Correlating Agricultural Use of Organophosphates with Outdoor Air Concentrations: A Particular Concern for Children

For the organophosphate pesticide chlorpyrifos, median inhalation noncancer, acute children’s exposures in agricultural communities are elevated above reference doses; for diazinon, similar exposures are nearly elevated. We used multivariate linear regression analysis to examine the temporal and spatial associations between agricultural use and measured air concentrations of chlorpyrifos, chlorpyrifos oxon, diazinon, and malathion. Agricultural use within a 3-mile radius on the monitoring day and use on the 2–4 prior days were significantly associated with air concentrations (p < 0.01) for all analytes except malathion; chlorpyrifos oxon showed the strongest association (p < 0.0001). In the final models, which included weather parameters, the proportion of variance (r (2), adjusted for the number of model variables) for all analytes ranged from 0.28 (p < 0.01) for malathion to 0.65 (p < 0.0001) for diazinon. Recent cellular, animal, and human evidence of toxicity, particularly in newborns, supports the public health concern indicated by initial risk estimates. Agricultural applications of organophosphates and their oxon products may have substantial volatization and off-field movement and are a probable source of exposures of public health concern

Chlorpyrifos Affects Phenotypic Outcomes in a Model of Mammalian Neurodevelopment: Critical Stages Targeting Differentiation in PC12 Cells

The organophosphate insecticide chlorpyrifos (CPF) adversely affects mammalian brain development through multiple mechanisms. To determine if CPF directly affects neuronal cell replication and phenotypic fate, and to identify the vulnerable stages of differentiation, we exposed PC12 cells, a model for mammalian neurodevelopment, to CPF concentrations spanning the threshold for cholinesterase inhibition (5–50 μM) and conducted evaluations during mitosis and in early and mid-differentiation. In undifferentiated cells, exposure to 5 μM CPF for 1–3 days reduced DNA synthesis significantly without eliciting cytotoxicity. At the same time, CPF increased the expression of tyrosine hydroxylase (TH), the enzymatic marker for the catecholamine phenotype, without affecting choline acetyltransferase (ChAT), the corresponding marker for the cholinergic phenotype. Upon exposure to nerve growth factor (NGF), PC12 cells developed neuritic projections in association with vastly increased TH and ChAT expression accompanying differentiation into the two phenotypes. CPF exposure begun at the start of differentiation significantly reduced ChAT but not TH activity. In contrast, when CPF was added in mid-differentiation (4 days of NGF pretreatment), ChAT was unaffected and TH was increased slightly. Thus, CPF exerts stage-specific effects, reducing DNA synthesis in the undifferentiated state, impairing development of the cholinergic phenotype at the start of differentiation, and promoting expression of the catecholaminergic phenotype both in undifferentiated and differentiated cells. CPF administration in vivo produces deficits in the number of neurons and cholinergic function, and because we were able to reproduce these effects in vitro, our results suggest that CPF directly influences the phenotypic fate of neuronal precursors

Comparative Developmental Neurotoxicity of Organophosphate Insecticides: Effects on Brain Development Are Separable from Systemic Toxicity

A comparative approach to the differences between systemic toxicity and developmental neurotoxicity of organophosphates is critical to determine the degree to which multiple mechanisms of toxicity carry across different members of this class of insecticides. We contrasted neuritic outgrowth and cholinergic synaptic development in neonatal rats given different organophosphates (chlorpyrifos, diazinon, parathion) at doses spanning the threshold for impaired growth and viability. Animals were treated daily on postnatal days 1–4 by subcutaneous injection so as to bypass differences in first-pass activation to the oxon or catabolism to inactive products. Evaluations occurred on day 5. Parathion (maximum tolerated dose, 0.1 mg/kg) was far more systemically toxic than was chlorpyrifos or diazinon (maximum tolerated dose, 1–5 mg/kg). Below the maximum tolerated dose, diazinon impaired neuritic outgrowth in the forebrain and brainstem, evidenced by a deficit in the ratio of membrane protein to total protein. Diazinon also decreased choline acetyltransferase activity, a cholinergic neuronal marker, whereas it did not affect hemicholinium-3 binding to the presynaptic choline transporter, an index of cholinergic neuronal activity. There was no m(2)-muscarinic acetylcholine receptor down-regulation, as would have occurred with chronic cholinergic hyper-stimulation. The same pattern was found previously for chlorpyrifos. In contrast, parathion did not elicit any of these changes at its maximum tolerated dose. These results indicate a complete dichotomy between the systemic toxicity of organophosphates and their propensity to elicit developmental neurotoxicity. For parathion, the threshold for lethality lies below that necessary for adverse effects on brain development, whereas the opposite is true for chlorpyrifos and diazinon

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Protecting eyewitness evidence: Examining the efficacy of a self-administered interview tool

Given the crucial role of eyewitness evidence, statements should be obtained as soon as possible after an incident. This is not always achieved due to demands on police resources. Two studies trace the development of a new tool, the Self-Administered Interview (SAI), designed to elicit a comprehensive initial statement. In Study 1, SAI participants reported more correct details than participants who provided a free recall account, and performed at the same level as participants given a Cognitive Interview. In Study 2, participants viewed a simulated crime and half recorded their statement using the SAI. After a delay of 1 week, all participants completed a free recall test. SAI participants recalled more correct details in the delayed recall task than control participants

Mass Spectrometric Analyses of Organophosphate Insecticide Oxon Protein Adducts

OBJECTIVE: Organophosphate (OP) insecticides continue to be used to control insect pests. Acute and chronic exposures to OP insecticides have been documented-to cause adverse health effects, but few OP-adducted proteins have been correlated with these illnesses at the molecular level. Our aim was to review the literature covering the current state of the art in mass spectrometry (MS) used to identify OP protein biomarkers. DATA SOURCES AND EXTRACTION: We identified general and specific research reports related to OP insecticides, OP toxicity, OP structure, and protein MS by searching PubMed and Chemical Abstracts for articles published before December 2008. DATA SYNTHESIS: A number of OP-based insecticides share common structural elements that result in predictable OP-protein adducts. The resultant OP-protein adducts show an increase in molecular mass that can be identified by MS and correlated with the OP agent. Customized OP-containing probes have also been used to tag and identify protein targets that can be identified by MS. CONCLUSIONS: MS is a useful and emerging tool for the identification of proteins that are modified by activated organophosphate insecticides. MS can characterize the structure of the OP adduct and also the specific amino acid residue that forms the key bond with the OP. Each protein that is modified in a unique way by an OP represents a unique molecular biomarker that with further research can lead to new correlations with exposure

Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample

<p>Abstract</p> <p>Background</p> <p>Common polymorphisms in the promoter of the <it>APOC3 </it>gene have been associated with hypertriglyceridemia and may impact on phenotypic expression of the metabolic syndrome (MetS). The rs7566605 marker, located near the <it>INSIG2 </it>gene, has been found to be associated with obesity, making it also a potential genetic determinant for MetS. The objective of this study is to examine the <it>APOC3 </it>-455T>C and the <it>INSIG2 </it>rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample.</p> <p>Methods</p> <p>Subjects were genotyped for both the <it>APOC3 </it>-455T>C and <it>INSIG2 </it>rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (≥18 years of age) from six different geographical ancestries.</p> <p>Results</p> <p>For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of ≥1 copy of <it>APOC3 </it>-455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with <it>APOC3 </it>-455T>C genotype. The <it>INSIG2 </it>rs7566605 polymorphism was not associated with MetS or measures of obesity.</p> <p>Conclusion</p> <p>Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in <it>APOC3 </it>was associated with an approximately 2-fold increased risk of MetS, whereas the <it>INSIG2 </it>rs7566605 polymorphism was not associated with MetS.</p

Talaromyces atroroseus, a new species efficiently producing industrially relevant red pigments

Some species of Talaromyces secrete large amounts of red pigments. Literature has linked this character to species such as Talaromyces purpurogenus, T. albobiverticillius, T. marneffei, and T. minioluteus often under earlier Penicillium names. Isolates identified as T. purpurogenus have been reported to be interesting industrially and they can produce extracellular enzymes and red pigments, but they can also produce mycotoxins such as rubratoxin A and B and luteoskyrin. Production of mycotoxins limits the use of isolates of a particular species in biotechnology. Talaromyces atroroseus sp. nov., described in this study, produces the azaphilone biosynthetic families mitorubrins and Monascus pigments without any production of mycotoxins. Within the red pigment producing clade, T. atroroseus resolved in a distinct clade separate from all the other species in multigene phylogenies (ITS, β-tubulin and RPB1), which confirm its unique nature. Talaromyces atroroseus resembles T. purpurogenus and T. albobiverticillius in producing red diffusible pigments, but differs from the latter two species by the production of glauconic acid, purpuride and ZG-1494α and by the dull to dark green, thick walled ellipsoidal conidia produced. The type strain of Talaromyces atroroseus is CBS 133442

Vetufebrus ovatus n. gen., n. sp. (Haemospororida: Plasmodiidae) vectored by a streblid bat fly (Diptera: Streblidae) in Dominican amber

This is the publisher’s final pdf. The published article is copyrighted by BioMed Central Ltd. and can be found at: http://www.parasitesandvectors.com/.Background: Both sexes of bat flies in the families Nycteribiidae and Streblidae (Diptera: Hippoboscoidea) reside in\ud the hair or on the wing membranes of bats and feed on blood. Members of the Nycteribiidae transmit bat malaria\ud globally however extant streblids have never been implemented as vectors of bat malaria. The present study\ud shows that during the Tertiary, streblids also were vectors of bat malaria.\ud Results: A new haemospororidan, Vetufebrus ovatus, n. gen., n. sp., (Haemospororida: Plasmodiidae) is described\ud from two oocysts attached to the midgut wall and sporozoites in salivary glands and ducts of a fossil bat fly\ud (Diptera: Streblidae) in Dominican amber. The new genus is characterized by ovoid oocysts, short, stubby\ud sporozoites with rounded ends and its occurrence in a fossil streblid. This is the first haemosporidian reported from\ud a streblid bat fly and shows that representatives of the Hippoboscoidea were vectoring bat malaria in the New\ud World by the mid-Tertiary.\ud Conclusions: This report is the first evidence of an extant or extinct streblid bat fly transmitting malaria.\ud Discovering a mid-tertiary malarial parasite in a fossil streblid that closely resembles members of a malarial genus\ud found in nycteribiid bat flies today shows how little we know about the vector associations of streblids. While no\ud malaria parasites have been found in extant streblids, they probably occur and it is possible that streblids were the\ud earliest lineage of flies that transmitted bat malaria to Chiroptera