Effects of trimethyltin (TMT) on glial and neuronal cells in aggregate cultures: dependence on the developmental stage.

Long-term effects of trimethyltin (TMT) applied at concentrations below the cytotoxic level were examined in three-dimensional cell cultures of fetal rat telencephalon using biochemical, immunochemical and morphological criteria. It was found that in immature cultures low concentrations of TMT (10(-8) M) specifically induced a gliotic response in astrocytes, with increased immunoreactivity for glial fibrillary acidic protein, and a greater number of astrocytic processes. Significant changes in oligodendrocytic and neuronal parameters were found only at 10(-6) M of TMT. In differentiated cultures, distinct changes in cell type-specific parameters occurred at 10(-6) M of TMT (the lowest effective concentration). In addition, different patterns of responses were found for astrocytes and oligodendrocytes, as compared to immature cultures. These results suggest that among neural cells, astroblasts are most sensitive to TMT, and that the glial responses to this neurotoxicant are development-dependent.

Audit report on the Peace Officers' Retirement, Accident and Disability System for the year ended June 30, 2015

Audit report on the Peace Officers' Retirement, Accident and Disability System for the year ended June 30, 2015

Report on the Peace Officers’ Retirement, Accident and Disability System, Schedule of Employer Pension Amounts required to implement Governmental Accounting Standards Board (GASB) Statement No. 68, Accounting and Financial Reporting for Pensions for the year ended June 30, 2015

Report on the Peace Officers’ Retirement, Accident and Disability System, Schedule of Employer Pension Amounts required to implement Governmental Accounting Standards Board (GASB) Statement No. 68, Accounting and Financial Reporting for Pensions for the year ended June 30, 2015

Developmental changes in the heavy subunit of neurofilaments in the corpus callosum of the cat.

In the corpus callosum of the cat, the heavy subunit of neurofilaments (NFH) can be demonstrated with the monoclonal antibody NE14, as early as P11, not at P3, and only in a few axons. At P18-19 and more markedly at P29, many more callosal axons have become positive to NE14 and this is similar to what is found in the adult. In contrast, callosal axons become positive to the neurofilament antibody SMI-32 only between P29 and P39 and remain positive in the adult. Treatment with alkaline phosphatase prevents axonal staining with NE14, but results in SMI-32 staining of a few callosal axons as early as P11, but not at P3. Between P11 and P19 the number of axons stained with SMI-32 after alkaline phosphatase treatment increases, in parallel with that of axons stained with NE14. Thus NE14 appears to recognize a phosphorylated form of NFH, while SMI-32 appears to recognize an epitope of NFH which is either masked by phosphate or inaccessible until between P29 and P39, unless the tissue is treated with alkaline phosphatase. These two forms of NFH appear towards the end of the period of massive developmental elimination of callosal axons. They are also synchronous with changes in the spacing of neurofilaments quantified in a separate ultrastructural study. These cytoskeletal changes may terminate the juvenile-labile state of callosal axons and allow further axial growth of the axon.

Genetic parameters and variability in physic nut accessions during early developmental stages

The objective of this work was to estimate the genetic parameters and variability among accessions (half-sib families) of physic nut (Jatropha curcas) during the early stages of development. For this study, 110 accessions in the first year of development of the physic nut germplasm bank, maintained at Embrapa Cerrados, DF, Brazil, were evaluated in situ. The experiment was established in a randomized complete block design, with two replicates and five plants per plot arranged in rows at 4x2 m spacing. Grain yield, total number of branches per plant, plant height, stem diameter, canopy projection on the row, canopy projection between rows, canopy volume, number of days until first flowering and height of the first inflorescence were evaluated. Estimates of vegetative genetic parameters showed the existence of genetic variability in the physic nut germplasm bank. Physic nut accessions of the germplasm bank were grouped into five similarity groups based on character divergence. Although preliminary, the obtained results are promising for showing potential for Jatropha improvement with selective efficiency.

Family Support Subsidy and Children at Home Program SFY 2015, October 30, 2015

The Family Support Subsidy (FSS) program provides a monthly payment to help families with the cost of raising a child with a developmental disability. Parents of children with disabilities were very active in getting state and federal policy makers to look at how they could divert some of the funds going to institutional care. Families with severely disabled children wanted to raise their children at home but were met with a lot of resistance and policy barriers when they tried to get home-based support.

Aging and Disability Resource Center and MHDS Commission Home Modification Assistance Program Plan, December 2015

This report was prepared as a directive to Aging and Disability Resource Centers and The Mental Health and Disability Commission to jointly develop a plan for a home modification assistance program to provide grants and individual income tax credits to assist with expenses related to the making or permanent home modifications that permit individual with a disability to remain in the homes.

Iowa Mental Health and Disability Services Commission, January 2016

This Annual Report of the Iowa Mental Health and Disability Services Commission (the Commission) is being submitted pursuant to Iowa Code § 225C.6(1)(h). The report is organized in two sections: (1) an overview of the activities of the Commission during 2015, and (2) recommendations formulated by the Commission for changes in Iowa law.

dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes

H3K4me3 is a histone modification that accumulates at the transcription-start site (TSS) of active genes and is known to be important for transcription activation. The way in which H3K4me3 is regulated at TSS and the actual molecular basis of its contribution to transcription remain largely unanswered. To address these questions, we have analyzed the contribution of dKDM5/LID, the main H3K4me3 demethylase in Drosophila, to the regulation of the pattern of H3K4me3. ChIP-seq results show that, at developmental genes, dKDM5/LID localizes at TSS and regulates H3K4me3. dKDM5/LID target genes are highly transcribed and enriched in active RNApol II and H3K36me3, suggesting a positive contribution to transcription. Expression-profiling show that, though weakly, dKDM5/LID target genes are significantly downregulated upon dKDM5/LID depletion. Furthermore, dKDM5/LID depletion results in decreased RNApol II occupancy, particularly by the promoter-proximal Pol lloser5 form. Our results also show that ASH2, an evolutionarily conserved factor that locates at TSS and is required for H3K4me3, binds and positively regulates dKDM5/LID target genes. However, dKDM5/LID and ASH2 do not bind simultaneously and recognize different chromatin states, enriched in H3K4me3 and not, respectively. These results indicate that, at developmental genes, dKDM5/LID and ASH2 coordinately regulate H3K4me3 at TSS and that this dynamic regulation contributes to transcription.

Developmental constraints on vertebrate genome evolution.

Constraints in embryonic development are thought to bias the direction of evolution by making some changes less likely, and others more likely, depending on their consequences on ontogeny. Here, we characterize the constraints acting on genome evolution in vertebrates. We used gene expression data from two vertebrates: zebrafish, using a microarray experiment spanning 14 stages of development, and mouse, using EST counts for 26 stages of development. We show that, in both species, genes expressed early in development (1) have a more dramatic effect of knock-out or mutation and (2) are more likely to revert to single copy after whole genome duplication, relative to genes expressed late. This supports high constraints on early stages of vertebrate development, making them less open to innovations (gene gain or gene loss). Results are robust to different sources of data -- gene expression from microarrays, ESTs, or in situ hybridizations; and mutants from directed KO, transgenic insertions, point mutations, or morpholinos. We determine the pattern of these constraints, which differs from the model used to describe vertebrate morphological conservation ("hourglass" model). While morphological constraints reach a maximum at mid-development (the "phylotypic" stage), genomic constraints appear to decrease in a monotonous manner over developmental time.

Use of aggregating brain cell cultures to study developmental effects of organophosphorus insecticides.

Aggregating brain cell cultures of fetal rat telencephalon can be grown in a chemically defined medium for extended periods of time. After a phase of intense mitotic activity, these three-dimensional cell cultures undergo extensive morphological differentiation, including synaptogenesis and myelination. To study the developmental toxicity of organophosphorus compounds (OP), aggregating brain cell cultures were treated with parathion. Protein content and cell type-specific enzyme activities were not affected up to a concentration of 10(5) M. Gliosis, characterized by an increased staining for glial fibrillary acidic protein (GFAP), was observed in immature and in differentiated cells. In contrast, uridine incorporation and myelin basic protein (MBP) immunoreactivity revealed strong differences in sensitivity between these two developmental stages. These results are in agreement with the view that in vivo the development-dependent toxicity is not only due to changes in hepatic detoxification, but also to age-related modifications in the susceptibility of the different populations of brain cells. Furthermore, they underline the usefulness of histotypic culture systems with a high developmental potential, such as aggregating brain cell cultures, and stress the importance of applying a large range of criteria for testing the developmental toxicity of potential neurotoxicants.

Developmental and metabolic brain alterations in rats exposed to bisphenol A during gestation and lactation.

In recent years, considerable research has focused on the biological effect of endocrine-disrupting chemicals. Bisphenol A (BPA) has been implicated as an endocrine-disrupting chemical (EDC) due to its ability to mimic the action of endogenous estrogenic hormones. The aim of this study was to assess the effect of perinatal exposure to BPA on cerebral structural development and metabolism after birth. BPA (1mg/l) was administered in the drinking water of pregnant dams from day 6 of gestation until pup weaning. At postnatal day 20, in vivo metabolite concentrations in the rat pup hippocampus were measured using high field proton magnetic resonance spectroscopy. Further, brain was assessed histologically for growth, gross morphology, glial and neuronal development and extent of myelination. Localized proton magnetic resonance spectroscopy ((1)H MRS) showed in the BPA-exposed rat a significant increase in glutamate concentration in the hippocampus as well as in the Glu/Asp ratio. Interestingly these two metabolites are metabolically linked together in the malate-aspartate metabolic shuttle. Quantitative histological analysis revealed that the density of NeuN-positive neurons in the hippocampus was decreased in the BPA-treated offspring when compared to controls. Conversely, the density of GFAP-positive astrocytes in the cingulum was increased in BPA-treated offspring. In conclusion, exposure to low-dose BPA during gestation and lactation leads to significant changes in the Glu/Asp ratio in the hippocampus, which may reflect impaired mitochondrial function and also result in neuronal and glial developmental alterations.