Mechanical stress regulation of plant growth and development.
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Curly tail mouse mutant embryos (ct/ct) develop spinal neural tube defects (NTD) in 54% of cases, comprising isolated tail flexion defects and spinal bifida with tail flexion defects. Both types of spinal NTD result from delayed closure of the posterior neuropore (PNP). Previous studies (Seller et al. [1979] Proc. R. Soc. Lond. Biol. 206:95-107; Seller and Perkins [1982] Prenat. Diagn. 2:297-300) described a paradoxical effect of retinoic acid (RA) on the phenotypic expression of the ct mutation: Treatment with low doses of RA on day 8 of gestation increased the incidence of total NTD, whereas low doses of RA administered on day 9 resulted in reduced incidence of total NTD. In order to investigate further the reported preventive effect of RA, we have carried out detailed analyses of the effects of maternal treatment with 5 mg/kg RA on the incidence of NTD at different developmental stages, and on the development and growth of ct/ct embryos. We found that 5 mg/kg RA reduces the incidence of spinal NTD in a stage-specific manner, without increasing the incidence of cranial NTD. The effect of RA is specific: There were no other alterations in morphogenesis, growth, development, resorption rate, or litter size. RA was more effective in the prevention of isolated tail flexion defects than of spina bifida. Prevention of isolated tail flexion defects was maximal (50% reduction) when RA was administered between 10 days 4 hours and 10 days 8 hours post coitum (p.c.) inclusive (24 to 34 somite stage).(ABSTRACT TRUNCATED AT 250 WORDS)
We have developed a simple, rapid, sensitive bioassay for megakaryocyte growth and development factor (MGDF) or thrombopoietin (TPO) based on its ability to stimulate the proliferation of the human megakaryoblastic cell line MO7e. The bioassay takes only 24 h, is reproducible and sensitive to less than 10 pg/ml of MGDF. It can be made specific for MGDF by including neutralizing antibodies specific for MGDF, and is suitable for detection of MGDF in both plasma and serum samples.
UNLABELLED: The management of leg length difference (LLD) and angular deformities of the leg remains controversial. Numerous treatment options have been proposed over the past years depending on the patient's general condition, skeletal age, function, and degree and configuration of the deformity. Our retrospective study consisted of 48 patients with 58 legs treated between 1970 and 1991 by Blount's epiphyseal stapling to equalise length or correct angular deformity. After an average follow-up of 16.5 years, all patients with idiopathic bow-legs or knock-knees (n=12) and 71% of LLD caused by overgrowth (e.g. Klippel-Trenaunay syndrome) showed good and excellent results at skeletal maturity, whereas the results of the treatment of LLD with undergrowth of the leg and angular deformities due to trauma, infection or general dysplasia and malformation were fair to poor because of the difficulty in prediction of growth development and growth potential, allowing only for partial correction of the deformity. Besides the restriction of the stapling procedure due to the aetiology of the deformity, the age of the patients at the time of surgery is important, as it determines the complication rate of this technique (loosening or dislocation of staples). Thus Blount's epiphyseodesis should not be performed before the age of 9 years in girls and 11 years in boys. CONCLUSION: Blount's epiphyseal stapling can be recommended as a safe procedure with predictably good results in idiopathic angular deformities of the leg and leg length difference caused by overgrowth.
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In a long-term prospective study 46 unselected infants born before 35 completed weeks of gestational age were followed up, and compared to 26 fullterm infants. At 9 and 18 months of chronological age their height and weight were still lower than that of fullterms, but the difference disappeared when age was corrected for gestational age at birth. The motor and neurological maturity and language development was delayed in the preterms still at 18 months, which could possibly also be explained by their lower biological age. Ten of the preterm infants showed, at one or several occasions during follow up, definite neurological abnormality. At 18 months of age two of them were handicapped, one with retrolental fibroplasia, nearly blind, and another with cerebral palsy (slight spastic diplegia). Five of them had late psychomotor development, while two were borderline and one normal. We defined pre- and perinatal risk groups, but found that development at 18 months was not correlated to degree of risk. Neither was there any correlation between neurological examination at term and later handicap or psychomotor retardation. We found more illness, mostly due to common infections, during the first 18 months in the preterm group, as measured by the number of visits to a doctor and days spent in hospital.
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In 340 women, cultured prospectively during their pregnancies, the rate of infection with Chlamydia trachomatis was 8.8%. The women with positive cultures tended to be younger and more often single and black than their counterparts with negative cultures. There were no statistically significant clinical differences between the two groups. Eighteen children born to Chlamydia culture-positive women and 16 born to negative women were followed for nine months to examine the potential effects of maternal infection on infant growth, development, and illness. Eleven of 18 study patients had culture or tear antibody evidence of Chlamydia infection, as opposed to one of the control subjects (P = 0.00093). Eight of these 11 had clinical conjunctivitis, and two of the eight developed pneumonia. Growth retardation and developmental abnormalities were not detected in either group. It is concluded that maternal carriage of C. trachomatis is associated with a high incidence of clinical illness in the offspring.
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Although nematodes like Caenorhabditis elegans are incapable of de novo cholesterol biosynthesis, they can utilize nonfunctional sterols by converting them into cholesterol and other sterols for cellular function. The results reported previously and presented here suggest that blocking of sterol conversion to cholesterol in C. elegans by 25-azacoprostane-HCl (azacoprostane) treatment causes a serious defect in germ cell development, growth, cuticle development, and motility behavior. To establish a biochemical basis for these physiological abnormalities, we performed proteomic analysis of mixed stage worms that had been treated with the drug. Our results from a differential display proteomic analysis revealed significant decreases in the levels of proteins involved in collagen and cytoskeleton organization such as protein disulfide isomerase (6.7-fold), beta-tubulin (5.41-fold), and NEX-1 protein (>30-fold). Also reduced were enzymes involved in energy production such as phosphoglycerate kinase (4.8-fold) and phosphoenolpyruvate carboxykinase (8.5-fold), a target for antifilarial drugs such as azacoprostane. In particular, reductions in the expression of lipoprotein families such as vitellogenin-2 (7.7-fold) and vitellogenin-6 (5.4-fold) were prominent in the drug-treated worms, indicating that sterol metabolism disturbance caused by azacoprostane treatment is tightly coupled with suppression of the lipid transfer-related proteins at the protein level. However, competitive quantitative reverse transcriptase polymerase chain reaction showed that the transcriptional levels of vit-2, vit-6, and their receptors (e.g. rme-2 and lrp-1) in drug-treated worms were 3- to 5-fold higher than those in the untreated group, suggesting a presence of a sterol regulatory element-binding protein (SREBP)-like pathway in these genes. In fact, multiple predicted sterol regulatory elements or related regulatory sequences responding to sterols were found to be located at the 5'-flanking regions in vit-2 and lrp-1 genes, and their transcriptional activities fluctuated highly in response to changes in sterol concentration. Thus, many physiological abnormalities caused by azacoprostane-mediated sterol metabolism disturbance appear to be exerted at least in part through SREBP pathway in C. elegans.
Collapsin response mediator proteins (CRMPs) have been implicated in signaling of axonal guidance, including semaphorins. We have previously identified a unique member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is phylogenetically divergent from the other four CRMPs. In this study, we have examined the distribution and function of CRAM in developing neurons. Immunohistochemical analysis showed accumulation of CRAM in the filopodia of growth cones. Experiments using cytochalasin D indicated that filopodial localization of CRAM was independent of filamentous actin. Overexpression of CRAM in neuronal cells significantly promoted filopodial growth and led to the formation of supernumerary growth cones, which acquired resistance to semaphorin-3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked filopodial formation and revealed an aberrant morphology of growth cones. We propose that CRAM regulates filopodial dynamics and growth cone development, thereby restricting the response of growth cone to repulsive guidance cues.
To better quantify the relative antibacterial activity of beta-lactam antibiotics in vitro, mathematical descriptions of bacterial growth were developed. Growth curves for the initial 2-to 4-hr period of exposure to antibiotic can be expressed as quadratic functions of time. Moreover, the rate of change of growth (a) shows a linear dependence on the logarithm of the antibiotic concentration. For some drug-organism interactions, the initial growth rate (k0) is also a concentration-dependent variable. This mathematical quantitation of the antibacterial action of a drug in vitro covers a range of concentrations above and below its minimal inhibitory concentration. The slope of the regression line of a on log concentration may vary for different microorganisms and antibiotics. However, several analogues yield parallel concentration-effect slopes, a circumstance allowing for the calculation of potency ratios. Two murine models were used to determine if these in vitro studies could predict activity in vivo. The relative efficacy in vivo also was expressed as a potency ratio, which was measured in terms of the number of bacteria in either homogenized kidney after intravenous challenge or an infected thigh muscle. For drugs with similar pharmacokinetics, the potency in vivo could be predicted from the value in vitro. However, for drugs with concentration curves in serum of different shapes, the potency in vivo varied from the value in vitro. A more prolonged course of drug in serum, which yielded a flatter concentration curve, appeared to be associated with greater activity in vivo.
We have mapped quantitative trait loci (QTLs) for commercially important traits (stem growth and form) and an adaptive trait (spring leaf flush) in a Populus F2 generation derived from a cross between interspecific F1 hybrids (P. trichocarpa x P. deltoides). Phenotypic data were collected over a 2-year period from a replicated clonal trial containing ramets of the parental, F1, and F2 trees. Contrary to the assumptions of simple polygenic models of quantitative trait inheritance, 1-5 QTLs of large effect are responsible for a large portion of the genetic variance in each of the traits measured. For example, 44.7% of the genetic variance in stem volume after 2 years of growth is controlled by just two QTLs. QTLs governing stem basal area were found clustered with QTLs for sylleptic branch leaf area, sharing similar chromosomal position and mode of action and suggesting a pleiotropic effect of QTLs ultimately responsible for stem diameter growth.
Polar transport of the plant hormone auxin controls many aspects of plant growth and development. A number of synthetic compounds have been shown to block the process of auxin transport by inhibition of the auxin efflux carrier complex. These synthetic auxin transport inhibitors may act by mimicking endogenous molecules. Flavonoids, a class of secondary plant metabolic compounds, have been suggested to be auxin transport inhibitors based on their in vitro activity. The hypothesis that flavonoids regulate auxin transport in vivo was tested in Arabidopsis by comparing wild-type (WT) and transparent testa (tt4) plants with a mutation in the gene encoding the first enzyme in flavonoid biosynthesis, chalcone synthase. In a comparison between tt4 and WT plants, phenotypic differences were observed, including three times as many secondary inflorescence stems, reduced plant height, decreased stem diameter, and increased secondary root development. Growth of WT Arabidopsis plants on naringenin, a biosynthetic precursor to those flavonoids with auxin transport inhibitor activity in vitro, leads to a reduction in root growth and gravitropism, similar to the effects of synthetic auxin transport inhibitors. Analyses of auxin transport in the inflorescence and hypocotyl of independent tt4 alleles indicate that auxin transport is elevated in plants with a tt4 mutation. In hypocotyls of tt4, this elevated transport is reversed when flavonoids are synthesized by growth of plants on the flavonoid precursor, naringenin. These results are consistent with a role for flavonoids as endogenous regulators of auxin transport.