Genotyping USA laboratory-maintained isolates and European clinical isolates of Dirofilaria immitis to assess macrocyclic lactone susceptibility or resistance at predictive SNP sites using droplet digital PCR.

Dirofilaria immitis is a parasitic nematode that causes cardiovascular dirofilariosis ("heartworm disease") primarily in canids. The principal approach for mitigating heartworm infection involves the use of macrocyclic lactone (ML) for prophylaxis. Recent research has substantiated the emergence of D. immitis displaying resistance to MLs in the USA. Numerous factors, such as the mobility of companion animals and competent vectors could impact the spread of drug resistance. Genomic analysis has unveiled that isolates resistant to ML exhibit unique genetic profiles when compared to their wild-type (susceptible) counterparts. Out of the ten single nucleotide polymorphism (SNP) markers validated in clinical samples of D. immitis from the USA, four have demonstrated their effectiveness in distinguishing between isolates with varying ML efficacy phenotypes. This study explores the potential of these confirmed SNPs for conducting surveillance studies. Genotypic analysis using SNP markers emerges as a valuable tool for carrying out surveys and evaluating individual clinical isolates. Two USA laboratory-maintained isolates (Berkeley, WildCat) and twenty-five random European clinical samples of either adult worms or microfilariae (mf) pools isolated from domestic dogs, were tested by droplet digital PCR (ddPCR)-based duplex assay. This approach elucidates genetic evidence pertaining to the development of drug resistance and provides baseline data on resistance related genotypes in Europe. The data on these clinical samples suggests genotypes consistent with the continued efficacy of ML treatment regimens in Europe. In addition, this assay can be significant in discriminating cases of drug-resistance from those possibly due to non-compliance to the recommended preventive protocols.

Adapting the Time-Domain Synthetic Aperture Focusing Technique (T-SAFT) to Laser Ultrasonics for Imaging the Subsurface Defects.

Traditional ultrasonic testing uses a single probe or phased array probe to investigate and visualize defects by adapting certain imaging algorithms. The time-domain synthetic aperture focusing technique (T-SAFT) is an imaging algorithm that employs a single probe to scan along the test specimen in various positions, to generate inspection images with better resolution. Both the T-SAFT and phased array probes are contact methods with limited bandwidth. This work aims to combine the advantages of the T-SAFT and phased array in a noncontact way with the aid of laser ultrasonics. Here, a pulsed laser beam is employed to generate ultrasonic waves in both thermoelastic and ablation regimes, whereas the laser Doppler vibrometer is used to acquire the generated signals. These two lasers are focused on the test specimen and, to avoid the plasma and crater influence in the ablation regime, the transmission beam and reception beam are separated by 5 mm. By moving the test specimen with a step size of 0.5 mm, a 1D linear phased array (41 and 43 elements) with a pitch of 0.5 mm was synthesized, and three side-drilled holes (Ø 8 mm-thermoelastic regime, Ø 10 mm and Ø 2 mm-ablation regime) were introduced for inspection. The A-scan data obtained from these elements were processed via the T-SAFT algorithm to generate the inspection images in various grid sizes. The results showed that the defect reflections obtained in the ablation regime have better visibility than those from the thermoelastic regime. This is due to the high-amplitude signals obtained in the ablation regime, which pave the way for enhancing the pixel intensity of each grid. Moreover, the separation distance (5 mm) does not have any significant effect on the defect location during the reconstruction process.

Enhanced structural integrity of Laser Powder Bed Fusion based AlSi10Mg parts by attaining defect free melt pool formations.

This research aims to fabricate an AlSi10Mg parts using Laser Powder Bed Fusion technique with enhanced structural integrity. The prime novelty of this research work is eliminating the balling and sparring effects, keyhole and cavity formation by attaining effective melt pool formation. Modelling of the Laser Powder Bed Fusion process parameters such as Laser power, scanning speed, layer thickness and hatch spacing is carried out through Complex Proportional Assessment technique to optimize the parts' surface attributes and to overcome the defects based on the output responses such as surface roughness on scanning and building side, hardness and porosity. The laser power of 350 W, layer thickness of 30 µm, scan speed of 1133 mm/s, and hatch spacing of 0.1 mm produces significantly desirable results to achieve maximum hardness and minimum surface roughness and holding the porosity of < 1%. The obtained optimal setting from this research improves the structural integrity of the printed AlSi10Mg parts.

Filarial DAF-12 sense the host serum to resume iL3 development during infection.

Nematode parasites enter their definitive host at the developmentally arrested infectious larval stage (iL3), and the ligand-dependent nuclear receptor DAF-12 contributes to trigger their development to adulthood. Here, we characterized DAF-12 from the filarial nematodes Brugia malayi and Dirofilaria immitis and compared them with DAF-12 from the non-filarial nematodes Haemonchus contortus and Caenorhabditis elegans. Interestingly, Dim and BmaDAF-12 exhibit high sequence identity and share a striking higher sensitivity than Hco and CelDAF-12 to the natural ligands Δ4- and Δ7-dafachronic acids (DA). Moreover, sera from different mammalian species activated specifically Dim and BmaDAF-12 while the hormone-depleted sera failed to activate the filarial DAF-12. Accordingly, hormone-depleted serum delayed the commencement of development of D. immitis iL3 in vitro. Consistent with these observations, we show that spiking mouse charcoal stripped-serum with Δ4-DA at the concentration measured in normal mouse serum restores its capacity to activate DimDAF-12. This indicates that DA present in mammalian serum participate in filarial DAF-12 activation. Finally, analysis of publicly available RNA sequencing data from B. malayi showed that, at the time of infection, putative gene homologs of the DA synthesis pathways are coincidently downregulated. Altogether, our data suggest that filarial DAF-12 have evolved to specifically sense and survive in a host environment, which provides favorable conditions to quickly resume larval development. This work sheds new light on the regulation of filarial nematodes development while entering their definitive mammalian host and may open the route to novel therapies to treat filarial infections.

Achieving effective interlayer bonding of PLA parts during the material extrusion process with enhanced mechanical properties.

The additive manufacturing technique of material extrusion has challenge of excessive process defects and not achieving the desired mechanical properties. The industry is trying to develop certification to better control variations in mechanical attributes. The current study is a progress towards understanding the evolution of processing defects and the correlation of mechanical behavior with the process parameters. Modeling of the 3D printing process parameters such as layer thickness, printing speed, and printing temperature is carried out through L27 orthogonal array using Taguchi approach. In addition, CRITIC embedded WASPAS is adopted to optimize the parts' mechanical attributes and overcome the defects. Flexural and tensile poly-lactic acid specimens are printed according to ASTM standards D790 and D638, respectively, and thoroughly analyzed based on the surface morphological analysis to characterize defects. The parametric significance analysis is carried out to explore process science where the layer thickness, print speed, and temperature significantly control the quality and strength of the parts. Mathematical optimization results based on composite desirability show that layer thickness of 0.1 mm, printing speed of 60 mm/s, and printing temperature of 200 °C produce significantly desirable results. The validation experiments yielded the maximum flexural strength of 78.52 MPa, the maximum ultimate tensile strength of 45.52 MPa, and maximum impact strength of 6.21 kJ/m2. It is established that multiple fused layers restricted the propagation of cracks with minimum thickness due to enhanced diffusion between the layers.

An investigation on osteoporosis based on guided wave propagation in multi-layered bone plates.

In this study, the multi-layer structure of bones has been used to simulate bone loss, and the guided waves were transmitted to the double-layer structured simulated bone plates, which are cortical bone and spongy bone. The soft tissue layer was simulated by water and the theoretical solution of the multilayer structure has been established. The guided waves were excited by the laser ultrasound technique and the Recursive Asymptotic Stiffness Matrix (RASM) was used to build a multilayer structure. Results show that, as the cortical bone is thinned, the dispersion relationship curve mode shifts toward high frequency and low phase velocity. Also, as the spongy bone density decreases, the dispersion relationship curve mode moves toward high frequency and high phase velocity. Further, it is found that, as the porosity rises, the mode of the dispersion relationship curve shifts to the direction of low frequency and low phase velocity. Through the addition of soft tissues and introduction of simultaneous changes in parameters, osteoporosis can be distinguished with high accuracy and hence this method can be applied to the detection of osteoporosis in the future.

Investigation on Microstructure, Nanohardness and Corrosion Response of Laser Cladded Colmonoy-6 Particles on 316L Steel Substrate.

316L steel is predominantly used in manufacturing the components of high-pressure boilers, heat exchangers, aerospace engines, oil and gas refineries, etc. Its notable percentage of chromium offers resistance against corrosion and is mostly implemented in harsh environments. However, long-term exposure to these components in such environments can reduce their corrosion resistance property. Particularly at high temperatures, the oxide film formed on this type of steel reacts with the chloride, sulfides, sulfates, fluorides and forms intermetallic compounds which affect its resistance, followed by failures and losses. This work is focused on investigating the hardness, microstructure and corrosion resistance of the laser cladded Colmonoy-6 particles on the 316L steel substrate. The cladded specimens were dissected into cubic shapes and the microstructure present in the cladded region was effectively analyzed using the FESEM along with the corresponding EDS mapping. For evaluating the hardness of the cladded samples, the nanoindentation technique was performed using the TI980 TriboIndenter and the values were measured. The potentiodynamic polarization curves were plotted for both the substrate and clad samples at 0, 18, 42 and 70 h for revealing the corrosion resistance behavior. In addition, the EIS analysis was carried out to further confirm the resistance offered by the samples. The surface roughness morphology was evaluated after the corrosion process using the laser microscope, and the roughness values were measured and compared with the substrate samples. The result showed that the cladded samples experience greater hardness, lower values of surface roughness and provide better corrosion resistance when compared with substrate samples. This is due to the deposition of precipitates of chromium-rich carbide and borides that enhances the above properties and forms a stable passive film that resists corrosion during the corrosion process.

Numerical Simulation and Non-Destructive Characterization of Material Property and Defect Analysis of Cortical Bone Using Laser Ultrasound Techniques.

The application of bone quality assessment has received extensive attention, and a large number of researchers continue to invest in related research activities. To get closer to the real situation, this study intends to investigate the long bones of cattle. A quantitative laser ultrasound visualization (QLUV) system was used to measure the images transmitted by the guided waves on the long bones, and the internal defects of the long bones were detected using wave propagation behavior. Then, linear scanning was performed through a laser ultrasound technique (LUT) to measure the dispersion curve of the cortical bone, and the results were compared with finite element simulations. Further, LUT was used to measure the material properties of the cortical bone in all directions. Finally, the long bones were scanned by computerized tomography to analyze the pore direction and distribution. Further, the relationship between pore direction and material properties was studied. The results showed that the obtained wave propagation image was consistent with the time-domain waveform signal and the finite element analysis results. The experimental and simulation results of wave velocity showed an error of 0.26 to 1.56% compared with the literature. The plate-shaped cortical bone showed that the phase velocity of the guided wave is higher than the circumferential direction. The defect location was identified through wave propagation behavior using the QLUV system. The elastic constant of the cortical bone was measured, and it showed the same trend as the results obtained from the tensile test in the literature. Also, the pore distribution indicated that the cortical bone porosity has the same trend as elastic constants. The elastic constants along the longitudinal direction were greater than the transversal direction. This laser ultrasound technique has been developed with an aim of having a better resolution and also as a potential application in osteoporosis conditions.

Surface alloying of FeCoCrNiMn particles on Inconel-718 using plasma-transferred arc technique: microstructure and wear characteristics.

Inconel-718 (IN-718) is a commonly used nickel-based superalloy in various fields, such as gas turbine and power generation applications. However, the lower wear and oxidation resistance hinder their wide usage. In this work, FeCoCrNiMn particles were mechanically ball-milled and preplaced on the IN-718 substrate. Then, the preplaced FeCoCrNiMn particles were scanned by heat source using plasma-transferred arc (PTA) technique. The effect of PTA alloying on the phase changes, microstructure, nanohardness and wear resistance has been investigated. The result showed that the PTA region contained different phases, such as FCC, BCC and intermetallic. No cracks were observed in the PTA alloyed region. Moreover, the porous free structure was viewed in the alloyed region, which revealed that the PTA alloying process was effectively used to perform the alloying process. More hard phases, such as NiFe, CoMn, Cr9Mn25Ni21, MnNi, FeCo, FeMn and MnCo, were formed on the PTA-alloyed region. The obtained wear rate of the substrate specimen at 30 N applied load is 2.45 × 10-3 mm3 m-1 and 1.79 × 10-3 mm3 m-1 for the PTA specimen. Similarly, the wear rate of the substrate specimen at 50 N is 5.38 × 10-3 mm3 m-1 and for the PTA sample, it is 2.29 × 10-3 mm3 m-1. The PTA specimen showed lower CoF than the substrate specimen due to increased surface hardness and minimum deformation of asperities. The primary wear type was mildly abrasive, accompanied by slight oxidative wear. Oxygen reacted with the surface alloying elements and formed different oxides, such as CoO, Cr2O3, MnO2, Mn2O3, Mn3O4, FeO and Fe2O3. These dense oxidation films covered the working surface and enhanced the wear resistance. The worn-out PTA surface showed that the wear scar depths were shallow and lower than the substrate, and reduced the roughness.

Fabrication of Coaxial and Confocal Transducer Based on Sol-Gel Composite Material for Optical Resolution Photoacoustic Microscopy.

We have newly developed coaxial and confocal optical-resolution photoacoustic microscopy based on sol-gel composite materials. This transducer contains a concave-shaped piezoelectric layer with a focus depth of 5 mm and a hole with a diameter of 3 mm at the center to pass a laser beam into a phantom. Therefore, this system can directly detect an excited photoacoustic signal without prisms or acoustic lenses. We demonstrate the capability of the system through pulse-echo and photoacoustic imaging experiments. The center frequency of the fabricated transducer is approximately 7 MHz, and its relative bandwidth is 86%. An ex-vivo experiment is conducted, and photoacoustic signals are clearly obtained. As a result, 2- and 3-dimensional maximum amplitude projection images are reconstructed.

Response of growth and development of the Pacific oyster (Crassostrea gigas) to thermal discharge from a nuclear power plant.

BACKGROUND: During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction. RESULTS: The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area. CONCLUSIONS: The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.

Characterization of wedge waves propagating along wedge tips with defects.

Wedge waves are guided acoustic waves propagating along the tip of a wedge with the energy tightly confined near the wedge. Anti-symmetric flexural (ASF) modes are wedge waves with their particle motion anti-symmetric with the apex mid-plane. This study investigates the behaviors of ASF modes propagation along wedge tips with perfect and imperfect rectangular defects. Numerical finite element simulations and experimental measurements using a laser ultrasound technique are employed to explore the behaviors of ASF modes interacting with defects. Complex reflections and transmissions involved with direct reflections and transmissions as well as the newly discovered mode conversions will be explored and quantified in numerical as well as experimental ways.

Synergistic effect of l-ascorbic acid and hyaluronic acid on the expressions of matrix metalloproteinase-3 and -9 in human chondrocytes.

Proinflammatory cytokines and reactive oxygen species (ROS) are known to be involved in the initiation and progression of osteoarthritis (OA). New evidence clarifying the correlation between ROS and inflammation has indicated that oxidative stress can up-regulate inflammatory cytokines. l-Ascorbic acid (AA), an antioxidant, has been shown to have anti-inflammatory effects and improve matrix deposition in chondrocytes. The purpose of this study was to examine the effects of hyaluronic acid (HA; 100 µg/mL) supplemented with AA (50 µg/mL) on human normal and interleukin-1 beta-stimulated (IL-1ß, 10 ng/mL) chondrocytes. HA, AA, and HA + AA treatment did not change cell morphology, viability, proliferation, and glycosaminoglycan production in normal chondrocytes. HA, AA, and HA + AA, by contrast, partially restored viability and morphology of hypertrophic chondrocytes, and HA and HA + AA further decreased the cytotoxicity of IL-1ß. Real-time PCR revealed that AA and HA + AA had no substantial effects on unstimulated chondrocytes, except for down-regulation of matrix metalloproteinase (MMP)-9 mRNA levels. For IL-1ß-stimulated chondrocytes, significant down-regulation of IL-1ß, tumor necrosis factor-alpha (TNF-α), MMP-3, and MMP-9 mRNA expression was found when cells were cultured in HA-supplemented media. Moreover, HA + AA supplementation further significantly decreased MMP-3 and MMP-9 mRNA expression. The protein production of MMP-3 was decreased, with a significant difference between the HA + AA group and HA group. The antioxidant capacity and superoxide dismutases activity were also partially restored in stimulated chondrocytes. HA supplemented with AA modulates MMPs expression and antioxidant fuction in chondrocytes. AA may enhance the anticatabolic effects of HA on OA chondrocytes. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1809-1817, 2018.

Genome-wide analysis of ivermectin response by Onchocerca volvulus reveals that genetic drift and soft selective sweeps contribute to loss of drug sensitivity.

BACKGROUND: Treatment of onchocerciasis using mass ivermectin administration has reduced morbidity and transmission throughout Africa and Central/South America. Mass drug administration is likely to exert selection pressure on parasites, and phenotypic and genetic changes in several Onchocerca volvulus populations from Cameroon and Ghana-exposed to more than a decade of regular ivermectin treatment-have raised concern that sub-optimal responses to ivermectin's anti-fecundity effect are becoming more frequent and may spread. METHODOLOGY/PRINCIPAL FINDINGS: Pooled next generation sequencing (Pool-seq) was used to characterise genetic diversity within and between 108 adult female worms differing in ivermectin treatment history and response. Genome-wide analyses revealed genetic variation that significantly differentiated good responder (GR) and sub-optimal responder (SOR) parasites. These variants were not randomly distributed but clustered in ~31 quantitative trait loci (QTLs), with little overlap in putative QTL position and gene content between the two countries. Published candidate ivermectin SOR genes were largely absent in these regions; QTLs differentiating GR and SOR worms were enriched for genes in molecular pathways associated with neurotransmission, development, and stress responses. Finally, single worm genotyping demonstrated that geographic isolation and genetic change over time (in the presence of drug exposure) had a significantly greater role in shaping genetic diversity than the evolution of SOR. CONCLUSIONS/SIGNIFICANCE: This study is one of the first genome-wide association analyses in a parasitic nematode, and provides insight into the genomics of ivermectin response and population structure of O. volvulus. We argue that ivermectin response is a polygenically-determined quantitative trait (QT) whereby identical or related molecular pathways but not necessarily individual genes are likely to determine the extent of ivermectin response in different parasite populations. Furthermore, we propose that genetic drift rather than genetic selection of SOR is the underlying driver of population differentiation, which has significant implications for the emergence and potential spread of SOR within and between these parasite populations.

Vibration Measurement Method of a String in Transversal Motion by Using a PSD.

A position sensitive detector (PSD) is frequently used for the measurement of a one-dimensional position along a line or a two-dimensional position on a plane, but is more often used for measuring static or quasi-static positions. Along with its quick response when measuring short time-spans in the micro-second realm, a PSD is also capable of detecting the dynamic positions of moving objects. In this paper, theoretical modeling and experiments are conducted to explore the frequency characteristics of a vibrating string while moving transversely across a one-dimensional PSD. The theoretical predictions are supported by the experiments. When the string vibrates at its natural frequency while moving transversely, the PSD will detect two frequencies near this natural frequency; one frequency is higher than the natural frequency and the other is lower. Deviations in these two frequencies, which differ from the string's natural frequency, increase while the speed of motion increases.

The Use of Flexible Ultrasound Transducers for the Detection of Laser-Induced Guided Waves on Curved Surfaces at Elevated Temperatures.

In this study, a flexible ultrasonic transducer (FUT) was applied in a laser ultrasonic technique (LUT) for non-destructive characterization of metallic pipes at high temperatures of up to 176 °C. Compared with normal ultrasound transducers, a FUT is a piezoelectric film made of a PZT/PZT sol-gel composite which has advantages due to its high sensitivity, curved surface adaptability and high temperature durability. By operating a pulsed laser in B-scan mode along with the integration of FUT and LUT, a multi-mode dispersion spectrum of a stainless steel pipe at high temperature can be measured. In addition, dynamic wave propagation behaviors are experimentally visualized with two dimensional scanning. The images directly interpret the reflections from the interior defects and also can locate their positions. This hybrid technique shows great potential for non-destructive evaluation of structures with complex geometry, especially in high temperature environments.

ABC-B transporter genes in Dirofilaria immitis.

Dirofilaria immitis is a filarial nematode causing infection and heartworm disease in dogs and other canids, cats, and occasionally in humans. Prevention with macrocyclic lactones (ML) is recommended during the mosquito transmission season. Recently, ML resistance has been reported. ABC-B transporter genes are thought to be involved in the mechanism of ML resistance in other nematodes. This study aimed to identify all the ABC-B transporter genes in D. immitis using as a reference the nDi.2.2 D. immitis whole genome, which is not completely annotated. Using bioinformatic tools and PCR amplification on pooled D. immitis genomic DNA and on pooled cDNA, nine ABC transporter genes including one pseudogene were characterized. Bioinformatic and phylogenetic analyses allowed identification of three P-glycoproteins (Pgps) (Dim-pgp-3 Dim-pgp-10, Dim-pgp-11), of two ABC-B half transporter genes (one ortholog of Cel-haf-4 and Cel-haf-9; and one ortholog of Cel-haf-1 and Cel-haf-3), of one ABC half transporter gene (ortholog of Cel-haf-5) that contained an ABC-C motif, and of one additional half transporter that would require functional study for characterization. The number of ABC-B transporter genes identified was lower than in Caenorhabditis elegans and Haemonchus contortus. Further studies are needed to understand their possible role in ML resistance in D. immitis. These ABC transporters constitute a base for ML resistance investigation in D. immitis and advance our understanding of the molecular biology of this parasite.

Characterisation of P-glycoprotein-9.1 in Haemonchus contortus.

BACKGROUND: The existence nematodes of veterinary importance such as Haemonchus contortus resistant to anthelmintic drugs, including the macrocyclic lactones, has become a major concern in animal health. Macrocyclic lactone resistance in H. contortus seems to be multigenic including the active efflux of these drugs by P-glycoproteins, members of the ABC transporter family, present in this parasite. The goals of the present work were to determine the activity of H. contortus P-glycoprotein 9.1 (Hco-PGP-9.1) and its interaction with the avermectins, ivermectin, abamectin, and also the milbemycin, moxidectin. Additionally, the localisation of Hco-PGP-9.1 was sought in adult worms. METHODS: Hco-Pgp-9.1 was cloned and expressed in mammalian cells and its expression profile was determined at the transcriptional and protein level by qRT-PCR and Western-blot, respectively. The nematode transport activity was assessed using the tracer dye Rhodamine 123. A ligand competition assay between different macrocyclic lactones and Rhodamine 123 was used to establish whether or not there was interaction between Hco-PGP-9.1 and the avermectins (abamectin and ivermectin) or moxidectin. In addition, immunostaining was carried out to localise Hco-PGP-9.1 expression in the transgenic cells and in adult female parasites. RESULTS: Hco-PGP-9.1 was expressed in the cell membrane of the transfected host cells and was able to extrude Rhodamine 123. Ivermectin and abamectin, but not moxidectin, had a pronounced inhibitory effect on the ability of Hco-PGP-9.1 to transport Rhodamine 123. Antibodies raised against Hco-PGP-9.1 epitopes localised to the uterus of adult female H. contortus. CONCLUSIONS: These results suggest a strong interaction of the avermectins with Hco-PGP-9.1. However, possibly due to its physico-chemical properties, moxidectin had markedly less effect on Hco-PGP-9.1. Because of the greater interaction of the avermectins than moxidectin with this transporter, it is more likely to contribute to avermectin resistance than to moxidectin resistance in H. contortus. Possible over expression of Hco-PGP-9.1 in the female reproductive system in resistant worms could reduce paralysis of the uterus by macrocyclic lactones, allowing continued egg release in drug challenged resistant worms.

Haemonchus contortus P-glycoproteins interact with host eosinophil granules: a novel insight into the role of ABC transporters in host-parasite interaction.

Eosinophils are one of the major mammalian effector cells encountered by helminths during infection. In the present study, we investigated the effects of eosinophil granule exposure on the sheep parasitic nematode Haemonchus contortus as a model. H. contortus eggs exposed to eosinophil granule products showed increased rhodamine 123 efflux and this effect was not due to loss of egg integrity. Rh123 is known to be a specific P-glycoprotein (Pgp) substrate and led to the hypothesis that in addition to their critical role in xenobiotic resistance, helminth ABC transporters such as Pgp may also be involved in the detoxification of host cytotoxic products. We showed by quantitative RT-PCR that, among nine different H. contortus Pgp genes, Hco-pgp-3, Hco-pgp-9.2, Hco-pgp-11 and, Hco-pgp-16 were specifically up-regulated in parasitic life stages suggesting a potential involvement of these Pgps in the detoxification of eosinophil granule products. Using exsheathed L3 larvae that mimic the first life stage in contact with the host, we demonstrated that eosinophil granules induced a dose dependent overexpression of Hco-pgp-3 and the closely related Hco-pgp-16. Taken together, our results provide the first evidence that a subset of helminth Pgps interact with, and could be involved in the detoxification of, host products. This opens the way for further studies aiming to explore the role of helminth Pgps in the host-parasite interaction, including evasion of the host immune response.

Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population.

This case-control study focused on estimating the association between miR-146a polymorphism and risk of nasopharyngeal carcinoma (NPC) in central-south China. In total, 160 patients with NPC and 200 healthy controls in central-south China were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models. Significant differences between NPC patients and controls were found in genotype (P=0.033 for GG versus CG versus CC; and odds ratio (OR)=0.568, 95% confidence interval (CI)=0.354-0.912, P=0.019 for CG versus CC; and OR=0.503, 95% CI=0.261-0.971, P=0.041 for CG versus CC; and OR=0.564, 95% CI=0.360-0.884, P=0.012 for GG+CG versus CC, respectively) and allelic analysis (P=0.025 for G versus C). Our findings suggested that polymorphism of mir-146a was associated with NPC in the central-southern Chinese population.