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Vegetable and synthetic tannins induce hormesis/toxicity in sea urchin early development and in algal growth.

Mimosa tannin and phenol-based synthetic tannin (syntan) were tested for toxicity to sea urchin (Paracentrotus lividus and Sphaerechinus granularis) early development and to marine algal growth (Dunaliella tertiolecta). Sea urchin embryogenesis was affected by vegetable tannin and syntan water extracts (VTWE and STWE) at levels >or=1mg/L. Developmental defects were significantly decreased at VTWE and STWE levels of 0.1 and 0.3mg/L when control cultures displayed suboptimal quality, i.e. <70% "viable" (normal or retarded) larvae. Fertilization success of sea urchin sperm was increased up to 0.3 mg/L STWE or VTWE, then was inhibited by increasing tannin levels (1-30 mg/L). Offspring abnormalities, following sperm exposure to VTWE or STWE, showed the same shift from hormesis to toxicity. Cell growth bioassays in D. tertiolecta exposed to VTWE or STWE (0.1-30 mg/L) showed non-linear concentration-related toxicity. Novel criteria are suggested in defining control quality that should reveal hormetic effects.

Animals↗

Pre-B and pre-T-cell receptors: conservation of strategies in regulating early lymphocyte development.

Early lymphocyte development is characterized by the regulated activity of the V(D)J recombinase and the positive and negative selection of cells based on the structure of their assembled antigen receptor genes. Developing B and T cells use remarkably similar signaling complexes, the pre-B-cell receptor (pre-BCR) and the pre-T-cell receptor (pre-TCR) respectively, to monitor the progress of antigen receptor gene assembly This review will compare and contrast the regulation and activities of the pre-BCR and pre-TCR signaling complexes. In addition, we will consider a number of critical but as yet unanswered questions prompted by such an analysis.

Animals↗

Early orofacial development.

Early orofacial development is a period of very rapid allometric growth and specialization of tissue. During the first three years of life, the brain achieves approximately 90% of its growth and the face reaches almost 65% of its adult size. Between birth and three years of age the oral cavity changes form and function, replacing gum pads with a dentition composed of twenty primary teeth. By three years of age, all succedaneous teeth are developing as well as the first permanent molars. Involvement with neonates and infants by neonatologists, pediatricians, and pediatric dentists begs a better appreciation of this rapidly changing period.

Child, Preschool↗

Early development of Ig-secreting cells in young of germ-free BALB/c mice fed a chemically defined ultrafiltered diet.

The influence of antigenic stimulation on the early development of the "spontaneously" occurring ("background") IgM-, IgG-, and IgA-secreting cells has been studied in mice. To evaluate the effect of such exogenous stimulation by an evolving microbial microflora, the young of BALB/c mice that were kept under germ-free conditions and fed a low molecular weight chemically defined synthetic diet (GF-CD) were compared with the young of conventional BALB/c mice fed natural ingredients (CV-NI). The young were first suckling maternal milk and between Days 15 and 18 changed to the same diet as their parents. Background Ig-secreting cells in the spleen were enumerated in the protein A plaque assay. The specificity repertoire of the IgM-secreting cells was determined with plaque assays specific for sheep red blood cells (SRBC) that were haptenized with different concentrations of nitroiodophenyl (NIP), 4-hydroxy-3.5-dinitrophenyl (NNP), and 2,4,6-trinitrophenyl (TNP). The results show that during the first few weeks of life the numbers of background IgM-, IgG-, and IgA-secreting cells in the spleen develop faster in CV-NI mice than in GF-CD mice. At 4 weeks of age equal numbers of IgM- and IgG-secreting cells were found in both groups of mice, but the number of IgA-secreting cells remained reduced in GF-CD mice during the whole period of observation. The frequencies of IgM-secreting cells specific for the differently haptenized SRBC were the same in both groups of mice during the observation period of 10 weeks. This suggests that the ontogenetic appearance of IgM-, IgG-, and IgA-secreting cells in the spleen, and the specificity repertoire of the IgM-secreting cells, as far as was tested in our panel, is independent of exogenous antigenic and/or mitogenic stimulation. However, during neonatal development the rate of development of the background Ig synthesis is enhanced by environmental antigenic stimulation.

Animal Feed↗

Cyclic assembly-disassembly of cortical microtubules during maturation and early development of starfish oocytes.

An extensive array of cortical microtubules in oocytes of the starfish Pisaster ochraceus undergoes multiple cycles of disappearance and reappearance during maturation and early development. These events were studied in isolated fragments of the oocyte cortex stained with antitubulin antibodies for indirect immunofluorescence. The meshwork of long microtubules is present in the cortex (a) of immature oocytes, i.e., before treatment with the maturation-inducing hormone 1-methyladenine, (b) for 10-20 min after treatment with 1-methyladenine, (c) after formation of the second polar body (in reduced numbers in unfertilized oocytes), and (d) in the intermitotic period between first and second cleavage divisions. The array of cortical microtubules is absent in oocytes (a) undergoing germinal vesicle breakdown, (b) during the two meiotic divisions (polar body divisions), and (c) during mitosis of the first and, perhaps, subsequent cleavage divisions. The cycle of assembly-disassembly of cortical microtubules is synchronized to the cycle of nuclear envelope breakdown and reformation and to the mitotic cycle; specifically, cortical microtubules are present when a nucleus is intact (germinal vesicle, female pronucleus, zygote nucleus, blastomere nucleus) and are absent whenever a meiotic or mitotic spindle is present. These findings are discussed in terms of microtubule organizing centers in eggs, possible triggers for microtubule assembly and disassembly, the eccentric location of the germinal vesicle, and the regulation of oocyte maturation and cell division.

Adenine↗

[A modified method of nuclear transfer for investigating early development of mouse embryos reconstructed with cumulus cell nuclei].

OBJECTIVE: To establish a fast, simple, efficient and minimally invasive method for nuclear transfer (NT) to study the early development of mouse embryos reconstructed with cumulus cell nuclei in vitro. METHODS: With a sharp-tipped enucleation needle, an incision approximately 25 mm in length was made in the zona pellucida of a rat oocyte, through which the first polar body was removed and the metaphase II chromosome-spindle complex was gently aspirated along with a minimal volume of the cytoplasm by slightly pressing and vacuum aspiration of the oocyte. A cumulus cell nuclei from C57BL/6j mouse, 10-12 mm in diameter, was inserted into the perivitelline space of the enucleated oocyte. The fusion of the donor-recipient pair was induced by electrofusion and nuclear formation was observed. The development of 2-cell, 4- to 8-cell and morula-stage embryos was observed after a 72-hour culture of the reconstructed oocytes in vitro. RESULTS: The modified NT method enabled one-step removal of the whole nucleus from the oocyte with confirmed reliability of complete nuclear removal by Hoechst 33342 staining of the removed nuclei examined under UV light. The process of enucleation took an average time of 15 s, and the survival rate of the enucleated oocytes reached 95%. The success rate of 76.7% was achieved for cumulus cell nucleus insertion into the zona pellucida of the enucleated oocytes and pronucleus formation occurred in 62.2% of the reconstructed oocytes with nuclear transfer. After 72 h of culture in vitro of the reconstructed oocytes in CZB medium, the percentage of embryos that developed into 2-cell, 4- to 8-cell and morula (more than 16 cells) stages were 57.5%, 39.1% and 27.6%, respectively. Microsatellite sequences (D7Mit22 and D4Mit204) were amplified from the DNA of the reconstructed embryos for identifying their origin, which was proved to be C57BL/6j mouse. CONCLUSION: The modified NT method is simple, minimally invasive, efficient and practicable to reconstruct mouse embryos with somatic cell nuclei.

Animals↗

Gene expression profiling of gilthead sea bream during early development and detection of stress-related genes by the application of cDNA microarray technology.

Large-scale gene expression studies were performed for one of the main European aquaculture species, the gilthead sea bream Sparus auratus L. For this purpose, a cDNA microarray containing 10,176 clones from a cDNA library of mixed embryonic and larval stages was constructed. In addition to its importance for aquaculture, the taxonomic position and the relatively small genome size of sea bream makes it a prospective model for evolutionary biology and comparative genomics. However, so far, no large-scale analysis of gene expression exists for this species. In the present study, gene expression was analyzed in gilthead sea bream during early development, a significant period in the determination of quantitative traits and therefore of considerable interest for aquaculture. Synexpression groups expressed primarily early and late in development were determined and were composed of both known and novel genes. Furthermore, it was possible to identify stress response genes induced by cortisol injections using the cDNA microarray generated. The creation of gene expression profiles for sea bream by microarray hybridization will accelerate identification of candidate genes involved in multifactorial traits and certain regulatory pathways and will also contribute to a better understanding of the genetic background of fish physiology, which may help to improve aquaculture practices.

Animals↗

Early development (5 to 48 months) in Williams syndrome. A study of 14 children.

At what age do children with Williams syndrome (WS) achieve major developmental milestones? Is their early development harmonious or are some of the typical discrepancies described in older children already noticeable? To address these questions we analysed information gathered over a five year period on 14 children with WS. Each child was evaluated at least twice between the ages of 5 and 48 months, using the Bayley Scales of Infant Development and during more informal observation sessions. Parents and professionals were also interviewed. This analysis provided us with an outline for "developmental norms" for children with WS and allowed us to conclude that, even before the age of 4 years, children with WS display a typical profile in their abilities. Expressive language skills are less delayed in contrast to the important delay in language comprehension and fine motor skills.

Age Factors↗

Early development of therapeutic biologics--pharmacokinetics.

Modern biologics are biotechnology-derived pharmaceuticals. They are mostly used for diagnosis, prevention and treatment of serious and chronic diseases. Today, therapeutic biologics range from traditional biologics like blood and blood components, fractionated blood products, and antitoxins to modern biologics such as monoclonal antibodies, cytokines (e.g. interferon, interleukine), tissue growth factors, vaccines directed against non-infectious disease targets, and gene transfer products. Chemical as well as pre-clinical development are major challenges for biologics due to their different physicochemical properties (mostly protein structure) compared to small molecules. They demonstrate much more complex pharmacokinetic behaviour, which strongly influences their pre-clinical testing strategy. Biologics are often highly species-specific in action and immunogenic in test animal species and humans. Immunogenicity of therapeutic biologics may influence their pharmacokinetic behaviour as well as pharmacodynamics and toxicity. Biologics are frequently regulated by different procedures compared to small molecules. New guidances are evolving which reflect the rapid development of new technologies in this field. Bioanalytical method development and validation is a prerequisite not exclusively for pharmacokinetic studies but for the whole pre-clinical and clinical development. Due to their unique properties, different kinds of bioanalytical assays (mass assays, activity assays, immunogenicity assays) are necessary in early development of biologics.

Animals↗

Latrunculin inhibits the microfilament-mediated processes during fertilization, cleavage and early development in sea urchins and mice.

Latrunculin A, a marine toxin from a Red Sea sponge, is a potent inhibitor of the microfilament-mediated processes of fertilization and early development in sea urchins and in mice. Sperm from sea urchins, but not those from Limulus or mice, were affected by latrunculin, and fertilization in both sea urchins and in mice was arrested but at different stages. Sea urchin sperm treated with 2.6 microM latrunculin are unable to assemble acrosomal processes and their ability to fertilize eggs is impaired. The unwinding of the Limulus sperm acrosomal process occurs in the presence of latrunculin. Treated mouse sperm are able to fertilize mouse oocytes in vitro, suggesting that microfilaments may not be required in this mammalian sperm. In sea urchin eggs, sperm incorporation, microvillar elongation and cytokinesis are inhibited. Microtubule-mediated motility occurs normally. 20 nM latrunculin prevents the morphogenetic movements during gastrulation. It reduces the viscosity of actin gels from sea urchin egg homogenates. In unfertilized mouse oocytes, it prevents the colcemid-induced dispersion of the meiotic chromosomes; accumulations of cortical actin are noted adjacent to the scattered chromosomes. Sperm incorporation during mouse fertilization in vitro is unaffected suggesting that sperm entry may occur independent of microfilament activity in mammals. However, the apposition of the pronuclei at the center of the egg cytoplasm does not occur, providing evidence that cytoplasmic microfilaments may be required for the motions leading to pronuclear union during mouse fertilization. It inhibits the second polar body formation and cytokinesis. These results indicate that latrunculin is a potent inhibitor of microfilament-mediated processes in sperm, eggs and embryos, and that it may prove to be a powerful new drug for exploring the cellular behavior of microfilaments in the maintenance of cell shape and during motility.

Acrosome↗

Potential role of Fc gamma R in early development of murine lymphoid cells: evidence for functional interaction between Fc gamma R on pre-thymocytes and an alternative, non-Ig ligand on thymic stromal cells.

During early development of the murine fetal thymus a fraction of Thy+ thymocytes express Fc gamma receptors. Concurrently, a small fraction of Thy- CD44- thymocytes bind recombinant soluble Fc gamma R. These findings suggested the possibility that Fc gamma R+ pre-T cells interact with a non-Ig ligand present on fetal thymic stromal cells. Evidence in support of this concept was the finding that experimental manipulation of this putative receptor-ligand pair by anti-receptor antibody or recombinant soluble Fc gamma R influenced the developmental pattern of alpha/beta-TCR+ T cells. The restricted expression of CD16 on some pre-B cells raises the possibility that an Fc gamma R-dependent step may play a similar role in B-cell development.

Animals↗

Type I and type II cytokeratin cDNAs from the zebrafish (Danio rerio) and expression patterns during early development.

Full-length cDNAs of a type I (zfCKI), and a type II (zfCKII) cytokeratin from the adult zebrafish, Danio rerio, were characterized and their expressions studied during early development and in the adult. The 1,426 bp long zfCKI cDNA encodes a 46.7 kD protein, whereas the 2,398 bp zfCKII cDNA encodes a protein of 58.6 kD. zfCKI and zfCKII each have a central rod domain that is characteristic of intermediate filaments and which share 73%-91% and 87%-93% similarity, respectively, with those of type I and type II cytokeratins from zebrafish, goldfish, and the rainbow trout. The central rod domains of zfCKI and zfCKII also contain the IF signature motif, IA[T/E]YR[K/R]LL[D/E]. zfCKI has, in addition, a leucine-zipper motif at a.a. residues 184-205 and 191-212. Both zfCKI and zfCKII mRNAs are expressed in the epidermis of the zebrafish. zfCKII mRNA was both maternally inherited and zygotically transcribed and was detected from the one-cell embryo to adult stages. zfCKII was also strongly expressed specifically during the 20-somites, protruding-mouth, and adult stages. In the adult, it was uniformly expressed in the skin, fins and scale epidermis. In contrast, zfCKI mRNA was undetectable in the oocyte but was zygotically transcribed from the epiboly stage onwards. Its expression in the skin was strong only up to the swimming larva stage and was weak and patchy in the adult. Both zfCKI and zfCKII were expressed in the neurons and glial cells of the brain and spinal cord. In the adult eye, zfCKI and zfCKII were expressed in the ganglion cell layer and the retina, but zfCKII was also strongly expressed in the cornea as well as in chondrocytes in the skull.

Aging↗

Protein synthesis in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension.

The purpose of this study was to determine the temporal alterations in protein synthesis and accumulation in the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension and to correlate these results with the pattern of development of polycythemia, right ventricular hypertrophy (RVH) and increased right ventricular pressure (RVP). In vitro synthesis of collagen and noncollagen protein was determined in the pulmonary trunks (PT) of rats exposed to chronic hypobaric hypoxia (0.5 atm/380 Torr) for 3, 7, 10, 14 or 21 days and in respective control groups of pair-fed normoxic rats. In vitro collagen synthesis was increased 1,150% (p less than 0.01) in PT from rats exposed to hypoxia for 3 days compared to PT from normoxic rats. When duration of hypoxic exposure increased, the percentage increase in collagen synthesis in PT from hypoxic vs. normoxic rats declined but remained significantly elevated (340%, p less than 0.005) after 21 days. Comparison of in vitro synthesis of noncollagen protein demonstrated a similar pattern of alteration with increasing hypoxic exposure. Synthesis of noncollagen protein was increased 750% in PT from hypoxic rats compared to normoxic controls at 7 days (p less than 0.0005) and decreased in parallel with collagen synthesis until 21 days when the difference in mean noncollagen protein synthesis was no longer statistically significant. In contrast, the accumulation of protein in vitro during hypoxic exposure, as determined from measurement of absolute protein and hydroxyproline content, demonstrated a pattern of continued increase with hypoxic exposure. Absolute protein content (microgram protein/vessel) was increased 330% in PT from hypoxic rats after 3 days compared to controls (p less than 0.005). By 21 days, mean absolute protein content of hypoxic PT was increased 500% compared to controls (p less than 0.0005). Absolute hydroxyproline content became significantly elevated in PT from hypoxic rats compared to controls after 7 days (123%, p less than 0.005 and the difference increased to 135% at 21 days (p less than 0.025). From comparison of these results with the pattern of changes in established indicators of pulmonary hypertension, herein reproduced, it is deduced that increased protein synthesis is a very early response of the pulmonary trunk to the stimulus of increased arterial blood pressure. Protein synthesis then declines while accumulation increases in a manner which suggests that the newly synthesized protein alters the response of the vessel to the continuing stimulus. It is proposed that increased accumulation of protein, particularly collagen, decreases the distension of the vessel wall caused by increased transmural pressure.

Animals↗

Functions of maternal mRNA in early development.

In this review, the types of mRNAs found in oocytes and eggs of several animal species, particularly Drosophila, marine invertebrates, frogs, and mice, are described. The roles that proteins derived from these mRNAs play in early development are discussed, and connections between maternally inherited information and embryonic pattern are sought. Comparisons between genetically identified maternally expressed genes in Drosophila and maternal mRNAs biochemically characterized in other species are made when possible. Regulation of the meiotic and early embryonic cell cycles is reviewed, and translational control of maternal mRNA following maturation and/or fertilization is discussed with regard to specific mRNAs.

Animals↗

Hedgehog pathway gene expression during early development of the molar tooth root in the mouse.

Sonic hedgehog is a secreted protein important for many aspects of embryonic development. In the developing tooth, Shh expression is restricted to the epithelial compartment and plays an important role during both initiation and subsequent coronal morphogenesis. We have investigated the expression of Shh and constituent members of the signalling pathway during early development of the molar tooth root in the mouse and find the presence of transcripts in Hertwig's epithelial root sheath. These epithelial cells of the root sheath and the surrounding apical mesenchyme of the dental papilla and follicle also expressed the Shh receptor Ptc1, agonist Smo and Gli downstream transcriptional effectors; however, this response occurred over short range. In contrast, the Shh antagonists Hip1 and Gas1 were both expressed at a distance from these responding cells, in more peripheral regions of the developing root. Transcripts of the Skn acyl transferase lacked specific expression in early root structures.

Animals↗

On the evolution of early development in the Nematoda.

The phylum Nematoda serves as an excellent model system for exploring how development evolves, using a comparative approach to developmental genetics. More than 100 laboratories are studying developmental mechanisms in the nematode Caenorhabditis elegans, and many of the methods that have been developed for C. elegans can be applied to other nematodes. This review summarizes what is known so far about steps in early development that have evolved in the nematodes, and proposes potential experiments that could make use of these data to further our understanding of how development evolves. The promise of such a comparative approach to developmental genetics is to fill a wide gap in our understanding of evolution--a gap spanning from mutations in developmental genes through to their phenotypic results, on which natural selection may act.

Animals↗

Cholesterol biosynthesis by the cornea. Comparison of rates of sterol synthesis with accumulation during early development.

The origin of the cholesterol needed by the cornea for growth and cell turnover was addressed by comparing absolute rates of sterol synthesis with rates of sterol accumulation during early development of the rabbit. Linearity of incorporation of 3H2O and [14C]mevalonate into digitonin-precipitable sterols with time of incubation in vitro and a lack of accumulation of 14C in intermediates of sterol biosynthesis indicated that tritiated water can validly be used to measure rates of sterol synthesis by the cornea. The rate of sterol synthesis per unit weight of rabbit cornea was constant between 14 and 60 days of age at an average 1.03 nmol of 3H of 3H2O incorporated/mg dry cornea per 8 h. Essentially all of the synthesized cholesterol and most of the cholesterol mass was present in corneal epithelium. The cumulative sterol synthesized over the 46-day period studied exceeded the observed rate of cholesterol accumulation by sixfold. Cholesterol synthesized in excess of the growth requirement was likely used to support turnover of the epithelium which was estimated at 9 days. Removal of cholesterol from the cornea by excretion into tear fluid and clearance by high density lipoproteins are also considered.

Animals↗

The early development of the fetal kidney-an in utero sonographic evaluation between 13 and 22 weeks' gestation.

OBJECTIVES: To establish a nomogram for early fetal kidney development during early gestation. METHODS: The study is a prospective, cross-sectional evaluation of 275 male and female fetuses between 13 and 22 weeks in normal singleton pregnancies. Measurements of fetal kidney length were performed by high resolution transvaginal ultrasonography between 14 and 17 weeks' gestation, and by transabdominal ultrasonography beyond 18 weeks' gestation. RESULTS: Adequate kidney length measurements were obtained in all 275 normal fetuses as well as in six fetuses with urinary tract anomalies. Kidney length as a function of gestational age was expressed by the regression equation: (square root) kidney length (mm) = -11.66 + 1.52 x gestational age (weeks). The correlation coefficient, r = 0.983 was found to be highly statistically significant (p < 0.0001). The normal mean and the 90% prediction limits were defined. Four cases with single kidney and two cases with posterior urethral valve had kidney length above the 95% upper limit. CONCLUSION: The present data offer a normal range of fetal kidney length from early stages of gestation that may allow intrauterine assessment of its development. It may also be helpful in the early prenatal diagnosis of renal abnormalities.

Adult↗