The Silent Crisis: Redefining Theoretical Approaches in Early Childhood Intervention Research with American Indians

This article discusses the theoretical context of the education of American Indian children. The unique needs of American Indian children and the lack of ECI provided, as well as the major theoretical approaches used by the dominant society in ECI program development are discussed. The linear model of time and human development – the view that the dominant society traditionally holds; and the nonlinear perspective of most American Indian communities is presented

More than teacher directed or child initiated: Preschool curriculum type, parent involvement, and children's outcomes in the child-parent centers.

This study investigated the contributions of curriculum approach and parent involvement to the short- and long-term effects of preschool participation in the Title I Chicago Child-Parent Centers. Data came from the complete cohort of 989 low-income children (93% African American) in the Chicago Longitudinal Study, who attended preschool in the 20 Child-Parent Centers in 1983-1985 and kindergarten in 1985-1986. We found that implementation of an instructional approach rated high by Head Teachers in teacher-directed and child-initiated activities was most consistently associated with children’s outcomes, including school readiness at kindergarten entry, reading achievement in third and eighth grades, and avoidance of grade retention. Parent involvement in school activities, as rated by teachers and by parents, was independently associated with child outcomes from school readiness at kindergarten entry to eighth grade reading achievement and grade retention above and beyond the influence of curriculum approach. Findings indicate that instructional approaches that blend a teacher-directed focus with child-initiated activities and parental school involvement are origins of the long-term effects of participation in the Child-Parent Centers

Developing Freight Analysis Zones at a State Level: A Cluster Analysis Approach

The ability to forecast freight to support transportation infrastructure decisions is limited by data availability at a level of detail meaningful to the transportation planner. The Freight Analysis Framework Version 2 is a national, comprehensive public freight database. The difficulty that transportation planners encounter when using this data is due to extensive aggregation. In this paper, the authors develop a methodology for creating freight analysis zones (FAZs) at a sub-state level by partitioning a state into meaningful zones that support freight transportation planning and analysis. The authors conc

Ecological interpretations of nitrogen isotope ratios of terrestrial plants and soils

Background Knowledge of biological and climatic controls in terrestrial nitrogen (N) cycling within and across ecosystems is central to understanding global patterns of key ecosystem processes. The ratios of 15N:14N in plants and soils have been used as indirect indices of N cycling parameters, yet our understanding of controls over N isotope ratios in plants and soils is still developing. Scope In this review, we provide background on the main processes that affect plant and soil N isotope ratios. In a similar manner to partitioning the roles of state factors and interactive controls in determining ecosystem traits, we review N isotopes patterns in plants and soils across a number of proximal factors that influence ecosystem properties as well as mechanisms that affect these patterns. Lastly, some remaining questions that would improve our understanding of N isotopes in terrestrial ecosystems are highlighted. Conclusion Compared to a decade ago, the global patterns of plant and soil N isotope ratios are more resolved. Additionally, we better understand how plant and soil N isotope ratios are affected by such factors as mycorrhizal fungi, climate, and microbial processing. A comprehensive understanding of the N cycle that ascribes different degrees of isotopic fractionation for each step under different conditions is closer to being realized, but a number of process-level questions still remain

Convergence Of Soil Nitrogen Isotopes Across Global Climate Gradients

Quantifying global patterns of terrestrial nitrogen (N) cycling is central to predicting future patterns of primary productivity, carbon sequestration, nutrient fluxes to aquatic systems, and climate forcing. With limited direct measures of soil N cycling at the global scale, syntheses of the N-15 : N-14 ratio of soil organic matter across climate gradients provide key insights into understanding global patterns of N cycling. In synthesizing data from over 6000 soil samples, we show strong global relationships among soil N isotopes, mean annual temperature (MAT), mean annual precipitation (MAP), and the concentrations of organic carbon and clay in soil. In both hot ecosystems and dry ecosystems, soil organic matter was more enriched in N-15 than in corresponding cold ecosystems or wet ecosystems. Below a MAT of 9.8 degrees C, soil delta N-15 was invariant with MAT. At the global scale, soil organic C concentrations also declined with increasing MAT and decreasing MAP. After standardizing for variation among mineral soils in soil C and clay concentrations, soil delta N-15 showed no consistent trends across global climate and latitudinal gradients. Our analyses could place new constraints on interpretations of patterns of ecosystem N cycling and global budgets of gaseous N loss.

Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals

Setting our sights on infectious diseases

In May 2019, the Wellcome Centre for Anti-Infectives Research (WCAIR) at the University of Dundee, UK, held an international conference with the aim of discussing some key questions around discovering new medicines for infectious diseases and a particular focus on diseases affecting Low and Middle Income Countries. There is an urgent need for new drugs to treat most infectious diseases. We were keen to see if there were lessons that we could learn across different disease areas and between the preclinical and clinical phases with the aim of exploring how we can improve and speed up the drug discovery, translational, and clinical development processes. We started with an introductory session on the current situation and then worked backward from clinical development to combination therapy, pharmacokinetic/pharmacodynamic (PK/PD) studies, drug discovery pathways, and new starting points and targets. This Viewpoint aims to capture some of the learnings

Quantitative High-Throughput Screen Identifies Inhibitors of the Schistosoma mansoni Redox Cascade

Schistosomiasis is a tropical disease associated with high morbidity and mortality, currently affecting over 200 million people worldwide. Praziquantel is the only drug used to treat the disease, and with its increased use the probability of developing drug resistance has grown significantly. The Schistosoma parasites can survive for up to decades in the human host due in part to a unique set of antioxidant enzymes that continuously degrade the reactive oxygen species produced by the host's innate immune response. Two principal components of this defense system have been recently identified in S. mansoni as thioredoxin/glutathione reductase (TGR) and peroxiredoxin (Prx) and as such these enzymes present attractive new targets for anti-schistosomiasis drug development. Inhibition of TGR/Prx activity was screened in a dual-enzyme format with reducing equivalents being transferred from NADPH to glutathione via a TGR-catalyzed reaction and then to hydrogen peroxide via a Prx-catalyzed step. A fully automated quantitative high-throughput (qHTS) experiment was performed against a collection of 71,028 compounds tested as 7- to 15-point concentration series at 5 µL reaction volume in 1536-well plate format. In order to generate a robust data set and to minimize the effect of compound autofluorescence, apparent reaction rates derived from a kinetic read were utilized instead of end-point measurements. Actives identified from the screen, along with previously untested analogues, were subjected to confirmatory experiments using the screening assay and subsequently against the individual targets in secondary assays. Several novel active series were identified which inhibited TGR at a range of potencies, with IC50s ranging from micromolar to the assay response limit (∼25 nM). This is, to our knowledge, the first report of a large-scale HTS to identify lead compounds for a helminthic disease, and provides a paradigm that can be used to jump-start development of novel therapeutics for other neglected tropical diseases

First report of the ectomycorrhizal status of boletes on the Northern Yucatan Peninsula, Mexico determined using isotopic methods

Despite their prominent role for tree growth, few studies have examined the occurrence of ectomycorrhizal fungi in lowland, seasonally dry tropical forests (SDTF). Although fruiting bodies of boletes have been observed in a dry tropical forest on the Northern Yucatan Peninsula, Mexico, their occurrence is rare and their mycorrhizal status is uncertain. To determine the trophic status (mycorrhizal vs. saprotrophic) of these boletes, fruiting bodies were collected and isotopically compared to known saprotrophic fungi, foliage, and soil from the same site. Mean δ15N and δ13C values differed significantly between boletes and saprotrophic fungi, with boletes 8.0‰ enriched and 2.5‰ depleted in 15N and 13C, respectively relative to saprotrophic fungi. Foliage was depleted in 13C relative to both boletes and saprotrophic fungi. Foliar δ15N values, on the other hand, were similar to saprotrophic fungi, yet were considerably lower relative to bolete fruiting bodies. Results from this study provide the first isotopic evidence of ectomycorrhizal fungi in lowland SDTF and emphasize the need for further research to better understand the diversity and ecological importance of ectomycorrhizal fungi in these forested ecosystems