Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies.

BACKGROUND: Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS: We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS: Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required

Diagnosing domestic and transboundary sources of fine particulate matter (PM2.5) in UK cities using GEOS-Chem

The UK is set to impose a stricter ambient annual mean fine particulate matter (PM2.5) standard than was first adopted fourteen years ago. This necessitates strengthened knowledge of the magnitude and sources that influence urban PM2.5 in UK cities to ensure compliance and improve public health. Here, we use a regional-scale chemical transport model (GEOS-Chem), validated with national ground-based observations, to quantify the influence of specific sources within and transported to the mid-sized UK city Leicester. Of the sources targeted, we find that agricultural emissions of ammonia (NH3) make the largest contribution (3.7 μg m−3 or 38 % of PM2.5) to annual mean PM2.5 in Leicester. Another important contributor is long-range transport of pollution from continental Europe accounting for 1.8 μg m−3 or 19 % of total annual mean PM2.5. City sources are a much smaller portion (0.2 μg m−3; 2 %). We also apply GEOS-Chem to the much larger cities Birmingham and London to find that agricultural emissions of NH3 have a greater influence than city sources for Birmingham (32 % agriculture, 19 % city) and London (25 % agriculture, 13 % city). The portion from continental Europe is 16 % for Birmingham and 28 % for London. Action plans aimed at national agricultural sources of NH3 and strengthened supranational agreements would be most effective at alleviating PM2.5 in most UK cities

The mass evolution of the first galaxies: stellar mass functions and star formation rates at 4<z<74 < z < 7 in the CANDELS GOODS-South field

We measure new estimates for the galaxy stellar mass function and star formation rates for samples of galaxies at $z \sim 4,~5,~6~\&~7$ using data in the CANDELS GOODS South field. The deep near-infrared observations allow us to construct the stellar mass function at $z \geq 6$ directly for the first time. We estimate stellar masses for our sample by fitting the observed spectral energy distributions with synthetic stellar populations, including nebular line and continuum emission. The observed UV luminosity functions for the samples are consistent with previous observations, however we find that the observed $M_{UV}$ - M$_{*}$ relation has a shallow slope more consistent with a constant mass to light ratio and a normalisation which evolves with redshift. Our stellar mass functions have steep low-mass slopes ($\alpha \approx -1.9$), steeper than previously observed at these redshifts and closer to that of the UV luminosity function. Integrating our new mass functions, we find the observed stellar mass density evolves from $\log_{10} \rho_{*} = 6.64^{+0.58}_{-0.89}$ at $z \sim 7$ to $7.36\pm0.06$ $\text{M}_{\odot} \text{Mpc}^{-3}$ at $z \sim 4$. Finally, combining the measured UV continuum slopes ($\beta$) with their rest-frame UV luminosities, we calculate dust corrected star-formation rates (SFR) for our sample. We find the specific star-formation rate for a fixed stellar mass increases with redshift whilst the global SFR density falls rapidly over this period. Our new SFR density estimates are higher than previously observed at this redshift.Comment: 28 pages, 23 figures, 2 appendices. Accepted for publication in MNRAS, August 7 201

Hawaiʻi Coral Disease database (HICORDIS):species-specific coral health data from across the Hawaiian archipelago

AbstractThe Hawaiʻi Coral Disease database (HICORDIS) houses data on colony-level coral health condition observed across the Hawaiian archipelago, providing information to conduct future analyses on coral reef health in an era of changing environmental conditions. Colonies were identified to the lowest taxonomic classification possible (species or genera), measured and assessed for visual signs of health condition. Data were recorded for 286,071 coral colonies surveyed on 1819 transects at 660 sites between 2005 and 2015. The database contains observations for 60 species from 22 genera with 21 different health conditions. The goals of the HICORDIS database are to: i) provide open access, quality controlled and validated coral health data assembled from disparate surveys conducted across Hawaiʻi; ii) facilitate appropriate crediting of data; and iii) encourage future analyses of coral reef health. In this article, we describe and provide data from the HICORDIS database. The data presented in this paper were used in the research article “Satellite SST-based Coral Disease Outbreak Predictions for the Hawaiian Archipelago” (Caldwell et al., 2016) [1]

OSM-11 Facilitates LIN-12 Notch Signaling during Caenorhabditis elegans Vulval Development

Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC) fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL) ligands, can interact with the lineage defective-12 (LIN-12) Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS) motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1) can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates

Environmental release, fate and ecotoxicological effects of manufactured ceria nanomaterials

Recent interest in the environmental fate and effects of manufactured CeO2 nanomaterials (nanoceria) has stemmed from its expanded use for a variety of applications including fuel additives, catalytic converters, chemical and mechanical planarization media and other uses. This has led to a wave of publications on the toxicological effects of nanoceria in ecological receptor species, but only limited information is available on possible environmental releases, concentrations in environmental media, or environmental transformations. In this paper, we make initial estimates of likely environmental releases and exposure concentrations in soils and water and compare them to published toxicity values. Insufficient information was available to estimate aquatic exposures, but we estimated inputs to a hypothetical wastewater treatment plant that could result in effluent concentrations that would result in acute toxicity to the most sensitive aquatic organisms tested so far, cyanobacteria. The purpose of this exercise is to identify which areas are lacking in data to perform either regional or site specific ecological risk assessments. While estimates can be made for releases from use as a diesel fuel additive, and predicted toxicity is low in most terrestrial species tested to date, estimates for releases from other uses are difficult at this stage. We recommend that future studies focus on environmentally realistic exposures that take into account potential environmental transformations of the nanoceria surface as well as chronic toxicity studies in benthic aquatic organisms, soil invertebrates and microorgansims

Degenerate recognition of MHC class I molecules with Bw4 and Bw6 motifs by a killer cell Ig-like receptor 3DL expressed by macaque NK cells

The killer cell immunoglobulin-like receptors (KIRs) expressed on the surface of natural killer (NK) cells recognize specific major histocompatibility complex class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In human immunodeficiency virus (HIV) infection, survival is linked to host KIR and MHC-I genotypes. In the simian immunodeficiency virus (SIV) macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. Here, we describe the first characterization of a KIR-MHC interaction in pig-tailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs

Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis

The energy-sensing AMP-activated protein kinase (AMPK) is activated by low nutrient levels. Functions of AMPK, other than its role in cellular metabolism, are just beginning to emerge. Here we use a chemical genetics screen to identify direct substrates of AMPK in human cells. We find that AMPK phosphorylates 28 previously unidentified substrates, several of which are involved in mitosis and cytokinesis. We identify the residues phosphorylated by AMPK in vivo in several substrates, including protein phosphatase 1 regulatory subunit 12C (PPP1R12C) and p21-activated protein kinase (PAK2). AMPK-induced phosphorylation is necessary for PPP1R12C interaction with 14-3-3 and phosphorylation of myosin regulatory light chain. Both AMPK activity and PPP1R12C phosphorylation are increased in mitotic cells and are important for mitosis completion. These findings suggest that AMPK coordinates nutrient status with mitosis completion, which may be critical for the organism's response to low nutrients during development, or in adult stem and cancer cells.National Institutes of Health (U.S.) (Grant R01-GM068762