma brain tumors is challenging, largely due to diffusion barriers preventing efficient drug dosing to tumors. To overcome these barriers, bacterial carriers that are actively motile and programmed to migrate and localize to tumor zones were designed. These carriers can induce apoptosis via hypoxia-controlled expression of a tumor suppressor protein p53 and a pro-apoptotic drug, Azurin. In a xenograft model of human glioblastoma in rats, bacterial carrier therapy conferred a significant survival benefit with 19% overall long-term survival of >100 days in treated animals relative to a median survival of 26 days in control untreated animals. Histological and proteomic analyses were performed to elucidate the safety and efficacy of these carriers, showing an absence of systemic toxicity and a restored neural environment in treated responders. In the treated non-responders, proteomic analysis revealed competing mechanisms of pro-apoptotic and drug-resistant activity. This bacterial carrier opens a versatile avenue to overcome diffusion barriers in glioblastoma by virtue of its active motility in extracellular space and can lead to tailored therapies via tumor-specific expression of tumoricidal proteins.

  1. TFE3-positive renal cell carcinomas are not always Xp11 translocation carcinomas: Report of a case with a TPM3-ALK translocation.

    Science.gov (United States)

    Thorner, Paul Scott; Shago, Mary; Marrano, Paula; Shaikh, Furqan; Somers, Gino R

    2016-10-01

    Translocation-associated renal cell carcinoma (RCC) is a distinct subtype of RCC with gene rearrangements of the TFE3 or TFEB loci. The TFE3 gene is located at Xp11 and can fuse to a number of translocation partners, resulting in high nuclear expression of TFE3 protein. TFE3 immunostaining is often used as a surrogate marker for a TFE3 translocation. We report a case of an RCC that expressed TFE3 but showed only gain of TFE3 rather than a translocation. Moreover, this case had a t(1;2) translocation fusing ALK and TMP3, identical to that seen in inflammatory myofibroblastic tumour. There was resulting overexpression of ALK protein in a cytoplasmic and membranous pattern. The patient was not treated with chemotherapy but following regional nodal recurrence, an ALK inhibitor was added and the patient remains alive one year later. There are only rare reports of RCC with an ALK-TMP3 fusion, and these tumours can express TFE3 on some unknown basis not related to a TFE3 translocation. Any RCC positive for TFE3 and lacking a translocation should be tested for ALK expression and translocation. Recognition of this subtype of RCC will allow ALK inhibitor therapy to be added, in the hope of improving patient outcome. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Phylogenomic analysis and predicted physiological role of the proton-translocating NADH:quinone oxidoreductase (complex I) across bacteria.

    Science.gov (United States)

    Spero, Melanie A; Aylward, Frank O; Currie, Cameron R; Donohue, Timothy J

    2015-04-14

    The proton-translocating NADH:quinone oxidoreductase (complex I) is a multisubunit integral membrane enzyme found in the respiratory chains of both bacteria and eukaryotic organelles. Although much research has focused on the enzyme's central role in the mitochondrial respiratory chain, comparatively little is known about its role in the diverse energetic lifestyles of different bacteria. Here, we used a phylogenomic approach to better understand the distribution of complex I across bacteria, the evolution of this enzyme, and its potential roles in shaping the physiology of different bacterial groups. By surveying 970 representative bacterial genomes, we predict complex I to be present in ~50% of bacteria. While this includes bacteria with a wide range of energetic schemes, the presence of complex I is associated with specific lifestyles, including aerobic respiration and specific types of phototrophy (bacteria with only a type II reaction center). A phylogeny of bacterial complex I revealed five main clades of enzymes whose evolution is largely congruent with the evolution of the bacterial groups that encode complex I. A notable exception includes the gammaproteobacteria, whose members encode one of two distantly related complex I enzymes predicted to participate in different types of respiratory chains (aerobic versus anaerobic). Comparative genomic analyses suggest a broad role for complex I in reoxidizing NADH produced from various catabolic reactions, including the tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation. Together, these findings suggest diverse roles for complex I across bacteria and highlight the importance of this enzyme in shaping diverse physiologies across the bacterial domain. Living systems use conserved energy currencies, including a proton motive force (PMF), NADH, and ATP. The respiratory chain enzyme, complex I, connects these energy currencies by using NADH produced during nutrient breakdown to generate a PMF, which is

  3. Studying bacterial multispecies biofilms

    DEFF Research Database (Denmark)

    Røder, Henriette Lyng; Sørensen, Søren Johannes; Burmølle, Mette

    2016-01-01

    , but the identity and significance of interspecies bacterial interactions is neglected in these analyses. There is therefore an urgent need for bridging the gap between metagenomic analysis and in vitro models suitable for studies of bacterial interactions.Bacterial interactions and coadaptation are important......The high prevalence and significance of multispecies biofilms have now been demonstrated in various bacterial habitats with medical, industrial, and ecological relevance. It is highly evident that several species of bacteria coexist and interact in biofilms, which highlights the need for evaluating...

  4. Structure and operation of the DNA-translocating type I DNA restriction enzymes

    Science.gov (United States)

    Kennaway, Christopher K.; Taylor, James E.; Song, Chun Feng; Potrzebowski, Wojciech; Nicholson, William; White, John H.; Swiderska, Anna; Obarska-Kosinska, Agnieszka; Callow, Philip; Cooper, Laurie P.; Roberts, Gareth A.; Artero, Jean-Baptiste; Bujnicki, Janusz M.; Trinick, John; Kneale, G. Geoff; Dryden, David T.F.

    2012-01-01

    Type I DNA restriction/modification (RM) enzymes are molecular machines found in the majority of bacterial species. Their early discovery paved the way for the development of genetic engineering. They control (restrict) the influx of foreign DNA via horizontal gene transfer into the bacterium while maintaining sequence-specific methylation (modification) of host DNA. The endonuclease reaction of these enzymes on unmethylated DNA is preceded by bidirectional translocation of thousands of base pairs of DNA toward the enzyme. We present the structures of two type I RM enzymes, EcoKI and EcoR124I, derived using electron microscopy (EM), small-angle scattering (neutron and X-ray), and detailed molecular modeling. DNA binding triggers a large contraction of the open form of the enzyme to a compact form. The path followed by DNA through the complexes is revealed by using a DNA mimic anti-restriction protein. The structures reveal an evolutionary link between type I RM enzymes and type II RM enzymes. PMID:22215814

  5. Na+-NQR (Na+-translocating NADH:ubiquinone oxidoreductase) as a novel target for antibiotics.

    Science.gov (United States)

    Dibrov, Pavel; Dibrov, Elena; Pierce, Grant N

    2017-09-01

    The recent breakthrough in structural studies on Na+-translocating NADH:ubiquinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae creates a perspective for the systematic design of inhibitors for this unique enzyme, which is the major Na+ pump in aerobic pathogens. Widespread distribution of Na+-NQR among pathogenic species, its key role in energy metabolism, its relation to virulence in different species as well as its absence in eukaryotic cells makes this enzyme especially attractive as a target for prospective antibiotics. In this review, the major biochemical, physiological and, especially, the pharmacological aspects of Na+-NQR are discussed to assess its 'target potential' for drug development. A comparison to other primary bacterial Na+ pumps supports the contention that NQR is a first rate prospective target for a new generation of antimicrobials. A new, narrowly targeted furanone inhibitor of NQR designed in our group is presented as a molecular platform for the development of anti-NQR remedies. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Structure and operation of the DNA-translocating type I DNA restriction enzymes.

    Science.gov (United States)

    Kennaway, Christopher K; Taylor, James E; Song, Chun Feng; Potrzebowski, Wojciech; Nicholson, William; White, John H; Swiderska, Anna; Obarska-Kosinska, Agnieszka; Callow, Philip; Cooper, Laurie P; Roberts, Gareth A; Artero, Jean-Baptiste; Bujnicki, Janusz M; Trinick, John; Kneale, G Geoff; Dryden, David T F

    2012-01-01

    Type I DNA restriction/modification (RM) enzymes are molecular machines found in the majority of bacterial species. Their early discovery paved the way for the development of genetic engineering. They control (restrict) the influx of foreign DNA via horizontal gene transfer into the bacterium while maintaining sequence-specific methylation (modification) of host DNA. The endonuclease reaction of these enzymes on unmethylated DNA is preceded by bidirectional translocation of thousands of base pairs of DNA toward the enzyme. We present the structures of two type I RM enzymes, EcoKI and EcoR124I, derived using electron microscopy (EM), small-angle scattering (neutron and X-ray), and detailed molecular modeling. DNA binding triggers a large contraction of the open form of the enzyme to a compact form. The path followed by DNA through the complexes is revealed by using a DNA mimic anti-restriction protein. The structures reveal an evolutionary link between type I RM enzymes and type II RM enzymes.

  7. Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH detection.

    Directory of Open Access Journals (Sweden)

    Liqiang Song

    Full Text Available The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60Co-γirradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes.

  8. A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

    Science.gov (United States)

    Okujava, Rusudan; Guye, Patrick; Lu, Yun-Yueh; Mistl, Claudia; Polus, Florine; Vayssier-Taussat, Muriel; Halin, Cornelia; Rolink, Antonius G; Dehio, Christoph

    2014-06-01

    Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps) into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs) infected with a ΔbepE mutant of B. henselae (Bhe) displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID) domain of BepEBhe (BID2.EBhe). Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d.) model for B. tribocorum (Btr) infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we propose that

  9. A translocated effector required for Bartonella dissemination from derma to blood safeguards migratory host cells from damage by co-translocated effectors.

    Directory of Open Access Journals (Sweden)

    Rusudan Okujava

    2014-06-01

    Full Text Available Numerous bacterial pathogens secrete multiple effectors to modulate host cellular functions. These effectors may interfere with each other to efficiently control the infection process. Bartonellae are Gram-negative, facultative intracellular bacteria using a VirB type IV secretion system to translocate a cocktail of Bartonella effector proteins (Beps into host cells. Based on in vitro infection models we demonstrate here that BepE protects infected migratory cells from injurious effects triggered by BepC and is required for in vivo dissemination of bacteria from the dermal site of inoculation to blood. Human endothelial cells (HUVECs infected with a ΔbepE mutant of B. henselae (Bhe displayed a cell fragmentation phenotype resulting from Bep-dependent disturbance of rear edge detachment during migration. A ΔbepCE mutant did not show cell fragmentation, indicating that BepC is critical for triggering this deleterious phenotype. Complementation of ΔbepE with BepEBhe or its homologues from other Bartonella species abolished cell fragmentation. This cyto-protective activity is confined to the C-terminal Bartonella intracellular delivery (BID domain of BepEBhe (BID2.EBhe. Ectopic expression of BID2.EBhe impeded the disruption of actin stress fibers by Rho Inhibitor 1, indicating that BepE restores normal cell migration via the RhoA signaling pathway, a major regulator of rear edge retraction. An intradermal (i.d. model for B. tribocorum (Btr infection in the rat reservoir host mimicking the natural route of infection by blood sucking arthropods allowed demonstrating a vital role for BepE in bacterial dissemination from derma to blood. While the Btr mutant ΔbepDE was abacteremic following i.d. inoculation, complementation with BepEBtr, BepEBhe or BIDs.EBhe restored bacteremia. Given that we observed a similar protective effect of BepEBhe on infected bone marrow-derived dendritic cells migrating through a monolayer of lymphatic endothelial cells we

  10. The Structures of Coiled-Coil Domains from Type III Secretion System Translocators Reveal Homology to Pore-Forming Toxins

    Energy Technology Data Exchange (ETDEWEB)

    Barta, Michael L.; Dickenson, Nicholas E.; Patil, Mrinalini; Keightley, Andrew; Wyckoff, Gerald J.; Picking, William D.; Picking, Wendy L.; Geisbrecht, Brian V. (UMKC); (OKLU)

    2012-03-26

    Many pathogenic Gram-negative bacteria utilize type III secretion systems (T3SSs) to alter the normal functions of target cells. Shigella flexneri uses its T3SS to invade human intestinal cells to cause bacillary dysentery (shigellosis) that is responsible for over one million deaths per year. The Shigella type III secretion apparatus is composed of a basal body spanning both bacterial membranes and an exposed oligomeric needle. Host altering effectors are secreted through this energized unidirectional conduit to promote bacterial invasion. The active needle tip complex of S. flexneri is composed of a tip protein, IpaD, and two pore-forming translocators, IpaB and IpaC. While the atomic structure of IpaD has been elucidated and studied, structural data on the hydrophobic translocators from the T3SS family remain elusive. We present here the crystal structures of a protease-stable fragment identified within the N-terminal regions of IpaB from S. flexneri and SipB from Salmonella enterica serovar Typhimurium determined at 2.1 {angstrom} and 2.8 {angstrom} limiting resolution, respectively. These newly identified domains are composed of extended-length (114 {angstrom} in IpaB and 71 {angstrom} in SipB) coiled-coil motifs that display a high degree of structural homology to one another despite the fact that they share only 21% sequence identity. Further structural comparisons also reveal substantial similarity to the coiled-coil regions of pore-forming proteins from other Gram-negative pathogens, notably, colicin Ia. This suggests that these mechanistically separate and functionally distinct membrane-targeting proteins may have diverged from a common ancestor during the course of pathogen-specific evolutionary events.

  11. Bacterial colonization and gut development in preterm neonates

    DEFF Research Database (Denmark)

    Cilieborg, Malene S.; Boye, Mette; Sangild, Per Torp

    2012-01-01

    Necrotizing enterocolitis (NEC) develops in 5–10% of preterm infants in association with enteral feeding and bacterial colonization. It remains unclear how diet and bacteria interact to protect or provoke the immature gastrointestinal tract. Understanding the factors that control bacterial...... colonization may provide the clue to prevent NEC, and studies in infants must be combined with animal models to understand the mechanisms of the microbiota–epithelium interactions. Analyses of infant fecal samples show that the density and distribution of bacterial species are highly variable......, such as mother's colostrum or milk, that help the immature intestinal immune system to respond appropriately to the highly variable bacterial colonization....

  12. Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

    Science.gov (United States)

    Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

    2017-01-01

    The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

  13. Hyaluronan synthase mediates dye translocation across liposomal membranes

    Directory of Open Access Journals (Sweden)

    Medina Andria P

    2012-01-01

    Full Text Available Abstract Background Hyaluronan (HA is made at the plasma membrane and secreted into the extracellular medium or matrix by phospolipid-dependent hyaluronan synthase (HAS, which is active as a monomer. Since the mechanism by which HA is translocated across membranes is still unresolved, we assessed the presence of an intraprotein pore within HAS by adding purified Streptococcus equisimilis HAS (SeHAS to liposomes preloaded with the fluorophore Cascade Blue (CB. Results CB translocation (efflux was not observed with mock-purified material from empty vector control E. coli membranes, but was induced by SeHAS, purified from membranes, in a time- and dose-dependent manner. CB efflux was eliminated or greatly reduced when purified SeHAS was first treated under conditions that inhibit enzyme activity: heating, oxidization or cysteine modification with N-ethylmaleimide. Reduced CB efflux also occurred with SeHAS K48E or K48F mutants, in which alteration of K48 within membrane domain 2 causes decreased activity and HA product size. The above results used liposomes containing bovine cardiolipin (BCL. An earlier study testing many synthetic lipids found that the best activating lipid for SeHAS is tetraoleoyl cardiolipin (TO-CL and that, in contrast, tetramyristoyl cardiolipin (TM-CL is an inactivating lipid (Weigel et al, J. Biol. Chem. 281, 36542, 2006. Consistent with the effects of these CL species on SeHAS activity, CB efflux was more than 2-fold greater in liposomes made with TO-CL compared to TM-CL. Conclusions The results indicate the presence of an intraprotein pore in HAS and support a model in which HA is translocated to the exterior by HAS itself.

  14. Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Directory of Open Access Journals (Sweden)

    Romain Kroum Gherardi

    2015-02-01

    Full Text Available Aluminum oxyhydroxide (alum is a crystaline compound widely used as an immunologic adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytozed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV, that obeys to CCL2 signaling the major inflammatory monocyte

  15. A Search for Gene Fusions/Translocations in Breast Cancer

    Science.gov (United States)

    2013-11-01

    cancer cell lines with validated AGTR1 4.0 3.0 2.0 1.0 0.0 -1.0 Normal Breast Fibroadenoma Breast Ductal Carcinoma A -1.0 1.0 2.0 3.0 4.0 5.0 4.0 3.0...in Breast Cancer PRINCIPAL INVESTIGATOR: Arul M. Chinnaiyan, M.D., Ph.D. CONTRACTING ORGANIZATION: University of Michigan...5a. CONTRACT NUMBER A Search for Gene Fusions/Translocations in Breast Cancer 5b. GRANT NUMBER W81XWH-08-1-0110 5c. PROGRAM

  16. Use of chromosome translocations for measuring prior environment exposures in humans

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J. D.

    1997-05-01

    Recent advances in cytogenetic methodology are beginning to have a major impact upon our ability to provide assessments of environmental exposure in humans. The advent of fluorescent-based techniques for `painting` whole chromosomes has made the analysis of chromosome translocations rapid, specific, sensitive and routine. Chromosome painting has been used to address a wide variety of scientific questions, resulting in an increased understanding of the biological consequences of adverse environmental exposure. This paper describes the use of chromosome translocations as a biological marker of exposure and effect in humans. The relevance of translocations is discussed, as are the advantages and disadvantages of painting compared to classical cytogenetic methods for translocation evaluation. The factors to consider in the use of translocations as a retrospective indicator of exposure are then described. Several theoretical parameters that are important to the use of translocations are provided, and the paper concludes with a vision for the future of cytogenetic methodology.

  17. Polymer translocation under a pulling force: Scaling arguments and threshold forces

    Science.gov (United States)

    Menais, Timothée

    2018-02-01

    DNA translocation through nanopores is one of the most promising strategies for next-generation sequencing technologies. Most experimental and numerical works have focused on polymer translocation biased by electrophoresis, where a pulling force acts on the polymer within the nanopore. An alternative strategy, however, is emerging, which uses optical or magnetic tweezers. In this case, the pulling force is exerted directly at one end of the polymer, which strongly modifies the translocation process. In this paper, we report numerical simulations of both linear and structured (mimicking DNA) polymer models, simple enough to allow for a statistical treatment of the pore structure effects on the translocation time probability distributions. Based on extremely extended computer simulation data, we (i) propose scaling arguments for an extension of the predicted translocation times τ ˜N2F-1 over the moderate forces range and (ii) analyze the effect of pore size and polymer structuration on translocation times τ .

  18. Paliperidone Prevents Brain Toll-Like Receptor 4 Pathway Activation and Neuroinflammation in Rat Models of Acute and Chronic Restraint Stress

    Science.gov (United States)

    MacDowell, KS; Caso, JR; Martín-Hernández, D; Madrigal, JL; Leza, JC

    2015-01-01

    Background: Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored. Methods: This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress–induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples. Results: Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1. Conclusions: Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies. PMID:25522409

  19. Paliperidone prevents brain toll-like receptor 4 pathway activation and neuroinflammation in rat models of acute and chronic restraint stress.

    Science.gov (United States)

    MacDowell, K S; Caso, J R; Martín-Hernández, D; Madrigal, J L; Leza, J C; García-Bueno, B

    2014-10-31

    Alterations in the innate immune/inflammatory system have been proposed to underlie the pathophysiology of psychotic disease, but the mechanisms implicated remain elusive. The main agents of the innate immunity are the family of toll-like receptors (TLRs), which detect circulating pathogen-associated molecular patterns and endogenous damage-associated molecular patterns (DAMPS). Current antipsychotics are able to modulate pro- and anti-inflammatory pathways, but their actions on TLRs remain unexplored. This study was conducted to elucidate the effects of paliperidone (1mg/Kg i.p.) on acute (6 hours) and chronic (6 hours/day during 21 consecutive days) restraint stress-induced TLR-4 pathway activation and neuroinflammation, and the possible mechanism(s) related (bacterial translocation and/or DAMPs activation). The expression of the elements of a TLR-4-dependent proinflammatory pathway was analyzed at the mRNA and protein levels in prefrontal cortex samples. Paliperidone pre-treatment prevented TLR-4 activation and neuroinflammation in the prefrontal cortices of stressed rats. Regarding the possible mechanisms implicated, paliperidone regulated stress-induced increased intestinal inflammation and plasma lipopolysaccharide levels. In addition, paliperidone also prevented the activation of the endogenous activators of TLR-4 HSP70 and HGMB-1. Our results showed a regulatory role of paliperidone on brain TLR-4, which could explain the therapeutic benefits of its use for the treatment of psychotic diseases beyond its effects on dopamine and serotonin neurotransmission. The study of the mechanisms implicated suggests that gut-increased permeability, inflammation, and bacterial translocation of Gram-negative microflora and HSP70 and HGMB1 expression could be potential adjuvant therapeutic targets for the treatment of psychotic and other stress-related psychiatric pathologies. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  20. Balanced translocation linked to psychiatric disorder, glutamate, and cortical structure/function

    OpenAIRE

    Thomson, Pippa A; Duff, Barbara; Blackwood, Douglas H R; Romaniuk, Liana; Watson, Andrew; Whalley, Heather C; Li, Xiang; Dauvermann, Maria R; Moorhead, T William J; Bois, Catherine; Ryan, Niamh M; Redpath, Holly; Hall, Lynsey; Morris, Stewart W; van Beek, Edwin J R

    2016-01-01

    Rare genetic variants of large effect can help elucidate the pathophysiology of brain disorders. Here we expand the clinical and genetic analyses of a family with a (1;11)(q42;q14.3) translocation multiply affected by major psychiatric illness and test the effect of the translocation on the structure and function of prefrontal, and temporal brain regions. The translocation showed significant linkage (LOD score 6.1) with a clinical phenotype that included schizophrenia, schizoaffective disorde...

  1. Home range and movements of male translocated problem tigers in Sumatra

    OpenAIRE

    Dolly Priatna; Yanto Santosa; Lilik B. Prasetyo; Agus P. Kartono

    2012-01-01

    The ranging behaviour of translocated problem tigers is poorly understood. The demand for releasing problem tigers back to the wild increases following the increasing the number of problem tigers that needs to be rescued in Sumatra in the last decade. In this study we estimate the home range size and obtain information on daily range of four translocated problem tigers, as well as discussing some potential factors determining the size of home range and their movement. We translocated four ad...

  2. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    International Nuclear Information System (INIS)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. As an exogeneous factor of possible influence, the meiotic effects of two types of radiation (fission neutrons and X-rays) administered at relatively low doses 2 and 3 hours before prometaphase-metaphase II (probably during metaphase-anaphase I), were determined in Rb4Bnr/+-males. (Auth.)

  3. Occurence of translocations between irradiated and intact chromosomes of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Myasnyankina, E.N.; Abeleva, Eh.A.; Generalova, M.V.

    1980-01-01

    Two translocations between irradiated father and intact mother autosomes are obtained in Drosophila melanogaster. Five out of 283 regular translocations (between the second and the third chromosomes of an irradiated male) are accompanied by a recombination over the second or the third chromosomes. Nine flies out of twenty considered to be recombinants, could originate due to mutations. The data obtained prove that intact female autosomes can take part in the exchange with homologic (recombinations) and heterologic (translocations) irradiated male autosomes

  4. Use of radioisotopes in studying factors responsible for alfalfa resistance to bacterial wiltxng

    International Nuclear Information System (INIS)

    Hanker, I.; Kudelova, A.

    1980-01-01

    Studies are summarized dealing with possible causes of vascular dysfunction and resistance of alfalfa to bacterial wilting caused by Corynebacterium insidiosum (McCull.) H.L. Jens from the physiological and biochemical points of view. Using 32 P, 35 S, 54 Mn, 45 Ca, 65 Zn, and 86 Rb the uptake, distribution, translocation, and metabolism of these elements in plants with a different resistance against diseases were investigated. The possible use is discussed of 86 Rb as a tracer of potassium. The results suggest that the resistance of alfalfa to bacterial wilting is probably determined by several factors. (author)

  5. Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence.

    Science.gov (United States)

    Kesten, Dov; Horovitz-Fried, Miriam; Brutman-Barazani, Tamar; Sampson, Sanford R

    2018-04-01

    Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus. Experiments were performed cultured L6 myoblasts, AML liver cells and 3T3-L1 adipocytes. Insulin treatment induced a rapid increase in nuclear IR protein levels within 2 to 5 min. Treatment with WGA, an inhibitor of nuclear import, reduced insulin-induced increases nuclear IR protein; IR was, however, translocated to a perinuclear location. Bioinformatics tools predicted a potential nuclear localization sequence (NLS) on IR. Immunofluorescence staining showed that a point mutation on the predicted NLS blocked insulin-induced IR nuclear translocation. In addition, blockade of nuclear IR activation in isolated nuclei by an IR blocking antibody abrogated insulin-induced increases in IR tyrosine phosphorylation and nuclear PKCδ levels. Furthermore, over expression of mutated IR reduced insulin-induced glucose uptake and PKB phosphorylation. When added to isolated nuclei, insulin induced IR phosphorylation but had no effect on nuclear IR protein levels. These results raise questions regarding the possible role of nuclear IR in IR signaling and insulin resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Tetrapropylammonium ion inhibits Na, K-ATPase by blocking a K+-translocation step

    International Nuclear Information System (INIS)

    Forbush, B. III

    1986-01-01

    Tetrapropylammonium ion (TPA) has previously been shown to inhibit the Na/K pump in human red cells in competition with K + at extracellular sites. The author investigated the action of TPA on the release of 86 Rb from the occluded state of Na, K-ATPase from dog kidney. Like K + and Rb + , TPA is found to prevent the release of one (''s'' for slower) of two tightly bound 86 Rb ions when the enzyme is phosphorylated from P/sub i/; the data are consistent with TPA binding to the K + ''f'' (faster) site with an affinity of ∼5mM. When 86 Rb is bound to the ''s'' site and unlabelled Rb + or K + to the ''f'' site by an appropriate sequence of additions, the 86 Rb can be released by addition of ATP to bring about the E 2 -E]3! conformational change and translocation. In contrast when TPA is bound to the ''f'' site there is no release of 86 Rb from the ''s'' site when ATP is added, suggesting that the conformational change is prevented by the bulky TPA molecule at the transport site. Addition of Na + (without nucleotide or P/sub i/) brings about an extremely rapid (>100s -1 ) release of 86 Rb when TPA is bound. The reason for this is not yet clear, but the effect dramatically illustrates simultaneous occupancy of binding sites by K + , TPA, and Na +

  7. Bacterial zoonoses transmitted by Household pets: State of the Art and Future perspectives for targeted research and policy actions

    NARCIS (Netherlands)

    Damborg, P.; Broens, E.M.; Chomel, B.B.; Guenther, S.; Pasmans, F.; Wagenaar, J.A.; Weese, J.S.; Wieler, L.H.; Windahl, U.; Vanrompay, D.; Guardabassi, L.

    2016-01-01

    The close contact between household pets and people offers favourable conditions for bacterial transmission. In this article, the aetiology, prevalence, transmission, impact on human health and preventative measures are summarized for selected bacterial zoonoses transmissible by household pets. Six

  8. Bacterial Zoonoses Transmitted by Household Pets : State-of-the-Art and Future Perspectives for Targeted Research and Policy Actions

    NARCIS (Netherlands)

    Damborg, P; Broens, E M; Chomel, B B; Guenther, S; Pasmans, F; Wagenaar, J A; Weese, J S; Wieler, L H; Windahl, U; Vanrompay, D; Guardabassi, L

    The close contact between household pets and people offers favourable conditions for bacterial transmission. In this article, the aetiology, prevalence, transmission, impact on human health and preventative measures are summarized for selected bacterial zoonoses transmissible by household pets. Six

  9. Balanced Autosomal Translocations in Two Women Reporting Recurrent Miscarriage.

    Science.gov (United States)

    Arumugam, Brindha; Samuel, Chandra R; Thyagarajan, Santhiya Sathiyavedu

    2016-12-01

    Spontaneous abortion or loss of fetus prior to 20 weeks of gestation is observed in 15-20% of clinically recognized pregnancies. Recurrent Miscarriage (RM) is defined as three or more consecutive pregnancy losses and it affects 1-2% of women. Parental chromosomal rearrangements account for 2-5% of RM. This report describes two couples with a clinical history of RM who were subjected to conventional cytogenetic analysis to ascertain the chromosomal aetiology. Analysis of GTG-banded metaphases obtained from cultured lymphocytes at approximately 500-band resolution revealed balanced translocation in the female spouses as 46,XX,t(8;11)(p11.2;q23.3) in BR27W and 46,XX,t(5;7)(p15.1;q32) pat in BR49W. Both the male partners exhibited 46,XY karyotype. Fluorescent In Situ Hybridization (FISH) analysis was subsequently carried out to confirm the balanced translocation using suitable whole chromosome paint probes. These balanced chromosomal abnormalities in the parents could be responsible for the repeated fetal losses. Hence, karyotype analysis should be a mandatory etiological investigation for couples with RM towards genetic counselling. Disruption of critical genes through these rearrangements could also underlie the pregnancy outcome.

  10. Translocation of the neonicotinoid seed treatment clothianidin in maize.

    Science.gov (United States)

    Alford, Adam; Krupke, Christian H

    2017-01-01

    Neonicotinoid seed treatments, typically clothianidin or thiamethoxam, are routinely applied to >80% of maize (corn) seed grown in North America where they are marketed as a targeted pesticide delivery system. Despite this widespread use, the amount of compound translocated into plant tissue from the initial seed treatment to provide protection has not been reported. Our two year field study compared concentrations of clothianidin seed treatments in maize to that of maize without neonicotinoid seed treatments and found neonicotinoids present in root tissues up to 34 days post planting. Plant-bound clothianidin concentrations followed an exponential decay pattern with initially high values followed by a rapid decrease within the first ~20 days post planting. A maximum of 1.34% of the initial seed treatment was successfully recovered from plant tissues in both study years and a maximum of 0.26% was recovered from root tissue. Our findings show neonicotinoid seed treatments may provide protection from some early season secondary maize pests. However, the proportion of the neonicotinoid seed treatment clothianidin translocated into plant tissues throughout the growing season is low overall and this observation may provide a mechanism to explain reports of inconsistent efficacy of this pest management approach and increasing detections of environmental neonicotinoids.

  11. Translocation of the neonicotinoid seed treatment clothianidin in maize.

    Directory of Open Access Journals (Sweden)

    Adam Alford

    Full Text Available Neonicotinoid seed treatments, typically clothianidin or thiamethoxam, are routinely applied to >80% of maize (corn seed grown in North America where they are marketed as a targeted pesticide delivery system. Despite this widespread use, the amount of compound translocated into plant tissue from the initial seed treatment to provide protection has not been reported. Our two year field study compared concentrations of clothianidin seed treatments in maize to that of maize without neonicotinoid seed treatments and found neonicotinoids present in root tissues up to 34 days post planting. Plant-bound clothianidin concentrations followed an exponential decay pattern with initially high values followed by a rapid decrease within the first ~20 days post planting. A maximum of 1.34% of the initial seed treatment was successfully recovered from plant tissues in both study years and a maximum of 0.26% was recovered from root tissue. Our findings show neonicotinoid seed treatments may provide protection from some early season secondary maize pests. However, the proportion of the neonicotinoid seed treatment clothianidin translocated into plant tissues throughout the growing season is low overall and this observation may provide a mechanism to explain reports of inconsistent efficacy of this pest management approach and increasing detections of environmental neonicotinoids.

  12. Pore formation by T3SS translocators: liposome leakage assay.

    Science.gov (United States)

    Faudry, Eric; Perdu, Caroline; Attrée, Ina

    2013-01-01

    Gram-negative bacteria utilize a dedicated membrane-embedded apparatus, the type III secretion system (T3SS), to inject proteins into host cells. The passage of the proteins across the target membrane is accomplished by a proteinaceous pore-the translocon-formed within the host-cell cytoplasmic membrane. Translocators bound to their chaperones can be expressed in Escherichia coli and subsequently dissociated from the chaperone by guanidine treatment. The pore formation properties of the translocators can then be studied by an in-vitro liposome leakage assay. Sulforhodamine-B is encapsulated within lipid vesicles during liposome preparation. At high concentration, this fluorochrome exhibits self-quenching limiting fluorescence emission. Upon pore formation, liposome leakage leads to the dilution of Sulforhodamine-B in the medium and fluorescence emission increases. Alternatively, fluorochromes coupled to large dextran molecules can be encapsulated in order to estimate pore dimensions. Here we describe protein expression and purification, dye-liposome preparation, and leakage assay conditions.

  13. Myeloid translocation genes differentially regulate colorectal cancer programs

    Science.gov (United States)

    Parang, Bobak; Bradley, Amber M.; Mittal, Mukul K.; Short, Sarah P.; Thompson, Joshua J.; Barrett, Caitlyn W.; Naik, Rishi D.; Bilotta, Anthony J.; Washington, Mary K.; Revetta, Frank L.; Smith, Jesse J.; Chen, Xi; Wilson, Keith T.; Hiebert, Scott W.; Williams, Christopher S.

    2016-01-01

    Myeloid translocation genes (MTGs), originally identified as chromosomal translocations in acute myelogenous leukemia, are transcriptional corepressors that regulate hematopoietic stem cell programs. Analysis of The Cancer Genome Atlas (TCGA) database revealed that MTGs were mutated in epithelial malignancy and suggested that loss of function might promote tumorigenesis. Genetic deletion of MTGR1 and MTG16 in the mouse has revealed unexpected and unique roles within the intestinal epithelium. Mtgr1−/− mice have progressive depletion of all intestinal secretory cells, and Mtg16−/− mice have a decrease in goblet cells. Furthermore, both Mtgr1−/− and Mtg16−/− mice have increased intestinal epithelial cell proliferation. We thus hypothesized that loss of MTGR1 or MTG16 would modify Apc1638/+-dependent intestinal tumorigenesis. Mtgr1−/− mice, but not Mtg16−/− mice, had a 10-fold increase in tumor multiplicity. This was associated with more advanced dysplasia, including progression to invasive adenocarcinoma, and augmented intratumoral proliferation. Analysis of ChIP-seq datasets for MTGR1 and MTG16 targets indicated that MTGR1 can regulate Wnt and Notch signaling. In support of this, immunohistochemistry and gene expression analysis revealed that both Wnt and Notch signaling pathways were hyperactive in Mtgr1−/− tumors. Furthermore, in human colorectal cancer (CRC) samples MTGR1 was downregulated at both the transcript and protein level. Overall our data indicates that MTGR1 has a context dependent effect on intestinal tumorigenesis. PMID:27270437

  14. Reverse translocation of tRNA in the ribosome.

    Science.gov (United States)

    Shoji, Shinichiro; Walker, Sarah E; Fredrick, Kurt

    2006-12-28

    A widely held view is that directional movement of tRNA in the ribosome is determined by an intrinsic mechanism and driven thermodynamically by transpeptidation. Here, we show that, in certain ribosomal complexes, the pretranslocation (PRE) state is thermodynamically favored over the posttranslocation (POST) state. Spontaneous and efficient conversion from the POST to PRE state is observed when EF-G is depleted from ribosomes in the POST state or when tRNA is added to the E site of ribosomes containing P-site tRNA. In the latter assay, the rate of tRNA movement is increased by streptomycin and neomycin, decreased by tetracycline, and not affected by the acylation state of the tRNA. In one case, we provide evidence that complex conversion occurs by reverse translocation (i.e., direct movement of the tRNAs from the E and P sites to the P and A sites, respectively). These findings have important implications for the energetics of translocation.

  15. Gamma-rays induced reciprocal translocations in Nigella damascena L

    International Nuclear Information System (INIS)

    Saha, Aditi; Datta, Animesh K.

    2000-01-01

    Gamma irradiations (5 kR, 10 kR and 20 kR) of Nigella damascena L. (cultivated variety Miss Jekyl) seeds (with moisture content 13.33%) induced 3 translocation heterozygotes (P-I from 5 kR, P-38 from 5 kR and P- 73 from 20 kR). These exhibited the formation of either a ring or a chain of 4 chromosomes in 30.7% to 68.1% meiocytes. Predominance of rings or equal proportion of rings and chains occurred in translocation heterozygotes P-38 and in P-I and P-73 respectively. The rings showed preponderance of adjacent orientation and the chains demonstrated frequent alternate orientation. Though pollen fertility was 16.5%, 24.8% and 17.1% in P-I, P-38 and P-73 respectively, frequency of viable pollen grains was nil in P-38 and P-73 and it was 5.2% in P-I. Seed sterility was complete in P-38 and P-73 but P-I yielded 2.11% filled seeds per capsule on selfing and 2.56% seeds/capsule on cross pollination. (author)

  16. HMGB1 Translocation After Ischemia in the Ovine Fetal Brain.

    Science.gov (United States)

    Zhang, Jiyong; Klufas, Daniel; Manalo, Karina; Adjepong, Kwame; Davidson, Joanne O; Wassink, Guido; Bennet, Laura; Gunn, Alistair J; Stopa, Edward G; Liu, Keyue; Nishibori, Masahiro; Stonestreet, Barbara S

    2016-06-01

    Inflammation contributes to the evolution of hypoxic-ischemic (HI) brain injury. High-mobility group box-1 (HMGB1) is a nuclear protein that is translocated from the nucleus and released after ischemia in adult rodents and thereby initiates inflammatory responses. However, there is very little information regarding the effects of HI on HMGB1 in immature brains. To investigate the effects of HI on HMGB1 in the term-equivalent fetal brain, ovine fetuses at 127 days gestation were studied after 30 minutes of carotid occlusion. Groups were sham-control and ischemia with 48 hours and ischemia with 72 hours of reperfusion. By immunohistochemistry, HMGB1 was found to be localized primarily in cell nuclei and partially in cytoplasmic compartments in the cerebral cortex of controls. Ischemia increased the area fraction of neuronal cells with cytoplasmic HMGB1 staining, and Western immunoblot revealed that cytosolic HMGB1 expression increased after ischemia (p the sham-control brains (p the nuclear to cytosolic compartments after ischemic brain injury in fetal sheep. This translocation may enable the action of HMGB1 as a proinflammatory cytokine that contributes to HI injury in the developing brain. © 2016 American Association of Neuropathologists, Inc. All rights reserved.

  17. DNA translocation through single-layer boron nitride nanopores.

    Science.gov (United States)

    Gu, Zonglin; Zhang, Yuanzhao; Luan, Binquan; Zhou, Ruhong

    2016-01-21

    Ultra-thin nanopores have become promising biological sensors because of their outstanding signal-to-noise ratio and spatial resolution. Here, we show that boron nitride (BN), which is a new two-dimensional (2D) material similar to graphene, could be utilized for making a nanopore with an atomic thickness. Using an all-atom molecular dynamics simulation, we investigated the dynamics of DNA translocation through the BN nanopore. The results of our simulations demonstrated that it is possible to detect different double-stranded DNA (dsDNA) sequences from the recording of ionic currents through the pore during the DNA translocation. Surprisingly, opposite to results for a graphene nanopore, we found the calculated blockage current for poly(A-T)40 in a BN nanopore to be less than that for poly(G-C)40. Also in contrast with the case of graphene nanopores, dsDNA models moved smoothly and in an unimpeded manner through the BN nanopores in the simulations, suggesting a potential advantage for using BN nanopores to design stall-free sequencing devices. BN nanopores, which display several properties (such as being hydrophilic and non-metallic) that are superior to those of graphene, are thus expected to find applications in the next generation of high-speed and low-cost biological sensors.

  18. Dynamics of end-pulled polymer translocation through a nanopore

    Science.gov (United States)

    Sarabadani, Jalal; Ghosh, Bappa; Chaudhury, Srabanti; Ala-Nissila, Tapio

    2017-11-01

    We consider the translocation dynamics of a polymer chain forced through a nanopore by an external force on its head monomer on the trans side. For a proper theoretical treatment we generalize the iso-flux tension propagation (IFTP) theory to include friction arising from the trans side subchain. The theory reveals a complicated scenario of multiple scaling regimes depending on the configurations of the cis and the trans side subchains. In the limit of high driving forces f such that the trans subchain is strongly stretched, the theory is in excellent agreement with molecular dynamics simulations and allows an exact analytic solution for the scaling of the translocation time τ as a function of the chain length N 0 and f. In this regime the asymptotic scaling exponents for τ ∼ N_0α fβ are α=2 , and β =-1 . The theory reveals significant correction-to-scaling terms arising from the cis side subchain and pore friction, which lead to a very slow approach to α =2 from below as a function of increasing N 0.

  19. Molecular determinants of nucleolar translocation of RNA helicase A

    International Nuclear Information System (INIS)

    Liu Zhe; Kenworthy, Rachael; Green, Christopher; Tang, Hengli

    2007-01-01

    RNA helicase A (RHA) is a member of the DEAH-box family of DNA/RNA helicases involved in multiple cellular processes and the life cycles of many viruses. The subcellular localization of RHA is dynamic despite its steady-state concentration in the nucleoplasm. We have previously shown that it shuttles rapidly between the nucleus and the cytoplasm by virtue of a bidirectional nuclear transport domain (NTD) located in its carboxyl terminus. Here, we investigate the molecular determinants for its translocation within the nucleus and, more specifically, its redistribution from the nucleoplasm to nucleolus or the perinucleolar region. We found that low temperature treatment, transcription inhibition or replication of hepatitis C virus caused the intranuclear redistribution of the protein, suggesting that RHA shuttles between the nucleolus and nucleoplasm and becomes trapped in the nucleolus or the perinucleolar region upon blockade of transport to the nucleoplasm. Both the NTD and ATPase activity were essential for RHA's transport to the nucleolus or perinucleolar region. One of the double-stranded RNA binding domains (dsRBD II) was also required for this nucleolar translocation (NoT) phenotype. RNA interference studies revealed that RHA is essential for survival of cultured hepatoma cells and the ATPase activity appears to be important for this critical role

  20. Translocation of cesium in plants after foliar deposition - Experiments and models

    International Nuclear Information System (INIS)

    Proehl, G.; Voigt, G.; Mueller, H.

    1991-01-01

    The translocation of cesium from the foliage to the edible parts as function of the time period between deposition and harvest has been determined for cereals, potatoes, green beans and carrots. From the results the following conclusions can be drawn: 1. The maximum of the cesium translocation is 40 to 50 and 70 to 90 days before harvest for cereals and potatoes respectively. For green beans a maximum was observed after deposition 15 days before harvest; 2. The variations of the translocation factors are less if the translocation is normalized to the yield; 3. The translocation factors are in good agreement with those of other investigators. The agreement between the experimental series is better for a normalization of the translocation factor on the yield; 4. For cereals and potatoes the translocation can be described with gaussian functions which are consistent with the physiological development of cereals and potatoes. Although the approach in ECOSYS tends to over predict slightly the translocation for barley and potatoes there is a good overall agreement between the experiments and this model; 5. According to the investigations available the translocation of cesium can be predicted within a factor of 3 for cereals and a factor of 4 for potatoes. Sources of the uncertainties besides the biological variability and the inherent experimental error are differences in the development of the plants due to weather conditions, farm management and plant diseases. (9 refs., 5 figs.)

  1. Translocation of a Polymer Chain across a Nanopore: A Brownian Dynamics Simulation Study

    Science.gov (United States)

    Tian, Pu; Smith, Grant D.

    2003-01-01

    We carried out Brownian dynamics simulation studies of the translocation of single polymer chains across a nanosized pore under the driving of an applied field (chemical potential gradient). The translocation process can be either dominated by the entropic barrier resulted from restricted motion of flexible polymer chains or by applied forces (or chemical gradient across the wall), we focused on the latter case in our studies. Calculation of radius of gyrations at the two opposite sides of the wall shows that the polymer chains are not in equilibrium during the translocation process. Despite this fact, our results show that the one-dimensional diffusion and the nucleation model provide an excellent description of the dependence of average translocation time on the chemical potential gradients, the polymer chain length and the solvent viscosity. In good agreement with experimental results and theoretical predictions, the translocation time distribution of our simple model shows strong non-Gaussian characteristics. It is observed that even for this simple tubelike pore geometry, more than one peak of translocation time distribution can be generated for proper pore diameter and applied field strengths. Both repulsive Weeks-Chandler-Anderson and attractive Lennard-Jones polymer-nanopore interaction were studied, attraction facilitates the translocation process by shortening the total translocation time and dramatically improve the capturing of polymer chain. The width of the translocation time distribution was found to decrease with increasing temperature, increasing field strength, and decreasing pore diameter.

  2. Use of wild–caught individuals as a key factor for success in vertebrate translocations

    Energy Technology Data Exchange (ETDEWEB)

    Rummel, L.; MartInez-AbraIn, A.; Mayol, J.; Ruiz-Olmo, J.; Mañas, F.; Jimenez, J.; Gomez, J.A.; Oro, D.

    2016-07-01

    Success of vertebrate translocations is crucial to improve efficacy and efficiency of conservation actions but it is often difficult to assess because negative results (failed translocations) are seldom published. We developed surveys and sent them to heads of conservation services in three major Spanish Mediterranean regions. The purpose of our surveys was to determine which methodological factor, that could easily be implemented in practice, was more influential for translocation success. These factors included the origin of translocated individuals (captive or wild) and translocation effort (propagule size and program duration). After analyzing 83 programs, corresponding to 34 different vertebrate species, by means of generalized linear mixed modelling, we found that ‘origin’ was more relevant for translocation success than ‘effort’, although we could not rule out some role of translocation effort. Variance in success of translocation programs involving individuals from wild sources was smaller and consequently results more predictable. Origin interacted with taxa so that success was higher when using wild birds and especially wild fish and mammals, but not when releasing reptiles. Hence, we suggest that, for any given effort, translocation results will be better for most vertebrate taxa if individuals from wild sources are used. When this is not feasible, managers should release captive–reared individuals for a long number of years rather than a short number of years. (Author)

  3. Interfering with bacterial gossip

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael

    2011-01-01

    defense. Antibiotics exhibit a rather limited effect on biofilms. Furthermore, antibiotics have an ‘inherent obsolescence’ because they select for development of resistance. Bacterial infections with origin in bacterial biofilms have become a serious threat in developed countries. Pseudomonas aeruginosa...... that appropriately target bacteria in their relevant habitat with the aim of mitigating their destructive impact on patients. In this review we describe molecular mechanisms involved in “bacterial gossip” (more scientifically referred to as quorum sensing (QS) and c-di-GMP signaling), virulence, biofilm formation......, resistance and QS inhibition as future antimicrobial targets, in particular those that would work to minimize selection pressures for the development of resistant bacteria....

  4. Bacterial surface adaptation

    Science.gov (United States)

    Utada, Andrew

    2014-03-01

    Biofilms are structured multi-cellular communities that are fundamental to the biology and ecology of bacteria. Parasitic bacterial biofilms can cause lethal infections and biofouling, but commensal bacterial biofilms, such as those found in the gut, can break down otherwise indigestible plant polysaccharides and allow us to enjoy vegetables. The first step in biofilm formation, adaptation to life on a surface, requires a working knowledge of low Reynolds number fluid physics, and the coordination of biochemical signaling, polysaccharide production, and molecular motility motors. These crucial early stages of biofilm formation are at present poorly understood. By adapting methods from soft matter physics, we dissect bacterial social behavior at the single cell level for several prototypical bacterial species, including Pseudomonas aeruginosa and Vibrio cholerae.

  5. Bacterial Meningitis in Infants

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-04-01

    Full Text Available A retrospective study of 80 infantile patients (ages 30-365 days; 47 male, 33 female with culture-proven bacterial meningitis seen over a 16 year period (1986-2001 is reported from Taiwan.

  6. Factitious Bacterial Meningitis Revisited

    Science.gov (United States)

    Peterson, E.; Thrupp, L.; Uchiyama, N.; Hawkins, B.; Wolvin, B.; Greene, G.

    1982-01-01

    Nonviable gram-negative bacilli were seen in smears of cerebrospinal fluid from eight infants in whom bacterial meningitis was ruled out. Tubes from commercial kits were the source of the factitious organisms. PMID:7153328

  7. Vimentin in Bacterial Infections

    DEFF Research Database (Denmark)

    Mak, Tim N; Brüggemann, Holger

    2016-01-01

    filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge...... about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria......-vimentin interactions are presented in this review: the role of vimentin in pathogen-binding on the cell surface and subsequent bacterial invasion and the interaction of cytosolic vimentin and intracellular pathogens with regards to innate immune signaling. Mechanistic insight is presented involving distinct bacterial...

  8. Rab GTPases and the Autophagy Pathway: Bacterial Targets for a Suitable Biogenesis and Trafficking of Their Own Vacuoles

    Directory of Open Access Journals (Sweden)

    María Milagros López de Armentia

    2016-03-01

    Full Text Available Autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. Intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. To degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a process that is regulated by Rab GTPases. Interestingly, in order to survive and replicate in the phagosome, some pathogens employ different strategies to manipulate vesicular traffic, inhibiting phagolysosomal biogenesis (e.g., Staphylococcus aureus and Mycobacterium tuberculosis or surviving in acidic compartments and forming replicative vacuoles (e.g., Coxiella burnetti and Legionella pneumophila. The bacteria described in this review often use secretion systems to control the host’s response and thus disseminate. To date, eight types of secretion systems (Type I to Type VIII are known. Some of these systems are used by bacteria to translocate pathogenic proteins into the host cell and regulate replicative vacuole formation, apoptosis, cytokine responses, and autophagy. Herein, we have focused on how bacteria manipulate small Rab GTPases to control many of these processes. The growing knowledge in this field may facilitate the development of new treatments or contribute to the prevention of these types of bacterial infections.

  9. Rab GTPases and the Autophagy Pathway: Bacterial Targets for a Suitable Biogenesis and Trafficking of Their Own Vacuoles.

    Science.gov (United States)

    López de Armentia, María Milagros; Amaya, Celina; Colombo, María Isabel

    2016-03-08

    Autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. Intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. To degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a process that is regulated by Rab GTPases. Interestingly, in order to survive and replicate in the phagosome, some pathogens employ different strategies to manipulate vesicular traffic, inhibiting phagolysosomal biogenesis (e.g., Staphylococcus aureus and Mycobacterium tuberculosis) or surviving in acidic compartments and forming replicative vacuoles (e.g., Coxiella burnetti and Legionella pneumophila). The bacteria described in this review often use secretion systems to control the host's response and thus disseminate. To date, eight types of secretion systems (Type I to Type VIII) are known. Some of these systems are used by bacteria to translocate pathogenic proteins into the host cell and regulate replicative vacuole formation, apoptosis, cytokine responses, and autophagy. Herein, we have focused on how bacteria manipulate small Rab GTPases to control many of these processes. The growing knowledge in this field may facilitate the development of new treatments or contribute to the prevention of these types of bacterial infections.

  10. Water-Soluble Coenzyme Q10 Inhibits Nuclear Translocation of Apoptosis Inducing Factor and Cell Death Caused by Mitochondrial Complex I Inhibition

    Directory of Open Access Journals (Sweden)

    Haining Li

    2014-07-01

    Full Text Available The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10 on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS production by dihydroethidine (DHE and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM. Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

  11. [INTESTINAL FAILURE AND YERSINIA PSEUDOTUBERCULOSIS TRANSLOCATION IN THE DEVELOPMENTOF EXPERIMENTAL GENERALIZED INFECTION].

    Science.gov (United States)

    Chicherin, I Yu; Pogorelky, I P; Lundovskikh, I A; Darmov, I V; Gorshkov, A S; Shabalina, M R

    2016-01-01

    To determine the value of intestinal failure and translocation of bacteria Y. pseudotuberculosis, and normal intestinal microbiota in the initiation and generalization of infection in experimental pseudotuberculosis in conventional white mice, as well as pathological manifestation of it as a response to the adhesion and colonization of the mucosus membrane by pathogenic bacteria Y. pseudotuberculosis. Experimental models of pseudotuberculosis in conventional white mice used the pathogenic Y. pseudotuberculosis 147 serotype I strain, containing a calcium-dependence plasmid with a molecular weight of 47 MDa. Cultivation of the pseudotuberculosis pathogen given its psychrophilic was performed on Hottinger agar at a temperature of (4-5) °C. The lactobacilli strain L plantarum 8P-A3 was isolated from a lyophilized commercial probiotic Lactobacterin (manufactured by "NPO Microgen", Russia) and used to obtain native culture supernatant fluid of lactobacilli, the composition of which was detected by gas-liquid chromatography with mass-selective detection. Gentamicin for parenteral administration was manufactured by JSC "Biochemist", Russia. Pathomorphological examination was performed on the 4-6th day of the experiment. Fragments of the small intestine, liver, kidneys, and lungs from dead animals were chosen for examination. Tissues were fixed in 10% neutral formalin, dehydrated in isopropanol and embedded in paraffin. Preparations were stained with Ehrlich hematoxylin and eosin, examined on the microscope "Mikmed-2" (JSC "LOMO", Russia) under magnification x 200-x1000. Statistical processing of the experimental results was carried out according to the method of Kerber in modification of I.P. Ashmarin and A.A. Vorobyov. The role of intestinal failure and translocation of bacteria Y. pseudotuberculosis, and normal intestinal microbiota in the initiation and generalization of infection in animals has been found. It has been proved that the oral administration of supernatant

  12. [Diagnosis of bacterial vaginosis].

    Science.gov (United States)

    Djukić, Slobodanka; Ćirković, Ivana; Arsić, Biljana; Garalejić, Eliana

    2013-01-01

    Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2-producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent's scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up-to-date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short-term and long-term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  13. Exploring bacterial outer membrane barrier to combat bad bugs.

    Science.gov (United States)

    Ghai, Ishan; Ghai, Shashank

    2017-01-01

    One of the main fundamental mechanisms of antibiotic resistance in Gram-negative bacteria comprises an effective change in the membrane permeability to antibiotics. The Gram-negative bacterial complex cell envelope comprises an outer membrane that delimits the periplasm from the exterior environment. The outer membrane contains numerous protein channels, termed as porins or nanopores, which are mainly involved in the influx of hydrophilic compounds, including antibiotics. Bacterial adaptation to reduce influx through these outer membrane proteins (Omps) is one of the crucial mechanisms behind antibiotic resistance. Thus to interpret the molecular basis of the outer membrane permeability is the current challenge. This review attempts to develop a state of knowledge pertinent to Omps and their effective role in antibiotic influx. Further, it aims to study the bacterial response to antibiotic membrane permeability and hopefully provoke a discussion toward understanding and further exploration of prospects to improve our knowledge on physicochemical parameters that direct the translocation of antibiotics through the bacterial membrane protein channels.

  14. Exploring bacterial outer membrane barrier to combat bad bugs

    Directory of Open Access Journals (Sweden)

    Ghai I

    2017-08-01

    Full Text Available Ishan Ghai,1 Shashank Ghai2 1School of Engineering and Life Sciences, Jacobs University, Bremen, 2Leibniz University, Hannover, Germany Abstract: One of the main fundamental mechanisms of antibiotic resistance in Gram-negative bacteria comprises an effective change in the membrane permeability to antibiotics. The Gram-negative bacterial complex cell envelope comprises an outer membrane that delimits the periplasm from the exterior environment. The outer membrane contains numerous protein channels, termed as porins or nanopores, which are mainly involved in the influx of hydrophilic compounds, including antibiotics. Bacterial adaptation to reduce influx through these outer membrane proteins (Omps is one of the crucial mechanisms behind antibiotic resistance. Thus to interpret the molecular basis of the outer membrane permeability is the current challenge. This review attempts to develop a state of knowledge pertinent to Omps and their effective role in antibiotic influx. Further, it aims to study the bacterial response to antibiotic membrane permeability and hopefully provoke a discussion toward understanding and further exploration of prospects to improve our knowledge on physicochemical parameters that direct the translocation of antibiotics through the bacterial membrane protein channels. Keywords: antibiotics, Gram-negative bacteria, cell envelope, protein channels, nanopores, influx, antibiotic resistance

  15. Translocation and neurotoxicity of CdTe quantum dots in RMEs motor neurons in nematode Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Yunli; Wang, Xiong; Wu, Qiuli; Li, Yiping; Wang, Dayong, E-mail: dayongw@seu.edu.cn

    2015-02-11

    Graphical abstract: - Highlights: • We investigated in vivo neurotoxicity of CdTe QDs on RMEs motor neurons in C. elegans. • CdTe QDs in the range of μg/L caused neurotoxicity on RMEs motor neurons. • Bioavailability of CdTe QDs may be the primary inducer for CdTe QDs neurotoxicity. • Both oxidative stress and cell identity regulate the CdTe QDs neurotoxicity. • CdTe QDs were translocated and deposited into RMEs motor neurons. - Abstract: We employed Caenorhabditis elegans assay system to investigate in vivo neurotoxicity of CdTe quantum dots (QDs) on RMEs motor neurons, which are involved in controlling foraging behavior, and the underlying mechanism of such neurotoxicity. After prolonged exposure to 0.1–1 μg/L of CdTe QDs, abnormal foraging behavior and deficits in development of RMEs motor neurons were observed. The observed neurotoxicity from CdTe QDs on RMEs motor neurons might be not due to released Cd{sup 2+}. Overexpression of genes encoding Mn-SODs or unc-30 gene controlling cell identity of RMEs neurons prevented neurotoxic effects of CdTe QDs on RMEs motor neurons, suggesting the crucial roles of oxidative stress and cell identity in regulating CdTe QDs neurotoxicity. In nematodes, CdTe QDs could be translocated through intestinal barrier and be deposited in RMEs motor neurons. In contrast, CdTe@ZnS QDs could not be translocated into RMEs motor neurons and therefore, could only moderately accumulated in intestinal cells, suggesting that ZnS coating might reduce neurotoxicity of CdTe QDs on RMEs motor neurons. Therefore, the combinational effects of oxidative stress, cell identity, and bioavailability may contribute greatly to the mechanism of CdTe QDs neurotoxicity on RMEs motor neurons. Our results provide insights into understanding the potential risks of CdTe QDs on the development and function of nervous systems in animals.

  16. The flavones apigenin and luteolin induce FOXO1 translocation but inhibit gluconeogenic and lipogenic gene expression in human cells.

    Directory of Open Access Journals (Sweden)

    Christiane Bumke-Vogt

    Full Text Available The flavones apigenin (4',5,7,-trihydroxyflavone and luteolin (3',4',5,7,-tetrahydroxyflavone are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1, an important mediator of insulin signal transduction. Insulin reversed the translocation of FOXO1 as shown by live cell imaging. The impact on the expression of target genes was evaluated in HepG2 (human hepatoma cells. The mRNA-expression of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK and glucose-6-phosphatase (G6Pc, the lipogenic enzymes fatty-acid synthase (FASN and acetyl-CoA-carboxylase (ACC were down-regulated by both flavones with smaller effective dosages of apigenin than for luteolin. PKB/AKT-, PRAS40-, p70S6K-, and S6-phosphorylation was reduced by apigenin and luteolin but not that of the insulin-like growth factor receptor IGF-1R by apigenin indicating a direct inhibition of the PKB/AKT-signaling pathway distal to the IGF-1 receptor. N-acetyl-L-cysteine did not prevent FOXO1 nuclear translocation induced by apigenin and luteolin, suggesting that these flavones do not act via oxidative stress. The roles of FOXO1, FOXO3a, AKT, sirtuin1 (SIRT1, and nuclear factor (erythroid-derived2-like2 (NRF2, investigated by siRNA knockdown, showed differential patterns of signal pathways involved and a role of NRF2 in the inhibition of gluconeogenic enzyme expression. We conclude that these flavones show an antidiabetic potential due to reduction of gluconeogenic and lipogenic capacity despite inhibition of the PKB/AKT pathway which justifies detailed investigation in vivo.

  17. Microenvironments to study migration and somal translocation in cortical neurons.

    Science.gov (United States)

    Zhao, Shifang; Fan, Wenqiang; Guo, Xiang; Xue, Longjian; Berninger, Benedikt; Salierno, Marcelo J; Del Campo, Aránzazu

    2018-02-01

    Migrating post-mitotic neurons of the developing cerebral cortex undergo terminal somal translocation (ST) when they reach their final destination in the cortical plate. This process is crucial for proper cortical layering and its perturbation can lead to brain dysfunction. Here we present a reductionist biomaterials platform that faithfully supports and controls the distinct phases of terminal ST in vitro. We developed microenvironments with different adhesive molecules to support neuronal attachment, neurite extension, and migration in distinct manners. Efficient ST occurred when the leading process of migratory neurons crossed from low-to high-adhesive areas on a substrate, promoting spreading of the leading growth cone. Our results indicate that elementary adhesive cell-substrate interactions strongly influence migratory behavior and the final positioning of neurons during their developmental journey. This in vitro model allows advanced experimentation to reveal the microenvironmental requirements underlying cortical layer development and disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. How filamentous plant pathogen effectors are translocated to host cells.

    Science.gov (United States)

    Lo Presti, Libera; Kahmann, Regine

    2017-08-01

    The interaction of microbes with "signature" plants is largely governed by secreted effector proteins, which serve to dampen plant defense responses and modulate host cell processes. Secreted effectors can function either in the apoplast or within plant cell compartments. How oomycetes and fungi translocate their effectors to plant cells is still poorly understood and controversial. While most oomycete effectors share a common 'signature' that was proposed to mediate their uptake via endocytosis, fungal effectors display no conserved motifs at the primary amino acid sequence level. Here we summarize current knowledge in the field of oomycete and fungal effector uptake and highlight emerging themes that may unite rather than set apart these unrelated filamentous pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Physical insights into the blood-brain barrier translocation mechanisms

    Science.gov (United States)

    Theodorakis, Panagiotis E.; Müller, Erich A.; Craster, Richard V.; Matar, Omar K.

    2017-08-01

    The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB. Moreover, we discuss various numerical and simulation approaches used to study the BBB, and possible future directions based on multi-scale methods. We anticipate that this review will motivate multi-disciplinary research on the BBB aiming at the design of effective drug therapies.

  20. Mitochondrial tRNA gene translocations in highly eusocial bees

    Directory of Open Access Journals (Sweden)

    Daniela Silvestre

    2006-01-01

    Full Text Available Mitochondrial gene rearrangement events, especially involving tRNA genes, have been described more frequently as more complete mitochondrial genome sequences are becoming available. In the present work, we analyzed mitochondrial tRNA gene rearrangements between two bee species belonging to the tribes Apini and Meliponini within the "corbiculate Apidae". Eleven tRNA genes are in different genome positions or strands. The molecular events responsible for each translocation are explained. Considering the high number of rearrangements observed, the data presented here contradict the general rule of high gene order conservation among closely related organisms, and also represent a powerful molecular tool to help solve questions about phylogeny and evolution in bees.

  1. Logic Gate Operation by DNA Translocation through Biological Nanopores.

    Directory of Open Access Journals (Sweden)

    Hiroki Yasuga

    Full Text Available Logical operations using biological molecules, such as DNA computing or programmable diagnosis using DNA, have recently received attention. Challenges remain with respect to the development of such systems, including label-free output detection and the rapidity of operation. Here, we propose integration of biological nanopores with DNA molecules for development of a logical operating system. We configured outputs "1" and "0" as single-stranded DNA (ssDNA that is or is not translocated through a nanopore; unlabeled DNA was detected electrically. A negative-AND (NAND operation was successfully conducted within approximately 10 min, which is rapid compared with previous studies using unlabeled DNA. In addition, this operation was executed in a four-droplet network. DNA molecules and associated information were transferred among droplets via biological nanopores. This system would facilitate linking of molecules and electronic interfaces. Thus, it could be applied to molecular robotics, genetic engineering, and even medical diagnosis and treatment.

  2. Microbial translocation and cardiometabolic risk factors in HIV infection

    DEFF Research Database (Denmark)

    Trøseid, Marius; Manner, Ingjerd W; Pedersen, Karin K

    2014-01-01

    The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has...... is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers...... increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms...

  3. Translocation, distribution, and environmental degradation of hexachlorophene in tomatoes.

    Science.gov (United States)

    Van Auken, O W; Hulse, M

    1979-01-01

    The translocation, distribution, metabolism and environmental degradation of hexachlorophene were investigated in tomato plants (Lycopersicon esculentum Mill cv. beefsteak). All plants were grown under standardized conditions and treated with leaf-applied 14C-ring-labeled hexachlorophene (HCP). Treatment time ranged from 0 to 70 days. Autoradiographic analyses were performed on all plants. Selected plant tissues were extracted and chromatographed, using thin layer (TLC) and gas liquid chromatography (GLC). Hexachlorophene was not translocated from the plant leaves. No metabolites of hexachlorophene was found. A slight, but statistically nonsignificant, amount of HCP was lost from the leaves and the inert controls. At the end of the 70-day treatment, based on TLC and regression analysis of thin layer chromatographic plates, averages of 89.5% and 75.9% of the applied HPC remained unaltered on the treated plants and controls, respectively. This indicated that 10.5% and 24.1%, respectively, of the original HCP had been altered. Differences between the treatments and controls were statistically significant after 28 days of exposure. Further analyses of the above data, using gas chromatographic methods, showed that as many as 14 peaks were found in the treated samples and the controls, including the parent material. Ultraviolet photolysis seemed to be the mechanism responsible for alteration of the hexachlorophene. Three extracted chlorinated compounds have been identified by GC-mass spectral (MS) analysis including 2,2'-dihydroxy-3,5',6,6'-tetrachlorodiphenylmethane, 2,2'-dihydroxy-3,5,5',6,6'-pentachlorodiphenylmethane, and 2,2'-dihydroxy-3,3',5,5',6,6'-hexachlorodiphenylmethane (parent HCP). Eleven other electrophylic compounds have been found in various treated plant or control extracts. Further analyses will be necessary to verify the identification of the other degradation products.

  4. Translocation of cell penetrating peptide engrafted nanoparticles across skin layers.

    Science.gov (United States)

    Patlolla, Ram R; Desai, Pinaki R; Belay, Kalayu; Singh, Mandip S

    2010-07-01

    The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24h, fluorescence was observed upto a depth of 120 microm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 microm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers. Published by Elsevier Ltd.

  5. Robertsonian translocation 13/14 associated with rRNA genes ...

    African Journals Online (AJOL)

    Alexander A. Dolskiy

    2017-12-01

    Dec 1, 2017 ... Robertsonian translocation 13/14 associated with rRNA genes ... Chromosome 13. Chromosome 14. Intellectual disability. a b s t r a c t. Background: The Robertsonian translocations inherited from parents with a normal ..... expression in lymphocyte of trisomy 21 babies/children: in vivo evaluation.

  6. Preimplantation genetic diagnosis by fluorescence in situ hybridization of reciprocal and Robertsonian translocations

    Directory of Open Access Journals (Sweden)

    Chun-Kai Chen

    2014-03-01

    Conclusion: There is a trend whereby the outcome for Robertsonian translocation group carriers is better than that for reciprocal translocation group carriers. Aneuploidy screening may possibly be added in order to improve the outcome, especially for individuals with an advanced maternal age. The emergence of an array-based technology should help improve this type of analysis.

  7. Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes

    NARCIS (Netherlands)

    van Roy, N.; Laureys, G.; van Gele, M.; Opdenakker, G.; Miura, R.; van der Drift, P.; Chan, A.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell

  8. Competition between Sec- and TAT-dependent protein translocation in Escherichia coli

    DEFF Research Database (Denmark)

    Cristóbal, S.; de Gier, J.-W.; Nielsen, Henrik

    1999-01-01

    Recently, a new protein translocation pathway, the twin-arginine translocation (TAT) pathway, has been identified in both bacteria and chloroplasts. To study the possible competition between the TAT- and the well-characterized Sec translocon-dependent pathways in Escherichia coli, we have fused...

  9. Comparison of experimentally determined translocation of 134Cs in potatoes with the radioecological code CHECOSYS

    International Nuclear Information System (INIS)

    Riesen, T.; Egli, J.; Andres, R.

    1997-01-01

    The verification and adoption of radioecological models is a continuous process. Greenhouse trials on the translocation of radiocaesium from leaves to potato tubers showed a 4-12 times higher translocation rate compared to the radioecological code CHECOSYS. The possible reasons for the differences are discussed. (author) 1 tab., 3 refs

  10. Proton transfer is rate-limiting for translocation of precursor proteins by the Escherichia coli translocase

    NARCIS (Netherlands)

    Driessen, Arnold J.M.; Wickner, William

    1991-01-01

    The protonmotive force stimulates translocation in vivo, in crude in vitro reactions, and in a purified, reconstituted reaction. Translocation activity is a function of the pH at the inner face of the membrane. Both the transmembrane pH gradient and the transmembrane electrical potential stimulate

  11. Comparative study of the reciprocal translocation rate in spermatocytes after irradiation of newborn and adult mice

    International Nuclear Information System (INIS)

    Pomerantseva, M.D.

    1978-01-01

    The yield of reciprocal translocations was investigated in spermatocytes of the CBA male mice irradiated immediately after their brith or after the irradiation of the stem spermatogonia at the age of 3 months. The irradiation doses were 100, 200, 400 R X-rays 300 R gamma-rays 60 Co. The yield of translocations in both groups was the same

  12. Live birth from a patient with a three-way balanced translocation t(5 ...

    African Journals Online (AJOL)

    Background: Three-way balanced translocations are unusual and can lead to infertility as well as abnormal embryos. In this case report, we describe a couple who experienced repeated miscarriages as a result of the male partner being a carrier of a three-way translocation t(5;8;12). Objectives: Array comparative genomic ...

  13. Preimplantation genetic diagnosis for X;autosome translocations : lessons from a case of misdiagnosis

    NARCIS (Netherlands)

    Van Echten-Arends, J.; Coonen, E.; Reuters, B.; Suijkerbuijk, R. F.; Dul, E. C.; Land, J. A.; van Ravenswaaij-Arts, C. M. A.

    2013-01-01

    Preimplantation genetic diagnosis (PGD) is offered to couples carrying a reciprocal translocation in an attempt to increase their chance of phenotypically normal offspring. For the selection of embryos that are balanced for the translocation chromosomes, it is critical to use a combination of DNA

  14. Nanomaterial translocation - the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs

    DEFF Research Database (Denmark)

    Kermanizadeh, Ali; Balharry, Dominique; Wallin, Håkan

    2015-01-01

    indicates that pulmonary exposure is associated with low (inhalation route-0.00001-1% of total applied dose-24 h) translocation of virtually insoluble NMs such as iridium, carbon black, gold and polystyrene, while slightly higher translocation has been observed for NMs with either slow (e.g. silver, cerium...

  15. Bacterial biofilms and antibiotic resistance

    Directory of Open Access Journals (Sweden)

    Liliana Caldas-Arias

    2015-04-01

    Full Text Available Biofilms give to bacteria micro-environmental benefits; confers protection against antimicrobials. Bacteria have antibiotic resistance by conventional and unusual mechanisms leading to delayed wound healing, to increase recurrent chronic infections and nosocomial contamination of medical devices. Objective: This narrative review aims to introduce the characteristics of Bacteria-biofilms, antimicrobial resistance mechanisms and potential alternatives for prevention and control of its formation. Methods: Search strategy was performed on records: PubMed / Medline, Lilacs, Redalyc; with suppliers such as EBSCO and thesaurus MeSH and DeCS. Conclusions: Knowledge and research performance of biofilm bacteria are relevant in the search of technology for detection and measuring sensitivity to antibiotics. The identification of Bacterial-biofilms needs no-traditional microbiological diagnosis.

  16. Antibiotic resistance of bacterial biofilms

    DEFF Research Database (Denmark)

    Hoiby, N.; Bjarnsholt, T.; Givskov, M.

    2010-01-01

    A biofilm is a structured consortium of bacteria embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and disinfectant chemicals as well as resisting phagocytosis...... to antibiotics. Biofilm growth is associated with an increased level of mutations as well as with quorum-sensing-regulated mechanisms. Conventional resistance mechanisms such as chromosomal beta-lactamase, upregulated efflux pumps and mutations in antibiotic target molecules in bacteria also contribute...... to the survival of biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy and they can be treated by chronic suppressive therapy. A promising strategy may be the use of enzymes that can dissolve the biofilm matrix (e.g. DNase and alginate lyase) as well as quorum...

  17. Autoproteolytic Activation of Bacterial Toxins

    Directory of Open Access Journals (Sweden)

    Aimee Shen

    2010-05-01

    Full Text Available Protease domains within toxins typically act as the primary effector domain within target cells. By contrast, the primary function of the cysteine protease domain (CPD in Multifunctional Autoprocessing RTX-like (MARTX and Clostridium sp. glucosylating toxin families is to proteolytically cleave the toxin and release its cognate effector domains. The CPD becomes activated upon binding to the eukaryotic-specific small molecule, inositol hexakisphosphate (InsP6, which is found abundantly in the eukaryotic cytosol. This property allows the CPD to spatially and temporally regulate toxin activation, making it a prime candidate for developing anti-toxin therapeutics. In this review, we summarize recent findings related to defining the regulation of toxin function by the CPD and the development of inhibitors to prevent CPD-mediated activation of bacterial toxins.

  18. Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal Motility, Inflammation and Increased Colonic Permeability in a Murine Model of Sepsis Are Most Pronounced When Administered in a Preventive Setup.

    Directory of Open Access Journals (Sweden)

    Sara Nullens

    Full Text Available During sepsis, gastrointestinal ileus, mucosal barrier dysfunction and bacterial translocation are accepted to be important triggers that can maintain or exacerbate the septic state. In the caecal ligation and puncture animal model of sepsis, we demonstrated that systemic and colonic interleukin-6 levels are significantly increased coinciding with an impaired colonic barrier function. We therefore aimed to study the effect of therapeutic or curative administration of anti-IL6 antibodies on overall GI motility, colonic permeability and translocation of intestinal bacteria in blood and mesenteric lymph nodes in the mouse caecal ligation and puncture model.OF-1 mice were randomized to either the preventive or curative protocol, in which they received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control solution. They subsequently underwent either the caecal ligation and puncture procedure, or sham-surgery. GI motility was assessed 48 h following the procedure, as well as colonic permeability, serum and colon cytokines, colonic tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph nodes were performed.Preventive administration of anti-interleukin-6 antibodies successfully counteracted the gastrointestinal motility disturbances and impaired colonic barrier function that could be observed in vehicle-treated septic animals. Serum and colonic levels of proinflammatory cytokines were significantly lower when animals were preventively treated with anti-interleukin-6 antibodies. A repetitive injection 24 h later resulted in the most pronounced effects. Curative treatment significantly lowered systemic and colonic inflammation markers while the effects on transit and permeability were unfortunately no longer significant.Caecal ligation and puncture resulted in septic ileus with an increased colonic permeability. Antibodies to interleukin-6 were able to ameliorate gastro-intestinal motility, suppress inflammation and

  19. Choking Prevention

    Science.gov (United States)

    ... Healthy Living Healthy Living Healthy Living Nutrition Fitness Sports Oral Health Emotional Wellness Growing Healthy Sleep Safety & Prevention Safety & Prevention Safety and Prevention Immunizations At Home ...

  20. Microbial translocation is correlated with HIV evolution in HIV-HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Jean-Jacques Tudesq

    Full Text Available Microbial translocation (MT is characterized by bacterial products passing into the blood through the gut barrier and is a key phenomenon in the pathophysiology of Human Immunodeficiency Virus (HIV infection. MT is also associated with liver damage in Hepatitis C Virus (HCV patients. The aim of the study was to assess MT in plasma of HIV-HCV co-infected patients. 16S rDNA (16 S Ribosomal DNA subunit marker and other markers of MT such as Lipopolysaccharide (LPS-binding protein (LBP, soluble CD14 (sCD14, intestinal fatty acid binding protein (I-FABP were used. Clinical, biological and immunological characteristics of the population were studied in order to correlate them with the intensity of the MT. We demonstrate that indirect markers of MT, LBP and CD14s, and a marker of intestinal permeability (I-FABP are significantly higher in HIV-HCV co-infected patients than in healthy controls (17.0 vs 2.6 μg/mL, p < 0.001; 1901.7 vs 1255.0 ng/mL, p = 0.018; 478.3 vs 248.1 pg/mL, p < 0.001, respectively, while a direct marker of MT (16S rDNA copies is not different between these two populations. However, plasma 16S rDNA was significantly higher in co-infected patients with long-standing HIV infections (RGM = 1.47 per 10 years, CI95% = [1.04:2.06], p = 0.03. Our findings show that in HIV-HCV co-infected patients, plasma 16S rDNA levels, directly reflecting MT, seem to be linked to the duration of HIV infection, while elevated levels of LBP and sCD14 reflect only a persistence of immune activation. The levels of these markers were not correlated with HCV evolution.

  1. Bacterial migration through punctured surgical gloves under real surgical conditions

    Directory of Open Access Journals (Sweden)

    Heidecke Claus-Dieter

    2010-07-01

    Full Text Available Abstract Background The aim of this study was to confirm recent results from a previous study focussing on the development of a method to measure the bacterial translocation through puncture holes in surgical gloves under real surgical conditions. Methods An established method was applied to detect bacterial migration from the operating site through the punctured glove. Biogel™ double-gloving surgical gloves were used during visceral surgeries over a 6-month period. A modified Gaschen-bag method was used to retrieve organisms from the inner glove, and thus-obtained bacteria were compared with micro-organisms detected by an intra-operative swab. Results In 20 consecutive procedures, 194 gloves (98 outer gloves, 96 inner gloves were examined. The rate of micro-perforations of the outer surgical glove was 10% with a median wearing time of 100 minutes (range: 20-175 minutes. Perforations occurred in 81% on the non-dominant hand, with the index finger most frequently (25% punctured. In six cases, bacterial migration could be demonstrated microbiologically. In 5% (5/98 of outer gloves and in 1% (1/96 of the inner gloves, bacterial migration through micro-perforations was observed. For gloves with detected micro-perforations (n = 10 outer layers, the calculated migration was 50% (n = 5. The minimum wearing time was 62 minutes, with a calculated median wearing time of 71 minutes. Conclusions This study confirms previous results that bacterial migration through unnoticed micro-perforations in surgical gloves does occur under real practical surgical conditions. Undetected perforation of surgical gloves occurs frequently. Bacterial migration from the patient through micro-perforations on the hand of surgeons was confirmed, limiting the protective barrier function of gloves if worn over longer periods.

  2. Yersinia pseudotuberculosis uses Ail and YadA to circumvent neutrophils by directing Yop translocation during lung infection.

    Science.gov (United States)

    Paczosa, Michelle K; Fisher, Michael L; Maldonado-Arocho, Francisco J; Mecsas, Joan

    2014-02-01

    A Yersinia pseudotuberculosis (Yptb) murine model of lung infection was previously developed using the serotype III IP2666NdeI strain, which robustly colonized lungs but only sporadically disseminated to the spleen and liver. We demonstrate here that a serotype Ib Yptb strain, IP32953, colonizes the lungs at higher levels and disseminates more efficiently to the spleen and liver compared with IP2666NdeI . The role of adhesins was investigated during IP32953 lung infection by constructing isogenic Δail, Δinv, ΔpsaE and ΔyadA mutants. An IP32953ΔailΔyadA mutant initially colonized but failed to persist in the lungs and disseminate to the spleen and liver. Yptb expressing these adhesins selectively bound to and targeted neutrophils for translocation of Yops. This selective targeting was critical for virulence because persistence of the ΔailΔyadA mutant was restored following intranasal infection of neutropenic mice. Furthermore, Ail and YadA prevented killing by complement-mediated mechanisms during dissemination to and/or growth in the spleen and liver, but not in the lungs. Combined, these results demonstratethat Ail and YadA are critical, redundant virulence factors during lung infection, because they thwart neutrophils by directing Yop-translocation specifically into these cells. © 2013 John Wiley & Sons Ltd.

  3. Nitric oxide-induced cell death in developing oligodendrocytes is associated with mitochondrial dysfunction and apoptosis-inducing factor translocation.

    Science.gov (United States)

    Baud, Olivier; Li, Jianrong; Zhang, Yumin; Neve, Rachael L; Volpe, Joseph J; Rosenberg, Paul A

    2004-10-01

    Reactive nitrogen species are thought to be involved in both hypoxic-ischemic and cytokine-induced brain injury, including periventricular leukomalacia (PVL), the major pathological substrate of cerebral palsy in premature infants. PVL appears to be the result of perinatal inflammatory events and hypoxic-ischemic injury to the cerebral white matter. The chronic disturbance of myelination resulting from PVL suggests that developing oligodendrocytes (OLs) are involved in its pathogenesis. We hypothesized that nitric oxide (NO) could participate in the pathogenesis of PVL through a toxic effect on developing OLs. Using primary cultures of highly enriched OLs we found that NO is toxic to developing OLs (O4+, O1-, MBP-), with an EC50 value of 236 +/- 125 microm of DETANOnoate. Peroxynitrite formation does not appear to be involved in NO toxicity in developing OLs, as determined by the failure of peroxynitrite scavengers as well as superoxide dismutase overexpression to prevent NO-induced toxicity. Similarly, several pathways involving PARP, excitotoxicity, guanylyl cyclase and caspase activation were not related to NO toxicity to developing OLs. NO toxicity to OLs resulted in ATP depletion and loss of mitochondrial membrane potential (DeltaPsi) in developing OLs. Apoptosis-inducing factor (AIF) has been shown to be involved in caspase-independent cell death, and we found that AIF translocated from mitochondria into the nucleus upon NO exposure. In conclusion, we suggest that the vulnerability of developing OLs to NO involves mitochondrial dysfunction and translocation of AIF from mitochondria to nuclei.

  4. Bacterial Cell Mechanics.

    Science.gov (United States)

    Auer, George K; Weibel, Douglas B

    2017-07-25

    Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

  5. Inhibition of HMGB1 Translocation by Green Tea Extract in Rats Exposed to Environmental Tobacco Smoke

    Directory of Open Access Journals (Sweden)

    Sirintip Chaichalotornkul

    2012-01-01

    Full Text Available Environmental tobacco smoke (ETS exposure is linked to carcinogenic, oxidative and inflammatory cellular reactions. Green tea polyphenol reportedly plays a role in the prevention of inflammation-related diseases. To evaluate the effects of green tea extract (GTE on cellular location of High Mobility Group Box-1 (HMGB1 protein, we studied the lung tissue in rats exposed to cigarette smoke (CS. Rats were divided into three groups; CS, CSG, and C, which were groups of CS-treated only, CS-treated with GTE dietary supplement, and the control, respectively. Our findings by immunocytochemistry showed that abundant HMGB1 translocated from the nucleus to the cytoplasm in the lung tissues of rats that were exposed to CS, whereas HMGB1 was localized to the nuclei of CSG and C group. For in vitro studies, cotinine stimulated the secretion of HMGB1 in a dose and time dependent manner and the HMGB1 level was suppressed by GTE in murine macrophage cell lines. Our results could suggest that GTE supplementation which could suppress HMGB1 may offer a beneficial effect against diseases.

  6. A putative twin-arginine translocation system in the phytopathogenic bacterium Xylella fastidiosa.

    Science.gov (United States)

    Ciapina, Luciane Prioli; Picchi, Simone Cristina; Lacroix, Jean-Marie; Lemos, Eliana Gertrudes de Macedo; Ödberg-Ferragut, Carmen

    2011-02-01

    The twin-arginine translocation (Tat) pathway of the xylem-limited phytopathogenic bacterium Xylella fastidiosa strain 9a5c, responsible for citrus variegated chlorosis, was explored. The presence of tatA, tatB, and tatC in the X. fastidiosa genome together with a list of proteins harboring 2 consecutive arginines in their signal peptides suggested the presence of a Tat pathway. The functional Tat dependence of X. fastidiosa OpgD was examined. Native or mutated signal peptides were fused to the β-lactamase. Expression of fusion with intact signal peptides mediated high resistance to ampicillin in Escherichia coli tat+ but not in the E. coli tat null mutant. The replacement of the 2 arginines by 2 lysines prevented the export of β-lactamase in E. coli tat+, demonstrating that X. fastidiosa OpgD carries a signal peptide capable of engaging the E. coli Tat machinery. RT-PCR analysis revealed that the tat genes are transcribed as a single operon. tatA, tatB, and tatC genes were cloned. Complementation assays in E. coli devoid of all Tat or TatC components were unsuccessful, whereas X. fastidiosa Tat components led to a functional Tat translocase in E. coli TatB-deficient strain. Additional experiments implicated that X. fastidiosa TatB component could form a functional heterologous complex with the E. coli TatC component.

  7. Characterisation of the gill mucosal bacterial communities of four butterflyfish species: a reservoir of bacterial diversity in coral reef ecosystems.

    Science.gov (United States)

    Reverter, Miriam; Sasal, Pierre; Tapissier-Bontemps, N; Lecchini, D; Suzuki, M

    2017-06-01

    While recent studies have suggested that fish mucus microbiota play an important role in homeostasis and prevention of infections, very few studies have investigated the bacterial communities of gill mucus. We characterised the gill mucus bacterial communities of four butterflyfish species and although the bacterial diversity of gill mucus varied significantly between species, Shannon diversities were high (H = 3.7-5.7) in all species. Microbiota composition differed between butterflyfishes, with Chaetodon lunulatus and C. ornatissimus having the most similar bacterial communities, which differed significantly from C. vagabundus and C. reticulatus. The core bacterial community of all species consisted of mainly Proteobacteria followed by Actinobacteria and Firmicutes. Chaetodonlunulatus and C. ornatissimus bacterial communities were mostly dominated by Gammaproteobacteria with Vibrio as the most abundant genus. Chaetodonvagabundus and C. reticulatus presented similar abundances of Gammaproteobacteria and Alphaproteobacteria, which were well represented by Acinetobacter and Paracoccus, respectively. In conclusion, our results indicate that different fish species present specific bacterial assemblages. Finally, as mucus layers are nutrient hotspots for heterotrophic bacteria living in oligotrophic environments, such as coral reef waters, the high bacterial diversity found in butterflyfish gill mucus might indicate external fish mucus surfaces act as a reservoir of coral reef bacterial diversity. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Bacterial meningitis in children

    International Nuclear Information System (INIS)

    Marji, S.

    2007-01-01

    To demonstrate the epidemiology, clinical manifestations and bacteriological profile of bacterial meningitis in children beyond the neonatal period in our hospital. This was a retrospective descriptive study conducted at Prince Rashid Hospital in Irbid, Jordan. The medical records of 50 children with the diagnosis of bacterial meningitis during 4 years period, were reviewed. The main cause of infection was streptococcus pneumoniae, followed by Haemophilus influenza and Niesseria meningitides. Mortality was higher in infants and meningococcal infection, while complications were more encountered in cases of streptococcus pneumoniae. Cerebrospinal fluid culture was positive in 11 cases and Latex agglutination test in 39. There is a significant reduction of the numbers of bacterial meningitis caused by Haemophilus influenza type B species. (author)

  9. Interfering with bacterial gossip

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Givskov, Michael

    2011-01-01

    Biofilm resilience poses major challenges to the development of novel antimicrobial agents. Biofilm bacteria can be considered small groups of “Special Forces” capable of infiltrating the host and destroying important components of the cellular defense system with the aim of crippling the host...... defense. Antibiotics exhibit a rather limited effect on biofilms. Furthermore, antibiotics have an ‘inherent obsolescence’ because they select for development of resistance. Bacterial infections with origin in bacterial biofilms have become a serious threat in developed countries. Pseudomonas aeruginosa...... that appropriately target bacteria in their relevant habitat with the aim of mitigating their destructive impact on patients. In this review we describe molecular mechanisms involved in “bacterial gossip” (more scientifically referred to as quorum sensing (QS) and c-di-GMP signaling), virulence, biofilm formation...

  10. Diagnosis of bacterial vaginosis

    Directory of Open Access Journals (Sweden)

    Đukić Slobodanka

    2013-01-01

    Full Text Available Bacterial vaginosis is a common, complex clinical syndrome characterized by alterations in the normal vaginal flora. When symptomatic, it is associated with a malodorous vaginal discharge and on occasion vaginal burning or itching. Under normal conditions, lactobacilli constitute 95% of the bacteria in the vagina. Bacterial vaginosis is associated with severe reduction or absence of the normal H2O2­producing lactobacilli and overgrowth of anaerobic bacteria and Gardnerella vaginalis, Atopobium vaginae, Mycoplasma hominis and Mobiluncus species. Most types of infectious disease are diagnosed by culture, by isolating an antigen or RNA/DNA from the microbe, or by serodiagnosis to determine the presence of antibodies to the microbe. Therefore, demonstration of the presence of an infectious agent is often a necessary criterion for the diagnosis of the disease. This is not the case for bacterial vaginosis, since the ultimate cause of the disease is not yet known. There are a variety of methods for the diagnosis of bacterial vaginosis but no method can at present be regarded as the best. Diagnosing bacterial vaginosis has long been based on the clinical criteria of Amsel, whereby three of four defined criteria must be satisfied. Nugent’s scoring system has been further developed and includes validation of the categories of observable bacteria structures. Up­to­date molecular tests are introduced, and better understanding of vaginal microbiome, a clear definition for bacterial vaginosis, and short­term and long­term fluctuations in vaginal microflora will help to better define molecular tests within the broader clinical context.

  11. Beneficial Effect of Alcohol Withdrawal on Gut Permeability and Microbial Translocation in Patients with Alcohol Use Disorder.

    Science.gov (United States)

    Donnadieu-Rigole, Hélène; Pansu, Nathalie; Mura, Thibault; Pelletier, Stéphanie; Alarcon, Régis; Gamon, Lucie; Perney, Pascal; Apparailly, Florence; Lavigne, Jean-Philippe; Dunyach-Remy, Catherine

    2018-01-01

    The human intestinal microbiota exerts beneficial or harmful effects in several disorders. Many factors, including alcohol consumption, may influence its composition and trigger bacterial translocation. Excessive alcohol consumption increases gut permeability and translocation of endotoxin into peripheral circulation. Although plasma endotoxin concentrations have been measured often, quantitative changes following alcohol withdrawal have never been described in subjects with alcohol use disorder (AUD). The aim of this study was to measure microbial translocation (MT) and gut permeability markers in patients with AUD, to compare these markers to healthy controls (HC) and to monitor markers during the first 6 weeks of abstinence. Sixty-five patients with AUD and hospitalized for alcohol withdrawal were included. Epidemiological, clinical, biological, and addictological data were gathered. Blood samples were collected at baseline, then 3 and 6 weeks after alcohol withdrawal. A hundred healthy volunteers were used as controls. Three markers of MT were monitored in plasma samples: sCD14 and lipopolysaccharide-binding protein (LBP) were quantified using ELISA, and 16S rDNA was quantified using real-time polymerase chain reaction. Zonulin and intestinal fatty acid binding protein (I-FABP) blood levels were also monitored as indirect markers of gut permeability, using ELISA. At baseline, LBP, 16S rDNA, sCD14 and I-FABP markers were significantly higher in patients with AUD than in HC. Six weeks after alcohol withdrawal plasma levels of sCD14 and LBP decreased significantly. Cannabis consumption and body mass index (BMI) before alcohol withdrawal influenced baseline MT levels and the decrease in MT markers after 6 weeks. Finally, markers of MT and gut permeability did not correlate with each other before and after alcohol withdrawal. Before alcohol withdrawal, MT markers were higher in patients with AUD than in HC. After 6 weeks of abstinence, an improvement in MT

  12. Adult bacterial meningitis

    DEFF Research Database (Denmark)

    Meyer, C N; Samuelsson, I S; Galle, M

    2004-01-01

    Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibi......Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin...

  13. Bacterial blight of cotton

    Directory of Open Access Journals (Sweden)

    Aïda JALLOUL

    2015-04-01

    Full Text Available Bacterial blight of cotton (Gossypium ssp., caused by Xanthomonas citri pathovar malvacearum, is a severe disease occurring in all cotton-growing areas. The interactions between host plants and the bacteria are based on the gene-for-gene concept, representing a complex resistance gene/avr gene system. In light of the recent data, this review focuses on the understanding of these interactions with emphasis on (1 the genetic basis for plant resistance and bacterial virulence, (2 physiological mechanisms involved in the hypersensitive response to the pathogen, including hormonal signaling, the oxylipin pathway, synthesis of antimicrobial molecules and alteration of host cell structures, and (3 control of the disease.

  14. Pediatric bacterial meningitis in French Guiana.

    Science.gov (United States)

    Elenga, N; Sicard, S; Cuadro-Alvarez, E; Long, L; Njuieyon, F; Martin, E; Kom-Tchameni, R; Balcaen, J; Moreau, B; Boukhari, R

    2015-01-01

    Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. Improving vaccination coverage would decrease the incidence of H. influenzae meningitis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. The impact of translocations on neutral and functional genetic diversity within and among populations of the Seychelles warbler

    NARCIS (Netherlands)

    Wright, David J.; Spurgin, Lewis G.; Collar, Nigel J.; Komdeur, Jan; Burke, Terry; Richardson, David S.

    Translocations are an increasingly common tool in conservation. The maintenance of genetic diversity through translocation is critical for both the short- and long-term persistence of populations and species. However, the relative spatio-temporal impacts of translocations on neutral and functional

  16. Muscle contraction increases carnitine uptake via translocation of OCTN2

    Energy Technology Data Exchange (ETDEWEB)

    Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

  17. Uptake, translocation, and toxicity of gold nanorods in maize

    Science.gov (United States)

    Moradi Shahmansouri, Nastaran

    Nanomaterials are widely used in many different products, such as electronics, cosmetics, industrial goods, biomedical uses, and other material applications. The heavy emission of nanomaterials into the environment has motived increasing concern regarding the effects on ecosystems, food chains, and, human health. Plants can tolerate a certain amount of natural nanomaterials, but large amounts of ENMs released from a variety of industries could be toxic to plants and possibly threaten the ecosystem. Employing phytoremediation as a contamination treatment method may show promise. However a pre-requisite to successful treatment is a better understanding of the behavior and effects of nanomaterials within plant systems. This study is designed to investigate the uptake, translocation, bioavailability, and toxicity of gold nanorods in maize plants. Maize is an important food and feed crop that can be used to understand the potential hazardous effects of nanoparticle uptake and distribution in the food chain. The findings could be an important contribution to the fields of phytoremediation, agri-nanotechnology, and nanoparticle toxicity on plants. In the first experiment, hydroponically grown maize seedlings were exposed to similar doses of commercial non-coated gold nanorods in three sizes, 10x34 nm, 20x75 nm, and 40x96 nm. The three nanorod species were suspended in solutions at concentrations of 350 mg/l, 5.8 mg/l, and 14 mg/l, respectively. Maize plants were exposed to all three solutions resulting in considerably lower transpiration and wet biomass than control plants. Likewise, dry biomass was reduced, but the effect is less pronounced than that of transpiration and wet biomass. The reduced transpiration and water content, which eventually proved fatal to exposed plants, were most likely a result of toxic effect of gold nanorod, which appeared to physically hinder the root system. TEM images proved that maize plants can uptake gold particles and accumulate them in

  18. Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt

    Science.gov (United States)

    Shaban, Lamyaa; Siam, Rania

    2009-01-01

    Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies. PMID:19778428

  19. Prevalence and antimicrobial resistance pattern of bacterial meningitis in Egypt

    Directory of Open Access Journals (Sweden)

    Shaban Lamyaa

    2009-09-01

    Full Text Available Abstract Infectious diseases are the leading cause of morbidity and mortality in the developing world. In Egypt bacterial diseases constitute a great burden, with several particular bacteria sustaining the leading role of multiple serious infections. This article addresses profound bacterial agents causing a wide array of infections including but not limited to pneumonia and meningitis. The epidemiology of such infectious diseases and the prevalence of Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae are reviewed in the context of bacterial meningitis. We address prevalent serotypes in Egypt, antimicrobial resistance patterns and efficacy of vaccines to emphasize the importance of periodic surveillance for appropriate preventive and treatment strategies.

  20. Domain Organization in Clostridium botulinum Neurotoxin Type E is Unique: Its Implication in Faster Translocation

    Energy Technology Data Exchange (ETDEWEB)

    Kumaran, D.; Eswaramoorthy, S; Furey, W; Navaza, J; Sax, M; Swaminathan, S

    2009-01-01

    Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.

  1. Dermatoglyphics and Reproductive Risk in a Family with Robertsonian Translocation 14q;21q

    Science.gov (United States)

    Kolgeci, Selim; Kolgeci, Jehona; Azemi, Mehmedali; Daka, Aferdita; Shala-Beqiraj, Ruke; Kurtishi, Ilir; Sopjani, Mentor

    2015-01-01

    Aim: The present study is carried out to evaluate the risk of giving birth to children with Down syndrome in a family with Robertsonian translocation 14q;21q, and to find the dermatoglyphic changes present in carriers of this translocation. Methods: Cytogenetics diagnosis has been made according to Moorhead and Seabright method, while the analysis of prints (dermatoglyphics analysis) was made with the Cummins and Midlo method. Results: Cytogenetic diagnosis has been made in a couple who suffered the spontaneous miscarriages and children with Down syndrome. Robertsonian translocation between chromosomes 14 and 21 (45, XX, der (14; 21) (q10; q10)) was found in a female partner who had four pregnancies, in two of which was found fetus karyotype with trisomy in chromosome 21 and pregnancies were terminated. The outcome of fourth pregnancy was twin birth, one of them with normal karyotype and another with Down syndrome due to Robertsonian translocation inherited by mother side. Specific dermatoglyphics traits are found in the child carrying Down syndrome, whereas several traits of dermatoglyphics characteristic of Down syndrome have been displayed among the silent carriers of Robertsonian translocation 14q;21q. Conclusion: Robertsonian translocation found in female partner was the cause of spontaneous miscarriages, of giving birth to a child with Down syndrome, and of trisomy of chromosome 21 due to translocation in two pregnancies. PMID:26236088

  2. Genetic variation in natural and translocated populations of the endangered Delmarva fox squirrel (Sciurus niger cinereus)

    Science.gov (United States)

    Lance, S.L.; Maldonado, J.E.; Bocetti, Carol I.; Pattee, O.H.; Ballou, J.D.; Fleischer, R.C.

    2003-01-01

    The Delmarva fox squirrel, Sciurus niger cinereus, is a federally listed endangered subspecies whose range has been reduced by 90%. In an attempt to increase both population size and range, translocation sites were established beginning in the 1960's by moving squirrels from the natural range to sites outside the current range. Although translocations have served as the primary component of the DFS recovery program, there has been very little post-release examination of the genetics of the translocation sites. In this study, we developed ten microsatellite loci, screened the three polymorphic loci, and sequenced a 330 bp fragment of the mitochondrial control region in order to assess levels of genetic variation in natural and translocated regions of Delmarva fox squirrels and to compare them to Southeastern fox squirrels (S. n. niger). Although we found low levels of microsatellite polymorphism, there were no differences in heterozygosity between natural and translocated regions, or between Delmarva and Southeastern fox squirrels. We found high levels of polymorphism in the mitochondrial control region. Our patterns of haplotype diversity suggest incomplete lineage sorting of the two subspecies. In general, our data suggest that the current levels of genetic variation in the translocated sites are representative of those found in the natural population, and we encourage the continued use of translocations as a major component of Delmarva fox squirrel recovery.

  3. Three-dimensional genome architecture influences partner selection for chromosomal translocations in human disease.

    Directory of Open Access Journals (Sweden)

    Jesse M Engreitz

    Full Text Available Chromosomal translocations are frequent features of cancer genomes that contribute to disease progression. These rearrangements result from formation and illegitimate repair of DNA double-strand breaks (DSBs, a process that requires spatial colocalization of chromosomal breakpoints. The "contact first" hypothesis suggests that translocation partners colocalize in the nuclei of normal cells, prior to rearrangement. It is unclear, however, the extent to which spatial interactions based on three-dimensional genome architecture contribute to chromosomal rearrangements in human disease. Here we intersect Hi-C maps of three-dimensional chromosome conformation with collections of 1,533 chromosomal translocations from cancer and germline genomes. We show that many translocation-prone pairs of regions genome-wide, including the cancer translocation partners BCR-ABL and MYC-IGH, display elevated Hi-C contact frequencies in normal human cells. Considering tissue specificity, we find that translocation breakpoints reported in human hematologic malignancies have higher Hi-C contact frequencies in lymphoid cells than those reported in sarcomas and epithelial tumors. However, translocations from multiple tissue types show significant correlation with Hi-C contact frequencies, suggesting that both tissue-specific and universal features of chromatin structure contribute to chromosomal alterations. Our results demonstrate that three-dimensional genome architecture shapes the landscape of rearrangements directly observed in human disease and establish Hi-C as a key method for dissecting these effects.

  4. Timing of translocation influences birth rate and population dynamics in a forest carnivore

    Science.gov (United States)

    Facka, Aaron N; Lewis, Jeffrey C.; Happe, Patricia; Jenkins, Kurt J.; Callas, Richard; Powell, Roger A.

    2016-01-01

    Timing can be critical for many life history events of organisms. Consequently, the timing of management activities may affect individuals and populations in numerous and unforeseen ways. Translocations of organisms are used to restore or expand populations but the timing of translocations is largely unexplored as a factor influencing population success. We hypothesized that the process of translocation negatively influences reproductive rates of individuals that are moved just before their birthing season and, therefore, the timing of releases could influence translocation success. Prior to reintroducing fishers (Pekania pennanti) into northern California and onto the Olympic Peninsula of Washington, we predicted that female fishers released in November and December (early) would have a higher probability of giving birth to kits the following March or April than females released in January, February, and March (late), just prior to or during the period of blastocyst implantation and gestation. Over four winters (2008–2011), we translocated 56 adult female fishers that could have given birth in the spring immediately after release. Denning rates, an index of birth rate, for females released early were 92% in California and 38% in Washington. In contrast, denning rates for females released late were 40% and 11%, in California and Washington, a net reduction in denning rate of 66% across both sites. To understand how releasing females nearer to parturition could influence population establishment and persistence, we used stochastic population simulations using three-stage Lefkovitch matrices. These simulations showed that translocating female fishers early had long-term positive influences on the mean population size and on quasi-extinction thresholds compared to populations where females were released late. The results from both empirical data and simulations show that the timing of translocation, with respect to life history events, should be considered during

  5. Production and Identification of Wheat-Agropyron cristatum 2P Translocation Lines

    Science.gov (United States)

    Li, Huanhuan; Lv, Mingjie; Song, Liqiang; Zhang, Jinpeng; Gao, Ainong; Li, Lihui; Liu, Weihua

    2016-01-01

    Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, possesses many potentially valuable traits that can be transferred to common wheat through breeding programs. The wheat-A. cristatum disomic addition and translocation lines can be used as bridge materials to introduce alien chromosomal segments to wheat. Wheat-A. cristatum 2P disomic addition line II-9-3 was highly resistant to powdery mildew and leaf rust, which was reported in our previous study. However, some translocation lines induced from II-9-3 have not been reported. In this study, some translocation lines were induced from II-9-3 by 60Co-γ irradiation and gametocidal chromosome 2C and then identified by cytological methods. Forty-nine wheat-A. cristatum translocation lines were obtained and various translcoation types were identified by GISH (genomic in situ hybridization), such as whole-arm, segmental and intercalary translocations. Dual-color FISH (fluorescent in situ hybridization) was applied to identify the wheat chromosomes involved in the translocations, and the results showed that A. cristatum 2P chromosome segments were translocated to the different wheat chromosomes, including 1A, 2A, 3A, 4A, 5A, 6A, 7A, 3B, 5B, 7B, 1D, 4D and 6D. Many different types of wheat-A. cristatum alien translocation lines would be valuable for not only identifying and cloning A. cristatum 2P-related genes and understanding the genetics and breeding effects of the translocation between A. cristatum chromosome 2P and wheat chromosomes, but also providing new germplasm resources for the wheat genetic improvement. PMID:26731742

  6. Tourette syndrome in a pedigree with a 7;18 translocation: Identification of a YAC spanning the translocation breakpoint at 18q22.3

    Energy Technology Data Exchange (ETDEWEB)

    Boghosian-Sell, L.; Overhauser, J. [Thomas Jefferson Univ., Philadelphia, PA (United States); Comings, D.E. [City of Hope Medical Center, Duarte, CA (United States)

    1996-11-01

    Tourette syndrome is a neuropsychiatric disorder characterized by the presence of multiple, involuntary motor and vocal tics. Associated pathologies include attention deficit disorder and obsessive-compulsive disorder (OCD). Extensive linkage analysis based on an autosomal dominant mode of transmission with reduced penetrance has failed to show linkage with polymorphic markers, suggesting either locus heterogeneity or a polygenic origin for Tourette syndrome. An individual diagnosed with Tourette syndrome has been described carrying a constitutional chromosome translocation. Other family members carrying the translocation exhibit features seen in Tourette syndrome including motor tics, vocal tics, and OCD. Since the disruption of specific genes by a chromosomal rearrangement can elicit a particular phenotype, we have undertaken the physical mapping of the 7;18 translocation such that genes mapping at the site of the breakpoint can be identified and evaluated for a possible involvement in Tourette syndrome. Using somatic cell hybrids retaining either the der(7) or the der(18), a more precise localization of the breakpoints on chromosomes 7 and 18 have been determined. Furthermore, physical mapping has identified two YAC clones that span the translocation breakpoint on chromosome 18 as determined by FISH. These YAC clones will be useful for the eventual identification of genes that map to chromosomes 7 and 18 at the site of the translocation. 41 refs., 3 figs., 1 tab.

  7. INTEGRATED CONSERVATION OF THE RARE AND ENDANGERED THERMOPHILOUS SPECIES CYPERUS POLYSTACHYUS: INVESTIGATION ON RECRUITMENT STRATEGIES AND SHORT-TERM ASSESSMENT OF TRANSLOCATION

    Directory of Open Access Journals (Sweden)

    G. FABRINI

    2010-01-01

    Full Text Available Cyperus polystachyus Rottb. is a threatened species occurring in Europe only in two sites located in wetland habitat in mediterranean Southern Italy. According to the IUCN red list for Italy (1997, the species is listed as critically endangered (CR. This study investigated recruitment and habitat limitations referred to the population located south of Rome, in the Tor Caldara Regional Reserve. The site is an isolated island of vegetation. Natural expansion of the species is highly limited by the absence of “wet” sites in the surroundings. Importantly the study also endorsed an “in wild translocation program”, which aimed to decrease the risk of species extinction linked to demographic stochasticity, extreme climatic events or mismanagement. Seed germination, seed and site limitations, and germplasm translocation were investigated. Seed viability and seed germination were tested at the Rome Botanical Garden; results showed that the species has high recruitment potential, especially in thermophilous conditions. Germplasm (seeds was translocated in a vegetation remnant within the Protected Area of Decima Malafede overseen by RomaNatura, a Regional Agency for the management of PAs, which, together with the National Environment Research Institute (ISPRA was one of the partners in this research. The site limitation and translocation studies were undertaken in a glade with a seasonal pond. Seeds were sown and seedlings planted within an experimental framework, protected by a metal cage to prevent grazing. The new site is within the natural dispersion range of the species in an area with similar ecological and biogeographic conditions. It is surrounded by thermophilous oak woodland and cultivated fields which exclude germplasm escape. Results showed that, due to the germination behaviour, the establishment is limited by the absence of microsites suitable for recruitment. Competition with perennial species and delayed germination are the main

  8. INTEGRATED CONSERVATION OF THE RARE AND ENDANGERED THERMOPHILOUS SPECIES CYPERUS POLYSTACHYUS: INVESTIGATION ON RECRUITMENT STRATEGIES AND SHORT-TERM ASSESSMENT OF TRANSLOCATION

    Directory of Open Access Journals (Sweden)

    R. CROSTI

    2010-04-01

    Full Text Available Cyperus polystachyus Rottb. is a threatened species occurring in Europe only in two sites located in wetland habitat in mediterranean Southern Italy. According to the IUCN red list for Italy (1997, the species is listed as critically endangered (CR. This study investigated recruitment and habitat limitations referred to the population located south of Rome, in the Tor Caldara Regional Reserve. The site is an isolated island of vegetation. Natural expansion of the species is highly limited by the absence of “wet” sites in the surroundings. Importantly the study also endorsed an “in wild translocation program”, which aimed to decrease the risk of species extinction linked to demographic stochasticity, extreme climatic events or mismanagement. Seed germination, seed and site limitations, and germplasm translocation were investigated. Seed viability and seed germination were tested at the Rome Botanical Garden; results showed that the species has high recruitment potential, especially in thermophilous conditions. Germplasm (seeds was translocated in a vegetation remnant within the Protected Area of Decima Malafede overseen by RomaNatura, a Regional Agency for the management of PAs, which, together with the National Environment Research Institute (ISPRA was one of the partners in this research. The site limitation and translocation studies were undertaken in a glade with a seasonal pond. Seeds were sown and seedlings planted within an experimental framework, protected by a metal cage to prevent grazing. The new site is within the natural dispersion range of the species in an area with similar ecological and biogeographic conditions. It is surrounded by thermophilous oak woodland and cultivated fields which exclude germplasm escape. Results showed that, due to the germination behaviour, the establishment is limited by the absence of microsites suitable for recruitment. Competition with perennial species and delayed germination are the main

  9. Utilization of rye as energy source affects bacterial translocation, intestinal viscosity, microbiota composition, and bone mineralization in broiler chickens

    Science.gov (United States)

    Two independent trials were conducted to evaluate the effect of two different dietary cereal types, corn versus rye, on digesta viscosity, gut integrity, and gut microbiota composition in commercial broiler chickens. In each experiment, day-of-hatch, off-sex broiler chickens were randomly assigned ...

  10. The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer's Disease.

    Science.gov (United States)

    Köhler, Cristiano A; Maes, Michael; Slyepchenko, Anastasiya; Berk, Michael; Solmi, Marco; Lanctôt, Krista L; Carvalho, André F

    2016-01-01

    Alzheimer's disease (AD), the most common form of dementia, is a progressive disorder manifested by gradual memory loss and subsequent impairment in mental and behavioral functions. Though the primary risk factor for AD is advancing age, other factors such as diabetes mellitus, hyperlipidemia, obesity, vascular factors and depression play a role in its pathogenesis. The human gastrointestinal tract has a diverse commensal microbial population, which has bidirectional interactions with the human host that are symbiotic in health, and in addition to nutrition, digestion, plays major roles in inflammation and immunity. The most prevalent hypothesis for AD is the amyloid hypothesis, which states that changes in the proteolytic processing of the amyloid precursor protein leads to the accumulation of the amyloid beta (Aβ) peptide. Aβ then triggers an immune response that drives neuroinflammation and neurodegeneration in AD. The specific role of gut microbiota in modulating neuro-immune functions well beyond the gastrointestinal tract may constitute an important influence on the process of neurodegeneration. We first review the main mechanisms involved in AD physiopathology. Then, we review the alterations in gut microbiota and gut-brain axis that might be relevant to mediate or otherwise affect AD pathogenesis, especially those associated with aging. We finally summarize possible mechanisms that could mediate the involvement of gut-brain axis in AD physiopathology, and propose an integrative model.

  11. The Bacterial Growth Curve.

    Science.gov (United States)

    Paulton, Richard J. L.

    1991-01-01

    A procedure that allows students to view an entire bacterial growth curve during a two- to three-hour student laboratory period is described. Observations of the lag phase, logarithmic phase, maximum stationary phase, and phase of decline are possible. A nonpathogenic, marine bacterium is used in the investigation. (KR)

  12. Bacterial fingerprints across Europe

    NARCIS (Netherlands)

    Glasner, Corinna

    2014-01-01

    Bacterial pathogens, such as Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae (CPE), impose major threats to human health worldwide. Both have a ‘Jekyll & Hyde’ character, since they can be present as human commensals, but can also become harmful invasive pathogens especially

  13. [Bacterial biofilms and infection].

    Science.gov (United States)

    Lasa, I; Del Pozo, J L; Penadés, J R; Leiva, J

    2005-01-01

    In developed countries we tend to think of heart disease and the numerous forms of cancer as the main causes of mortality, but on a global scale infectious diseases come close, or may even be ahead: 14.9 million deaths in 2002 compared to cardiovascular diseases (16.9 million deaths) and cancer (7.1 million deaths) (WHO report 2004). The infectious agents responsible for human mortality have evolved as medical techniques and hygienic measures have changed. Modern-day acute infectious diseases caused by specialized bacterial pathogens such as diphtheria, tetanus, cholera, plague, which represented the main causes of death at the beginning of XX century, have been effectively controlled with antibiotics and vaccines. In their place, more than half of the infectious diseases that affect mildly immunocompromised patients involve bacterial species that are commensal with the human body; these can produce chronic infections, are resistant to antimicrobial agents and there is no effective vaccine against them. Examples of these infections are the otitis media, native valve endocarditis, chronic urinary infections, bacterial prostatitis, osteomyelitis and all the infections related to medical devices. Direct analysis of the surface of medical devices or of tissues that have been foci of chronic infections shows the presence of large numbers of bacteria surrounded by an exopolysaccharide matrix, which has been named the "biofilm". Inside the biofilm, bacteria grow protected from the action of the antibodies, phagocytic cells and antimicrobial treatments. In this article, we describe the role of bacterial biofilms in human persistent infections.

  14. EDITORIAL SPONTANEOUS BACTERIAL PERITONITIS ...

    African Journals Online (AJOL)

    hi-tech

    Spontaneous bacterial peritonitis (SBP) frequent]y occurs in patients with liver cirrhosis and ascites. It is defined as an infection of previously sterile ascitic fluid without any demonstrable intrabdominal source of infection. It is now internationally agreed that a polymorphonuclear (PMN) cell count in the ascitic fluid of over 250 ...

  15. Bacterial membrane proteomics.

    Science.gov (United States)

    Poetsch, Ansgar; Wolters, Dirk

    2008-10-01

    About one quarter to one third of all bacterial genes encode proteins of the inner or outer bacterial membrane. These proteins perform essential physiological functions, such as the import or export of metabolites, the homeostasis of metal ions, the extrusion of toxic substances or antibiotics, and the generation or conversion of energy. The last years have witnessed completion of a plethora of whole-genome sequences of bacteria important for biotechnology or medicine, which is the foundation for proteome and other functional genome analyses. In this review, we discuss the challenges in membrane proteome analysis, starting from sample preparation and leading to MS-data analysis and quantification. The current state of available proteomics technologies as well as their advantages and disadvantages will be described with a focus on shotgun proteomics. Then, we will briefly introduce the most abundant proteins and protein families present in bacterial membranes before bacterial membrane proteomics studies of the last years will be presented. It will be shown how these works enlarged our knowledge about the physiological adaptations that take place in bacteria during fine chemical production, bioremediation, protein overexpression, and during infections. Furthermore, several examples from literature demonstrate the suitability of membrane proteomics for the identification of antigens and different pathogenic strains, as well as the elucidation of membrane protein structure and function.

  16. Seizures Complicating Bacterial Meningitis

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-09-01

    Full Text Available The clinical data of 116 patients, 1 month to <5 years of age, admitted for bacterial meningitis, and grouped according to those with and without seizures during hospitalization, were compared in a study at Buddhist Dalin Tzu Chi General Hospital, Chang Gung Memorial Hospital and other centers in Taiwan.

  17. Diagnosis of bacterial infection

    African Journals Online (AJOL)

    rapid and easy-to-use test for bacterial infections. Clearly, this is a very ... detect antigens or specific antibodies, e.g. group A streptococcal antigen testing can be employed to reduce antibiotic use. Culture-based tests are often ... White blood cell count 12 000 cells/mm³; or the presence of >10% ...

  18. Bacterial Meningitis Outcome

    OpenAIRE

    J Gordon Millichap

    1995-01-01

    The neurologic, psychological, and educational outcomes of bacterial meningitis in 130 children evaluated at a mean age of 8 years, and 6 years after their meningitis, are reported from the Department of Paediatrics and Clinical Epidemiology and Biostatistics Unit, University of Melbourne, and the Royal Children’s Hospital, Victoria, Australia.

  19. Alignment of threat, effort, and perceived success in North American conservation translocations.

    Science.gov (United States)

    Brichieri-Colombi, Typhenn A; Moehrenschlager, Axel

    2016-12-01

    The use of conservation translocations to mitigate human effects on biodiversity is increasing, but how these efforts are allocated remains unclear. Based on a comprehensive literature review and online author survey, we sought to determine the goals of translocation efforts, whether they focus on species and regions with high threat and likelihood of perceived success, and how success might be improved. We systematically searched the ISI Web of Knowledge and Academic Search Complete databases to determine the species and regions of conservation translocations and found 1863 articles on conservation translocations in the United States, Canada, Mexico, Central America, and Caribbean published from 1974 to 2013. We questioned 330 relevant authors to determine the motivation for translocations, how translocations were evaluated, and obstacles encountered. Conservation translocations in North America were geographically widespread (in 21 countries), increased in frequency over time for all animal classes (from 1 in 1974 to 84 in 2013), and included 279 different species. Reintroductions and reinforcements were more common in the United States than in Canada and Mexico, Central America, or the Caribbean, and their prevalence was correlated with the number of species at risk at national and state or provincial levels. Translocated species had a higher threat status at state and provincial levels than globally (International Union for Conservation of Nature Red List categorization), suggesting that translocations may have been motivated by regional priorities rather than global risk. Our survey of authors was consistent with these results; most translocations were requested, supported, or funded by government agencies and downlisting species at national or state or provincial levels was the main goal. Nonetheless, downlisting was the least reported measure of success, whereas survival and reproduction of translocated individuals were the most reported. Reported barriers

  20. Variant Philadelphia translocations with different breakpoints in six chronic myeloid leukemia patients

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    Dilhan Kuru

    2011-09-01

    Full Text Available Objective: The Philadelphia (Ph chromosome, consisting of the t(9;22(q34;q11 translocation, is observed in ~90% of patients with chronic myeloid leukemia (CML. Variant Ph translocations are observed in 5%-10% of CML patients. In variant translocations 3 and possibly more chromosomes are involved. Herein we report 6 CML patients with variant Ph translocations.Materials and Methods: Bone marrow samples were examined using conventional cytogenetic meth ods. Fluorescence in situ hybridization (FISH with whole-chromosome paints and BCR-ABL 1D probes were used to confirm and/or complement the findings, and identify rearrangements beyond the resolution of conventional cytogenetic methods. Results: Variant Ph translocations in the 6 patients were as follows: t(7;22(p22;q11, t(9;22;15(q34;q11;q22, t(15;22(p11;q11, t(1;9;22;3(q24;q34;q11;q21, t(12;22(p13;q11, and t(4;8;9;22(q11;q13;q34;q11.Conclusion: Among the patients, 3 had simple and 3 had complex variant Ph translocations. Two of the presented cases had variant Ph chromosomes not previously described, 1 of which had a new complex Ph translocation involving chromosomes 1, 3, 9, 22, and t(1;9;22;3(q24;q34;q11;q21 apart from a clone with a classical Ph, and the other case had variant Ph translocation with chromosomes 4, 8, 9, and 22, and t(4;8;9;22(q11;q13;q34;q11 full complex translocation. Number of studies reported that some patients with variant Ph translocation were poor responders to imatinib. All of our patients with variant Ph translocations had suboptimal responses to imatinib, denoting a poor prognosis also. Variant Ph translocations may be important as they are associated with prognosis and therapy for CML patients.

  1. High speed translocation of /sup 86/Rb in the phloem of Tradescantia viridis

    Energy Technology Data Exchange (ETDEWEB)

    Penot, M.

    1976-01-01

    An autoradiographic study of the rooted shoots of Tradescantia viridis showed a high speed translocation of /sup 86/Rb applied to a leaf for short periods of time (5 to 2.5 min). The speed of this translocation (between 840 and 1.440 cm h/sup -1/) speaks for the existence of a very rapid phloem component translocating ions to an active sink, represented here by the growing roots. Pretreatment with cycloheximide (48 h, 50 mg 1/sup -1/) decreases the quantity of this long distance transport but not the velocity.

  2. Ready Experimental Translocation of Mycobacterium canettii Yields Pulmonary Tuberculosis.

    Science.gov (United States)

    Bouzid, Fériel; Brégeon, Fabienne; Lepidi, Hubert; Donoghue, Helen D; Minnikin, David E; Drancourt, Michel

    2017-12-01

    Mycobacterium canettii , which has a smooth colony morphology, is the tuberculous organism retaining the most genetic traits from the putative last common ancestor of the rough-morphology Mycobacterium tuberculosis complex. To explore whether M. canettii can infect individuals by the oral route, mice were fed phosphate-buffered saline or 10 6 M. canettii mycobacteria and sacrificed over a 28-day experiment. While no M. canettii was detected in negative controls, M. canettii -infected mice yielded granuloma-like lesions for 4/4 lungs at days 14 and 28 postinoculation (p.i.) and positive PCR detection of M. canettii for 5/8 mesenteric lymph nodes at days 1 and 3 p.i. and 5/6 pooled stools collected from day 1 to day 28 p.i. Smooth M. canettii colonies grew from 68% of lungs and 36% of spleens and cervical lymph nodes but fewer than 20% of axillary lymph nodes, livers, brown fat samples, kidneys, or blood samples throughout the 28-day experiment. Ready translocation in mice after digestive tract challenge demonstrates the potential of ingested M. canettii organisms to relocate to distant organs and lungs. The demonstration of this relocation supports the possibility that populations may be infected by environmental M. canettii . Copyright © 2017 American Society for Microbiology.

  3. Melanosome transfer to and translocation in the keratinocyte.

    Science.gov (United States)

    Boissy, Raymond E

    2003-01-01

    Complexion coloration in humans is primarily regulated by the amount and type of melanin synthesized by the epidermal melanocyte. However, additional and equally contributing factors consist of (1) efficient transfer of melanin from the melanocytes to the neighboring keratinocytes and (2) distribution and degradation of the transferred melanosomes by the recipient keratinocytes. Once synthesized in the cell body of the epidermal melanocyte, pigmented melanosomes are translocated down the dendrites and captured at the dendritic tips via various cytoskeletal elements. Molecules recently identified that participate in this process consist of Rab27a, myosin-Va and melanophilin. Eventually, these peripherally localized melanosomes are transferred to keratinocytes by a presently undefined mechanism. The protease-activated receptor-2 (PAR-2) and unidentified surface lectins and glycoproteins facilitate this transfer process. Once incorporated into the keratinocytes, melanosomes are distributed individually or as clusters, aggregated towards the apical pole of the nucleus, and degraded as the keratinocytes undergo terminal differentiation and desquamation. Ultraviolet irradiation (UVR) can modulate the process of melanosome transfer from the melanocytes to the keratinocytes. UVR can upregulate expression of PAR-2 and lectin-binding receptors and increase phagocytic activity of cultured keratinocytes. Therefore, many cellular and molecular events that occur after melanogenesis contribute to skin color.

  4. Movilidad y desarrollo translocal en la Nicaragua (semi-rural

    Directory of Open Access Journals (Sweden)

    Griet Steel

    2012-08-01

    Full Text Available Este artículo pretende contribuir al debate sobre los vínculos entre la movilidad y el desarrollo, explorando el concepto de desarrollo translocal. Basado en trabajo de campo en los municipios de Matiguás y Muy Muy, éste analiza cómo la movilidad da forma a las estrategias de vida de los hogares (semi-rurales en Nicaragua, y explora cómo los diferentes miembros de un hogar utilizan la movilidad física como una estrategia de vida. Argumenta que los habitantes de áreas (semi-rurales consideran distintos tipos de movimientos como estrategias importantes para establecer enlaces entre personas y lugares, y para alcanzar un mejor bienestar en su comunidad natal. Al mismo tiempo muestra cómo la movilidad se forma en una arena de poder, lo que afecta su potencial. De esta manera, este artículo contribuye a un entendimiento dinámico y multidimensional de cómo los procesos de desarrollo dan forma a – y son formados por – la movilidad y la interconectividad.

  5. Cholesterol Hydroperoxide Generation, Translocation, and Reductive Turnover in Biological Systems.

    Science.gov (United States)

    Girotti, Albert W; Korytowski, Witold

    2017-12-01

    Cholesterol is like other unsaturated lipids in being susceptible to peroxidative degradation upon exposure to strong oxidants like hydroxyl radical or peroxynitrite generated under conditions of oxidative stress. In the eukaryotic cell plasma membrane, where most of the cellular cholesterol resides, peroxidation leads to membrane structural and functional damage from which pathological states may arise. In low density lipoprotein, cholesterol and phospholipid peroxidation have long been associated with atherogenesis. Among the many intermediates/products of cholesterol oxidation, hydroperoxide species (ChOOHs) have a number of different fates and deserve special attention. These fates include (a) damage-enhancement via iron-catalyzed one-electron reduction, (b) damage containment via two-electron reduction, and (c) inter-membrane, inter-lipoprotein, and membrane-lipoprotein translocation, which allows dissemination of one-electron damage or off-site suppression thereof depending on antioxidant location and capacity. In addition, ChOOHs can serve as reliable and conveniently detected mechanistic reporters of free radical-mediated reactions vs. non-radical (e.g., singlet oxygen)-mediated reactions. Iron-stimulated peroxidation of cholesterol and other lipids underlies a newly discovered form of regulated cell death called ferroptosis. These and other deleterious consequences of radical-mediated lipid peroxidation will be discussed in this review.

  6. Embelin-Induced Phosphatidylserine Translocation in the Erythrocyte Cell Membrane

    Directory of Open Access Journals (Sweden)

    Ghada Bouguerra

    2015-11-01

    Full Text Available Background/Aims: The antihelminthic, contraceptive, anti-inflammatory and anticancer phytochemical embelin is at least in part effective against malignancy by inducing suicidal death or apoptosis of tumor cells. Erythrocytes are similarly able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+-activity ([Ca2+]i, ceramide formation, oxidative stress as well as activation of p38 kinase and protein kinase C (PKC. The present study tested, whether and how embelin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies and reactive oxygen species (ROS from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA fluorescence. Results: A 48 hours exposure of human erythrocytes to embelin (≥25 µM significantly increased the percentage of annexin-V-binding cells and hemolysis. Embelin did not significantly modify [Ca2+]i. The effect of embelin on annexin-V-binding was not blunted by removal of extracellular Ca2+, by p38 kinase inhibitor SB203580 (2 µM or by PKC inhibitor staurosporine (1 µM. Embelin did, however, significantly increase the ceramide abundance. Conclusions: Embelin stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect involving ceramide formation.

  7. Micro-Evolution in Grasshoppers Mediated by Polymorphic Robertsonian Translocations

    Science.gov (United States)

    Colombo, Pablo C.

    2013-01-01

    This review focuses on grasshoppers that are polymorphic for Robertsonian translocations because in these organisms the clarity of meiotic figures allows the study of both chiasma distribution and the orientation of trivalents and multivalents in metaphase I. Only five species of such grasshoppers were found in the literature, and all of them were from the New World: Oedaleonotus enigma (Scudder) (Orthoptera: Acrididae), Leptysma argentina Bruner, Dichroplus pratensis Bruner, Sinipta dalmani Stål, and Cornops aquaticum Bruner. A general feature of these species (except O. enigma) is that fusion carriers suffer a marked reduction of proximal and interstitial (with respect to the centromere) chiasma frequency; this fact, along with the reduction in the number of linkage groups with the consequent loss of independent segregation, produces a marked decrease of recombination in fusion carriers. This reduction in recombination has led to the conclusion that Robertsonian polymorphic grasshopper species share some properties with inversion polymorphic species of Drosophila, such as the central-marginal pattern (marginal populations are monomorphic, central populations are highly polymorphic). This pattern might be present in D. pratensis, which is certainly the most complex Robertsonian polymorphism system in the present study. However, L. argentina and C. aquaticum do not display this pattern. This issue is open to further research. Since C. aquaticum is soon to be released in South Africa as a biological control, the latitudinal pattern found in South America may repeat there. This experiment's outcome is open and deserves to be followed. PMID:23909914

  8. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    International Nuclear Information System (INIS)

    Tomita, Hiroshi; Tabata, Kitako; Takahashi, Maki; Nishiyama, Fumiaki; Sugano, Eriko

    2016-01-01

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  9. Light induces translocation of NF-κB p65 to the mitochondria and suppresses expression of cytochrome c oxidase subunit III (COX III) in the rat retina

    Energy Technology Data Exchange (ETDEWEB)

    Tomita, Hiroshi, E-mail: htomita@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan); Clinical Research, Innovation and Education Center, Tohoku University Hospital, 1-1 Seiryo, Aoba, Sendai, Miyagi 980-8574 (Japan); Tabata, Kitako, E-mail: ktabata@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Takahashi, Maki, E-mail: mqdelta@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Nishiyama, Fumiaki, E-mail: t2114018@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Sugano, Eriko, E-mail: sseriko@iwate-u.ac.jp [Laboratory of Visual Neuroscience, Graduate Course in Biological Sciences, Iwate University Division of Science and Engineering, 4-3-5 Ueda, Morioka, Iwate 020-8551 (Japan); Soft-Path Engineering Research Center (SPERC), Faculty of Science and Engineering, Iwate University, Morioka 020-8551 (Japan)

    2016-05-13

    The transcription factor nuclear factor kappaB (NF-κB) plays various roles in cell survival, apoptosis, and inflammation. In the rat retina, NF-κB activity increases after exposure to damaging light, resulting in degeneration of photoreceptors. Here, we report that in dark-adapted rats exposed for 6 h to bright white light, the p65 subunit of retinal NF-κB translocates to the mitochondria, an event associated with a decrease in expression of cytochrome c oxidase subunit III (COX III). However, sustained exposure for 12 h depleted p65 from the mitochondria, and enhanced COX III expression. Treatment with the protective antioxidant PBN prior to light exposure prevents p65 depletion in the mitochondria and COX III upregulation during prolonged exposure, and apoptosis in photoreceptor cells. These results indicate that COX III expression is sensitive to the abundance of NF-κB p65 in the mitochondria, which, in turn, is affected by exposure to damaging light. - Highlights: • Damaging light exposure of the retina induces NF-κB p65 mitochondrial translocation. • NF-κB p65 mitochondrial translocation is associated with the decrease of COX III expression. • Prolonged light exposure depletes mitochondrial p65 resulting in the increase in COX III expression. • NF-κB p65 and COX III expression play an important role in the light-induced photoreceptor degeneration.

  10. Corticosteroids for Bacterial Keratitis

    Science.gov (United States)

    Srinivasan, Muthiah; Mascarenhas, Jeena; Rajaraman, Revathi; Ravindran, Meenakshi; Lalitha, Prajna; Glidden, David V.; Ray, Kathryn J.; Hong, Kevin C.; Oldenburg, Catherine E.; Lee, Salena M.; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.; Acharya, Nisha R.

    2013-01-01

    Objective To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers. Methods Randomized, placebo-controlled, double-masked, multicenter clinical trial comparing prednisolone sodium phosphate, 1.0%, to placebo as adjunctive therapy for the treatment of bacterial corneal ulcers. Eligible patients had a culture-positive bacterial corneal ulcer and received topical moxifloxacin for at least 48 hours before randomization. Main Outcome Measures The primary outcome was best spectacle-corrected visual acuity (BSCVA) at 3 months from enrollment. Secondary outcomes included infiltrate/scar size, reepithelialization, and corneal perforation. Results Between September 1, 2006, and February 22, 2010, 1769 patients were screened for the trial and 500 patients were enrolled. No significant difference was observed in the 3-month BSCVA (−0.009 logarithm of the minimum angle of resolution [logMAR]; 95% CI, −0.085 to 0.068; P = .82), infiltrate/scar size (P = .40), time to reepithelialization (P = .44), or corneal perforation (P > .99). A significant effect of corticosteroids was observed in subgroups of baseline BSCVA (P = .03) and ulcer location (P = .04). At 3 months, patients with vision of counting fingers or worse at baseline had 0.17 logMAR better visual acuity with corticosteroids (95% CI, −0.31 to −0.02; P = .03) compared with placebo, and patients with ulcers that were completely central at baseline had 0.20 logMAR better visual acuity with corticosteroids (−0.37 to −0.04; P = .02). Conclusions We found no overall difference in 3-month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial corneal ulcers. Application to Clinical Practice Adjunctive topical corticosteroid use does not improve 3-month vision in patients with bacterial corneal ulcers. PMID:21987582

  11. Common mechanisms of DNA translocation motors in bacteria and viruses using one-way revolution mechanism without rotation.

    Science.gov (United States)

    Guo, Peixuan; Zhao, Zhengyi; Haak, Jeannie; Wang, Shaoying; Wu, Dong; Meng, Bing; Weitao, Tao

    2014-01-01

    Biomotors were once described into two categories: linear motor and rotation motor. Recently, a third type of biomotor with revolution mechanism without rotation has been discovered. By analogy, rotation resembles the Earth rotating on its axis in a complete cycle every 24h, while revolution resembles the Earth revolving around the Sun one circle per 365 days (see animations http://nanobio.uky.edu/movie.html). The action of revolution that enables a motor free of coiling and torque has solved many puzzles and debates that have occurred throughout the history of viral DNA packaging motor studies. It also settles the discrepancies concerning the structure, stoichiometry, and functioning of DNA translocation motors. This review uses bacteriophages Phi29, HK97, SPP1, P22, T4, and T7 as well as bacterial DNA translocase FtsK and SpoIIIE or the large eukaryotic dsDNA viruses such as mimivirus and vaccinia virus as examples to elucidate the puzzles. These motors use ATPase, some of which have been confirmed to be a hexamer, to revolve around the dsDNA sequentially. ATP binding induces conformational change and possibly an entropy alteration in ATPase to a high affinity toward dsDNA; but ATP hydrolysis triggers another entropic and conformational change in ATPase to a low affinity for DNA, by which dsDNA is pushed toward an adjacent ATPase subunit. The rotation and revolution mechanisms can be distinguished by the size of channel: the channels of rotation motors are equal to or smaller than 2 nm, that is the size of dsDNA, whereas channels of revolution motors are larger than 3 nm. Rotation motors use parallel threads to operate with a right-handed channel, while revolution motors use a left-handed channel to drive the right-handed DNA in an anti-chiral arrangement. Coordination of several vector factors in the same direction makes viral DNA-packaging motors unusually powerful and effective. Revolution mechanism that avoids DNA coiling in translocating the lengthy genomic

  12. Biosensors for Whole-Cell Bacterial Detection

    Science.gov (United States)

    Rushworth, Jo V.; Hirst, Natalie A.; Millner, Paul A.

    2014-01-01

    SUMMARY Bacterial pathogens are important targets for detection and identification in medicine, food safety, public health, and security. Bacterial infection is a common cause of morbidity and mortality worldwide. In spite of the availability of antibiotics, these infections are often misdiagnosed or there is an unacceptable delay in diagnosis. Current methods of bacterial detection rely upon laboratory-based techniques such as cell culture, microscopic analysis, and biochemical assays. These procedures are time-consuming and costly and require specialist equipment and trained users. Portable stand-alone biosensors can facilitate rapid detection and diagnosis at the point of care. Biosensors will be particularly useful where a clear diagnosis informs treatment, in critical illness (e.g., meningitis) or to prevent further disease spread (e.g., in case of food-borne pathogens or sexually transmitted diseases). Detection of bacteria is also becoming increasingly important in antibioterrorism measures (e.g., anthrax detection). In this review, we discuss recent progress in the use of biosensors for the detection of whole bacterial cells for sensitive and earlier identification of bacteria without the need for sample processing. There is a particular focus on electrochemical biosensors, especially impedance-based systems, as these present key advantages in terms of ease of miniaturization, lack of reagents, sensitivity, and low cost. PMID:24982325

  13. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy

    DEFF Research Database (Denmark)

    Xu, Ming-Jiang; Feng, Dechun; Wu, Hailong

    2015-01-01

    knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were...... or E. coli. These mice also had increased enteric bacterial translocation from the gut to the mesenteric lymph nodes and exhibited reduced liver regeneration after PHx. Treatment with interleukin (IL)-6 stimulated hepatocytes to produce LCN2 in vitro and in vivo. Hepatocyte-specific ablation of the IL...

  14. Corruption of innate immunity by bacterial proteases.

    Science.gov (United States)

    Potempa, Jan; Pike, Robert N

    2009-01-01

    The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from non-specific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host's innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections.

  15. Corruption of Innate Immunity by Bacterial Proteases

    Science.gov (United States)

    Potempa, Jan; Pike, Robert N.

    2009-01-01

    The innate immune system of the human body has developed numerous mechanisms to control endogenous and exogenous bacteria and thus prevent infections by these microorganisms. These mechanisms range from physical barriers such as the skin or mucosal epithelium to a sophisticated array of molecules and cells that function to suppress or prevent bacterial infection. Many bacteria express a variety of proteases, ranging from non-specific and powerful enzymes that degrade many proteins involved in innate immunity to proteases that are extremely precise and specific in their mode of action. Here we have assembled a comprehensive picture of how bacterial proteases affect the host’s innate immune system to gain advantage and cause infection. This picture is far from being complete since the numbers of mechanisms utilized are as astonishing as they are diverse, ranging from degradation of molecules vital to innate immune mechanisms to subversion of the mechanisms to allow the bacterium to hide from the system or take advantage of it. It is vital that such mechanisms are elucidated to allow strategies to be developed to aid the innate immune system in controlling bacterial infections. PMID:19756242

  16. A Common Structural Motif in the Binding of Virulence Factors to Bacterial Secretion Chaperones

    Energy Technology Data Exchange (ETDEWEB)

    Lilic,M.; Vujanac, M.; Stebbins, C.

    2006-01-01

    Salmonella invasion protein A (SipA) is translocated into host cells by a type III secretion system (T3SS) and comprises two regions: one domain binds its cognate type III secretion chaperone, InvB, in the bacterium to facilitate translocation, while a second domain functions in the host cell, contributing to bacterial uptake by polymerizing actin. We present here the crystal structures of the SipA chaperone binding domain (CBD) alone and in complex with InvB. The SipA CBD is found to consist of a nonglobular polypeptide as well as a large globular domain, both of which are necessary for binding to InvB. We also identify a structural motif that may direct virulence factors to their cognate chaperones in a diverse range of pathogenic bacteria. Disruption of this structural motif leads to a destabilization of several chaperone-substrate complexes from different species, as well as an impairment of secretion in Salmonella.

  17. Eudesmane-Type Sesquiterpene Lactones Inhibit Nuclear Translocation of the Nuclear Factor κB Subunit RelB in Response to a Lymphotoxin β Stimulation.

    Science.gov (United States)

    Quach, Hue Tu; Kondo, Tetsuya; Watanabe, Megumi; Tamura, Ryuichi; Yajima, Yoshiki; Sayama, Shinsei; Ando, Masayoshi; Kataoka, Takao

    2017-01-01

    The transcription factor nuclear factor κB (NF-κB) regulates various biological processes, including inflammatory responses. We previously reported that eudesmane-type sesquiterpene lactones inhibited multiple steps in the canonical NF-κB signaling pathway induced by tumor necrosis factor-α and interleukin-1α. In contrast, the biological activities of eudesmane-type sesquiterpene lactones on the non-canonical NF-κB signaling pathway remain unclear. In the present study, we found that (11S)-2α-bromo-3-oxoeudesmano-12,6α-lactone, designated santonin-related compound 2 (SRC2), inhibited NF-κB luciferase reporter activity induced by lymphotoxin β (LTβ) in human lung carcinoma A549 cells. Although SRC2 did not prevent the processing of the NF-κB subunit p100 induced by LTβ, it inhibited the nuclear translocation of RelB and p52 in response to the LTβ stimulation. In contrast to (-)-dehydroxymethylepoxyquinomicin, SRC2 inhibited the LTβ-induced nuclear translocation of the RelB (C144S) mutant in a manner similar to wild-type RelB. While eudesmane derivatives possessing an α-bromoketone moiety or α,β-unsaturated carbonyl moieties inhibited LTβ-induced NF-κB luciferase reporter activity, eudesmane derivatives possessing an α-bromoketone moiety exhibited stronger inhibitory activity on the LTβ-induced nuclear translocation of RelB than those possessing a single α-methylene-γ-lactone moiety. The results of the present study revealed that SRC2 inhibits the nuclear translocation of RelB in the non-canonical NF-κB signaling pathway induced by LTβ.

  18. Metabolic signatures of bacterial vaginosis.

    Science.gov (United States)

    Srinivasan, Sujatha; Morgan, Martin T; Fiedler, Tina L; Djukovic, Danijel; Hoffman, Noah G; Raftery, Daniel; Marrazzo, Jeanne M; Fredricks, David N

    2015-04-14

    Bacterial vaginosis (BV) is characterized by shifts in the vaginal microbiota from Lactobacillus dominant to a microbiota with diverse anaerobic bacteria. Few studies have linked specific metabolites with bacteria found in the human vagina. Here, we report dramatic differences in metabolite compositions and concentrations associated with BV using a global metabolomics approach. We further validated important metabolites using samples from a second cohort of women and a different platform to measure metabolites. In the primary study, we compared metabolite profiles in cervicovaginal lavage fluid from 40 women with BV and 20 women without BV. Vaginal bacterial representation was determined using broad-range PCR with pyrosequencing and concentrations of bacteria by quantitative PCR. We detected 279 named biochemicals; levels of 62% of metabolites were significantly different in women with BV. Unsupervised clustering of metabolites separated women with and without BV. Women with BV have metabolite profiles marked by lower concentrations of amino acids and dipeptides, concomitant with higher levels of amino acid catabolites and polyamines. Higher levels of the signaling eicosanoid 12-hydroxyeicosatetraenoic acid (12-HETE), a biomarker for inflammation, were noted in BV. Lactobacillus crispatus and Lactobacillus jensenii exhibited similar metabolite correlation patterns, which were distinct from correlation patterns exhibited by BV-associated bacteria. Several metabolites were significantly associated with clinical signs and symptoms (Amsel criteria) used to diagnose BV, and no metabolite was associated with all four clinical criteria. BV has strong metabolic signatures across multiple metabolic pathways, and these signatures are associated with the presence and concentrations of particular bacteria. Bacterial vaginosis (BV) is a common but highly enigmatic condition that is associated with adverse outcomes for women and their neonates. Small molecule metabolites in the

  19. Characterization of uptake and translocation of radioactive herbicides in a parasitic-host system

    International Nuclear Information System (INIS)

    Diaz S, Jorge; Lopez G, Francisca; Garcia T, Luis

    1999-01-01

    Uptake and translocation of [14C]-propyzamide applied to the sunflower seed by coating or soaking, of [14C]-imazapyr and [14C]-glyphosate both applied at post emergence, were studied in sunflower (Helianthus annuus L.) parasitising or not by nodding broom rape (Orobanche cumana Wallr.).