Infection with parasitic nematodes confounds vaccination efficacy

T helper (Th) cells produce signature cytokine patterns, induced largely by intracellular versus extracellular pathogens that provide the cellular and molecular basis for counter regulatory expression of protective immunity during concurrent infections. The production of IL-12 and IFN-γ, for example, resulting from exposure to many bacterial, viral, and protozoan pathogens is responsible for Th1-derived protective responses that also can inhibit development of Th2-cells expressing IL-4-dependent immunity to extracellular helminth parasites and vice versa. In a similar manner, concurrent helminth infection alters optimal vaccine-induced responses in humans and livestock; however, the consequences of this condition have not been adequately studied especially in the context of a challenge infection following vaccination. Demands for new and effective vaccines to control chronic and emerging diseases, and the need for rapid deployment of vaccines for bio security concerns requires a systematic evaluation of confounding factors that limit vaccine efficacy. One common albeit overlooked confounder is the presence of gastrointestinal nematode parasites in populations of humans and livestock targeted for vaccination. This is particularly important in areas of the world were helminth infections are prevalent, but the interplay between parasites and emerging diseases that can be transmitted worldwide make this a global issue. In addition, it is not clear if the epidemic in allergic disease in industrialized countries substitutes for geohelminth infection to interfere with effective vaccination regimens. This presentation will focus on recent vaccination studies in mice experimentally infected with Heligmosomoides polygyrus to model the condition of gastrointestinal parasite infestation in mammalian populations targeted for vaccination. In addition, a large animal vaccination and challenge model against Mycoplasma hyopneumonia in swine exposed to Ascaris suum will provide a specific example of the need for further work in this area, and for controlled field studies to assess the impact of other similar scenarios.     

Improved connectivity analysis using multiple low-cost paths to evaluate habitat for the endangered San Martin titi monkey (Plecturocebus oenanthe) in north-central Peru

Context

Graph-theoretic evaluations of habitat connectivity often rely upon least-cost path analyses to evaluate connectedness of habitat patches, based on an underlying cost surface. We present two improvements upon these methods.

Objectives

As a case study to test these methods, we evaluated habitat connectivity for the endangered San Martin titi monkey (Plecturocebus oenanthe) in north-central Peru, to prioritize habitat patches for conservation.

Methods

First, rather than using a single least-cost path between habitat patches, we analyzed multigraphs made up of multiple low-cost paths. This allows us to differentiate between patches connected through a single narrow corridor, and patches connected by a wide swath of traversable land. We evaluate potential movement pathways by iteratively removing paths and recomputing connectivity metrics. Second, instead of performing a sensitivity analysis by varying costs uniformly across the landscape, we generated landscapes with spatially varying costs.

Results

This approach produced a more informative assessment of connectivity than standard graph analyses. Of the 4340 habitat patches considered across the landscape, we identified the most important 100, those frequently ranked highly through repeated network modifications, for multiple metrics and cost surfaces.

Conclusions

These methods represent a novel approach for assessing connectivity, better accounting for spatial configurations of habitat patches and uncertainty in cost surfaces. The ability to identify habitat patches with more possible routes to other patches is of interest for resiliency planning and prioritization in the face of continued habitat loss and climate change. These methods should be broadly applicable to conservation planning for other wildlife species.

     

Perspective: shedding light on spotted lanternfly impacts in the USA

Spotted lanternfly (SLF), Lycorma delicatula (Hemiptera: Fulgoridae) is an invasive phloem‐feeding planthopper currently being quarantined in a 24 000 km² area in eastern Pennsylvania, New Jersey, Maryland, and Delaware, with a second population under quarantine in a 46 km² area in Virginia. Because this insect feeds on over 70 species of plants, it has the potential to impact a wide range of sectors, and as a result, there has been great public speculation that the economic impact of SLF could be severe. SLF is a large‐bodied voracious feeder that reduces plant resources directly by feeding, and indirectly, from sooty mold that grows on its excrement and blocks photosynthesis. SLF is causing severe damage to vineyards from feeding, and is a significant nuisance pest. It has high potential for spread via human‐mediated transport, particularly of egg cases, and may therefore significantly impact commerce in the near future. The ultimate impacts of this insect are not yet known, and will depend upon its longer term impacts on plant and tree health, and the extent to which its range expands. © 2019 Society of Chemical Industry     

Targeted Isolation of Antibiotic Brominated Alkaloids from the Marine Sponge Pseudoceratina durissima Using Virtual Screening and Molecular Networking

Many targeted natural product isolation approaches rely on the use of pre-existing bioactivity information to inform the strategy used for the isolation of new bioactive compounds. Bioactivity information can be available either in the form of prior assay data or via Structure Activity Relationship (SAR) information which can indicate a potential chemotype that exhibits a desired bioactivity. The work described herein utilizes a unique method of targeted isolation using structure-based virtual screening to identify potential antibacterial compounds active against MRSA within the marine sponge order Verongiida. This is coupled with molecular networking-guided, targeted isolation to provide a novel drug discovery procedure. A total of 12 previously reported bromotyrosine-derived alkaloids were isolated from the marine sponge species Pseudoceratina durissima, and the compound, (+)-aeroplysinin-1 (1) displayed activity against the MRSA pathogen (MIC: <32 µg/mL). The compounds (1–3, 6 and 9) were assessed for their central nervous system (CNS) interaction and behavioral toxicity to zebrafish (Danio rerio) larvae, whereby several of the compounds were shown to induce significant hyperactivity. Anthelmintic activity against the parasitic nematode Haemonchus contorutus was also evaluated (2–4, 6–8).     

Atomic-resolution imaging of oxygen in perovskite ceramics

Using an imaging mode based on the adjustment of a negative value of the spherical-aberration coefficient of the objective lens of a transmission electron microscope, we successfully imaged all types of atomic columns in the dielectric SrTiO3 and the superconductor YBa2Cu3O7. In particular, we were able to view the oxygen atoms which, due to their low scattering power, were not previously accessible, and this allowed us to detect local nonstoichiometries or the degree of oxygen-vacancy ordering. This technique offers interesting opportunities for research into oxides, minerals, and ceramics. In particular, this holds for the huge group of perovskite-derived electroceramic materials in which the local oxygen content sensitively controls the electronic properties.     

埋地油气管道并行敷设技术发展现状

国内几个大型管道工程项目相继采用并行敷设技术施工。介绍了中亚天然气管道、西部原油成品油管道、大连新港-大连石化原油管道的工程概况。一些学者基于现有标准和规范,分别从工程、经济、安全、设计等角度探讨了油气管道并行敷设管间距的确定原则;一些学者则借助数值模拟计算方法,分析了成品油管道对与其同沟敷设的加热输送原油管道的热力影响规律;另有工程技术人员针对并行敷设技术在具体实施和运用过程中存在的施工、防腐、维修等难题,对施工工艺进行了有益的探索。而综合考虑多种因素对管间距的影响,输气管道与输油管道、输气管道的同沟敷设,以及同沟敷设管道工艺系统和站场设置的优化,将成为油气管道同沟敷设技术领域的新课题。     

The relevance of marine chemical ecology to plankton and ecosystem function: an emerging field

Marine chemical ecology comprises the study of the production and interaction of bioactive molecules affecting organism behavior and function. Here we focus on bioactive compounds and interactions associated with phytoplankton, particularly bloom-forming diatoms, prymnesiophytes and dinoflagellates. Planktonic bioactive metabolites are structurally and functionally diverse and some may have multiple simultaneous functions including roles in chemical defense (antipredator, allelopathic and antibacterial compounds), and/or cell-to-cell signaling (e.g., polyunsaturated aldehydes (PUAs) of diatoms). Among inducible chemical defenses in response to grazing, there is high species-specific variability in the effects on grazers, ranging from severe physical incapacitation and/or death to no apparent physiological response, depending on predator susceptibility and detoxification capability. Most bioactive compounds are present in very low concentrations, in both the producing organism and the surrounding aqueous medium. Furthermore, bioactivity may be subject to synergistic interactions with other natural and anthropogenic environmental toxicants. Most, if not all phycotoxins are classic secondary metabolites, but many other bioactive metabolites are simple molecules derived from primary metabolism (e.g., PUAs in diatoms, dimethylsulfoniopropionate (DMSP) in prymnesiophytes). Producing cells do not seem to suffer physiological impact due to their synthesis. Functional genome sequence data and gene expression analysis will provide insights into regulatory and metabolic pathways in producer organisms, as well as identification of mechanisms of action in target organisms. Understanding chemical ecological responses to environmental triggers and chemically-mediated species interactions will help define crucial chemical and molecular processes that help maintain biodiversity and ecosystem functionality.     

Chemical Profiling (HPLC-NMR & HPLC-MS), Isolation,and Identification of Bioactive Meroditerpenoids from the Southern Australian Marine Brown Alga Sargassum paradoxum

A phytochemical investigation of a southern Australian marine brown alga, Sargassum paradoxum, resulted in the isolation and identification of four new (5, 9, 10, and 15) and nine previously reported (1, 2, 6–8, and 11–14) bioactive meroditerpenoids. HPLC-NMR and HPLC-MS were central to the identification of a new unstable compound, sargahydroquinal (9), and pivotal in the deconvolution of eight (1, 2, 5–7, and 10–12) other meroditerpenoids. In particular, the complete characterization and identification of the two main constituents (1 and 2) in the crude dichloromethane extract was achieved using stop-flow HPLC-NMR and HPLC-MS. This study resulted in the first acquisition of gHMBCAD NMR spectra in the stop-flow HPLC-NMR mode for a system solely equipped with a 60 μL HPLC-NMR flow cell without the use of a cold probe, microcoil, or any pre-concentration.     

Paired-end mapping reveals extensive structural variation in the human genome

Structural variation of the genome involves kilobase- to megabase-sized deletions, duplications, insertions, inversions, and complex combinations of rearrangements. We introduce high-throughput and massive paired-end mapping (PEM), a large-scale genome-sequencing method to identify structural variants (SVs) approximately 3 kilobases (kb) or larger that combines the rescue and capture of paired ends of 3-kb fragments, massive 454 sequencing, and a computational approach to map DNA reads onto a reference genome. PEM was used to map SVs in an African and in a putatively European individual and identified shared and divergent SVs relative to the reference genome. Overall, we fine-mapped more than 1000 SVs and documented that the number of SVs among humans is much larger than initially hypothesized; many of the SVs potentially affect gene function. The breakpoint junction sequences of more than 200 SVs were determined with a novel pooling strategy and computational analysis. Our analysis provided insights into the mechanisms of SV formation in humans.     

Characterization of glucocerebrosides and the active metabolite 4,8-sphingadienine from Arisaema amurense and Pinellia ternata by NMR and CD spectroscopy and ESI-MS/CID-MS

Sphingolipid metabolites regulate cellular processes such as cell proliferation, differentiation, and apoptosis. In this study, glucocerebrosides (GluCer) from rhizomes of Arisaema amurense and Pinellia ternata were fully characterized using 1- and 2-dimensional nuclear magnetic spin resonance (NMR) and circular dichroism (CD) spectroscopy and tandem collision-induced dissociation mass spectrometry (ESI-MS/CID-MS). Three new acylated and seven known GluCer were elucidated with 4,8-sphingadienine (4,8-SD, d18:2) as backbone. 4,8-SD is a metabolite after enzymatical hydrolysis of GluCer in the gut lumen. In this study, 4,8-SD was hydrolyzed from GluCer and chromatographically purified on silica gel. In contrast to the GluCer, 4,8-SD showed cytotoxic effects in the WST-1 assay. GluCer with 4,8-SD as sphingoid backbone are present in plants consumed as food, such as spinach, soy, and eggplant.