Optically pure heterobimetallic helicates from self-assembly and click strategies

Single diastereomer, diamagnetic, octahedral Fe(II) tris chelate complexes are synthesised that contain three pendant pyridine proligands pre-organised for coordination to a second metal. They bind Cu(I) and Ag(I) with coordination geometry depending on the identity of the metal and the detail of the ligand structure, but for example homohelical (ΔFe,ΔCu) configured systems with unusual trigonal planar Cu cations are formed exclusively in solution as shown by VT-NMR and supported by DFT calculations. Similar heterobimetallic tris(triazole) complexes are synthesised via clean CuAAC reactions at a tris(alkynyl) complex, although here the configurations of the two metals differ (ΔFe,ΛCu), leading to the first optically pure heterohelicates. A second series of Fe complexes perform less well in either strategy as a result of lack of preorganisation

Uist Lagoons Survey

Scotland has around a hundred saline lagoons, coastal lochs that are not quite as saline as the sea. A small number of organisms are confined to these lochs, but most of these are very small and belong to groups that are difficult to identify. A consortium of specialists in identification at the National Museum of Scotland and ecologists sampled most of the saline lagoons on designated sites (SSSI and SAC) in the Uists, the area believed to have the best biodiversity of lagoon organisms in Scotland. The study not only confirmed the presence of these specialist species, but also that they were more widely distributed in the Uists than had been believed. Samples of the organisms have been placed in the permanent collections of the National Museum of Scotland and (for plants) in the Royal Botanic Gardens Edinburgh, where they will be available for future study

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Evaluation of two lyophilized molecular assays to rapidly detect foot-and-mouth disease virus directly from clinical samples in field settings

Accurate, timely diagnosis is essential for the control, monitoring and eradication of foot‐and‐mouth disease (FMD). Clinical samples from suspect cases are normally tested at reference laboratories. However, transport of samples to these centralized facilities can be a lengthy process that can impose delays on critical decision making. These concerns have motivated work to evaluate simple‐to‐use technologies, including molecular‐based diagnostic platforms, that can be deployed closer to suspect cases of FMD. In this context, FMD virus (FMDV)‐specific reverse transcription loop‐mediated isothermal amplification (RT‐LAMP) and real‐time RT‐PCR (rRT‐PCR) assays, compatible with simple sample preparation methods and in situ visualization, have been developed which share equivalent analytical sensitivity with laboratory‐based rRT‐PCR. However, the lack of robust ‘ready‐to‐use kits’ that utilize stabilized reagents limits the deployment of these tests into field settings. To address this gap, this study describes the performance of lyophilized rRT‐PCR and RT‐LAMP assays to detect FMDV. Both of these assays are compatible with the use of fluorescence to monitor amplification in real‐time, and for the RT‐LAMP assays end point detection could also be achieved using molecular lateral flow devices. Lyophilization of reagents did not adversely affect the performance of the assays. Importantly, when these assays were deployed into challenging laboratory and field settings within East Africa they proved to be reliable in their ability to detect FMDV in a range of clinical samples from acutely infected as well as convalescent cattle. These data support the use of highly sensitive molecular assays into field settings for simple and rapid detection of FMDV

The three-dimensional Anderson model of localization with binary random potential

We study the three-dimensional two-band Anderson model of localization and compare our results to experimental results for amorphous metallic alloys (AMA). Using the transfer-matrix method, we identify and characterize the metal-insulator transitions as functions of Fermi level position, band broadening due to disorder and concentration of alloy composition. The appropriate phase diagrams of regions of extended and localized electronic states are studied and qualitative agreement with AMA such as Ti-Ni and Ti-Cu metallic glasses is found. We estimate the critical exponents nu_W, nu_E and nu_x when either disorder W, energy E or concentration x is varied, respectively. All our results are compatible with the universal value nu ~ 1.6 obtained in the single-band Anderson model.Comment: 9 RevTeX4 pages with 11 .eps figures included, submitted to PR

Direct detection and characterization of foot-and-mouth disease virus in East Africa using a field-ready real-time PCR platform

Effective control and monitoring of foot-and-mouth disease (FMD) relies upon rapid and accurate disease confirmation. Currently, clinical samples are usually tested in reference laboratories using standardized assays recommended by The World Organisation for Animal Health (OIE). However, the requirements for prompt and serotype-specific diagnosis during FMD outbreaks, and the need to establish robust laboratory testing capacity in FMD-endemic countries have motivated the development of simple diagnostic platforms to support local decision-making. Using a portable thermocycler, the T-COR™ 8, this study describes the laboratory and field evaluation of a commercially available, lyophilized pan-serotype-specific real-time RT-PCR (rRT-PCR) assay and a newly available FMD virus (FMDV) typing assay (East Africa-specific for serotypes: O, A, Southern African Territories [SAT] 1 and 2). Analytical sensitivity, diagnostic sensitivity and specificity of the pan-serotype-specific lyophilized assay were comparable to that of an OIE-recommended laboratory-based rRT-PCR (determined using a panel of 57 FMDV-positive samples and six non-FMDV vesicular disease samples for differential diagnosis). The FMDV-typing assay was able to correctly identify the serotype of 33/36 FMDV-positive samples (no cross-reactivity between serotypes was evident). Furthermore, the assays were able to accurately detect and type FMDV RNA in multiple sample types, including epithelial tissue suspensions, serum, oesophageal–pharyngeal (OP) fluid and oral swabs, both with and without the use of nucleic acid extraction. When deployed in laboratory and field settings in Tanzania, Kenya and Ethiopia, both assays reliably detected and serotyped FMDV RNA in samples (n = 144) collected from pre-clinical, clinical and clinically recovered cattle. These data support the use of field-ready rRT-PCR platforms in endemic settings for simple, highly sensitive and rapid detection and/or characterization of FMDV

An allele of IKZF1 (Ikaros) conferring susceptibility to childhood acute lymphoblastic leukemia protects against type 1 diabetes.

OBJECTIVE: IKZF1 encoding Ikaros, an essential regulator of lymphopoiesis and immune homeostasis, has been implicated in the development of childhood acute lymphoblastic leukemia (C-ALL). Because recent genome-wide association (GWA) studies have linked a region of the 3'-UTR of IKZF1 with C-ALL susceptibility, we tested whether IKZF1 is associated with the autoimmune disease type 1 diabetes. RESEARCH DESIGN AND METHODS: rs10272724 (T>C) near IKZF1 at 7p12 was genotyped in 8,333 individuals with type 1 diabetes, 9,947 control subjects, and 3,997 families of European ancestry. Association was tested using logistic regression in the case-control data and by the transmission disequilibrium test in the families. Expression data for IKZF1 by rs10272724 genotype were obtained using quantitative PCR of mRNA/cDNA generated from peripheral blood mononuclear cells from 88 individuals, whereas expression data for five other neighboring genes were obtained from the online Genevar dataset. RESULTS: The minor allele of rs10272724 (C) was found to be protective from type 1 diabetes (odds ratio 0.87 [95% CI 0.83-0.91]; P = 1.1 × 10(-11)). rs10272724 was not correlated with levels of two transcripts of IKZF1 in peripheral blood mononuclear cells. CONCLUSIONS: The major susceptibility genotype for C-ALL confers protection from type 1 diabetes. Our finding strengthens the link between autoimmunity and lymphoid cancers. Further investigation is warranted for the genetic effect marked by rs10272724, its impact on IKZF1, and the role of Ikaros and other family members, Ailios (IKZF3) and Eos (IKZF4), in autoimmunity

Detection of capripoxvirus DNA using a field-ready nucleic acid extraction and real-time PCR platform

Capripoxviruses, comprising sheep pox virus, goat pox virus and lumpy skin disease virus cause serious diseases of domesticated ruminants, notifiable to The World Organization for Animal Health. This report describes the evaluation of a mobile diagnostic system (Enigma Field Laboratory) that performs automated sequential steps for nucleic acid extraction and real-time PCR to detect capripoxvirus DNA within laboratory and endemic field settings. To prepare stable reagents that could be deployed into field settings, lyophilized reagents were used that employed an established diagnostic PCR assay. These stabilized reagents demonstrated an analytical sensitivity that was equivalent, or greater than the established laboratory-based PCR test which utilizes wet reagents, and the limit of detection for the complete assay pipeline was approximately one log10 more sensitive than the laboratory-based PCR assay. Concordant results were generated when the mobile PCR system was compared to the laboratory-based PCR using samples collected from Africa, Asia and Europe (n = 10) and experimental studies (n = 9) representing clinical cases of sheep pox, goat pox and lumpy skin disease. Furthermore, this mobile assay reported positive results in situ using specimens that were collected from a dairy cow in Morogoro, Tanzania, which was exhibiting clinical signs of lumpy skin disease. These data support the use of mobile PCR systems for the rapid and sensitive detection of capripoxvirus DNA in endemic field settings

Existing evidence on the use of participatory scenarios in ecological restoration: a systematic map

Background and context: The scale of land degradation worldwide has led to nearly one billion hectares committed to restoration globally. However, achieving such restoration targets will necessitate complex trade-offs against limited time, competing knowledge, costs, resources and varying stakeholder and societal preferences. Participatory scenarios allow a way to identify collaborative solutions for restoration planning and implementation best suited for the local cultures and societies they are tied to. They can be used to navigate uncertainties surrounding future trajectories of restored areas by evaluating trade-offs in outcomes. This research aims to systematically map the evidence on the use of participatory scenarios in restoration planning. We use the following research question: What evidence exists on the use of participatory scenarios in ecological restoration? This is answered by examining the characteristics of the evidence base, types of study design, types of outcomes, trade-offs in outcomes, and the role of participants. Methods: A comprehensive and reproducible search strategy was followed using bibliographic databases, web-based searches, and targeted searching. Search results underwent a two-step screening process according to eligibility criteria. Metadata on key areas of interest were extracted from included texts and were narratively synthesised alongside data visualisations to answer the research questions. Review findings:18,612 records were initially identified, and 106 articles were included in the final map. Most studies were conducted in Europe and North America, focusing on restoring agricultural land or forests. Most texts used mixed methods and explored multiple outcome types, but environmental outcomes were the most assessed. Within environmental outcomes, indicators for ecological function were assessed more frequently than structural or compositional indicators. The most common reason for choosing outcomes and indicators was stakeholder interest. Trade-offs in social, ecological, and economic outcomes were mainly examined across space using mapping techniques, while far fewer studies looked at trade-offs across stakeholders and time. Participants were mostly included in the scenario creation step and were usually chosen purposefully by the research team. Conclusions: It is difficult to understand how useful scenarios are for restoration planning because few texts reported how scenarios fed into the process. Despite this, the range of outcomes used and different method types adopted suggests participatory scenarios allow for integrating different knowledge and approaches, alongside facilitating the use of qualitative or semi-quantitative data when this is more appropriate or quantitative data is not widely available. To better use participatory scenarios as a tool for ecological restoration planning, decision-makers can push for greater levels and definitions of participation from the offset of restoration projects with specified, regular, and structured communication and participation channels. We also recommend more systematic methods of participant selection, such as stakeholder analysis. Further research is needed to understand the effectiveness of participatory scenarios in restoration planning and whether the participation of stakeholders was successful in meeting objectives. To improve the evidence base, future studies should clearly evaluate their effectiveness in the restoration planning process and their success in meeting their participatory objectives