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PubMed2005

Lung development is not necessary for diaphragm development in mice.

BACKGROUND/PURPOSE: Congenital diaphragmatic hernia affects approximately 1 in every 2000 live births. The etiology of these diaphragmatic defects is unknown. Using mice with a targeted deletion of fibroblast growth factor 10 (FGF10), which display a complete lack of lung tissue, we have examined the relationship between lung hypoplasia and diaphragmatic development. METHODS: The diaphragms of FGF10 null mice were examined at 2 embryonic time-points and compared with their heterozygous and wild-type littermates. RESULTS: FGF10 null mice had phenotypically normal diaphragms when compared with wild-type littermates at both time-points studied. CONCLUSION: Normal diaphragm development appears to occur independent of lung development in mice.

Animals↗

PubMed2004

Pegylated recombinant human megakaryocyte growth and development factor suppresses the development of megakaryoblastic leukemia in mice.

We examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on the development of L-8057, a murine megakaryoblastic leukemia that expresses the thrombopoietin receptor c-Mpl, in mice. PEG-rHuMGDF administration prolonged survival of L-8057 leukemic mice, in which L-8057 cell growth in the spleen was decreased. L-8057 cells harvested from PEG-rHuMGDF-treated leukemic mice had decreased ability to generate leukemic colonies in vitro as well as to induce leukemia in vivo. PEG-rHuMGDF administration also resulted in prolonged survival of mice transplanted with a c-Mpl-expressing erythroleukemia, but had no effect on survival of mice transplanted with a myeloblastic leukemia that does not possess c-Mpl. Thus, PEG-rHuMGDF suppresses the development of c-Mpl-expressing leukemia in vivo in mice.

Animals↗

PubMed2004

Cullin-3 regulates pattern formation, external sensory organ development and cell survival during Drosophila development.

Ubiquitin-mediated proteolysis regulates the steady-state abundance of proteins and controls cellular homoeostasis by abrupt elimination of key effector proteins. A multienzyme system targets proteins for destruction through the covalent attachment of a multiubiquitin chain. The specificity and timing of protein ubiquitination is controlled by ubiquitin ligases, such as the Skp1-Cullin-F box protein complex. Cullins are major components of SCF complexes, and have been implicated in degradation of key regulatory molecules including Cyclin E, beta-catenin and Cubitus interruptus. Here, we describe the genetic identification and molecular characterisation of the Drosophila Cullin-3 homologue. Perturbation of Cullin-3 function has pleiotropic effects during development, including defects in external sensory organ development, pattern formation and cell growth and survival. Loss or overexpression of Cullin-3 causes an increase or decrease, respectively, in external sensory organ formation, implicating Cullin-3 function in regulating the commitment of cells to the neural fate. We also find that Cullin-3 function modulates Hedgehog signalling by regulating the stability of full-length Cubitus interruptus (Ci155). Loss of Cullin-3 function in eye discs but not other imaginal discs promotes cell-autonomous accumulation of Ci155. Conversely, overexpression of Cullin-3 results in a cell-autonomous stabilisation of Ci155 in wing, haltere and leg, but not eye, imaginal discs suggesting tissue-specific regulation of Cullin-3 function. The diverse nature of Cullin-3 phenotypes highlights the importance of targeted proteolysis during Drosophila development.

Amino Acid Sequence↗

PubMed2006

Physical training in developing rats does not influence the kindling development in the adult life.

The positive effect of physical exercise programs on seizure frequency and severity has been demonstrated both in adult human and animals. However, this investigation during animal brain development has not been examined. To this purpose, the present work was aimed to analyse the effect of physical exercise training in rats after weaning on the kindling process in the adulthood. Thirty rats were divided into 3 groups: the first group (EX=10) was submitted to daily bout of aerobic exercise (60 min running on the treadmill at 24/26 m/min) between P21 and 60 days of age. After this period of training, animals were submitted to 60 min running at the same speed and kindling stimulated one min post-exercise. The second group (SHAM=10) was maintained in the treadmill for the same time as the trained group without being submitted to physical exercise. The third group served as control (CTL=10). The number of stimulations required to reach stage 5 for the EX group was not statistically different from CTL and SHAM groups. However, the EX group spent a longer time and a shorter afterdischarge (AD) in stage 1 compared to the CTL and SHAM groups. The number of stimulations and AD duration in stage 2, 3 and 4 was not statistically different between all the groups. Taken together, our study showed that although forced physical exercise in developing rats does not exert significant influence to reach the stage 5 of amygdala kindling in the adult life its interference during the process of epileptogenesis indicate a positive effect of exercise in developing brain.

Animals↗

PubMed2003

Strategy for developing and optimizing liquid chromatography methods in pharmaceutical development using computer-assisted screening and Plackett-Burman experimental design.

We describe a three-step method development/optimization strategy for HPLC assay/impurity methods for pharmaceuticals, which include multiple-column/mobile phase screening using a system equipped with a column-switching device, further optimization of separation by using multiple organic modifiers in the mobile phase, and multiple-factor method optimization using Plackett-Burman experimental designs. In the first two steps, commercially available chromatography optimization software, DryLab, was used to perform computer simulations. This allows the method developer to evaluate each condition (one column/mobile phase combination) with retention data from two scouting gradient runs. This approach significantly reduces the number of runs in method development. After a satisfactory separation was obtained, we used a method optimization step with Plackett-Burman experimental designs. The purpose of the 16-injection set experiments was to evaluate nine method factors with regard to method precision, accuracy, sensitivity and specificity. The results provided logical justifications in selecting method parameters such as column temperature, detection wavelength, injection volume, and sample solvent, etc. In data analysis, instead of the traditional mathematical manipulations, we used the graphical methods to examine and present data by creating the so-called main effect plots. Because replicates of design points were not run, the data did not allow the testing of statistical significance. However, it provided visual presentations in a way that is easy to understand for the method developer and end user alike.

Chromatography, High Pressure Liquid↗

PubMed2000

The African yam bean seed lectin affects the development of the cowpea weevil but does not affect the development of larvae of the legume pod borer.

Artificial feeding assays were used to study the effect of purified galactose-specific lectins from African yam beans (Sphenostylis stenocarpa) on development of larvae of the cowpea weevil, Callosobruchus maculatus (Coleoptera : Bruchidae) and the legume pod-borer, Maruca vitrata (Lepidoptera : Pyrialidae). Inhibition of development of C. maculatus was observed when larvae were fed on artificial cowpea seeds containing 0.2%, 2.0% and 5.0% (wt/wt) of dietary lectin. Larval mortality was between 30% and 88%, while delays in total developmental time ranged between 7 and 13 days. The lectin had no effect on development of larvae of M. vitrala, when tested through topical artificial diet incorporation assays, except at the extremely high dose of 35% dietary level.

Animals↗

PubMed1997

Practice-led education and development project: developing styles in clinical supervision.

This paper is the second installment which reports a study conducted by the authors following successful application to the Yorkshire Regional Health Authority in response to a call for proposals for studies into practice-led education and development. The aim of the project is to pilot and evaluate an approach to leadership development based upon a conceptual model of reflectivity within a learning organization whilst developing and evaluating a model of supervised practice.

Education, Nursing, Baccalaureate↗

PubMed1997

Distribution of NADPH-d positive neurons during postnatal development of the rat somatosensory cortex correlates with gradients of neurogenesis and development.

The expression of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) was studied in the rat somatosensory cortex during postnatal development from day 6 to 120. Distribution of labeled neurons was quantified in dorso-medial and ventro-lateral aspects of the cortex, and correlated with known tridimensional gradients of histogenetic development and maturation of cortical neurons. NADPH positive neurons were non-pyramidal cells that in all developmental periods were more numerous in infragranular than in supragranular layers of the cortex. Additionally, more labeled cells were found in ventro-lateral than dorso-medial infragranular layers and in anterior than posterior aspects of the cerebral cortex. These patterns of distribution correlate well with the gradients of histogenetic development and with the pattern of maturation of cortical neurons.

Animals↗

PubMedDate not supplied

GABA and GABA(A) receptor antagonists alter developing cone photoreceptor development in neonatal rabbit retina.

Gamma aminobutyric acid (GABA) has been established as an important developmental signal in a number of regions of the central nervous system (CNS), including retina. Our previous studies have shown that GABAergic horizontal cells act as the initial synaptic target for developing cone photoreceptors in neonatal rabbit retina. Since intraocular injections of the GABA(A) receptor antagonists, picrotoxin or bicuculline, disrupt cone synaptogenesis in vivo, GABA released from horizontal cells may provide a necessary signal for cone axon growth and/or synapse formation. In the current report, we have used cultured retinal explants to examine the effects of GABA(A) receptor antagonists on other aspects of developing cones. These include the distribution pattern of cone cell bodies across the outer surface of the retina and the expression of GABA(A) receptors within both cone cell bodies and axonal processes. Peanut agglutinin (PNA), a plant lectin that specifically labels cone plasma membrane and extracellular matrix, was used to monitor cone development, and a GABA(A) receptor antibody against the beta2/3 subunits of the protein was used to label GABA(A) receptors. Results showed that cones maintained in the explant culture express GABA(A) receptors in a temporal and spatial pattern similar to that observed in vivo, namely a low expression of receptors on cone cell bodies at postnatal day 1 (P1), peaking around P3 and diminishing by P7. Neonatal retinal explants exposed to the GABA(A) receptor antagonists, bicuculline (10 microM) or SR95531 (5 microM), for 24 h in culture showed disruption of the normal distribution of cone cell bodies. When GABA (100 microM) was added along with either antagonist, cone cell bodies appeared normal. Neither bicuculline nor SR95531 alone had any effect on the general morphology of other retinal layers, suggesting that these GABA(A) receptor antagonists at the concentrations used were not acting as nonspecific disruption agents. The effects of GABA antagonists were confined to the first week after birth with no disruption seen in P9 or adult explant cultures. These data provide a direct demonstration of the necessity for GABAergic input to cones during active synaptogenesis. As we have previously shown, GABA(A) receptor activation causes a substantial increase in intracellular calcium concentrations in cones and thereby could provide a mechanism by which GABA regulates cone maturation.

Animals↗

PubMed2001

Strategic planning for ICCD clubhouse implementation: development of the Clubhouse Research and Evaluation Screening Survey (CRESS). International Center for Clubhouse Development.

The Clubhouse Research and Evaluation Screening Survey (CRESS) is a brief instrument designed to predict clubhouse readiness for certification assessment and, hence, performance in regard to expected model outcomes. The development of CRESS provides a practical example of the methodological challenges involved in creating a brief and valid screening instrument. Developed over a period of 5 years, CRESS is grounded in a series of workgroups, surveys, and pilot studies conducted by Fountain House and the International Center for Clubhouse Development (ICCD) in New York City. CRESS is shown to have criterion-oriented validity for the measurement of ICCD clubhouse model-related performance, as well as demonstrated ease in administration to a national sample of mental health programs.

Certification↗

PubMed2000

Developing psychosocial care: the development and evaluation of a short course which aims to introduce psychosocial interventions to inpatient staff.

Following on from the author's previous article (Baker 2000) which emphasizes the need to develop psychosocial interventions within inpatient care, the author describes the process of developing and implementing a short course aiming to introduce psychosocial interventions to inpatient staff. The article also discusses the evaluation of this course and identifies some of the difficulties for acute staff in developing these skills.

Acute Disease↗

PubMed2003

Cell shape, division and development: the 2002 American Society for Microbiology (ASM) conference on prokaryotic development.

In the last decade, the use of cytological techniques, together with the analysis of complete genomes, has dramatically advanced our understanding of bacterial development. Work on several well-developed model systems such as Bacillus subtilis, Caulobacter crescentus, Myxococcus xanthus and Streptomyces spp., has provided us with an in-depth understanding of processes such as sporulation, multicellular behaviour and the bacterial cell cycle. At the same time, these studies have revolutionized our view of the bacterial cell and shown it to be a highly complex entity with spatial and temporal organization. The recent American Society for Microbiology (ASM) conference on prokaryotic development demonstrated that several laboratories have now started to connect data obtained through functional genomic analysis with subcellular organization, thereby generating three-dimensional regulatory networks. This meeting report highlights new findings in the field, such as regulation of protein localization during sporulation and the cell cycle, control of cell-cell interaction and the initiation of cell division.

Bacillus subtilis↗

PubMed1991

The psychomotor development during the first year of life of infants exposed to intrauterine alcohol of various duration. Fetal alcohol exposure and development.

The developmental abilities of 80 children exposed to alcohol of various duration in utero were assessed 1 to 3 times during their first year of life. The occurrence of developmental delay increased towards the end of the first year. The longer the exposure the more common and severe was the developmental delay. If alcohol consumption could be reduced by the second trimester only a slight abnormality of motor development was seen at the age of 12 months. If heavy maternal drinking continued throughout the second trimester cognitive development was also delayed. Psychomotor retardation by the age of one year occurred in 38% of children who had been exposed to continuous heavy alcohol consumption during pregnancy. The psychomotor retardation diagnosed at the age of one year could be found earlier in 80% of the children but pure motor or pure cognitive delay only in some cases. The beneficial effect of reducing maternal alcohol consumption before the last trimester of the child's development was clear.

Alcohol Drinking↗

PubMed2001

Development of a two-part transcription probe to determine the completeness of temporal and spatial compartmentalization of gene expression during bacterial development.

We have developed a two-part test, using the Bacillus subtilis sacB/SacY transcription antitermination system, to evaluate the completeness of temporal and spatial compartmentalization of gene expression during bacterial cell development. Transcription of sacY(1-55) (encoding a constitutively active form of the antiterminator, SacY) is directed by one promoter, whereas transcription of sacB'-'lacZ (the target of SacY action) is directed by the same or another promoter. To obtain beta-galactosidase activity, SacY(1-55) needs to be present when sacB'-'lacZ is being transcribed. We tested the system by analyzing the spatial compartmentalization of the activities of RNA polymerase final sigma factors, which are tightly regulated during sporulation of B. subtilis: final sigma(F) and then final sigma(G) in the prespore, final sigma(E) and then final sigma(K) in the mother cell. We have confirmed that the activities of final sigma(F) and final sigma(E) are spatially compartmentalized. We have demonstrated that there is also sharp temporal compartmentalization, with little or no overlap in the activities of final sigma(F) and final sigma(G) or of final sigma(E) and final sigma(K). In contrast, we found no compartmentalization of the activity of the main vegetative factor, final sigma(A), which continued to be active alongside all of the sporulation-specific final sigma factors. We also found no temporal compartmentalization of expression of loci that are activated during the development of competent cells of B. subtilis, a developmental program distinct from spore formation. A possible mechanism to explain the temporal compartmentalization of final sigma(F) and final sigma(G) activities is that the anti-sigma factor SpoIIAB transfers from final sigma(G) to final sigma(F).

Bacillus subtilis↗

PubMed2006

Minor neurological dysfunction, cognitive development and somatic development at the age of 3 to 11 years in very-low-birthweight infants with transient periventricular echodensities.

AIM: To determine, using strict exclusion criteria, whether transient periventricular echodensities (TPE) in very-low-birthweight infants lead to minor neurological dysfunction and problems in cognitive and somatic development in children without major neurological impairments. METHODS: 23 children with TPE were matched to 23 children without TPE. Exclusion criteria were small for gestational age, microcephaly at birth, diplegia, asphyxia, psychomotor retardation, intraventricular haemorrhage grade III/IV, major surgical interventions and malformations. The Kaufman Assessment Battery for Children, Draw-a-Man Test and neuropaediatric examination were used for evaluation. RESULTS: There were no differences in demographic data, growth and socio-economic status. Significant differences with lower results in the TPE group were found in fine motor skills and in the Draw-a-Man Test. In the Kaufman Assessment Battery for Children, all subscales were below average in the TPE group, except the sequential processing scale. In the control group, all subscales were within the average range. CONCLUSION: By using strict exclusion criteria to eliminate other risk factors for minimal neurological dysfunction and poor cognitive development, we were able to focus on the effect of TPE. TPE seem to affect cognitive development and cause minor neurological dysfunction.

Case-Control Studies↗

PubMed1997

Laminin alpha1 chain synthesis in the mouse developing lung: requirement for epithelial-mesenchymal contact and possible role in bronchial smooth muscle development.

Laminins, the main components of basement membranes, are heterotrimers consisting of alpha, beta, and gamma polypeptide chains linked together by disulfide bonds. Laminins-1 and -2 are both composed of beta1 and gamma1 chains and differ from each other on their alpha chain, which is alpha1 and alpha2 for laminin-1 and -2, respectively. The present study shows that whereas laminins-1 and -2 are synthesized in the mouse developing lung and in epithelial-mesenchymal cocultures derived from it, epithelial and mesenchymal monocultures lose their ability to synthesize the laminin alpha1 chain. Synthesis of laminin alpha1 chain however returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical, since laminin alpha1 chain is not detected in monocultures exposed to coculture-conditioned medium or in epithelial-mesenchymal cocultures in which heterotypic cell-cell contact is prevented by an interposing filter. Immunohistochemical studies on cocultures treated with brefeldin A, an inhibitor of protein secretion, indicated both epithelial and mesenchymal cells synthesize laminin alpha1 chain upon heterotypic cell- cell contact. In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin alpha1, alpha2, and beta/gamma chains. Lung explants exposed to monoclonal antibodies to laminin alpha1 chain exhibited alterations in peribronchial cell shape and decreased smooth muscle development, as indicated by low levels of smooth muscle alpha actin and desmin. Taken together, our studies suggest that laminin alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.

Animals↗

PubMed1967

Studies on the maintenance of oral development in Tetrahymena pyriformis GL-C. II. The relationship of protein synthesis to cell division and oral organelle development.

The effects of puromycin on synchronized Tetrahymena pyriformis were investigated at two different concentrations, 43 microg per ml and 430 microg per ml. The rate of incorporation of histidine-(14)C into hot TCA-insoluble material was reduced by 30% at the low concentration and by 80-90% at the high concentration. The rate of oxygen uptake was lowered by only 10-20% at both concentrations. Cell division was prevented at both concentrations, if the drug was added prior to a "transition point" at about 45 min after the end of the synchronizing treatment. Development of "anarchic field" oral primordia was arrested, while primordia in early stages of membranelle differentiation were resorbed. Resorption began shortly after addition of the drug, and proceeded most rapidly at the lower concentration. If the drug was added after the "transition point," cell division and oral primordium formation were completed with only slight delay at the low concentration, and with considerable delay (in some cases complete arrest) at the high concentration. The results thus indicate that protein synthesis is involved in the later as well as the earlier stages of development; what specially characterizes the earlier stages, prior to the "transition point," is a dramatic response to partial inhibition of protein synthesis. It is suggested that this response involves the activation or release of a latent intracellular degradative system which is specific for developing structures.

Amino Acids↗

PubMed1958

The development in vitro of particles from cytoplasm. I. Observations on particle development in bacteriologic media.

A system is described in which microscopically visible particles develop from cytoplasmic proteins incubated in vitro. The conditions required for the development of particles are those usually associated with enzymic reactions. The particles are believed to develop as a result of enzyme action on cytoplasmic proteins in the presence of compounds having certain specific chemical configurations. The relation of the particles to various "microorganisms," described in the literature as etiologic agents of disease, and to the problem of seemingly positive blood cultures is discussed.

Cytoplasm↗