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Behavioral consequences in rats from chronic exposure to 10 PPM halothane during early development.

Albino rats were chronically exposed for 40 hours a week to 10 ppm halothane in air during early development (conception to day 60), adult life (day 60 to day 135), or both. An unexposed group served as a control. Rats exposed during early development made 30 percent more errors than rats unexposed during this period when tested on a shock-motivated visual-discrimination task, or a food-motivated spatial-discrimination task. However, the relative rate of learning was the same for all groups. Exposure during early development also lowered the jump and flinch thresholds to electric footshock as compared to animals not so treated.

Age Factors↗

A view to regressive autism through home movies. Is early development really normal?

OBJECTIVE: To describe early development of children with regressive autism. METHOD: Home movies from the first 18 months of life of three groups of children with early onset autism (EOA), regressive autism (RA) and typical development (TD) were rated through the Grid for Attention in Infants in three age ranges. Different ANOVA and post hoc-tests were conducted on frequencies of behaviours. RESULTS: Differently from TD, for both RA and EOA non-social attention is higher than social attention across ages. While EOA is characterized by an early deficit in social attention, in RA social attention increases until the first birthday when its decrease proceeds at the same rate as the increase of non-social attention. CONCLUSION: We hypothesize that the intense interest towards objects can be the first sign of an atypical development also in RA; this distinguishing feature lead us to believe that regression, based on the assumption of a previous normal development, is only apparent.

Age Factors↗

Temporal and tissue-specific expression of kallikrein (Klk) genes and identification of a novel Klk messenger ribonucleic acid transcript during early development in the mouse.

The kallikreins are a multigene family of serine proteases that act on a diverse number of substrates, including several growth factors and extracellular matrix (ECM) glycoproteins and proteinases. Recently, this family has been implicated in the process of early development and embryo implantation. In this study, we used reverse transcription-polymerase chain reaction with gene-specific primers and Southern hybridization to elucidate the temporal and tissue-specific expression patterns of the mouse kallikreins Klk1, Klk3, Klk5, Klk9, and Klk21 during early development in the embryo, uterus, and decidua. We observed the expression of Klk1 (tissue kallikrein), Klk3 (gamma-nerve growth factor), Klk9 (epidermal growth factor-binding protein), and Klk21 in the early conceptus (until the 2-cell stage). Only Klk21 continued to be expressed in the blastocyst until Day 7.5 of pregnancy. Expression of Klk9 reappeared at Day 7.5 and was consistently detected until Day 11, the last day studied; Klk1 was again expressed in the embryo from Day 9.5, with decreased levels by Day 11. In contrast, in the uterus or decidua, there was no expression of Klk1 until Day 7.5, when mRNA transcripts were abundant; transcripts then decreased in the Day 9.5 and Day 11 uterus. Expression of Klk21 in the uterus and decidua displayed a similar pattern but was detected at much lower levels. Interestingly, a novel Klk21-like mRNA was also detected in uterine tissue samples but not in embryonic samples; Klk3, Klk5, and Klk9 were not consistently expressed in the uterus or decidua over this time. This is the first report of the expression of specific kallikreins during early development. The distinct gene- and tissue-specific expression patterns presented in this study, in conjunction with the well-characterized roles of kallikreins in regulation of protein activation, ECM degradation, and proliferative events, suggests the involvement of the kallikrein gene family during early development.

Amino Acid Sequence↗

Events at early development: are they associated with early word production and neurodevelopmental abilities at the preschool age?

BACKGROUND: Obstetrical and neonatal complications and/or an adverse parenting environment are risk factors for language impairment, but little is known about their effects on early word production (late talking). AIMS: To determine obstetrical and neonatal risk factors in children with delayed word production; to assess the influence of the parenting environment on word production; to determine whether the toddler's vocabulary competence is related to his/her social competence; to document the neurodevelopmental outcome at the late preschool age. STUDY DESIGN: Prospective follow-up study. Based on word production at 18 months, children were retrospectively classified into consistent or transient late talkers and controls. SUBJECTS: Full-term infants, N=30 (mean GA 40.3+/-1.1 weeks, mean birth weight 3577+/-267 g) were assessed at 18 and 24 months; and 5 years and 7 months. METHODS: Austrian Communicative Development Inventories; Bayley Scales of Infant Development; Griffiths Developmental Scales. OUTCOME MEASURES: Peabody Picture Vocabulary Test; Kaufman Assessment Battery for Children; Touwen's neurological examination. RESULTS AND CONCLUSIONS: Lower Apgar scores and the need for neonatal intensive care were associated with delayed word production. The parents' educational and vocational levels were lower in late talkers. Early vocabulary competence correlated with social competence. With regard to the prediction of lexical and cognitive outcomes, late talkers did not differ from controls. Minor neurological dysfunctions (MND) were seen in nearly half of the late talkers and indicate the necessity to follow these children into school age, when MND might become more obvious and literacy can be assessed.

Birth Weight↗

[Early development: some data about autism and language disorders].

INTRODUCTION: The early development of children who have been diagnosed as suffering from autism and children with specific language disorder (SLD) is still an area of research that receives little attention. There is a need for descriptive patterns of the early stages in the development of the two groups that foster the formation of reliable early diagnoses. Aims. In this study we attempt to determine the incidence of different symptoms in the first two years in the life of children who were later diagnosed as suffering from autism or SLD and to confirm or refute the data that suggests a pattern of onset of the disorder that differs from one group to the other. PATIENTS AND METHODS: We compare the data concerning the development of a sample made up of 42 children with autism and 41 children with SLD, which was carried out by means of a retrospective analysis of the information obtained from the families in the evaluation and diagnosis processes that were conducted in our centre. More specifically, we compare information about the following variables: family history, parents' age at the time of pregnancy, parents' profession, position at birth and incidence by sex, information about prenatal, perinatal and postnatal aspects, eating and sleeping problems, the presence or absence of signs of passivity, traces of alarm during the first year, age of the child when the first suspicions appeared, symptoms or difficulties that are described, data linked to medical neurological explorations carried out and data related to motor development. RESULTS: Although there are numerous similarities in many of the variables studied in both groups, it seems that the earlier onset of symptoms, passivity and the absence of pointing behaviour are more frequent in the group with autism than in children with SLD. The latter present a specific difficulty in language, tantrums and poorer motor competencies. CONCLUSIONS: At present there is no single symptom in early development that is exclusive to any of the disorders described above, although it is possible to determine some significant differences between the two groups. There is also a need to conduct more studies in the same line as this one that take into account the patterns of early development of other the autistic spectrum disorders.

Attention↗

Cloning of cDNAs encoding retinoic acid receptors RAR gamma 1, RAR gamma 2, and a new splicing variant, RAR gamma 3, from Aambystoma mexicanum and characterization of their expression during early development.

To analyze retinoic acid (RA) receptor (RAR) expression during early development in the urodele embryo, we have isolated cDNAs for four members of the axolotl (Ambystoma mexicanum) RAR family, namely RAR alpha (NR1B1), aRAR gamma 1 (NR1B3a), aRAR gamma 2 (NR1B3b), and a new splicing variant of aRAR gamma 2, aRAR gamma 3 (NR1B3c), which contains an insertion of five hydrophobic amino acids in the C-terminal region of the DNA binding domain. The temporal expression pattern of the RAR gamma isoforms was established by RT-PCR using total RNA from embryos of different stages. The expression of aRAR gamma 2 coincides with neurulation and is enhanced in the extremities of the embryo's anteroposterior axis. The aRAR gamma 3 is specifically expressed during gastrulation and early neurulation, whereas aRAR gamma 1 is expressed later during organogenesis. Global aRAR gamma 2 mRNA levels, as well as their spatio-temporal expression pattern in the neurula, were not affected by treatment with RA. These results show that several RARs are expressed in the axolotl embryo during early development, and reveal the existence of a new RAR gamma variant.

Alternative Splicing↗

Induced thermotolerance during early development of murine and bovine embryos.

During early development, elevated temperatures have deleterious effects on embryonic viability and development. The primary objective of the current study was to determine the ontogeny of induced thermotolerance during early murine embryonic development. Embryos were either retrieved from superovulated ICR female mice at the 2 cell and 4 cell stages and cultured thereafter or were retrieved from oviducts or uterine horns at the desired stage of development. Induction of thermotolerance was detected by evaluating viability and further development after embryos were exposed to homeothermic temperature (37 degrees C), mild heat shock (40 degrees C for 1 h), severe heat shock (42 degrees C for 1 h or 43 degrees C for 2 h), or mild heat shock followed by severe heat shock (to induce thermotolerance). Induction of thermotolerance was observed beginning at the 8 cell stage when embryos were developed in culture from the 2 cell to 4 cell stage. When embryos were developed in vivo (i.e., were retrieved from the reproductive tract at the desired stage of development), thermotolerance was not induced until the blastocyst stage of development. The induction of thermotolerance was dependent on serum supplementation since induction of thermotolerance was not observed when embryos were placed in medium without serum. Induced thermotolerance could also be demonstrated in bovine blastocysts. In conclusion, embryos acquire the ability to undergo thermotolerance as they progress through development. The timing of processes leading to acquisition of thermotolerance can, however, be hastened by exposure of embryos to in vitro conditions.

Adaptation, Physiological↗

Changes in cardiac energy metabolism during early development of female SHR.

We investigated effects of hypertension and early development on myocardial energy metabolism as reflected by maximal enzyme activities, glucose transporter content, and endogenous substrates in female Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Left ventricular hypertrophy and systolic hypertension were evident in SHR at 6 weeks of age and these differences increased at 14 and 22 weeks of age. 3-Hydroxyacyl-CoA dehydrogenase (HOAD) activity in the left ventricle was 18% lower in 6-week-old rats than both 14- and 22-week-old rats, but not different between WKY rats and SHR. Hexokinase activity was 15% lower in 6-week-old SHR than WKY rats and decreased progressively with age in both strains. Glucose transporter (GLUT) 1 content was nearly twofold greater in 6-week-old rats than both 14- and 22-week-old rats. We found no difference in citrate synthase activity or GLUT4 content among groups. Glycogen concentration was 44% lower in SHR than WKY rats, whereas triglyceride was slightly (16%) higher in SHR than WKY rats. Older animals had higher levels both glycogen and triglyceride than younger animals. We conclude that the left ventricle of both SHR and WKY rats may change from predominantly glucose to fatty acid oxidation for energy production during early development.

3-Hydroxyacyl CoA Dehydrogenases↗

Genesis and fate of the perireticular thalamic nucleus during early development.

A striking feature of the internal capsule during early development is that it is full of small neurones. Later, this group of neurones, called the perireticular thalamic nucleus, appears to have reduced in size, and only a few scattered cells are seen. In an effort to understand better the developmental history of the perireticular nucleus this study examines: i) the period of cell generation in the nucleus, ii) the magnitude of cell loss in the nucleus, and iii) the subsequent fate of cells in the nucleus during development. The perireticular cells are generated very early in development, being among the first generated in the thalamus (rats: E13-14; cats: E21-30). In rats, the first perireticular cells are generated at about the same developmental stage as the first subplate cells, which are among the first generated cells of the cortex: in cats, the first perireticular cells are generated well before those in the subplate (E24-30). In rats, the number of perireticular cells during developmental peaks at P5 (approximately 30,000) and then declines sharply (approximately 98%) by P15 (approximately 750), when adult-like patterns are seen. This dramatic loss of perireticular cells is due to both cell death and a migration of cells into the adjacent globus pallidus. The majority of the perireticular cells which migrate into the globus pallidus, however, are likely to die also. The presence of pyknotic profiles (indicators of dying cells) in the rat perireticular nucleus points to cell death as a contributor to the reduction in cell number during development. In this study, a period of relatively high pyknotic profile incidence (number of pyknotic cells per 1,000 "living" cells) is recorded in the perireticular nucleus over a 5 day period, from P2 to P7 (13.5-15.5). Similar values and patterns are recorded in the reticular nucleus and globus pallidus, except that in these structures, a period of relatively high pyknotic profile incidence (15-20) occurs over a shorter period (3 days; P2-5). Previous studies have suggested that some perireticular cells migrate into and settle within the adjacent globus pallidus. This study, with the use of long-term survivals after tracer injections in rats, shows that none (or very few) of these perireticular cells which migrate into the globus pallidus survive into more mature postnatal stages. Tracer (biotinylated dextran) was injected into the sensory nuclei of the dorsal thalamus at early stages (P7) and the rats were allowed to survive for either a day thereafter (to P8) or until well after the period of cell death was complete (to P16 or P21). In the short-term survivals (to P8), there are many dextran-labelled cells seen in the globus pallidus and in the perireticular nucleus. In the long-term survivals (to P16 or P21), by contrast, there are no dextran-labelled cells apparent in the globus pallidus or in the perireticular nucleus. It is likely that these cells in the globus pallidus, as with those in the perireticular nucleus, undergo cell death during development.

Animals↗

Changes in whole-body thyroxine and triiodothyronine concentrations and total content during early development and metamorphosis of the toad Bufo marinus.

This study describes changes in the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the toad Bufo marinus during development from early embryonic stages through metamorphosis. Both the total content and concentrations of T4 and T3 were calculated to assess whether changes in these hormones might derive from changes in body mass or water content rather than from changes in hormone production or metabolism. Three clutches of eggs were collected from ponds during the day following fertilization and raised through metamorphosis. Samples of five or more individuals were collected daily for thyroid hormone measurement and body mass determination. Hormones were measured by radioimmunoassay utilizing miniature Sephadex columns after whole-body extraction. Both T4 and T3 were elevated at gastrulation (1 day after fertilization), but declined to low levels within the first week. This is the first report that thyroid hormones occur in anuran embryos prior to thyroid differentiation. This suggests that thyroid hormones are deposited in the anuran egg during oogenesis in a manner similar to that described for teleost fishes and the domestic hen. Levels of T3 and T4 began to rise at about 2 weeks after fertilization (stage 31; staged according to Limbaugh and Volpe, 1957) and peaked during early metamorphic climax (stage 43). This pattern coincides well with the notion that thyroid hormones are central regulators of metamorphosis in B. marinus as has been shown in other amphibians examined to date. Generally, both total content and concentration of the two hormones varied in parallel. Overall, whereas individual mass and water changes may affect the magnitude of hormone changes, they appear to have little input into their direction.

Animals↗

Early development and unstable genes in schizophrenia: preliminary results.

BACKGROUND: Trinucleotide repeats have been associated with schizophrenia, but the evidence, based on cross-sectional clinical information, is equivocal. AIMS: To examine the relationship between genomic CAG/CTG repeat size and premorbid development in schizophrenia. METHOD: Early development and premorbid functioning of 22 patients with DSM-IV diagnosis of schizophrenia were assessed by parental interviews. Repeat expansion detection (RED) technique was used to measure genomic CAG/CTG repeat size, and PCR for CAG repeat size at the ERDA-1 and CTG 18.1 loci. RESULTS: There was an inverse association between CAG/CTG size and perinatal complications. Patients with speech and motor developmental delay had larger repeats. The results were not due to expansion in the ERDA-1 and CTG 18.1 genes. CONCLUSIONS: CAG/CTG repeat expansion is associated with speech and motor developmental delay in schizophrenia. We propose that the developmental model may be useful for research into the genetics of schizophrenia.

Adult↗

A comparison of the early development of ischaemic damage following permanent middle cerebral artery occlusion in rats as assessed using magnetic resonance imaging and histology.

Recent developments in diffusion-weighted imaging (DWI) have enabled the pathological changes that occur during cerebral ischaemia to be studied. The present studies utilised DWI to investigate the development of early ischaemic changes following permanent middle cerebral artery (MCA) occlusion in the rat, which represents a model of stroke. An increased DWI signal was seen in the region of the occluded MCA and this was detectable as early as 1 h postocclusion. DWI images were obtained at nine stereotactic levels throughout the brain, providing a quantifiable measure of the volume of increased signal intensity in each animal. At 1 h post-MCA occlusion the hyperintense areas were seen in the frontoparietal cortex and lateral caudate nucleus; these areas represent the core of the infarct and no protection is seen with any compounds in these areas. There was a progressive increase in the area of hyperintensity up to 4 h post-MCA occlusion, and at this time point the hyper-intensity was seen in the dorsolateral cortex and caudate nucleus. At 4 h post-MCA occlusion there was a significant correlation between the volume of hemispheric and cortical ischaemic damage measured using DWI and histology. Thus, it appears that the increased DWI signal seen during the early time points after MCA occlusion was demarcating tissue that was destined for infarction. The area beyond the hyperintense region at 1 h represents the so-called "penumbral" region, because with increasing time (post-MCA occlusion) this area became incorporated into the infarct. There was also a slight increase in infarct size between 4 and 24 h, when assessed using DWI or histology, although two groups of animals were being compared, as opposed to the time-course study, in which just one group of animals was used. At 24 h post-MCA occlusion there was a good correlation between DWI, histology, and conventional T2 weighted imaging. There was no further increase in size of the infarct between 24 h and 7 days as assessed using histology and T2-weighted imaging. DWI could not be used to quantify infarct volume at 7 days because there was no uniform signal in the damaged area. At 7 days the area of infarction actually appeared to be darker in the diffusion-weighted images. The hyperintensity seen in diffusion-weighted images appears to decrease some time between 24 h and 7 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

AsgD, a new two-component regulator required for A-signalling and nutrient sensing during early development of Myxococcus xanthus.

Myxococcus xanthus has a complex life cycle that includes fruiting body formation. One of the first stages in development has been called A-signalling. The asg (A-signalling) mutants have been proposed to be deficient in producing A-signal, resulting in development arresting at an early stage. In this paper, we report the identification of a new asg locus asgD. This locus appears to be involved in both environmental sensing and intercellular signalling. Expression of asgD was undetected during vegetative growth, but increased dramatically within 1 h of starvation. The AsgD protein is predicted to contain 773 amino acids and to be part of a two-component regulatory system because it has a receiver domain located at the N-terminus and a histidine protein kinase at the C-terminus. An asgD null mutant was defective in fruiting body formation and sporulation on CF medium. However, the defects of the mutant were complemented extracellularly when cells were mixed with wild-type strains or with bsgA, csgA, dsgA or esgA mutants, but were not complemented extracellularly by asgA, asgB or asgC mutants. In addition, the mutant was rescued by a subset of A-factor amino acids. Surprisingly, when the mutant was plated on stringent starvation medium rather than CF, cells were able to form fruiting bodies. Thus, it appears that AsgD is directly or indirectly involved in sensing nutritionally limiting conditions. The discovery of the asgD locus provides an important sensory transduction component of early development in M. xanthus.

Amino Acid Sequence↗

Early development of the forebrain and midbrain: a longitudinal ultrasound study from 7 to 12 weeks of gestation.

The purpose of this longitudinal study was to describe embryonic development in vivo. Twenty-nine healthy pregnant women were examined five times with transvaginal ultrasound between 7 and 12 weeks of gestation. Brain structures such as the hemispheres, the choroid plexus of the lateral ventricles, the diencephalon, and the mesencephalon were identified and, if possible, measured. It was possible to identify the cavities of the hemispheres, the diencephalon and the mesencephalon during week 7. The choroid plexus of the lateral ventricles became visible during week 8. The growth of the length, width and height of the hemispheres and the choroid plexus of the lateral ventricles was curvilinear, that of the mesencephalon and diencephalon was linear except for the width of the diencephalon. The width of the diencephalon, the future third ventricle, was 1.1 mm during week 7. It decreased to 0.8 mm at 12 weeks. Apart from the rhombencephalon, the cavity of the diencephalon was the large dominating brain structure during embryonic development. In early fetal life the cerebral hemispheres took over this dominance. The study was in full agreement with descriptions in the embryological literature, both concerning the anatomical features and their chronological formation.

Journal Article↗

Effects of rRNA gene copy number and nucleolar variation on early development: inhibition of gastrulation in rDNA-deficient chick embryos.

Because of their structural and catalytic functions during protein synthesis, the 18S, 5.8S, and 28S ribosomal RNAs (rRNAs) are essential for the support of differentiation, development, and growth. The genes encoding these RNAs are present in high copy number in all eukaryotes. Although there is evidence for the existence of variation for rRNA gene copy number within higher vertebrate species, there is little knowledge concerning the effects of such variation, especially reductions, on development and viability of homeothermic vertebrates. The main objective of this study was to determine the developmental potential of chick embryos containing defined deficiencies for rRNA gene copy number in order to assess the contribution of rDNA cluster size variation to embryonic mortality in homeothermic vertebrates. This was achieved by studying a strain of chickens containing nucleolar size polymorphisms that reflect rDNA cluster size polymorphisms. Embryos exhibiting a nucleolar phenotype of one large and one very small nucleolus (Pp) are heterozygous for a reduced rDNA cluster (+/p1) and were shown in the present study to contain about 66% of the complement of rRNA genes in normal individuals (+/+) that show two large equal-sized nucleoli (PP). The +/p1 embryos were found to develop and grow normally. Embryos exhibiting a nucleolar phenotype of two very small nucleoli (pp) are homozygous for the rDNA-deficient cluster (p1/p1) and contained about 45% of the normal rDNA complement of genes. These p1/p1 embryos were arrested in their development during early gastrulation. They exhibited a characteristic morphology consisting of a dorsal invagination that was strikingly different from the primitive streak formed in +/+ and +/p1 individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Ancient evidence for the origin and early development of chronobiology and biometeorology in Bulgaria.

Chronobiology and biometeorology have developed since ancient times of world history (China, Greece, etc.). Different authors have studied the origin and early development of medicine and related sciences in Bulgaria (Apostolov et al 1982, Georgiev 1987, etc.). They have reported that early medical postulates have incorporated the notion of temporal patterns of health and disease and their dependence on the environment. However, these authors have neither emphasized the above relationships nor considered them possible origins of both chronobiology and biometeorology in Bulgaria. The aim was to present evidence for the possible origin and early development of chronobiological and biometeorological perceptions in ancient Bulgaria. Different sources from ancient Bulgarian history were searched and analyzed. Ancient sources from Bulgarian history, relevant to the aim of this study, were reviewed. The evidence on chronobiological and biometeorological understandings in ancient times was obtained from the "Protobulgarian Calendar", Preslav's Rosette, etc. Here, only the most important of Protobulgarian, Thracian and Slavonic sources were presented. It was concluded that chronobiology and biometeorology had also their origin and early development in ancient Bulgarian times.

Bulgaria↗

RLIP mediates downstream signalling from RalB to the actin cytoskeleton during Xenopus early development.

The Ras protein activates at least three different pathways during early development. Two of them regulate mesodermal gene expression and the third is thought to participate in the control of actin cytoskeleton dynamics via the Ral protein. From a yeast two-hybrid screen of a Xenopus maternal cDNA library, we identified the Xenopus orthologue of the Ral interacting protein (RLIP, RIP1 or RalBP1), a putative effector of small G protein Ral. Previously, we observed that a constitutively activated form of Ral GTPase (XralB G23V) induced bleaching of the animal hemisphere and disruption of the cortical actin cytoskeleton. To demonstrate that RLIP is the effector of RalB in early development, we show that the artificial targeting of RLIP to the membrane induces a similar phenotype to that of activated RalB. We show that overexpression of the Ral binding domain (RalBD) of XRLIP, which binds to the effector site of Ral, acts in competition with the endogenous effector of Ral and protects against the destructive effect of XralB G23V on the actin cytoskeleton. In contrast, the XRLIP has a synergistic effect on the activated form of XralB, which is dependent on the RalBD of RLIP. We provide evidence for the involvement of RLIP by way of its RalBD on the dynamics of the actin cytoskeleton and propose that signalling from Ral to RLIP is required for gastrulation.

ATP-Binding Cassette Transporters↗