Aberrant splicing of a nicotinic acetylcholine receptor alpha 6 subunit is associated with spinosad tolerance in the thrips predator Orius laevigatus.

This is the final version. Available from Elsevier via the DOI in this record. Susceptibility to insecticides is one of the limiting factors preventing wider adoption of natural enemies to control insect pest populations. Identification and selective breeding of insecticide tolerant strains of commercially used biological control agents (BCAs) is one of the approaches to overcome this constraint. Although a number of beneficial insects have been selected for increased tolerance to insecticides the molecular mechanisms underpinning these shifts in tolerance are not well characterised. Here we investigated the molecular mechanisms of enhanced tolerance of a lab selected strain of Orius laevigatus (Fieber) to the commonly used biopesticide spinosad. Transcriptomic analysis showed that spinosad tolerance is not a result of overexpressed detoxification genes. Molecular analysis of the target site for spinosyns, the nicotinic acetylcholine receptor (nAChR), revealed increased expression of truncated transcripts of the nAChR α6 subunit in the spinosad selected strain, a mechanism of resistance which was described previously in insect pest species. Collectively, our results demonstrate the mechanisms by which some beneficial biological control agents can evolve insecticide tolerance and will inform the development and deployment of insecticide-tolerant natural enemies in integrated pest management strategies.Biotechnology and Biological Sciences Research Counci

Free nitrous acid-based nitrifying sludge treatment in a two-sludge system enhances nutrient removal from low-carbon wastewater

© 2017 Elsevier Ltd A new method to enhance nutrient removal from low carbon-wastewater was developed. The method consists of a two-sludge system (i.e., an anaerobic-anoxic-oxic reactor coupled to a nitrifying reactor (N-SBR)) and a nitrifying-sludge treatment unit using free nitrous acid (FNA). Initially, 65.1 ± 2.9% in total nitrogen removal and 69.6 ± 3.4% in phosphate removal were obtained without nitrite accumulation. When 1/16 of the nitrifying sludge was daily treated with FNA at 1.1 mg N/L for 24 h, ∼28.5% of nitrite was accumulated in the N-SBR, and total nitrogen and phosphate removal increased to 72.4 ± 3.2% and 76.7 ± 2.9%, respectively. About 67.8% of nitrite was accumulated at 1.9 mg N/L FNA, resulting in 82.9 ± 3.8% in total nitrogen removal and 87.9 ± 3.5% in phosphate removal. Fluorescence in-situ hybridization analysis showed that FNA treatment reduced the abundance of nitrite oxidizing bacteria (NOB), especially that of Nitrospira sp

Approach of describing dynamic production of volatile fatty acids from sludge alkaline fermentation

© 2017 Elsevier Ltd In this work, a mathematical model was developed to describe the dynamics of fermentation products in sludge alkaline fermentation systems for the first time. In this model, the impacts of alkaline fermentation on sludge disintegration, hydrolysis, acidogenesis, acetogenesis, and methanogenesis processes are specifically considered for describing the high-level formation of fermentation products. The model proposed successfully reproduced the experimental data obtained from five independent sludge alkaline fermentation studies. The modeling results showed that alkaline fermentation largely facilitated the disintegration, acidogenesis, and acetogenesis processes and severely inhibited methanogenesis process. With the pH increase from 7.0 to 10.0, the disintegration, acidogenesis, and acetogenesis processes respectively increased by 53%, 1030%, and 30% while methane production decreased by 3800%. However, no substantial effect on hydrolysis process was found. The model also indicated that the pathway of acetoclastic methanogenesis was more severely inhibited by alkaline condition than that of hydrogentrophic methanogenesis

Live Poultry Exposure and Public Response to Influenza A(H7N9) in Urban and Rural China during Two Epidemic Waves in 2013-2014

Background The novel influenza A(H7N9) virus has caused 2013 spring and 2013-2014 winter waves of human infections since its first emergence in China in March 2013. Exposure to live poultry is a risk factor for H7N9 infection. Public psychobehavioral responses often change during progression of an epidemic. Methods We conducted population-based surveys in southern China to examine human exposure to live poultry, and population psychological response and behavioral changes in the two waves. In Guangzhou, an urban area of Guangdong province, we collected data using telephone surveys with random digit dialing in May-June 2013 and again in December 2013 to January 2014. In Zijin county, a rural area of the same province, we used door-to-door surveys under a stratified sampling design in July 2013 and again in December 2013 to January 2014. All responses were weighted by age and sex to the respective adult populations. Findings Around half of the urban respondents (53.8%) reported having visited LPMs in the previous year in the first survey, around double that reported in the second survey (27.7%). In the rural surveys, around half of the participants reported raising backyard poultry in the past year in the first survey, increasing to 83.2% participants in the second survey. One third of urban subjects supported the permanent closure of LPMs in the first and second surveys, and factors associated with support for closure included female sex, higher level of worry towards H7N9, and worry induced by a hypothetical influenza-like illness. Conclusions Our study indicated high human exposure to live poultry and low support for permanent closure of markets in both urban and rural residents regardless of increased worry during the epidemic.published_or_final_versio

Islet isolation assessment in man and large animals

Recent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity and in vitro and in vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 μ diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason, in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers. © 1990 Casa Editrice il Ponte

Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy

Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tumour radioresistance; therefore, it is recognised as an excellent target during radiation therapy. However, the inhibition of HIF-1 in unsuitable timing can suppress rather than enhance the effect of radiation therapy because its anti-angiogenic effect increases the radioresistant hypoxic fraction. In this study, we imaged changes of HIF-1 activity after treatment with radiation and/or an HIF-1 inhibitor, YC-1, and optimised their combination. Hypoxic tumour cells were reoxygenated 6 h postirradiation, leading to von Hippel-Lindau (VHL)-dependent proteolysis of HIF-1α and a resultant decrease in HIF-1 activity. The activity then increased as HIF-1α accumulated in the reoxygenated regions 24 h postirradiation. Meanwhile, YC-1 temporarily but significantly suppressed HIF-1 activity, leading to a decrease in microvessel density and an increase in tumour hypoxia. On treatment with YC-1 and then radiation, the YC-1-mediated increase in tumour hypoxia suppressed the effect of radiation therapy, whereas on treatment in the reverse order, YC-1 suppressed the postirradiation upregulation of HIF-1 activity and consequently delayed tumour growth. These results indicate that treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the therapeutic effect of radiation, and the suppression of the postirradiation upregulation of HIF-1 activity is important for the best therapeutic benefit

Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015

Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls.published_or_final_versio

Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer

BACKGROUND: The sigma-2 receptor has been validated as a biomarker for proliferating tumours. Second mitochondria-derived activator of caspase (Smac) is a protein released from mitochondria into the cytosol, leading to apoptosis. In this study, we investigated a sigma-2 ligand as a tumour-targeting drug delivery agent for treating ovarian cancer. METHODS: A sigma-2 ligand, SW 43, was conjugated with a Smac mimetic compound (SMC), SW IV-52s, to form SW III-123. The delivery function of the sigma-2 moiety and cell killing mechanisms of SW III-123 were examined in human ovarian cancer cell lines. RESULTS: SW III-123 internalisation into ovarian cancer cells was mediated by sigma-2 receptors. SW III-123, but not SW IV-52s or SW 43, exhibited potent cytotoxicity in human ovarian cancer cell lines SKOV-3, CaOV-3 and BG-1 after 24-h treatment, suggesting that the sigma-2 ligand successfully delivered SMC into ovarian cancer cells. SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-κB-inducing kinase (NIK) and phosphorylation of NF-κB p65, suggesting that SW III-123 activated both canonical and noncanonical NF-κB pathways in SKOV-3 cells. SW III-123 cleaved caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFα) antibody markedly blocked SW III-123-induced cell death and caspase-3 activity in SKOV-3 cells, indicating that SW III-123 activated both intrinsic and extrinsic apoptotic pathways and induced TNFα-dependent cell death in SKOV-3 cells. CONCLUSION: Sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2-conjugated SMC exemplifies a novel class of therapeutic drugs for treating ovarian cancer

Janus monolayers of transition metal dichalcogenides.

Structural symmetry-breaking plays a crucial role in determining the electronic band structures of two-dimensional materials. Tremendous efforts have been devoted to breaking the in-plane symmetry of graphene with electric fields on AB-stacked bilayers or stacked van der Waals heterostructures. In contrast, transition metal dichalcogenide monolayers are semiconductors with intrinsic in-plane asymmetry, leading to direct electronic bandgaps, distinctive optical properties and great potential in optoelectronics. Apart from their in-plane inversion asymmetry, an additional degree of freedom allowing spin manipulation can be induced by breaking the out-of-plane mirror symmetry with external electric fields or, as theoretically proposed, with an asymmetric out-of-plane structural configuration. Here, we report a synthetic strategy to grow Janus monolayers of transition metal dichalcogenides breaking the out-of-plane structural symmetry. In particular, based on a MoS2 monolayer, we fully replace the top-layer S with Se atoms. We confirm the Janus structure of MoSSe directly by means of scanning transmission electron microscopy and energy-dependent X-ray photoelectron spectroscopy, and prove the existence of vertical dipoles by second harmonic generation and piezoresponse force microscopy measurements

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

© Churchill LivingstoneInfiltrating CD1a+ dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (P<0.001), tumour size (P<0.01) and lymph node status (P<0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P=0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.B.J.Coventry and J. Morto