Discovery to Development: Insecticides for Malaria Vector Control

This report provides an outline of a program for the discovery of new public health insecticides for malaria vector control. The status of malaria vector control is first reviewed in terms of the chemical, physical chemical, and biochemical properties of the current WHOPES-recommended and approved vector control agents. This review provides a basis for a discussion on the critical need for discovery and development of multiple new chemical malaria vector control agents with novel and diverse modes of action. The Innovative Vector Control Consortium (IVCC) New Active Ingredient Target Product Profile (TPP) describes the essential attributes for a successful new malaria vector control agent and then serves as the basis for development of a discovery cascade. The cascade addresses these attributes experimentally at each stage of the discovery process – from design and assembly of an appropriate collection of chemicals for screening, through development of testing protocols to sort candidates, and into the detailed profiling of advanced pre-development candidates against TPP requirements. In addition, this program defines a staged development system to provide intermediate guidance to the insecticide explorer regarding the progress of their discovery program against the ultimate product goal

Implementing integrated measurements of essential biodiversity variables at a national scale

Funding: the Strategic Science Investment Funding for Crown Research Institutes from the Ministry of Business, Innovation and Employment.1. There is a global need for observation systems that deliver regular, timely data on state and trends in biodiversity, but few have been implemented, and fewer still at national scales. We describe the implementation of measurement of Essential Biodiversity Variables (EBVs) on an 8 km × 8 km grid throughout New Zealand, with multiple components of biodiversity (vegetation, birds, and some introduced mammals) measured simultaneously at each sample point. 2. Between 2011 and 2017, all public land was sampled nationally (ca. 1,350 points) and some private land (ca. 500 points). Synthetic appraisals of the state of New Zealand's biodiversity, not possible previously, can be derived from the first measurement of species distribution, population abundance, and taxonomic diversity EBVs. 3. Native bird counts (all species combined) were about 2.5 times greater per sample point in natural forests and shrublands than in non‐woody ecosystems, and native bird counts exceeded those of non‐native birds across all natural forests and shrublands. 4. Non‐native plants, birds, and mammals are invasive throughout, but high‐rainfall forested regions are least invaded, and historically deforested rain shadow regions are most invaded. 5. National reporting of terrestrial biodiversity across New Zealand's public land is established and becoming normalised, in the same manner as national and international reporting of human health and education statistics. The challenge is extending coverage across all private land. Repeated measurements of these EBVs, which began in 2017, will allow defensible estimates of biodiversity trends.Publisher PDFPeer reviewe

Prognostic impact of multidrug resistance gene expression on the management of breast cancer in the context of adjuvant therapy based on a series of 171 patients

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy±radiotherapy±hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt–PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff–Bloom–Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P=0.0005) and high SBR grade (P=0.003), size ⩾5 cm (P=0.038), high T stage (P=0.013), presence of intravascular embolus (P=0.034), and >3 N+ (P=0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer

CCDC 1429468: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 1429469: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

Relationship between kamahi foliar AvailN and possum browse category.

<p>Relationship between the available nitrogen concentration (mean ± SE) of kamahi foliage and possum browse category at Line 2 for trees in possum control zone (open circles) and non-control zone (closed circles) during a) Spring 2010; b) Summer 2011; c) Autumn 2011; d) Spring 2011. Note the single data point in panel c for the moderate browse category.</p