Extensive differential protein phosphorylation as intraerythrocytic Plasmodium falciparumschizonts develop into extracellular invasive merozoites

Pathology of the most lethal form of malaria is caused by Plasmodium falciparum asexual blood stages and initiated by merozoite invasion of erythrocytes. We present a phosphoproteome analysis of extracellular merozoites revealing 1765 unique phosphorylation sites including 785 sites not previously detected in schizonts. All MS data have been deposited in the ProteomeXchange with identifier PXD001684 (http://proteomecentral.proteomexchange.org/dataset/PXD001684). The observed differential phosphorylation between extra and intraerythrocytic life-cycle stages was confirmed using both phospho-site and phospho-motif specific antibodies and is consistent with the core motif [K/R]xx[pS/pT] being highly represented in merozoite phosphoproteins. Comparative bioinformatic analyses highlighted protein sets and pathways with established roles in invasion. Within the merozoite phosphoprotein interaction network a subnetwork of 119 proteins with potential roles in cellular movement and invasion was identified and suggested that it is coregulated by a further small subnetwork of protein kinase A (PKA), two calcium-dependent protein kinases (CDPKs), a phosphatidyl inositol kinase (PI3K), and a GCN2-like elF2-kinase with a predicted role in translational arrest and associated changes in the ubquitinome. To test this notion experimentally, we examined the overall ubiquitination level in intracellular schizonts versus extracellular merozoites and found it highly upregulated in merozoites. We propose that alterations in the phosphoproteome and ubiquitinome reflect a starvation-induced translational arrest as intracellular schizonts transform into extracellular merozoites

On the interaction of Velar Fronting and Labial Harmony

This article documents the typological occurrence and interactions of two seemingly independent error patterns, namely Velar Fronting and Labial Harmony, in a cross-sectional investigation of the sound systems of 235 children with phonological delays (ages 3;0 to 7;9). The results revealed that the occurrence of Labial Harmony depends on the occurrence of Velar Fronting, and that, when these processes co-occurred, all three predicted types of interactions were attested. A constrained version of Optimality Theory is put forward that offers a unified explanation for the implicational relationship between these error patterns and their observed interactions. The findings are compared with the results from other studies and are considered for their theoretical and clinical implicationsNational Institutes of Health DC00433, RR7031K, DC00076, DC001694 (PI: Gierut)This is an Accepted Manuscript of an article published by Taylor & Francis in Clinical Linguistics & Phonetics on March 2011, available online: http://wwww.tandfonline.com/10.3109/02699206.2010.522300

The Daily Mile as a public health intervention : a rapid ethnographic assessment of uptake and implementation in South London, UK

Background: Existing evidence identifies health benefits for children of additional daily physical activity (PA) on a range of cardiovascular and metabolic outcomes. The Daily Mile (TDM) is a popular scheme designed to increase children’s PA within the school day. Emerging evidence indicates that participation in TDM can increase children’s PA, reduce sedentarism and reduce skinfold measures. However, little is known about the potential effects of TDM as a public health intervention, and the benefits and disbenefits that might flow from wider implementation in ‘real world’ settings. Methods: We aimed to identify how TDM is being implemented in a naturalistic setting, and what implications this has for its potential impact on population health. We undertook a rapid ethnographic assessment of uptake and implementation in Lewisham, south London. Data included interviews (n = 22) and focus groups (n = 11) with stakeholders; observations of implementation in 12 classes; and analysis of routine data sources to identify school level factors associated with uptake. Results: Of the 69 primary schools in one borough, 33 (48%) had adopted TDM by September 2018. There were no significant differences between adopters and non-adopters in mean school population size (means 377 vs 397, P = 0.70), mean percentage of children eligible for free school meals (16.2 vs 14.3%, P = 0.39), or mean percentage of children from Black and Minority Ethnic populations (76.3 vs 78.2%, P = 0.41). Addressing obesity was a key incentive for adoption, although a range of health and educational benefits were also hypothesised to accrue from participation. Mapping TDM to the TIDierR-PHP checklist to describe the intervention in practice identified that considerable adaption happened at the level of borough, school, class and pupil. Population health effects are likely to be influenced by the interaction of intervention and context at each of these levels. Conclusions: Examining TDM in ‘real world’ settings surfaces adaptions and variations in implementation. This has implications for the likely effects of TDM, and points more broadly to an urgent need for more appropriate methods for evaluating public health impact and implementation in complex contexts

Diffusion theory and knowledge dissemination, utilization and integration

Many accomplishments of public health have been distributed unevenly among populations. This article reviews the concepts of applying evidence-based practice in public health in the face of the varied cultures and circumstances of practice in these varied populations. Key components of EBPH include: making decisions based on the best available scientific evidence, using data and information systems systematically, applying program planning frameworks, engaging the community and practitioners in decision making, conducting sound evaluation, and disseminating what is learned. The usual application of these principles has overemphasized the scientific evidence as the starting point, whereas this review suggests engaging the community and practitioners as an equally important starting point to assess their needs, assets and circumstances, which can be facilitated with program planning frameworks and use of local assessment and surveillance data

Structural and Financial Characteristics of U.S. Farms: 2001 Family Farm Report

Family farms vary widely in size and other characteristics, ranging from very small retirement and residential farms to establishments with sales in the millions of dollars. The farm typology developed by the Economic Research Service (ERS) categorizes farms into groups based primarily on occupation of the operator and sales class of the farm. The typology groups reflect operators' expectations from farming, position in the life cycle, and dependence on agriculture. The groups differ in their importance to the farm sector, product specialization, program participation, and dependence on farm income. These (and other) differences are discussed in this report.Agricultural Resource Management Study (ARMS), family farms, farm businesses, farm financial situation, farm operator household income, farm operators, farm structure, farm typology, female farm operators, government payments, spouses of farm operators, taxes, Agricultural Finance, Farm Management,

The coronal fricative problem

This paper examines a range of predicted versus attested error patterns involving coronal fricatives (e.g. [s, z, θ, ð]) as targets and repairs in the early sound systems of monolingual English-acquiring children. Typological results are reported from a cross-sectional study of 234 children with phonological delays (ages 3 years; 0 months to 7;9). Our analyses revealed different instantiations of a putative developmental conspiracy within and across children. Supplemental longitudinal evidence is also presented that replicates the cross-sectional results, offering further insight into the life-cycle of the conspiracy. Several of the observed typological anomalies are argued to follow from a modified version of Optimality Theory with Candidate Chains (McCarthy, 2007).National Institutes of Health DC00433, RR7031K, DC00076, DC001694 (PI: Gierut

On the interaction of deaffrication and consonant harmony

Error patterns in children's phonological development are often described as simplifying processes that can interact with one another with different consequences. Some interactions limit the applicability of an error pattern, and others extend it to more words. Theories predict that error patterns interact to their full potential. While specific interactions have been documented for certain pairs of processes, no developmental study has shown that the range of typologically predicted interactions occurs for those processes. To determine whether this anomaly is an accidental gap or a systematic peculiarity of particular error patterns, two commonly occurring processes were considered, namely Deaffrication and Consonant Harmony. Results are reported from a cross-sectional and longitudinal study of 12 children (age 3;0 - 5;0) with functional phonological delays. Three interaction types were attested to varying degrees. The longitudinal results further instantiated the typology and revealed a characteristic trajectory of change. Implications of these findings are explored.National Institutes of Health DC00433, RR7031K, DC00076, DC001694 (PI: Gierut

Spitzer observations of HH54 and HH7-11: mapping the H2 ortho-to-para ratio in shocked molecular gas

We report the results of spectroscopic mapping observations carried out toward the Herbig-Haro objects HH7-11 and HH54 over the 5.2 - 37 micron region using the Infrared Spectrograph of the Spitzer Space Telescope. These observations have led to the detection and mapping of the S(0) - S(7) pure rotational lines of molecular hydrogen, together with emissions in fine structure transitions of Ne+, Si+, S, and Fe+. The H2 rotational emissions indicate the presence of warm gas with a mixture of temperatures in the range 400 - 1200 K, consistent with the expected temperature behind nondissociative shocks of velocity ~ 10 - 20 km/s, while the fine structure emissions originate in faster shocks of velocity 35 - 90 km/s that are dissociative and ionizing. Maps of the H2 line ratios reveal little spatial variation in the typical admixture of gas temperatures in the mapped regions, but show that the H2 ortho-to-para ratio is quite variable, typically falling substantially below the equilibrium value of 3 attained at the measured gas temperatures. The non-equilibrium ortho-to-para ratios are characteristic of temperatures as low as ~ 50 K, and are a remnant of an earlier epoch, before the gas temperature was elevated by the passage of a shock. Correlations between the gas temperature and H2 ortho-to-para ratio show that ortho-to-para ratios < 0.8 are attained only at gas temperatures below ~ 900 K; this behavior is consistent with theoretical models in which the conversion of para- to ortho-H2 behind the shock is driven by reactive collisions with atomic hydrogen, a process which possesses a substantial activation energy barrier (E_A/k ~ 4000 K) and is therefore very inefficient at low temperature.Comment: 45 pages, including 16 figures. Accepted for publication in Ap

Report on the 2013 Rapid Assessment Survey of Marine Species at New England Bays and Harbors

Introduced species (i.e., non-native species that have become established in a new location) have increasingly been recognized as a concern as they have become more prevalent in marine and terrestrial environments (Mooney and Cleland 2001; Simberloff et al. 2005). The ability of introduced species to alter population, community, and ecosystem structure and function, as well as cause significant economic damage is well documented (Carlton 1989, 1996b, 2000; Cohen and Carlton 1995; Cohen et al. 1995; Elton 1958; Meinesz et al. 1993; Occhipinti-Ambrogi and Sheppard 2007; Pimentel et al. 2005; Thresher 2000). The annual economic costs incurred from managing the approximately 50,000 introduced species in the United States alone are estimated to be over $120 billion (Pimentel et al. 2005). Having a monitoring network in place to track new introductions and distributional changes of introduced species is critical for effective management, as these efforts may be more successful when species are detected before they have the chance to become established. A rapid assessment survey is one such method for early detection of introduced species. With rapid assessment surveys, a team of taxonomic experts record and monitor marine species–providing a baseline inventory of native, introduced, and cryptogenic (i.e., unknown origin) species (as defined by Carlton 1996a)–and document range expansions of previously identified species. Since 2000, five rapid assessment surveys have been conducted in New England. These surveys focus on recording species at marinas, which often are in close proximity to transportation vectors (i.e., recreational boats). Species are collected from floating docks and piers because these structures are accessible regardless of the tidal cycle. Another reason for sampling floating docks and other floating structures is that marine introduced species are often found to be more prevalent on artificial surfaces than natural surfaces (Glasby and Connell 2001; Paulay et al. 2002). The primary objectives of these surveys are to: (1) identify native, introduced, and cryptogenic marine species, (2) expand on data collected in past surveys, (3) assess the introduction status and range extensions of documented introduced species, and (4) detect new introductions. This report presents the introduced, cryptogenic, and native species recorded during the 2013 survey

The Binding of Plasmodium falciparum Adhesins and Erythrocyte Invasion Proteins to Aldolase Is Enhanced by Phosphorylation.

Aldolase has been implicated as a protein coupling the actomyosin motor and cell surface adhesins involved in motility and host cell invasion in the human malaria parasite Plasmodium falciparum. It binds to the cytoplasmic domain (CTD) of type 1 membrane proteins of the thrombospondin-related anonymous protein (TRAP) family. Other type 1 membrane proteins located in the apical organelles of merozoites, the form of the parasite that invades red blood cells, including apical membrane antigen 1 (AMA1) and members of the erythrocyte binding ligand (EBL) and reticulocyte binding homologue (RH) protein families have been implicated in host cell binding and invasion. Using a direct binding method we confirm that TRAP and merozoite TRAP (MTRAP) bind aldolase and show that the interaction is mediated by more than just the C-terminal six amino acid residues identified previously. Single amino acid substitutions in the MTRAP CTD abolished binding to aldolase. The CTDs of AMA1 and members of the EBL and RH protein families also bound to aldolase. MTRAP competed with AMA1 and RH4 for binding to aldolase, indicating overlapping binding sites. MTRAP CTD was phosphorylated in vitro by both calcium dependent kinase 1 (CDPK1) and protein kinase A, and this modification increased the affinity of binding to aldolase by ten-fold. Phosphorylation of the CTD of members of the EBL and RH protein families also increased their affinity for aldolase in some cases. To examine whether or not MTRAP expressed in asexual blood stage parasites is phosphorylated, it was tagged with GFP, purified and analysed, however no phosphorylation was detected. We propose that CTD binding to aldolase may be dynamically modulated by phosphorylation, and there may be competition for aldolase binding between different CTDs. The use and efficiency of alternate invasion pathways may be determined by the affinity of adhesins and cell invasion proteins for aldolase, in addition to their host ligand specificity