Sp110 transcription is induced and required by Anaplasma phagocytophilum for infection of human promyelocytic cells

<p>Abstract</p> <p>Background</p> <p>The tick-borne intracellular pathogen, <it>Anaplasma phagocytophilum </it>(Rickettsiales: Anaplasmataceae) causes human granulocytic anaplasmosis after infection of polymorphonuclear leucocytes. The human Sp110 gene is a member of the nuclear body (NB) components that functions as a nuclear hormone receptor transcriptional coactivator and plays an important role in immunoprotective mechanisms against pathogens in humans. In this research, we hypothesized that Sp110 may be involved in the infection of human promyelocytic HL-60 cells with <it>A. phagocytophilum</it>.</p> <p>Methods</p> <p>The human Sp110 and <it>A. phagocytophilum msp4 </it>mRNA levels were evaluated by real-time RT-PCR in infected human HL-60 cells sampled at 0, 12, 24, 48, 72 and 96 hours post-infection. The effect of Sp110 expression on <it>A. phagocytophilum </it>infection was determined by RNA interference (RNAi). The expression of Sp110 was silenced in HL-60 cells by RNAi using pre-designed siRNAs using the Nucleofector 96-well shuttle system (Amaxa Biosystems, Gaithersburg, MD, USA). The <it>A. phagocytophilum </it>infection levels were evaluated in HL-60 cells after RNAi by real-time PCR of <it>msp4 </it>and normalizing against human <it>Alu </it>sequences.</p> <p>Results</p> <p>While Sp110 mRNA levels increased concurrently with <it>A. phagocytophilum </it>infections in HL-60 cells, the silencing of Sp110 expression by RNA interference resulted in decreased infection levels.</p> <p>Conclusion</p> <p>These results demonstrated that Sp110 expression is required for <it>A. phagocytophilum </it>infection and multiplication in HL-60 cells, and suggest a previously undescribed mechanism by which <it>A. phagocytophilum </it>modulates Sp110 mRNA levels to facilitate establishment of infection of human HL-60 cells.</p

Antimicrobial effect of vancomycin electro-transferred water against methicillin-resistant Staphylococcus aureus

Background: There is a number of alternative and complementary therapeutics that are unproven or have not been properly tested. For past twenty years, the transfer of bio-energetic information has been recognized as a novel scientific approach capable of contributing to improved therapy in the management of several diseases through the so-called bio-resonance therapy (BRT). Although BRT was discovered in the late 1980s, it is still poorly studied. The aim of this study was to evaluate the antibacterial effect of water samples transferred with electronic information of vancomycin, a well known drug against methicillin-resistant Staphylococcus aureus (MRSA), by using a BRT device on bacterial cultures.Material and Methods: MRSA cultures were treated with vancomycin electro-transferred water samples, vancomycin (4.0 and 8.0 μg/mL), sham electro-transferred (water to water) and non-transferred water samples (medium alone). Growth inhibition was evaluated in liquid and solid culture medium, spectrophotometrically and by CFU determination respectively.Results: The obtained data showed that by transferring vancomycin (4.0 and 8.0 μg/mL) information to water samples, the growth of cultured MRSA was significantly (p&lt; 0.05) inhibited (up to 35%), compared with those cultures treated with electro-transferred water to water or cultured in medium alone (0% growth inhibition).Conclusion: This in vitro study suggests that water samples that are electronically transferred with vibration sustained information of vancomycin are capable of inhibiting growth of axenically cultured methicillin resistant S. aureus.Key words: Antimicrobial effect, electro-transferred water, bio-resonance, vancomycin, Sthaphylococcus aureus

Polyornithine-based polyplexes to boost effective gene silencing in CNS disorders.

Gene silencing therapies have successfully suppressed the translation of target proteins, a strategy that holds great promise for the treatment of central nervous system (CNS) disorders. Advances in the current knowledge on multimolecular delivery vehicles are concentrated on overcoming the difficulties in delivery of small interfering (si)RNA to target tissues, which include anatomical accessibility, slow diffusion, safety concerns, and the requirement for specific cell uptake within the unique environment of the CNS. The present work addressed these challenges through the implementation of polyornithine derivatives in the construction of polyplexes used as non-viral siRNA delivery vectors. Physicochemical and biological characterization revealed biodegradability and biocompatibility of our polyornithine-based system and the ability to silence gene expression in primary oligodendrocyte progenitor cells (OPCs) effectively. In summary, the well-defined properties and neurological compatibility of this polypeptide-based platform highlight its potential utility in the treatment of CNS disorders

Anti-giardia activity of hexane extract of Citrus aurantifolia (Christim) swingle and some of its constituents

Background: Giardia lamblia is a parasite that causes giardiasis in humans and other mammals. The common treatment includes different drugs, which were described to produce unpleasant side effects. Citrus aurantifolia, popularly known as “lima”, is a plant used in traditional medicine to treat gastrointestinal symptoms. The aim of the present study was to evaluate the anti-Giardia activity of 10 pure compounds obtained from a hexanic extract of Mexican lime on the basis of trophozoite growth inhibition.Materials and Methods: A hexanic extract obtained from fresh fruit peels of Citrus aurantifolia was tested on G. lamblia strain 0989:IMSS trophozoites cultured in TYI-S-33 medium. The concentration of all standard drugs, analyzed by gas chromatography, was adjusted at 10 mg/mL. Metronidazole was used as a positive control. Growth inhibition was determined by counting the number of trophozoites using a Neubauer chamber. The 50% inhibitory concentration (IC50) of each drug was calculated by probit analysis and 95% confidence limits were calculated.Results: 4-hexen-3-one, citral and geraniol showed IC50 values of 34.2, 64.5 and 229.49 μg/ml in axenic cultures after 24 hr of incubation, respectively. When these results were compared with a positive control of metronidazole; 4-hexen-3-one was 66 times; citral was 112 and geraniol was 441 times less active respectively. The other tested compounds did not inhibit the growth of cultured G. lamblia trophozoites.Conclusion: The obtained results lead us to propose that these tested compounds from C. aurantifolia have potential for use as therapeutic agents against giardiasis.Keywords: antigiardial ; Citrus aurantifolia; antiprotozoal activity; Giardia lambli

Effects of comorbidities on quality of life in Filipino people with tuberculosis.

BACKGROUND: We investigated health-related quality of life (HrQoL) in Filipino people undergoing TB treatment, and whether HrQoL was negatively impacted by comorbidity with undernutrition, diabetes (DM) and anaemia.METHODS: Adult participants were enrolled in public facilities in Metro Manila (three sites) and Negros Occidental (two sites). Multivariate linear regression was used to model the four correlated domain scores from a WHOQOL-BREF questionnaire (physical, psychological, social, environmental). A forward-stepwise approach was used to select a final multivariable model with inclusion based on global tests of significance at P < 0.1.RESULTS: In 446 people on drug-susceptible TB treatment, DM and moderate/severe anaemia were not associated with HrQoL. After adjustment for age, sex, education, food insecurity, treatment adherence, inflammation, Category I or II TB treatment, treatment phase, current side effects and inhibited ability to work, moderate/severe undernutrition (body mass index < 17 kg/m²) was associated with lower HrQoL (P = 0.003) with reduced psychological (coefficient: -1.02, 95% CI -1.54 to -0.51), physical (-0.62, 95% CI -1.14 to -0.09) and environmental domain scores (-0.45, 95% CI -0.88 to -0.01). In 225 patients with known HIV status in Metro Manila, HIV was associated with modestly reduced HrQoL (P = 0.014).CONCLUSION: Nutritional status and food insecurity represent modifiable risk factors for poor HrQoL that may be alleviated through interventions

Seasonal dynamics of Arctic soils: Capturing year-round processes in measurements and soil biogeochemical models

The Arctic is undergoing rapid changes in climate, altering the status and functioning of high-latitude soils and permafrost. The vast majority of studies on Arctic soils and permafrost are conducted during the summer period due to ease of accessibility, sampling, instrument operation, and making measurements, in comparison to during winter and transition seasons. However, there is increasing evidence that microbial activity continues in Arctic soils outside of the summer period. Moreover, it is becoming clear that understanding the seasonal dynamics of Arctic soils is of critical importance, especially considering that the under-studied winter is the period that is most sensitive to climate warming. Soil biogeochemical models have advanced our understanding of the functioning and fate of soils in the Arctic, however it is vital that seasonality in biotic and abiotic processes is accurately captured in these models. Here we synthesize recent investigations and observations of the year-round functioning of Arctic soils, review soil biogeochemical modelling frameworks, and highlight certain processes and behaviors that are shaped by seasonality and thus warrant particular consideration within these models. More attention to seasonal processes will be critical to improving datasets and soil biogeochemical models that can be used to understand the year-round functioning of soils and the fate of the soil carbon reservoir in the Arctic

Polarimetric receiver in the forty gigahertz band: new instrument for the Q-U-I joint Tenerife experiment

This paper describes the analysis, design and characterization of a polarimetric receiver developed for covering the 35 to 47 GHz frequency band in the new instrument aimed at completing the ground-based Q-U-I Joint Tenerife Experiment. This experiment is designed to measure polarization in the Cosmic Microwave Background. The described high frequency instrument is a HEMT-based array composed of 29 pixels. A thorough analysis of the behaviour of the proposed receiver, based on electronic phase switching, is presented for a noise-like linearly polarized input signal, obtaining simultaneously I, Q and U Stokes parameters of the input signal. Wideband subsystems are designed, assembled and characterized for the polarimeter. Their performances are described showing appropriate results within the 35-to-47 GHz frequency band. Functionality tests are performed at room and cryogenic temperatures with adequate results for both temperature conditions, which validate the receiver concept and performance.The authors would like to thank the Spanish Ministry of Economy, Industry and Competitiveness for the financial support provided through the CONSOLIDER-INGENIO 2010 program under the grant CSD2010-00064 and under the grant ESP2015-70646-C2-2-R

Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and Venezuela

Antennal sensilla patterns were used to analyze population variation of domestic Rhodnius prolixus from six departments and states representing three biogeographical regions of Colombia and Venezuela. Discriminant analysis of the patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel and flagellar segments showed clear differentiation between R. prolixus populations east and west of the Andean Cordillera. The distribution of thick and thin-walled trichoids on the second flagellar segment also showed correlation with latitude, but this was not seen in the patterns of other sensilla. The results of the sensilla patterns appear to be reflecting biogeographic features or population isolation rather than characters associated with different habitats and lend support to the idea that domestic R. prolixus originated in the eastern region of the Andes.Fil: Esteban, Lyda. Universidad Industrial de Santander; ColombiaFil: Angulo, Víctor Manuel. Universidad Industrial de Santander; ColombiaFil: Dora Feliciangeli, M.. Universidad de Carabobo; VenezuelaFil: Catala, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentin

Molecular detection of tick-borne bacteria and protozoa in cervids and wild boars from Portugal

Background: Wildlife can act as reservoir of different tick-borne pathogens, such as bacteria, parasites and viruses. The aim of the present study was to assess the presence of tick-borne bacteria and protozoa with veterinary and zoonotic importance in cervids and wild boars from the Centre and South of Portugal.Methods: One hundred and forty one blood samples from free-ranging ungulates including 73 red deer (Cervus elaphus), 65 wild boars (Sus scrofa) and three fallow deer (Dama dama) were tested for the presence of Anaplasma marginale/A. ovis, A. phagocytophilum, Anaplasma/Ehrlichia spp., Babesia/Theileria spp., Borrelia burgdorferi (sensu lato) (s.l.), and Rickettsia spp. DNA by PCR.Results: Anaplasma spp. DNA was detected in 33 (43.4 %) cervids (31 red deer and two fallow deer) and in two (3.1 %) wild boars while Theileria spp. were found in 34 (44.7 %) cervids (32 red deer and two fallow deer) and in three (4.6 %) wild boar blood samples. Sequence analysis of msp4 sequences identified A. marginale, A. ovis, while the analysis of rDNA sequence data disclosed the presence of A. platys and A. phagocytophilum and T. capreoli and Theileria sp. OT3. Anaplasma spp./Theileria spp. mixed infections were found in 17 cervids (22.4 %) and in two wild boars (3.1 %). All samples were negative for Babesia sp., B. burgdorferi (s.l.), Ehrlichia sp. or Rickettsia sp.Conclusions: This is the first detection of Anaplasma marginale, A. ovis, A. phagocytophilum, A. platys, Theileria capreoli and Theileria sp. OT3 in cervids and wild boars from Portugal. Further studies concerning the potential pathogenicity of the different species of Anaplasma and Theileria infecting wild ungulates, the identification of their vector range, and their putative infectivity to domestic livestock and humans should be undertaken

Discovering study-specific gene regulatory networks

This article has been made available through the Brunel Open Access Publishing Fund.Microarrays are commonly used in biology because of their ability to simultaneously measure thousands of genes under different conditions. Due to their structure, typically containing a high amount of variables but far fewer samples, scalable network analysis techniques are often employed. In particular, consensus approaches have been recently used that combine multiple microarray studies in order to find networks that are more robust. The purpose of this paper, however, is to combine multiple microarray studies to automatically identify subnetworks that are distinctive to specific experimental conditions rather than common to them all. To better understand key regulatory mechanisms and how they change under different conditions, we derive unique networks from multiple independent networks built using glasso which goes beyond standard correlations. This involves calculating cluster prediction accuracies to detect the most predictive genes for a specific set of conditions. We differentiate between accuracies calculated using cross-validation within a selected cluster of studies (the intra prediction accuracy) and those calculated on a set of independent studies belonging to different study clusters (inter prediction accuracy). Finally, we compare our method's results to related state-of-the art techniques. We explore how the proposed pipeline performs on both synthetic data and real data (wheat and Fusarium). Our results show that subnetworks can be identified reliably that are specific to subsets of studies and that these networks reflect key mechanisms that are fundamental to the experimental conditions in each of those subsets