Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model

Affiliation: Département de Biochimie, Université de Montréal

Suppression of root-knot nematode through innovative mustard biofumigation

The nematicidal activity of mustard plant against hatching, migration and mortality of the root-knot nematode Meloidogyne javanica was investigated. In vitro test confirmed that mixing the sandy clay soil mixture with mustard as 4% as a biofumigant significantly reduce the percentage of egg hatching at all different incubation periods 24, 48, 72, 96 and 168 h, compared to control treatment (un-amended mixture soil and eggs in free water). Results indicate that the percentage of egg hatching reduction was 88.5, 90, 81.4, 74 and 69.4%, respectively. Mustard mixed with soil as a biofumigant led to high percentage of larval mortality at the different intervals periods in vitro. The percentage of larval mortality was 94, 100, 90.5, 90.5, and 79.4%, respectively compared to control. Laboratory results confirmed that the highest reduction in egg hatching and larval mortality was obtained after incubation period for 48 h. In vivo experiment reveals that the incorporation of the soil pots with mustard at all different doses used 3, 5% (48 h before nematode inoculation, or soil infestation with nematode), and 5% (one week before nematode inoculation or 7% of soil weight) significantly reduces all the nematode parameters compared to plant treated nematode alone. All nematode parameters i.e. the number of galls per root system, gall index, number of egg masses per root system, as well as number of juveniles per 250g soil showed high reduction with mixing the soil pots with mustard at 5% (one week before nematode inoculation), followed by the same treatment for 48h before nematode inoculation. Mustard application, one week before nematode inoculation, reduced the nematode parameters by 97, 64, 97, and 93%, respectively, compared to control. The percent of chemical components i.e. total sugars, total amino acids and total phenols were markedly enhanced compared to positive and negative control. The highest percentage was obtained with mustard at 5% one week before nematode inoculation by 68.7, 57.3 and 45%, respectively. Finally, we have to conclude that this modified technology is an innovative and can be used efficiently to control Root-knot nematode under organic agriculture and Global GAP agricultural systems instead of these carcinogenic nematicides.

Memory suppression can help people “unlearn” behavioral responses—but only for nonemotional memories

When encountering reminders of memories that we prefer not to think about, we often try to exclude those memories from awareness. Past studies have revealed that such suppression attempts can reduce the subsequent recollection of unwanted memories. In the present study, we examined whether the inhibitory effects extend even to associated behavioral responses. Participants learned cue–target pairs for emotional and nonemotional targets and were additionally trained in behavioral responses for each cue. Afterward, they were shown the cues and instructed either to think or to avoid thinking about the targets without performing any behaviors. In a final test phase, behavioral performance was tested for all of the cues. When the targets were neutral, participants’ attempts to avoid retrieval reduced accuracy and increased reaction times in generating behavioral responses associated with cues. By contrast, behavioral performance was not affected by suppression attempts when the targets were emotional. These results indicate that controlling unwanted recollection is powerful enough to inhibit associated behavioral responses—but only for nonemotional memories.

Subchronic effects of fluoxetine on conditioned suppression produced by a hot air blast

Conditioned suppression is an animal model of anxiety disorders that has been broadly used to investigate the behavioral effects of different drugs. However, various methodological variables (e.g., the type of aversive stimulus) that supposedly interfere with the acquisition of conditioned suppression may also contribute to conflicting results among the studied drugs. Additionally, few studies have sought to investigate the effects of selective serotonin reuptake inhibitors (SSRIs). The present study investigated the effect of subchronic 5-day administration of 5 mg/kg fluoxetine in the retention of conditioned suppression produced by a hot air blast (HAB). The subjects were 12 albino Wistar rats distributed into an Experimental Group (EG) and Control Group (CG). After sessions were conducted to pair two stimuli, a sound and HAB, fluoxetine (EG) or saline (CG) was administered. Twentyfour hours after the last injection, a test session was conducted. The results showed no difference between groups. Fluoxetine (5 mg/kg) did not exert anxiolytic effects in this model of conditioned suppression produced by a HAB. Keywords: conditioned suppression; fluoxetine; subchronic; hot air blast.

Suppression of vibrations in a nonlinear half-car model using a magneto-rheological damper

The present work investigates the nonlinear response of a half-car model. The disturbances of the road are assumed to be sinusoidal. After constructing the bifurcation diagram, we use the 0-1 test to identify chaotic motions. The main objective of this study is to eliminate chaotic behavior of the chassis and reduce its vibrations. To accomplish this, a semi-active vehicle suspension control system, using magneto-rheological dampers, is proposed. The proposed semi-active control strategy consists of two nonlinear control laws: a feedforward control, and a feedback control. They are obtained by considering the SDRE (State Dependent Riccati Equation) control, where the control parameter is the voltage applied to the coils of the magneto-rheological dampers. Numerical results show that the proposed control method is effective in significantly reducing of the chassis vibration, increasing, therefore, passenger comfort.

Suppression of Hypoxia-Inducible Factor-1 alpha Contributes to the Antiangiogenic Activity of Red Propolis Polyphenols in Human Endothelial Cells

Polyphenol-enriched fractions from natural sources have been proposed to interfere with angiogenesis in pathological conditions. We recently reported that red propolis polyphenols (RPP) exert antiangiogenic activity. However, molecular mechanisms of this activity remain unclear. Here, we aimed at characterizing molecular mechanisms to explain the impact of RPP on endothelial cells' (EC) physiology. We used in vitro and ex and in vivo models to test the hypothesis that RPP inhibit angiogenesis by affecting hypoxia-inducible factor-1 alpha (HIF1 alpha) stabilization in EC. RPP (10 mg/L) affected angiogenesis by reducing migration and sprouting of EC, attenuated the formation of new blood vessels, and decreased the differentiation of embryonic stem cells into CD31-positive cells. Moreover, RPP (10 mg/L) inhibited hypoxia- or dimethyloxallylglycine-induced mRNA and protein expression of the crucial angiogenesis promoter vascular endothelial growth factor (VEGF) in a time-dependent mariner. Under hypoxic conditions, RPP at 10 mg/L, supplied for 1-4 h, decreased HIF1 alpha protein accumulation, which in turn attenuated VEGF gene expression. In addition, RPP reduced the HIF1 alpha protein half-life from similar to 58 min to 38 min under hypoxic conditions. The reduced HIF1 alpha protein half-life was associated with an increase in the von Hippel-Lindau (pVHL)-dependent proteasomal degradation of HIF1 alpha. RPP (10 mg/L, 4 h) downregulated Cdc42 protein expression. This caused a corresponding increase in pVHL protein levels and a subsequent degradation of HIF1 alpha. In summary, we have elucidated the underlying mechanism for the antiangiogenic action of RPP, which attenuates HIF1 alpha protein accumulation and signaling. J. Nutr. 142: 441-447, 2012.

Inhibition of the NMDA receptor/Nitric Oxide pathway in the dorsolateral periaqueductal gray causes anxiolytic-like effects in rats submitted to the Vogel conflict test

Abstract Background Several studies had demonstrated the involvement of the dorsolateral portion of periaqueductal grey matter (dlPAG) in defensive responses. This region contains a significant number of neurons containing the enzyme nitric oxide synthase (NOS) and previous studies showed that non-selective NOS inhibition or glutamate NMDA-receptor antagonism in the dlPAG caused anxiolytic-like effects in the elevated plus maze. Methods In the present study we verified if the NMDA/NO pathway in the dlPAG would also involve in the behavioral suppression observed in rats submitted to the Vogel conflict test. In addition, the involvement of this pathway was investigated by using a selective nNOS inhibitor, Nω-propyl-L-arginine (N-Propyl, 0.08 nmol/200 nL), a NO scavenger, carboxy-PTIO (c-PTIO, 2 nmol/200 nL) and a specific NMDA receptor antagonist, LY235959 (4 nmol/200 nL). Results Intra-dlPAG microinjection of these drugs increased the number of punished licks without changing the number of unpunished licks or nociceptive threshold, as measure by the tail flick test. Conclusion The results indicate that activation of NMDA receptors and increased production of NO in the dlPAG are involved in the anxiety behavior displayed by rats in the VCT.

Modeling and Vibration Suppression for Telescopic Systems of Structural Members with Clearance

Telescopic systems of structural members with clearance are found in many applications, e.g., mobile cranes, rack feeders, fork lifters, stacker cranes (see Figure 1). Operating these machines, undesirable vibrations may reduce the performance and increase safety problems. Therefore, this contribution has the aim to reduce these harmful vibrations. For a better understanding, the dynamic behaviour of these constructions is analysed. The main interest is the overlapping area of each two sections of the above described systems (see markings in Figure 1) which is investigated by measurements and by computations. A test rig is constructed to determine the dynamic behaviour by measuring fundamental vibrations and higher frequent oscillations, damping coefficients, special appearances and more. For an appropriate physical model, the governing boundary value problem is derived by applying Hamilton’s principle and a classical discretisation procedure is used to generate a coupled system of nonlinear ordinary differential equations as the corresponding truncated mathematical model. On the basis of this model, a controller concept for preventing harmful vibrations is developed.

Platelet-activating factor is crucial in psoralen and ultraviolet A-induced immune suppression, inflammation, and apoptosis.

Psoralen plus UVA (PUVA) is used as a very effective treatment modality for various diseases, including psoriasis and cutaneous T-cell lymphoma. PUVA-induced immune suppression and/or apoptosis are thought to be responsible for the therapeutic action. However, the molecular mechanisms by which PUVA acts are not well understood. We have previously identified platelet-activating factor (PAF), a potent phospholipid mediator, as a crucial substance triggering ultraviolet B radiation-induced immune suppression. In this study, we used PAF receptor knockout mice, a selective PAF receptor antagonist, a COX-2 inhibitor (presumably blocking downstream effects of PAF), and PAF-like molecules to test the role of PAF receptor binding in PUVA treatment. We found that activation of the PAF pathway is crucial for PUVA-induced immune suppression (as measured by suppression of delayed type hypersensitivity to Candida albicans) and that it plays a role in skin inflammation and apoptosis. Downstream of PAF, interleukin-10 was involved in PUVA-induced immune suppression but not inflammation. Better understanding of PUVA's mechanisms may offer the opportunity to dissect the therapeutic from the detrimental (ie, carcinogenic) effects and/or to develop new drugs (eg, using the PAF pathway) that act like PUVA but have fewer side effects.

Role of MicroRNA Modulation in the Interferon-α/Ribavirin Suppression of HIV-1 In Vivo.

BACKGROUND Interferon-α (IFN-α) treatment suppresses HIV-1 viremia and reduces the size of the HIV-1 latent reservoir. Therefore, investigation of the molecular and immunologic effects of IFN-α may provide insights that contribute to the development of novel prophylactic, therapeutic and curative strategies for HIV-1 infection. In this study, we hypothesized that microRNAs (miRNAs) contribute to the IFN-α-mediated suppression of HIV-1. To inform the development of novel miRNA-based antiretroviral strategies, we investigated the effects of exogenous IFN-α treatment on global miRNA expression profile, HIV-1 viremia, and potential regulatory networks between miRNAs and cell-intrinsic anti-HIV-1 host factors in vivo. METHODS Global miRNA expression was examined in longitudinal PBMC samples obtained from seven HIV/HCV-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated interferon-α/ribavirin therapy (IFN-α/RBV). We implemented novel hybrid computational-empirical approaches to characterize regulatory networks between miRNAs and anti-HIV-1 host restriction factors. RESULTS miR-422a was the only miRNA significantly modulated by IFN-α/RBV in vivo (p<0.0001, paired t test; FDR<0.037). Our interactome mapping revealed extensive regulatory involvement of miR-422a in p53-dependent apoptotic and pyroptotic pathways. Based on sequence homology and inverse expression relationships, 29 unique miRNAs may regulate anti-HIV-1 restriction factor expression in vivo. CONCLUSIONS The specific reduction of miR-422a is associated with exogenous IFN-α treatment, and likely contributes to the IFN-α suppression of HIV-1 through the enhancement of anti-HIV-1 restriction factor expression and regulation of genes involved in programmed cell death. Moreover, our regulatory network analysis presents additional candidate miRNAs that may be targeted to enhance anti-HIV-1 restriction factor expression in vivo.

The video head impulse test during post-rotatory nystagmus: physiology and clinical implications.

The aim of this study was to test the effects of a sustained nystagmus on the head impulse response of the vestibulo-ocular reflex (VOR) in healthy subjects. VOR gain (slow-phase eye velocity/head velocity) was measured using video head impulse test goggles. Acting as a surrogate for a spontaneous nystagmus (SN), a post-rotatory nystagmus (PRN) was elicited after a sustained, constant-velocity rotation, and then head impulses were applied. 'Raw' VOR gain, uncorrected for PRN, in healthy subjects in response to head impulses with peak velocities in the range of 150°/s-250°/s was significantly increased (as reflected in an increase in the slope of the gain versus head velocity relationship) after inducing PRN with slow phases of nystagmus of high intensity (>30°/s) in the same but not in the opposite direction as the slow-phase response induced by the head impulses. The values of VOR gain themselves, however, remained in the normal range with slow-phase velocities of PRN < 30°/s. Finally, quick phases of PRN were suppressed during the first 20-160 ms of a head impulse; the time frame of suppression depended on the direction of PRN but not on the duration of the head impulse. Our results in normal subjects suggest that VOR gains measured using head impulses may have to be corrected for any superimposed SN when the slow-phase velocity of nystagmus is relatively high and the peak velocity of the head movements is relatively low. The suppression of quick phases during head impulses may help to improve steady fixation during rapid head movements.

DNA damage-induced Fas ligand expression by epidermal dendritic cells mediates UV-induced immune suppression of contact hypersensitivity

Exposure to UVB radiation induces local and systemic immune suppression, evidenced by inhibition of the contact hypersensitivity response (CHS). Epidermal dendritic cells, the primary antigen presenting cells responsible for the induction of CHS, are profoundly altered in phenotype and function by UVB exposure and possess UV-specific DNA damage upon migrating to skin-draining lymph nodes. Expression of the proapoptotic protein FasL has been demonstrated in both skin and lymph node cells following UVB exposure. Additionally, functional FasL expression has recently been demonstrated to be required in the phenomenon of UV-induced immune suppression. To test the hypothesis that FasL expression by DNA-damaged Langerhans cells migrating to the skin-draining lymph nodes is a crucial event in the generation of this phenomenon, mice were given a single 5KJ/m2 UV-B exposure and sensitized to 0.5% FITC through the exposed area. Dendritic cells (DC) harvested from skin-draining lymph nodes (DLN) 18 hours following sensitization by magnetic CD11c-conjugated microbeads expressed high levels of Iab, CD80 and CD86, DEC-205 and bore the FITC hapten, suggesting epidermal origin. Radioimmunoassay of UV-specific DNA damage showed that DC contained the vast majority of cyclobutane pyrimidine dimers (CPDs) found in the DLN after UVB and exhibited increased FasL mRNA expression, a result which correlated with greatly increased FasL-mediated cytotoxicity. The ability of DCs to transfer sensitization to naïve hosts was lost following UVB exposure, a phenomenon which required DC FasL expression, and was completely reversed by cutaneous DNA repair. Collectively, these results demonstrate the central importance of DNA damage-induced FasL expression on migrating dendritic cells in mediating UV-induced suppression of contact hypersensitivity. ^

Molecular mechanism of jet fuel induced immune suppression

Dermal exposure to jet fuel suppresses the immune response. Immune regulatory cytokines, and biological modifiers, including platelet activating factor, prostaglandin E2, and interleukin-10 have all been implicated in the pathway leading to immunosuppression. It is estimated that approximately 260 different hydrocarbons are found in JP-8 (jet propulsion-8) jet fuel, and the identity of the immunotoxic compound is not known. The recent availability of synthetic jet fuel (S-8), which is devoid of aromatic hydrocarbons, made it feasible to design experiments to test the hypothesis that the aromatic hydrocarbons are responsible for jet fuel induced immune suppression. Applying S-8 to the skin of mice does not up-regulate the expression of epidermal cyclooxygenase-2 nor does it induce immune suppression. Adding back a cocktail of 7 of the most prevalent aromatic hydrocarbons found in jet fuel to S-8 up-regulated cyclooxygenase-2 expression and induced immune suppression. Cyclooxygenase-2 induction can be initiated by reactive oxygen species (ROS). JP-8 treated keratinocytes increased ROS production, S-8 did not. Antioxidant pre-treatment blocked jet fuel induced immune suppression and cyclooxygenase-2 up-regulation. Accumulation of reactive oxygen species induces oxidant stress and affects activity of ROS sensitive transcription factors. JP-8 induced activation of NFκB while S-8 did not. Pre-treatment with antioxidants blocked activation of NFκB and parthenolide, an NFκB inhibitor, blocked jet fuel induced immune suppression and cyclooxygenase-2 expression in skin of treated mice. p65 siRNA transfected keratinocytes demonstrated NFκB is critically involved in jet fuel induced COX-2 expression. These findings clearly implicate the aromatic hydrocarbons found in jet fuel as the agents responsible for inducing immune suppression, in part by the production of reaction oxygen species, NFκB dependent up-regulation of cyclooxygenase-2, and the production of immune regulatory factors and cytokines. ^

Effects of exogeneous p53 on growth suppression, apoptosis, and differentiation in oral cancer cell lines

The p53 gene is known to be one of the most commonly mutated genes in human cancers. Many squamous cell carcinomas of the head and neck (SCCHNs) have been shown to contain nonfunctional p53 as well. The use of p53-mediated gene therapy to treat such cancers has become an intensive area of research. Although there have been varied treatment responses to p53 gene therapy, the role that endogenous p53 status plays in this response has not been thoroughly examined. Because of this, the hypothesis of this study examined the role that the endogenous p53 status of cells plays in their response to p53 gene therapy. To test this, an adenoviral vector containing p53 (p53FAd) was administered to three squamous cell carcinoma lines with varied endogenous p53. The SCC9 cell line demonstrates no p53 protein expression, the SCC4 cell line displays overexpression of a mutant p53 protein, and the 1986LN cell line displays low to no expression of wild-type p53 protein as a consequence of human papillomavirus infection. After treatment with p53FAd, the cells were examined for evidence of exogenous p53 expression, growth suppression, alterations in cellular proteins, G1 growth arrest, apoptosis, and differentiation state. Each cell line exhibited exogenous p53 protein. Growth suppression was seen most prominently in the SCC9 cells, to some extent in the 1986LN cells, and little was seen with the SCC4 cells. WAF1/p21 protein was induced in all three cell lines, while PCNA, bcl-2, and bax expression was not significantly affected in any of the lines. Apoptosis developed first in SCC9 cells, next in 1986LN cells, with little seen in the SCC4 cells. The SCC9 line was the only line to show significant GI growth arrest. No significant differences were observed in the overall expression of differentiation markers, aside from increased keratin 13 mRNA levels in all three lines indicating a possible tendency toward differentiation. This study indicates that the endogenous p53 status of squamous cell carcinomas appears to play a critical role in determining the response to p53 adenoviral gene therapy. ^

Full scale test for explosion water barriers in small cross-section galleries

Underground coal mines explosions generally arise from the inflammation of a methane/air mixture. This explosion can also generate a subsequent coal dust explosion. Traditionally such explosions have being fought eliminating one or several of the factors needed by the explosion to take place. Although several preventive measures are taken to prevent explosions, other measures should be considered to reduce the effects or even to extinguish the flame front. Unlike other protection methods that remove one or two of the explosion triangle elements, namely; the ignition source, the oxidizing agent and the fuel, explosion barriers removes all of them: reduces the quantity of coal in suspension, cools the flame front and the steam generated by vaporization removes the oxygen present in the flame. Passive water barriers are autonomous protection systems against explosions that reduce to a satisfactory safety level the effects of methane and/or flammable dust explosions. The barriers are activated by the pressure wave provoked in the explosion destroying the barrier troughs and producing a uniform dispersion of the extinguishing agent throughout the gallery section in quantity enough to extinguish the explosion flame. Full scale tests have been carried out in Polish Barbara experimental mine at GIG Central Mining Institute in order to determine the requirements and the optimal installation conditions of these devices for small sections galleries which are very frequent in the Spanish coal mines. Full scale tests results have been analyzed to understand the explosion timing and development, in order to assess on the use of water barriers in the typical small crosssection Spanish galleries. Several arrangements of water barriers have been designed and tested to verify the effectiveness of the explosion suppression in each case. The results obtained demonstrate the efficiency of the water barriers in stopping the flame front even with smaller amounts of water than those established by the European standard. According to the tests realized, water barriers activation times are between 0.52 s and 0.78 s and the flame propagation speed are between 75 m/s and 80 m/s. The maximum pressures (Pmax) obtained in the full scale tests have varied between 0.2 bar and 1.8 bar. Passive barriers protect effectively against the spread of the flame but cannot be used as a safeguard of the gallery between the ignition source and the first row of water troughs or bags, or even after them, as the pressure could remain high after them even if the flame front has been extinguished.