Satellite Rearing of Aedes Mosquito Eggs: Synchronized Empirical Test of a Novel Mass Rearing Model.

Mosquito suppression strategies based on "rear and release" of male mosquitoes are attracting renewed interest from governments, municipalities, and private businesses. These include irradiation-based sterile insect technique, Wolbachia-based technologies, and genetic modification. Each of these approaches requires the mass rearing and release of adult male mosquitoes, which typically is accomplished via a rearing facility near the release site. Although some release programs have relied on centralized rearing and shipment of adult males, adult male mosquitoes are relatively fragile, and their fitness can be diminished by temperature fluctuations, humidity, nutritional deficiencies, and other stresses that occur during shipment. Furthermore, expensive, expedited shipment is typically used to maximize the amount of adult lifetime in the field following the release. In contrast, Aedes aegypti and Ae. albopictus eggs can be desiccated and stored for long periods. They are small, and many millions of eggs can be shipped without specialized environmental conditions and using less expensive means. Here we examine a model in which mosquito eggs are centrally produced and then mailed to satellite rearing facilities. As a control, a replicate set of eggs was reared at the factory of origin. At each of the rearing sites, cloud-based software was used to track and compare rearing at the different locations. The results demonstrate similar rearing outcomes (i.e., egg hatch, immature development, and number of adult males) at each of the different sites for both species. We discuss the outcome in relation to downstream applications and potential future studies.

Spatiotemporal reorganization of corticostriatal networks encodes motor skill learning.

Motor skill learning requires the activity of the dorsal striatum, with a differential global implication of the dorsomedial and dorsolateral territories. We investigate here whether and how specific striatal neurons encode the acquisition and consolidation of a motor skill. Using ex vivo two-photon calcium imaging after rotarod training, we report that highly active (HA) striatal populations arise from distinct spatiotemporal reorganization in the dorsomedial (DMS) and dorsolateral (DLS) striatum networks and are correlated with learning performance. The DMS overall activity decreases in early training, with few and sparsely distributed HA cells, while the DLS shows a progressive and long-lasting formation of HA cell clusters. These reorganizations result from reinforcement of synaptic connections to the DMS and anatomical rearrangements to the DLS. Targeted silencing of DMS or DLS HA cells with the cFos-TRAP strategy strongly impairs individual performance. Our data reveal that discrete domains of striatal populations encode acquisition and long-lasting retention of a motor skill.

On-Farm Experimentation to transform global agriculture.

Restructuring farmer-researcher relationships and addressing complexity and uncertainty through joint exploration are at the heart of On-Farm Experimentation (OFE). OFE describes new approaches to agricultural research and innovation that are embedded in real-world farm management, and reflects new demands for decentralized and inclusive research that bridges sources of knowledge and fosters open innovation. Here we propose that OFE research could help to transform agriculture globally. We highlight the role of digitalization, which motivates and enables OFE by dramatically increasing scales and complexity when investigating agricultural challenges.

Valosin-containing protein ATPase activity regulates the morphogenesis of Zika virus replication organelles and virus-induced cell death.

With no available therapies, infections with Zika virus (ZIKV) constitute a major public health concern as they can lead to congenital microcephaly. In order to generate an intracellular environment favourable to viral replication, ZIKV induces endomembrane remodelling and the morphogenesis of replication factories via enigmatic mechanisms. In this study, we identified the AAA+ type ATPase valosin-containing protein (VCP) as a cellular interaction partner of ZIKV non-structural protein 4B (NS4B). Importantly, its pharmacological inhibition as well as the expression of a VCP dominant-negative mutant impaired ZIKV replication. In infected cells, VCP is relocalised to large ultrastructures containing both NS4B and NS3, which are reminiscent of dengue virus convoluted membranes. Moreover, short treatment with the VCP inhibitors NMS-873 or CB-5083 drastically decreased the abundance and size of ZIKV-induced convoluted membranes. Furthermore, NMS-873 treatment inhibited ZIKV-induced mitochondria elongation previously reported to be physically and functionally linked to convoluted membranes in case of the closely related dengue virus. Finally, VCP inhibition resulted in enhanced apoptosis of ZIKV-infected cells strongly suggesting that convoluted membranes limit virus-induced cytopathic effects. Altogether, this study identifies VCP as a host factor required for ZIKV life cycle and more precisely, for the maintenance of viral replication factories. Our data further support a model in which convoluted membranes regulate ZIKV life cycle by impacting on mitochondrial functions and ZIKV-induced death signals in order to create a cytoplasmic environment favourable to viral replication.

An open-source software for monitoring intrafraction motion during external beam radiation therapy based on superimposition of contours of projected ROIs on cine-MV images.

PURPOSE: To present an open-source software (https://github.com/CHUSRadOncPhys/FluoMV) for monitoring intrafraction motion that is based on the visualization of superimposed contours of projected region-of-interests from DICOM RTSTRUCT files on cine-MV images acquired and displayed in real-time during radiation therapy delivery. Clinical use with prostate gold fiducial markers is presented. METHODS: Projections of regions of interest (ROI) in the reference frame of the electronic portal imaging device are computed offline for different gantry angles before the first treatment fraction. During treatment delivery, the contrast of portal images is automatically adjusted using a histogram equalization algorithm. The projections associated with the current gantry angle are then superimposed on the images in real time. This allows the therapist to evaluate if the imaged structures of interest remain within their respective contours during treatment delivery and to potentially interrupt the treatment if deemed necessary. The spatial accuracy of the method was evaluated by imaging a ball bearing phantom in a set-up where the position of the projected ROI is highly sensitive to gantry angle errors. The visibility of fiducial markers during one fraction of seven different volumetric modulated arc therapy (VMAT) prostate treatments is characterized. RESULTS: The geometric validation showed a negligible systematic error µ < 0.1 mm for the position of the projections. The random errors associated with the time accuracy of the gantry angle readout were characterized by standard deviations σ ≤ 0.6 mm. The VMAT clinical treatments showed that the fiducial markers were frequently visible, allowing for a meaningful clinical use. CONCLUSIONS: The results demonstrate that the method presented is sufficiently accurate to be used for intrafraction monitoring of patients. The fact that this method could be implemented on many modern linacs at little to no cost and with no additional dose delivered to the patients makes this solution very attractive for improving patient care and safety in radiation therapy.

The Interplay between Dengue Virus and the Human Innate Immune System: A Game of Hide and Seek.

With 40% of the world population at risk, infections with dengue virus (DENV) constitute a serious threat to public health. While there is no antiviral therapy available against this potentially lethal disease, the efficacy of the only approved vaccine is not optimal and its safety has been recently questioned. In order to develop better vaccines based on attenuated and/or chimeric viruses, one must consider how the human immune system is engaged during DENV infection. The activation of the innate immunity through the detection of viruses by cellular sensors is the first line of defence against those pathogens. This triggers a cascade of events which establishes an antiviral state at the cell level and leads to a global immunological response. However, DENV has evolved to interfere with the innate immune signalling at multiple levels, hence dampening antiviral responses and favouring viral replication and dissemination. This review elaborates on the interplay between DENV and the innate immune system. A special focus is given on the viral countermeasure mechanisms reported over the last decade which should be taken into consideration during vaccine development.

Independent re-analysis of alleged mind-matter interaction in double-slit experimental data.

A two year long experimental dataset in which authors of Radin, et al., 2016 claim to find evidence of mind-matter interaction is independently re-analyzed. In this experiment, participants are asked to periodically shift their attention towards or away from a double-slit optical apparatus. Shifts in fringe visibility of the interference pattern are monitored and tested against the common sense null hypothesis that such shifts should not correlate with the participant's attention state. We propose a deeper analysis of the dataset, identifying all the necessary arbitrary pre-analysis choices one needs to make, and carefully assessing the results' robustness regarding these choices. Results are twofold. Firstly, even with a conservative correction for the multiple statistical tests the analysis calls for, we confirm the existence of significant although small anomalies in the direction predicted by the mind-matter interaction hypothesis. On the other hand, and unlike Radin, et al., 2016, we also report significant although even smaller anomalies in the control dataset. This leads us to conclude that this particular dataset does not provide strong evidence of mind-matter interaction, yet certainly contains inexplicable anomalies that should motivate replication attempts in highly controlled environments.

Viruses Seen by Our Cells: The Role of Viral RNA Sensors.

The role of the innate immune response in detecting RNA viruses is crucial for the establishment of proper inflammatory and antiviral responses. Different receptors, known as pattern recognition receptors (PRRs), are present in the cytoplasm, endosomes, and on the cellular surface. These receptors have the capacity to sense the presence of viral nucleic acids as pathogen-associated molecular patterns (PAMPs). This recognition leads to the induction of type 1 interferons (IFNs) as well as inflammatory cytokines and chemokines. In this review, we provide an overview of the significant involvement of cellular RNA helicases and Toll-like receptors (TLRs) 3, 7, and 8 in antiviral immune defenses.

Impact Evaluation of Seasonal Malaria Chemoprevention under Routine Program Implementation: A Quasi-Experimental Study in Burkina Faso.

Seasonal malaria chemoprevention (SMC) for children < 5 is a strategy that is gaining popularity in West African countries. Although its efficacy to reduce malaria incidence has been demonstrated in trials, the effects of SMC implemented in routine program conditions, outside of experimental contexts, are unknown. In 2014 and 2015, a survey was conducted in 1,311 households located in Kaya District (Burkina Faso) where SMC had been recently introduced. All children < 72 months were tested for malaria and anemia. A pre-post study with control group was designed to measure SMC impact during high transmission season. A difference-in-differences approach was coupled in the analysis with propensity score weighting to control for observable and time-invariant nonobservable confounding factors. SMC reduced the parasitemia point and period prevalence by 3.3 and 24% points, respectively; this translated into protective effects of 51% and 62%. SMC also reduced the likelihood of having moderate to severe anemia by 32%, and history of recent fever by 46%. Self-reported coverage for children at the first cycle was 83%. The SMC program was successfully added to a package of interventions already in place. To our knowledge, with prevalence < 10% during the peak of the transmission season, this is the first time that malaria can be reported as hypo-endemic in a sub-Sahelian setting in Burkina Faso. SMC has great potential, and along with other interventions, it could contribute to approaching the threshold where elimination strategies will be envisioned in Burkina Faso.

The Feasibility of Structural Health Monitoring Using the Fundamental Shear Horizontal Guided Wave in a Thin Aluminum Plate.

Structural health monitoring (SHM) is emerging as an essential tool for constant monitoring of safety-critical engineering components. Ultrasonic guided waves stand out because of their ability to propagate over long distances and because they can offer good estimates of location, severity, and type of damage. The unique properties of the fundamental shear horizontal guided wave (SH0) mode have recently generated great interest among the SHM community. The aim of this paper is to demonstrate the feasibility of omnidirectional SH0 SHM in a thin aluminum plate using a three-transducer sparse array. Descriptions of the transducer, the finite element model, and the imaging algorithm are presented. The image localization maps show a good agreement between the simulations and experimental results. The SH0 SHM method proposed in this paper is shown to have a high resolution and to be able to locate defects within 5% of the true location. The short input signal as well the non-dispersive nature of SH0 leads to high resolution in the reconstructed images. The defect diameter estimated using the full width at half maximum was 10 mm or twice the size of the true diameter.

Multi-scale structural community organisation of the human genome.

BACKGROUND: Structural interaction frequency matrices between all genome loci are now experimentally achievable thanks to high-throughput chromosome conformation capture technologies. This ensues a new methodological challenge for computational biology which consists in objectively extracting from these data the structural motifs characteristic of genome organisation. RESULTS: We deployed the fast multi-scale community mining algorithm based on spectral graph wavelets to characterise the networks of intra-chromosomal interactions in human cell lines. We observed that there exist structural domains of all sizes up to chromosome length and demonstrated that the set of structural communities forms a hierarchy of chromosome segments. Hence, at all scales, chromosome folding predominantly involves interactions between neighbouring sites rather than the formation of links between distant loci. CONCLUSIONS: Multi-scale structural decomposition of human chromosomes provides an original framework to question structural organisation and its relationship to functional regulation across the scales. By construction the proposed methodology is independent of the precise assembly of the reference genome and is thus directly applicable to genomes whose assembly is not fully determined.

Importin ß1 targeting by hepatitis C virus NS3/4A protein restricts IRF3 and NF-κB signaling of IFNB1 antiviral response.

In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating the innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-ß (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection. Notably, importin ß1 (IMPß1) knockdown-a hub protein highly targeted by several viruses-decreases the nuclear translocation of both transcription factors and prevents IFNB1 and IFIT1 induction, correlating with a rapid increased of viral proteins and virus-mediated apoptosis. Here we show that NS3/4A triggers the cleavage of IMPß1 and inhibits nuclear transport to disrupt IFNB1 production. Importantly, mutated IMPß1 resistant to cleavage completely restores signaling, similar to the treatment with BILN 2061 protease inhibitor, correlating with the disappearance of cleavage products. Overall, the data indicate that HCV NS3/4A targeting of IMPß1 and related modulators of IRF3 and NF-κB nuclear transport constitute an important innate immune subversion strategy and inspire new avenues for broad-spectrum antiviral therapies.

Correction: Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response.

[This corrects the article DOI: 10.1371/journal.ppat.1005772.].

Association of a Network of Interferon-Stimulated Genes with a Locus Encoding a Negative Regulator of Non-conventional IKK Kinases and IFNB1.

Functional genomic analysis of gene expression in mice allowed us to identify a quantitative trait locus (QTL) linked in trans to the expression of 190 gene transcripts and in cis to the expression of only two genes, one of which was Ypel5. Most of the trans-expression QTL genes were interferon-stimulated genes (ISGs), and their expression in mouse macrophage cell lines was stimulated in an IFNB1-dependent manner by Ypel5 silencing. In human HEK293T cells, YPEL5 silencing enhanced the induction of IFNB1 by pattern recognition receptors and phosphorylation of TBK1/IKBKE kinases, whereas co-immunoprecipitation experiments revealed that YPEL5 interacted physically with IKBKE. We thus found that the Ypel5 gene (contained in a locus linked to a network of ISGs in mice) is a negative regulator of IFNB1 production and innate immune responses that interacts functionally and physically with TBK1/IKBKE kinases.

Spliceosome SNRNP200 Promotes Viral RNA Sensing and IRF3 Activation of Antiviral Response.

Spliceosomal SNRNP200 is a Ski2-like RNA helicase that is associated with retinitis pigmentosa 33 (RP33). Here we found that SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its amino-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1. We show that SNRNP200 relocalizes into TBK1-containing cytoplasmic structures upon infection, in contrast to the RP33-associated S1087L mutant, which is also unable to rescue antiviral response of SNRNP200 knockdown cells. This functional rescue correlates with the Sec63-1-mediated binding of viral RNA. The hindered IFN-ß production of knockdown cells was further confirmed in peripheral blood cells of RP33 patients bearing missense mutation in SNRNP200 upon infection with Sendai virus (SeV). This work identifies a novel immunoregulatory role of the spliceosomal SNRNP200 helicase as an RNA sensor and TBK1 adaptor for the activation of IRF3-mediated antiviral innate response.

The Use of ClusterMine360 for the Analysis of Polyketide and Nonribosomal Peptide Biosynthetic Pathways.

Polyketides and nonribosomal peptides constitute two large families of microbial natural products. Over the past 20 years a broad range of microbial polyketide and nonribosomal peptide biosynthetic pathways have been characterized leading to a surfeit of genetic data on polyketide and nonribosomal peptide biosynthesis. We developed the ClusterMine360 database, which stores the antiSMASH-based annotation of gene clusters in the NCBI database, linking the structure of the natural product to the biosynthetic gene cluster. This database is searchable and enables the user to access multiple sequence files for phylogenetic analysis of polyketide and nonribosomal peptide biosynthetic genes. Herein we describe how to add compound families and gene clusters to the database and search it using key words or structures to identify specific gene clusters. We also describe how to download multiple sequence files for specific catalytic domains from polyketide and nonribosomal peptide biosynthesis.

Diagnostic Accuracy of Rapid Antigen Detection Tests for Respiratory Syncytial Virus Infection: Systematic Review and Meta-analysis.

Respiratory syncytial virus (RSV) rapid antigen detection tests (RADT) are extensively used in clinical laboratories. We performed a systematic review and meta-analysis to evaluate the accuracy of RADTs for diagnosis of RSV infection and to determine factors associated with accuracy estimates. We searched EMBASE and PubMed for diagnostic-accuracy studies of commercialized RSV RADTs. Studies reporting sensitivity and specificity data compared to a reference standard (reverse transcriptase PCR [RT-PCR], immunofluorescence, or viral culture) were considered. Two reviewers independently extracted data on study characteristics, diagnostic-accuracy estimates, and study quality. Accuracy estimates were pooled using bivariate random-effects regression models. Heterogeneity was investigated with prespecified subgroup analyses. Seventy-one articles met inclusion criteria. Overall, RSV RADT pooled sensitivity and specificity were 80% (95% confidence interval [CI], 76% to 83%) and 97% (95% CI, 96% to 98%), respectively. Positive- and negative-likelihood ratios were 25.5 (95% CI, 18.3 to 35.5) and 0.21 (95% CI, 0.18 to 0.24), respectively. Sensitivity was higher in children (81% [95% CI, 78%, 84%]) than in adults (29% [95% CI, 11% to 48%]). Because of this disparity, further subgroup analyses were restricted to pediatric data (63 studies). Test sensitivity was poorest using RT-PCR as a reference standard and highest using immunofluorescence (74% versus 88%; P < 0.001). Industry-sponsored studies reported significantly higher sensitivity (87% versus 78%; P = 0.01). Our results suggest that the poor sensitivity of RSV RADTs in adults may preclude their use in this population. Furthermore, industry-sponsored studies and those that did not use RT-PCR as a reference standard likely overestimated test sensitivity.

In situ nitrogen mineralization, nitrification, and ammonia volatilization in maize field fertilized with urea in Huanghuaihai region of northern China.

Nitrogen (N) fertilization potentially affects soil N mineralization and leaching, and can enhance NH3 volatilization, thus impacting crop production. A fertilizer experiment with five levels of N addition (0, 79, 147, 215 and 375 kg N ha(-1)) was performed in 2009 and 2010 in a maize field in Huanghuaihai region, China, where > 300 kg N ha(-1) has been routinely applied to soil during maize growth period of 120 days. Responses of net N mineralization, inorganic N flux (0-10 cm), NH3 volatilization, and maize yield to N fertilization were measured. During the growth period, net N mineralization and nitrification varied seasonally, with higher rates occurring in August and coinciding with the R1 stage of maize growth. Soil NO3(-)-N contributed to more than 60% of inorganic N flux during maize growth. Cumulative NH3 volatilization increased with N additions, with total NH3 volatilization during maize growth accounting for about 4% of added N. Relative to the control, mean maize yield in the fertilizer treatments increased by 17% and 20% in 2009 and 2010, respectively. However, grain yield, aboveground biomass, and plant N accumulation did not increase with added N at levels > 215 kg N ha(-1). These results suggest that the current N rate of 300 kg N ha(-1) is not only excessive, but also reduces fertilizer efficacy and may contribute to environmental problems such as global warming and eutrophication of ground water and streams.

Bootstrapping under constraint for the assessment of group behavior in human contact networks.

The increasing availability of time- and space-resolved data describing human activities and interactions gives insights into both static and dynamic properties of human behavior. In practice, nevertheless, real-world data sets can often be considered as only one realization of a particular event. This highlights a key issue in social network analysis: the statistical significance of estimated properties. In this context, we focus here on the assessment of quantitative features of specific subset of nodes in empirical networks. We present a method of statistical resampling based on bootstrapping groups of nodes under constraints within the empirical network. The method enables us to define acceptance intervals for various null hypotheses concerning relevant properties of the subset of nodes under consideration in order to characterize by a statistical test its behavior as "normal" or not. We apply this method to a high-resolution data set describing the face-to-face proximity of individuals during two colocated scientific conferences. As a case study, we show how to probe whether colocating the two conferences succeeded in bringing together the two corresponding groups of scientists.

Structure, thermodynamics and dynamics of the isotropic phase of spherical non-ionic surfactant micelles.

We investigate a non-ionic surfactant (C(12)E(8))/water binary mixture, over a wide range of concentrations and temperatures (i.e. 1-35 wt.% of C(12)E(8) and 10-60 °C in temperature) by means of different experimental techniques: Small-Angle Neutron Scattering (SANS), Quasi Elastic Light Scattering (QELS) and High Frequency Rheology. The aims of this work are to provide information on structure, thermodynamics and dynamics of the isotropic phase of such a micellar system and, by combining these different types of information, to obtain a comprehensive image of the behaviour of this phase. Our results demonstrate that structural, thermodynamic and dynamic properties of these solutions are fully monitored by the temperature-induced changes in the ethylene-glycol chain hydration. They confirm that C(12)E(8) micelles are spherical and do not grow in the investigated range of concentrations and temperatures. They demonstrate that the interaction potential between C(12)E(8) micelles is more complicated than what was previously described, with an additional repulsive interaction. They allow us to put forward explanations for the Isotropic-Ordered phase transition as well as for the temperature behaviour of the viscosity of C(12)E(8) micellar solutions. Our investigation provides new and valuable information on the dynamics of these mixtures that reflect the complexity of the interaction potential between the C(12)E(8) micelles. It shows that concentrated solutions exhibit a viscoelastic behaviour that can be described by a simple Maxwell model.