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PubMed1997

Does the respiratory rate in sea urchin embryos increase during early development without proliferation of mitochondria?

During early development of the sea urchin, the respiratory rate, enhanced upon fertilization, is maintained up to hatching (pre-hatching period) and then gradually increases to a maximum at the gastrula stage (post-gastrula period). Except for a short duration after fertilization, respiration in embryos is strongly inhibited by CN- and antimycin A. During the whole span of early development, the amounts of proteins, cytochromes and the specific activities of cytochrome c oxidase and reduced nicotinamide adenine dinucleotide (NADH) cytochrome c reductase in mitochondria are practically the same as in unfertilized eggs. A marked augmentation of mitochondrial respiration after hatching probably occurs without net increase in whole mitochondrial intrinsic capacities. Carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) or tetramethyl p-phenylenediamine (TMPD) enhances the respiratory rate in the pre-hatching period but hardly augments the respiration in the post-gastrula period. In the presence of both FCCP and TMPD, the respiratory rate in the pre-hatching period was as high as in the post-gastrula period. Probably, electron transport in the mitochondrial respiratory chain is regulated by acceptor control and limitation of cytochrome c reduction in the pre-hatching period and released from those regulations in the post-gastrula period. Acceptor control of respiration is experimentally reproduced in isolated mitochondria by making adenine nucleotide levels as those levels in the pre-hatching period.

Animals↗

PubMed1998

Presence of pre-rRNAs before activation of polymerase I transcription in the building process of nucleoli during early development of Xenopus laevis.

During the early development of Xenopus laevis, we followed in individual nuclei the formation of a nucleolus by examining simultaneously its structural organization and its transcriptional competence. Three distinct situations were encountered with different frequencies during development. During the first period of general transcriptional quiescence, the transcription factor UBF of maternal origin, was present in most nuclei at the ribosomal gene loci. In contrast, fibrillarin, a major protein of the processing machinery, was found in multiple prenucleolar bodies (PNBs) whereas nucleolin was dispersed largely in the nucleoplasm. During the second period, for most nuclei these PNBs had fused into two domains where nucleolin concentrated, generating a structure with most features expected from a transcriptionally competent nucleolus. However, RNA polymerase I-dependent transcription was not detected using run-on in situ assays whereas unprocessed ribosomal RNAs were observed. These RNAs were found to derive from a maternal pool. Later, during a third period, an increasing fraction of the nuclei presented RNA polymerase I-dependent transcription. Thus, the structural organization of the nucleolus preceded its transcriptional competence. We conclude that during the early development of X. laevis, the organization of a defined nucleolar structure, is not associated with the transcription process per se but rather with the presence of unprocessed ribosomal RNAs.

Animals↗

PubMed1991

Suppressed aggression accelerates early development of essential hypertension.

Predictors for early development of essential hypertension were identified in a prospective study of 98 normotensive and 23 borderline hypertensive subjects of both sexes aged 18-24 years. Baseline examination included psychological tests as well as resting and stress-induced cardiovascular and neurohormonal measurements. During the 30 (+/- 4 s.d.)-month follow up, 14 out of 98 (14%) initially normotensive subjects developed borderline hypertension, while of 23 borderline hypertensive subjects, 11 (48%) remained in the borderline group (141-159/91-94 mmHg), another five (22%) increased to greater than 160/95 mmHg and seven (30%) normalized blood pressure to less than 140/90 mmHg. In the 98 normotensive subjects, the height of casual systolic blood pressure at entry was the best predictor of subsequent borderline hypertension, correctly classifying 75% of the subjects in a stepwise discriminant analysis. Stress-induced blood pressure responses, together with measures of sympathetic nervous system activity (11%) and psychological factors (6%), were relatively weak predictors of subsequent pressure classification. In the 23 borderline hypertensives, the height of systolic blood pressure induced by mental stress was the single best predictor for sustained borderline or subsequent established hypertension, classifying 74%. When all 121 subjects were taken together, the greatest increases in blood pressure were found in those subjects who had suppressed aggression, particularly those who also had normal-high or borderline blood pressure at entry. Thus, suppressed aggression emerged as a superimposed permissive factor for a steeper trajectory or acceleration of early development of hypertension.

Adolescent↗

PubMed1995

Epilepsy in early development: the lesson from surgery for early intractable seizures.

This report examines the impact on development and the problems involved in assessing development in very young children with early-onset intractable seizures, particularly infantile spasms. A review of studies on medically and surgically treated children with infantile spasms underscores the relationship between seizure control and developmental outcome. About 50% of children with markedly intractable infantile spasms attained seizure control and significant improvement in the use of nonverbal communication, a developmental measure that has been used in other populations of developmentally delayed children. With the exception of duration of illness, clinical measures of age of onset of infantile spasms, type of surgery, and side of surgery did not appear to be related to the postoperative change in nonverbal communication. The neuropathology findings of surgically treated children with infantile spasms suggest that the underlying pathology occurs early in brain development. In conclusion, the cumulative effect of uncontrolled seizures and the underlying pathology might impact the early development of children with intractable infantile spasms.

Age of Onset↗

PubMed2004

Pharmaceutical evaluation of early development candidates "the 100 mg-approach".

Early development candidates are often selected for pre-clinical and clinical development based primarily on pharmacological and toxicological data. In order to choose the best compounds from a biopharmaceutical point of view, physicochemical parameters such as solubility, dissolution rate, hygroscopicity, lipophilicity, pKa, stability, polymorphism and particle characteristics need to be evaluated as early as possible and above all with the highest accuracy. However, the low amounts of drug substance available in early development often compromise data quality, and therefore, hamper an early pharmaceutical assessment. This article summarises the Aventis approach on early pharmaceutical compound profiling with the aim of providing a high quality assessment requiring not more than 100 mg of drug substance. In particular, the evaluation criteria, process and miniaturised analytical technology that can be applied for this purpose are discussed.

Drug Design↗

PubMed2001

[Development and the developmental disorders of human brain. I. Early development of the cerebrum].

The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early development of mostly the spinal cord and the brain stem. Regionalization of the brain has been related to genes that play a part in it. A characteristic developmental disorder for this early phase in the development of the forebrain is holoprosencephaly, a brain patterning disorder. Numerous genes play a part in its occurrence; abnormal function of signal factors as well as of transcription factors may lead to holoprosencephaly.

Brain↗

PubMed1989

The appearance of acetylated alpha-tubulin during early development and cellular differentiation in Xenopus.

Early development in Xenopus is characterized by dramatic changes in the organization of the microtubule cytoskeleton. We have used whole-mount immunocytochemistry to follow the expression of the acetylated form of alpha-tubulin during early Xenopus development. In the egg and early embryo, the monoclonal anti-acetylated tubulin antibody 6-11B-1 stained meiotic and mitotic spindles, midbody microtubules, and what appears to be the central region of the sperm aster; the antibody did not stain the sperm aster itself or the cortical microtubule system associated with the rotation of the fertilized egg. Following gastrulation, acetylated tubulin disappeared from all but mitotic midbody microtubules. During the course of neurulation high levels of acetylated tubulin reappeared in the precursors of the ciliated epidermal cells (stage 15), transiently in neural folds (stage 16/17), in neuronal processes (stage 18/19), and in somas (stage 21). The changing pattern of anti-acetylated tubulin staining during Xenopus development raises intriguing questions as to the physiological significance of tubulin acetylation.

Acetylation↗

PubMed1994

The kinesin-related protein Eg5 associates with both interphase and spindle microtubules during Xenopus early development.

We have examined the changing abundance and distribution of the kinesin-related protein Eg5 during oogenesis and early development in Xenopus laevis. Antibodies raised against proteins synthesized from parts of a novel Eg5 gene expressed in eggs were used for Western blotting and immunofluorescence. Eg5 protein was highly enriched in oocytes and eggs compared with other adult tissues. It accumulated during the latter stages of oogenesis and increased a further threefold during oocyte maturation. Its level then gradually declined during early development. In oocytes, eggs, and early embryos, Eg5 protein could be detected throughout the cytoplasm and in subcortical aggregates. Eg5 staining was found concentrated in meiotic and mitotic spindles, mainly toward the poles. Some Eg5 staining colocalized with microtubules in interphase cells, including the aligned subcortical microtubules in fertilized eggs implicated in the cortical rotation that specifies the dorsoventral axis. Interphase association of Eg5 with microtubules during early development was confirmed by copelleting the protein with microtubules from egg homogenates. In tadpoles and tissue culture cells, Eg5 colocalized with spindle microtubules throughout mitosis but not with interphase microtubules. These results suggest that the Eg5 microtubule motor may function in meiosis, mitosis, and interphase during early development.

Amino Acid Sequence↗

PubMed1980

Effects of dietary protein and EFA deficiency on liver delta 5, delta 6 and delta 9 desaturase activities in the early developing rat.

The influence of protein restriction and EFA deficiency during early development in the rat on the activities of delta 5, delta 6 and delta 9 desaturases was studied. The effect of these diets on body weights and in the fatty acid composition of liver phospholipids was also investigated. The results indicate that the body weights of pups were lowered by feeding the dams both the low-protein and the EFA-deficient diet. The activities of delta 5, delta 6 and delta 9 desaturases were reduced in about 60% by protein deficiency but a rise in the activity of delta 9 desaturase of 362.2% was promoted by feeding the dams the low-fat diet. The fatty acid composition of liver phospholipids indicates that partial deprivation of proteins during early development is associated with a decreased ratio of arachidonate to linoleate. Besides the low-fat group shows in the fatty acid composition of liver phospholipids the typical pattern of EFA deficiency, increased 18:1 and 20:3 omega 9 and decreased 18:2 and 20:4. It is evident from the current investigation that partial deprivation of protein during early development may impair the conversion of linoleate to arachidonate in the rat and that the lack of arachidonic acid observed in the liver cells during protein deficiency would be the consequence of this impairment.

Animals↗

PubMed1995

Factors involved in nuclear reprogramming during early development in the rabbit.

Mechanisms of nuclear reprogramming and assessment of potential malfunctions that could be deleterious for development were evaluated in rabbit zygotes, parthenotes, and nuclear transfer embryos by analysis of DNA replication, nucleolar fibrillarin label, and localization of nuclear material reactive to the MPM-2 antibody. Nuclear transfer embryos were derived from G1/early S-phase donor nuclei and MII oocytes. In nuclear transfer embryos, DNA rereplication was likely to have occurred because label was incorporated, possibly in the centromeric regions of the chromosomes, prior to premature chromosome condensation and again following pronuclear formation. In parthenotes, DNA replication began very late in the cell cycle, which may be due to deficiencies in the artificial activation stimulus. The presence of fibrillarin label in the nucleolus was used as an indication of nucleolar transcriptional activity. Fibrillarin label was absent in embryos of all types up to the 16-32-cell stage. Although fibrillarin reappeared in nuclear transfer and parthenote embryos at the appropriate stage, not all blastomeres showed label indicating impaired development in these embryos. Labelling of phosphorylated epitopes by MPM-2 antibody showed a change in pattern of labelling during early development. Early cleavage stage embryos did not exhibit labelling over the spindle poles as did blastomeres from 32-cell embryos and tissue culture cells. All cell types exhibited labelling during interphase as dots located primarily over the nucleus in blastomeres from 32-cell embryos and in tissue culture cells, together with cytoplasmic label in embryos at early cleavage stages. Nuclear transplant embryos had a normal pattern of MPM-2 label. In contrast, the appearance of MPM-2 label in parthenotes depended on the type of calcium stimulation. These results demonstrate defects in DNA synthesis, nucleolar activity, and specific phosphorylation events, likely resulting from an improper activation stimulus and chromosome condensation in the transplanted nucleus.

Animals↗

PubMed1995

Programming of a repressed but committed chromatin structure during early development.

The determination of chromatin for transcription during early development as well as the requirement for trans-acting factors during this period has been analysed in Xenopus. Basal transcription is repressed both during oogenesis and after the mid-blastula transition (MBT), and transactivators are required to relieve this repression. In contrast, transactivators cannot overcome the generalized transcriptional repression which occurs in embryos before MBT. However, they do bind to promoters leading to a repressed but preset chromatin structure. Experiments involving the pre-binding of TATA binding protein (TBP) or of the strong transactivator GAL4-VP16 further show that there is no limiting factor before the MBT, and that it is the recruitment and stabilization of the basal transcription machinery and not of transactivators which is repressed during early development. This multi-step process in gene activation, with activation of promoters temporally uncoupled from their commitment, may be of importance in the regulation of early embryonic events by providing molecular signposts for future determinations.

Animals↗

PubMed2026

Transcriptomic and metabolomic analyses revealed the action mechanism of nesfatin-1 gene on glucolipid metabolism during early development stage of largemouth bass.

Nesfatin-1 has biological roles including the suppression of food intake and the regulation of glucose and lipid metabolism. However, the information available regarding nesfatin-1 in the glycolipid metabolism in the early development stage of fish is still limited. In order to investigate the role of the nesfatin-1 gene in the early development stage of the largemouth bass (Micropterus salmoides), the nesfatin-1 gene was knocked down using siRNA interference technology. Then, we evaluated its mRNA expression levels, transcriptomes and metabolomes. The mRNA expression levels of nesfatin-1 gene were appreciably decreased at 48 h, 72 h and 96 h after injection of nesfatin-1 siRNA in the early development stage. The omics results revealed that knockdown of the nesfatin-1 gene induced 1833 differentially expressed genes (DEGs) and 2370 differentially expressed metabolites (DEMs). Bioinformatic analysis enriched the most affected molecular pathways (sphingolipid metabolism, fatty acid elongation, amino sugar and nucleotide sugar metabolism and biosynthesis of unsaturated fatty acids) and metabolic pathways (biosynthesis of unsaturated fatty acids, sphingolipid metabolism and amino sugar and nucleotide sugar metabolism) in early development stage of largemouth bass. In amino sugar and nucleotide sugar metabolism, increased expression levels of genes such as chic, chs1, and gck genes, alongside decreased expression levels of the chia.1 gene, resulted in significantly elevated concentrations of N-Acetyl-D-glucosamine, β-d-fructose 6-phosphate, β-d-Fructose, D-mannose 6-phosphate, d-glucose, d-glucose 1-phosphate, UDP-glucose, and UDP-glucuronate, whilst the concentration of UDP-N-acetyl-α-D-glucosamine was markedly reduced. Therefore, the nesfatin-1 gene may influence the early development stage of largemouth bass by affecting signaling pathways associated with glycolipid metabolism. Our findings further expand the understanding of molecular mechanisms of the nesfatin-1 gene, and provide further theoretical support for the initial breeding and feed adaptation of largemouth bass.

Animals↗

PubMed2002

Origins and early development of the case-control study: Part 1, Early evolution.

This paper traces the origins and early development of the case-control study, focusing on its evolution in the 19th and early 20th century. As with other forms of clinical investigation, the case-control study emerged from practices that originally belonged to the realm of patient care. This form of disease investigation can be viewed as the knitting together of medical concepts (caseness, disease etiology, and a focus on the individual)--and medical procedures (anamnesis, grouping of cases into series; and comparisons of the diseased and the healthy)--that are of ancient origin, but which were seldom brought together until the 20th century. The analytic form of the case-control study can be found in 19th century medical literature, but did not appear to be viewed as a special or distinct methodology. A number of clinical investigations, and several sociological studies, in the first half of this century can be described as case-control studies, the most fully developed of which was Janet Lane-Claypon's 1926 study of breast cancer.

Case-Control Studies↗

PubMed1979

Tissue-specific changes in nuclear RNA content during early development of Triturus vulgaris.

During early development of Triturus vulgaris, as a measure for nuclear activity in neuroectoderm, mesoderm and endoderm, nuclear RNA content was determined by cytochemical methods. In the first stages of gastrulation, that is to say during the early phase of neural induction, the RNA content of the inducing system is considerably higher than in the reacting system. Then, with a phase-shift of about 10 h, the RNA content of the neuroectoderm increases quickly also. In the following stages the nuclear RNA content of both regions is reduced. A second continuous increase in the RNA amount coincides with the formation of the neural tube. In the mesoderm, enhancement of RNA content correlates with cytodifferentiation of the chorda. In all stages the RNA content of the endoderm is higher than in the other tissues and it becomes successively diminished from the early gastrula to the tailbud stage.

Animals↗

PubMed2004

Development and application of a universal method for quantitation of anionic constituents in active pharmaceutical ingredients during early development using suppressed conductivity ion chromatography.

A universal method for quantitation of anionic substances in active pharmaceutical ingredients (API) during early development was developed using ion chromatography (IC). The method was developed to allow rapid characterization of APIs in support of early clinical studies The method parameters were chosen to allow quantitation of monovalent, divalent, and trivalent inorganic ions as well as monvalent and divalent carboxylic acids. These parameters were also chosen to ensure appropriate performance for regulated analyses using less than 10mg of API per replicate. The method was applied to and validated for a range of anionic analytes in APIs of varying hydrophobicity to demonstrate applicability to various analyses encountered during early development of pharmaceuticals.

Anions↗

PubMed1998

New data on the early development of Hysterothylacium aduncum (Nematoda, Anisakidae).

This note reports on incidental observations of the early development of the third-stage larvae of Hysterothylacium aduncum from gadid fishes. Gravid H. aduncum females were collected from Pollachius virens, Pollachius pollachius. Gadus morhua, and Molva molva in Norwegian waters. The eggs were incubated at 20 per thousand salinity and 5 C. Spontaneous hatching of third-stage larvae was observed 10-25 days after egg deposition. These larvae were long lived and could infect Acartia tonsa copepods, the infections being maintained for up to 34 days. The morphology of the third-stage larvae in the copepods and some traits of the life cycle were similar to those reported in previous studies. However, our results disagree with evidence suggesting that H. aduncum eggs rarely hatch, and hatched larvae have lower survival and a poorer ability to infect the first intermediate host than unhatched ones. It is difficult to account for these discrepancies because information on the early development of Hysterothylacium species is incomplete. However, we tentatively suggest that differences in the early development of H. aduncum may indicate the existence of at least 2 different taxonomic entities in the North Atlantic, which is consistent with previous evidence based on morphological traits.

Animals↗

PubMed1999

Early development and fitness in birds and mammals.

Conditions experienced during early development affect survival and reproductive performance in many bird and mammal species. Factors affecting early development can therefore have an important influence both on the optimization of life histories and on population dynamics. The understanding of these evolutionary and dynamic consequences is just starting to emerge.

Journal Article↗

PubMed1995

Isolation of cDNAs from maternal mRNAs specifically present during early development.

In many animals the regulation of early embryonic development is under the control of mRNAs of maternal origin. We describe here the construction and characterization of a subtractive cDNA library to isolate genes whose expression is restricted to early development. Such genes might be potentially involved in developmental diseases, if accidentally expressed during adult life. Seven yet unknown genes preferentially expressed in the oocyte and present during early development were isolated from this library by differential screening. Their transcription patterns provide evidence for a selective expression during oogenesis and the existence of a gene family specifically implicated in functions linked to early embryogenesis.

Animals↗