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Developmental and methylmercury effects on brain protein synthesis.

Sprague-Dawley rats (ages 1 to 21 days, alternate days) were chosen for study. Animals were injected with methylmercuric chloride (8 mg/kg IP); 12 hr later each animal was injected with uniformly labeled L-(14C)leucine, allowed 30 min for incorporation, and decapitated. Brains were analyzed for amounts of radioactivity incorporated into TCA precipitable protein. When compared to baseline curves for control animals, curves of treated animals were compressed overall and had age-dependent increases and decreases in rates of protein synthesis.

Aging

Differential experience following developmental lead exposure: effects on brain and behavior.

Long Evans hooded rat pups were exposed to lead (Pb) via the maternal milk supply from Postnatal Day 1 (PN 1) to PN 25. Mothers were fed diets containing either 4% Pb CO3 (High Pb), 0.4% Pb CO3 (Low Pb) or 2.2% Na2 CO3 (Controls) throughout this period. Pups were weaned at PN 30 and littermates randomly assigned to either an Enriched or Isolated environment for a period of 30 days. Increases in activity levels and decreases in passive avoidance latencies were observed in Pb exposed animals. However, there were minimal effects due to Pb on symmetrical maze performance. Experience in the enriched environment had no effect on open field activity levels but resulted in a marked reduction in symmetrical maze errors. While enrichment had no effect on passive avoidance performance in High Pb animals, it was capable of raising latencies in Low Pb animals to Control values. Thus, the therapeutic value of environmental enrichment in Pb exposed animals depends on both the task employed and the severity of the pre-enrichment brain damage. From both brain regional analysis and behavioral testing results, it appeared that the hippocampus was a major site of Pb action. From comparison of blood Pb levels of our animals and those reported in children, it became apparent that the rat may have a greater tolerance for Pb, and as such, caution must be used in making direct comparisons between the two species in terms of blood Pb levels.

Animals

Housing and mothering: their effects upon the developmental levels of 3-year-old children.

The development of 200 3-year-old children was measured, using Gesell parameters of development. The levels of development were matched against the adequacy, or inadequacy, of maternal care and housing, the scales for which were derived from a questionnaire completed by the children's mothers. Housing was not found to affect the children's developmental levels, while the adequacy of maternal care was highly significantly related to satisfactory child development.

Adult

The effect of rifampicin on the developmental phases of germinating spores of Clostridum sp., MSp+.

The effect of rifampicin on the developmental phases of germinating spores of Clostridium botulinum, MSp+, has been studied. At sublethal concentrations of rifampicin (0.05 ng/ml) the time periods required for outgrowth and vegetative growth was significantly prolonged because of the inhibition of RNA and protein synthesis. However, rifampicin had essentially no effect on DNA synthesis or on subsequent spore formation. Chemical analyses showed that the amount of protein present in vegetative cells of the rifampicin-treated cultures was twice as great as in the untreated cultures but the total protein content of endospores was the same in both cases. It was revealed in ultrastructural studies of rifampicin (0.1 ng/ml) treated cultures, examined after 22 h, that septum formation and normal cell division of the emerging cell was blocked and a few cells showed constriction which produced one normal and one protoplast-like daughter cell.

Bacterial Proteins

Effects of BUdR on developmental functions of Dictyostelium discoideum.

The development of Dictyostelium discoideum cells, as measured by spore yield, is somewhat more sensitive to the presence of BUdR during vegetative growth than is growth itself. Observations on the development of control and BUdR-grown cells, their protein labelling patterns and assays of 4 developmentally regulated proteins all reveal a consistent picture. BUdR appears to block spore formation by partially inhibiting several or many different earlier events during development. The relative sensitivity of development compared to growth to inhibition by the drug may be a consequence of the nature of the developmental process rather than of some unique specificity of the inhibitor.

3',5'-Cyclic-AMP Phosphodiesterases

Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.

Many physiological osteocalcin-regulated functions are affected in adult offspring of mothers experiencing unhealthy pregnancy. Furthermore, osteocalcin signaling during gestation influences cognition and adrenal steroidogenesis in adult mice. Together these observations suggest that osteocalcin may broadly function during pregnancy to determine organismal homeostasis in adult mammals. To test this hypothesis, we analyzed in unchallenged wildtype and Osteocalcin-deficient, newborn and adult mice of various genotypes and origin maintained on different genetic backgrounds, the functions of osteocalcin in the pancreas, liver and testes and their molecular underpinnings. This analysis revealed that providing mothers are Osteocalcin-deficient, Osteocalcin haploinsufficiency in embryos hampers insulin secretion, liver gluconeogenesis, glucose homeostasis, testes steroidogenesis in adult offspring; inhibits cell proliferation in developing pancreatic islets and testes; and disrupts distinct programs of gene expression in these organs and in the brain. This study indicates that osteocalcin exerts dominant functions in most organs it influences. Furthermore, through their synergistic regulation of multiple physiological functions, osteocalcin of maternal and embryonic origins contributes to the establishment and maintenance of organismal homeostasis in newborn and adult offspring.

Animals

[Effect of raised temperature on the developmental cycle of Candida utilis yeasts].

The effect of the submaximal temperature (41.5 degrees C) on growth was studied with a synchronous periodic yeast culture. If the cells were subjected to the action of elevated temperature at the beginning of the growth cycle, the formation of buds was not inhibited in contrast to the separation of nuclei between the daughter and parent cells. If the cells started their growth cycle at the optimal temperature of 32 degrees C and, after spending 0.6 of the cycle at this temperature, were subjected to a temperature of 41.5 degrees C, the separation of nuclei between the daughter and parent cells took place, but the cells were not entirely separated one from another.

Candida

Contrast effects in the rat: a developmental study.

Two experiments investigated and development of positive and negative contrast effects in the consummatory behavior of juvenile and adult rats. Over a 4-day session, animals were given alternating 30-sec presentations of 2 bottles containing either 32 or 4% sucrose solutions. In Experiment I, different groups of rats were tested both cross-sectionally and longitudinally using a cohort-sequential design. Cross-sectionally, animals at all ages exhibited both types of contrast and demonstrated increasing positive contrast effects with greater age. Discrepancies between the longitudinal and cross-sectional samples were found to be due to the repeated testing procedure of the former design. Experiment II replicated the positive and negative contrast effects in the juvenile animals, indicating that the processes responsible for contrast effects are operating in the rat at a very early age.

Age Factors

Effects of vestibular stimulation on nystagmus response and motor performance in the developmentally delayed infant.

The effects were studied of 10 days' exposure to daily repetitive, specific vestibular stimulation on motor performance of children with Down's syndrome and normal children. A quantitative assessment of vestibular function was made in these children including the habituation response of postrotatory nystagmus. Control groups were included. Both the children with Down's syndrome and the normal children who received vestibular therapy demonstrated positive effects when evaluated using a quantitative motor skills assessment test. Control and treatment children showed vestibular habituation, with treatment children evidencing the greater change. This change may reflect the acquisition of an increased level of central nervous system inhibitory control.

Child, Preschool

Influence of illness on developmental progress in children under two.

Illnesses occurring in children under two were recorded in relation to a systematic programme of child surveillance in one general practice.The most important result of this study was that although illness does have a detectable effect on developmental progress, the degree of that influence is for the most part small.Illnesses experienced between 0 and 7 months have less influence upon seven-month developmental scores than upon 24-month developmental scores, but have a greater influence upon the latter than do illnesses experienced between 7 and 24 months.There was a significantly higher consultation rate for boys and for children from social classes 3b, 4, and 5.

Age Factors

The effects of chorion type on normal and abnormal developmental variation in monozygous twins.

To determine the effects, if any, of chorion type on normal and abnormal developmental variation in monozygous (MZ) twins, we tested the hypothesis that disparate environments that are related to chorion type have no effect on this variation. The parameters studied included congenital anomalies and dermatoglyphics (total ridge count and right-left asymmetry). With the exception of total ridge count, analyses of these data failed to reject the null hypothesis. Dichorionic MZ twins had a significantly greater within-pair variation than monochorionic MZ twins for total ridge count. In summary, then, these data could offer little support to prior speculation that monochorial placenta may present less favorable environments for feta development.

Analysis of Variance

Gene expression in Dictyostelium discoidium: mutually antagonistic roles of cyclic-AMP and ammonia.

Cyclic-AMP and ammonia have been previously identified as extracellular signals during Dictyostelium development. Both are important in controlling morphological movements and cyclic-AMP also in inducing gene expression. The work in tis paper is concerned with their effects on developmental gene expression. Cyclic-AMP was found to act as an inducer during the aggregative (as exemplified by phosphodiesterase) and the post-aggregative (glycogen phosphorylase, UDP-galactose polysaccharide transferase, prespore vacuoles and stalk cells) phases of gene expression. Ammonia inhibited the appearance of each of the above markers and antagonized the inductive effects of cyclic-AMP on them. This inhibition by ammonia of cyclic-AMP inducible gene expression may involve a step linking elevated intracellular cyclic-AMP levels to gene activation. It has been suggested that the specification of cells within the aggregate into the stalk and spore pathways of differentiation might be controlled by cyclic-AMP and ammonia. In this model for pattern formation cyclic-AMP would induce stalk cell differentiation and ammonia spore formation. The present results argue against this idea since cyclic-AMP induces and ammonia inhibits differentiation along both pathways. The function of these agents may rather be to coordinate the rates of biochemical differentiation of individual cells and link them to the overall morphological changes occurring during development.

3',5'-Cyclic-AMP Phosphodiesterases

The effect of LH on the fertilizability and developmental capacity of rat oocytes matured in vitro.

The effect of adding LH (10 microgram NIH-LH-B8/ml) to the medium in which oocytes were undergoing maturation in vitro was studied. The fertilizability of the oocytes was evaluated in the sterile oviduct of a unilaterally ovariectomized, mated recipient. Freshly ovulated oocytes, used as a control of the method, were fertilized at a rate of 72%. Only 14% of oocytes matured in culture (without LH) were penetrated by spermatozoa, and 11% were fertilized normally. Addition of LH to the medium increased these proportions to 43 and 33% respectively. Oocytes matured in the presence of LH were able to develop into apparently normal rats. It is concluded that, although oocytes can mature in vitro spontaneously, and that these matured oocytes can be fertilized, addition of LH increases the numbers 3-fold. LH therefore has a direct maturation-promoting action on the rat oocyte-cumulus complex in vitro.

Animals

Diversity at the HYP1 locus in potato cyst nematodes does not result from developmentally-programmed somatic mutations.

Most genetic diversity stems from spontaneous mutations, that is, errors in DNA repair or replication. But for dozens of organisms across the tree of life, mutations at specific loci are not spontaneous but developmentally programmed: effectively, some organisms edit their own DNA sequences. This is perhaps most common among pathogens and parasites, many of which use editing to diversify genes that produce important antigens. Plant-parasitic potato cyst nematodes are damaging agricultural pests that establish a lifelong feeding site inside the root of their host plant. We previously observed extensive diversity of rare alleles at HYP1, the most highly expressed gene that encodes a protein secreted by potato cyst nematodes during parasitism. Importantly, HYP1 alleles differ from each other by complex, in-frame rearrangements of short repeated sequence motifs within a single exon. Combining several lines of evidence, we previously hypothesized that potato cyst nematodes use developmentally-programmed mutations, or editing, to diversify HYP1 alleles in the soma. In the current work, we now test this hypothesis. We employ highly accurate long-read DNA sequencing of a simplified genetic system to identify potential rare edited alleles, we use a transgenic yeast system to describe large de novo mutations at HYP1, and we interpret our findings in light of key population genetic parameters as well as the genetic diversity surrounding HYP1 and across the genome.

Animals

Dysfunctional labor XII. Long-term effects on infant.

Developmental studies were done at 3 and 4 years of age in a series of 656 children and the results were correlated with the preceding labor pattern and the type of delivery. It was determined that there were significant adverse effects among offspring delivered by midforceps procedures or born following labors characterized by prolonged deceleration, secondary arrest of dilatation, or arrest of descent.

Child, Preschool

A neuropharmacological analysis of central nervous system catecholamine systems in development protein malnutrition.

Four experiments were performed to evaluate the effects of developmental protein deprivation on the behavioral response of adult rats to treatments known to affect central nervous system catecholamine systems. Results showed no group differences between protein malnourished and control animals in locomotor responsiveness to d- or l-amphetamine, recovery from behavioral asymmetry produced by a unilateral lesion of the substantia nigra, or in the development of response patterns indicative of denervation supersensitivity. However, a dose-dependent diminution in the ability of apomorphine to produce stereotyped behavior was noted in the malnourished group, suggesting that a class of brain dopamine receptors may be impaired or may have undergone homeostatic modification as a result of the undernutrition procedure.

Amphetamine

A behavior analysis approach to high-rate myoclonic seizures.

Epilepsy represents a serious medical and social problem. In the majority of cases, seizures are successfully managed by a variety of anticonvulsant medications, even though these drugs may potentiate significant physical and developmental side effects. A small group of studies to date have offered evidence that behavioral procedures can successfully manage some seizure disorders and are particularly desirable treatment choices when seizure disorders are intractable to drug management or when drug side effects are to be avoided. The present case adds to this small but growing group of studies in that it demonstrates the use of behavioral procedures in the analysis and treatment of high-rate myoclonic seizures. Seizures were evaluated on a hospital ward and in a controlled experimental setting. The data indicated a variable rate of seizures across days and activities and a reduction of seizure frequency in the controlled setting when time-out was made contingent on seizures. A program of contingent rest' was then applied on the hospital ward that demonstrated a reduction in myoclonic seizure frequency and the apparent prevention of several grand mal episodes. An observer calibration procedure showed high correspondence between behaviorally and physiologically recorded seizures. A discussion of issues in behavioral medicine research follows.

Behavior Therapy