Genotoxicants Target Distinct Molecular Networks in Neonatal Neurons

BACKGROUND: Exposure of the brain to environmental agents during critical periods of neuronal development is considered a key factor underlying many neurologic disorders. OBJECTIVES: In this study we examined the influence of genotoxicants on cerebellar function during early development by measuring global gene expression changes. METHODS: We measured global gene expression in immature cerebellar neurons (i.e., granule cells) after treatment with two distinct alkylating agents, methylazoxymethanol (MAM) and nitrogen mustard (HN2). Granule cell cultures were treated for 24 hr with MAM (10–1,000 μM) or HN2 (0.1–20 μM) and examined for cell viability, DNA damage, and markers of apoptosis. RESULTS: Neuronal viability was significantly reduced (p < 0.01) at concentrations > 500 μM for MAM and > 1.0 μM for HN2; this correlated with an increase in both DNA damage and markers of apoptosis. Neuronal cultures treated with sublethal concentrations of MAM (100 μM) or HN2 (1.0 μM) were then examined for gene expression using large-scale mouse cDNA microarrays (27,648). Gene expression results revealed that a) global gene expression was predominantly up-regulated by both genotoxicants; b) the number of down-regulated genes was approximately 3-fold greater for HN2 than for MAM; and c) distinct classes of molecules were influenced by MAM (i.e, neuronal differentiation, the stress and immune response, and signal transduction) and HN2 (i.e, protein synthesis and apoptosis). CONCLUSIONS: These studies demonstrate that individual genotoxicants induce distinct gene expression signatures. Further study of these molecular networks may explain the variable response of the developing brain to different types of environmental genotoxicants

Sensitivity and Specificity of Multiple Kato-Katz Thick Smears and a Circulating Cathodic Antigen Test for Schistosoma mansoni Diagnosis Pre- and Post-repeated-Praziquantel Treatment

Two Kato-Katz thick smears (Kato-Katzs) from a single stool are currently recommended for diagnosing Schistosoma mansoni infections to map areas for intervention. This ‘gold standard’ has low sensitivity at low infection intensities. The urine point-of-care circulating cathodic antigen test (POC-CCA) is potentially more sensitive but how accurately they detect S. mansoni after repeated praziquantel treatments, their suitability for measuring drug efficacy and their correlation with egg counts remain to be fully understood. We compared the accuracies of one to six Kato-Katzs and one POC-CCA for the diagnosis of S. mansoni in primary-school children who have received zero to ten praziquantel treatments. We determined the impact each diagnostic approach may have on monitoring and evaluation (M&E) and drug-efficacy findings

Mitochondria localization induced self-assembly of peptide amphiphiles for cellular dysfunction

Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.clos

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

Tillandsia lampropoda C.B. Sm.

Honduras, Francisco Morazan , Piedra Herrada, West slope of Cerro de Uyuca. Pine-oak forest. LAT(14.0158)N. LONG(87.0401)W. ALT 1500 Pinares abiertos. Brácteas rojas y amarillas, epífita en Quercus

Hechtia dichoroantha Donn. Sm.

Honduras, Francisco Morazan San Antonio de Oriente, Quebrada El Gallo, Rocky wooded river bank. Pine-oak region. LAT(14.0056)N. LONG(87.0008)W. ALT 900 - 1000 Calys rose, corolla pinkish-white, inflorescence 0.5-1 m. tall, common on rocky. Part two

Hechtia dichoroantha Donn. Sm.

Honduras, El Paraiso , Galeras, Near Galeras. LAT(13.5425)N. LONG(86.5858)W. ALT 90

Danaea elliptica Sm.

Honduras, Atlantida, Tela, San Alejo. LAT (15°42'28'' N) N; LONG (87°35' W) W. ALT (210). Honduras. Dense wet mixed forest. Dept. Atlántida: Vicinity of ìSan Alejo, 150 - 270m., at base of hills south of San Alejo near ìRío San Alejo. April 22 - 27, 1947

Hechtia dichoroantha Donn. Sm.

Honduras, El Paraiso , Las Casitas, LAT(13.5425)N. LONG(86.5858)W. ALT 950 Fls. calix rose, corolla white-pinkish, inflorescence 1-1.5 m. tall, leaves to 1 m. long, common on rocky slopes in dense colonies. Part two