Measuring growth rate in high-throughput growth phenotyping

Growth rate is an important variable and parameter in biology with a central role in evolutionary, functional genomics, and systems biology studies. In this review the pros and cons of the different technologies presently available for high-throughput measurements of growth rate are discussed. Growth rate can be measured in liquid microcultivation of individual strains, in competition between strains, as growing colonies on agar, as division of individual cells, and estimated from molecular reporters. Irrespective of methodology, statistical issues such as spatial biases and batch effects are crucial to investigate and correct for to ensure low false discovery rates. The rather low correlations between studies indicate that cross-laboratory comparison and standardization are pressing issue to assure high-quality and comparable growth-rate data.     

Cranial growth and growth dimorphism in Ateles geoffroyi

With the exception of the work of Schultz (1960), cranial growth in Ateles is not well documented. This paper describes the results of a detailed quantitative study of cranial ontogeny in male and female Ateles geoffroyi. Using Euclidean Distance Matrix Analysis (EDMA), local areas of form change due to growth within spider monkey crania are identified. We found substantial change local to the zygomatic region in the face, identified mediolaterally directed changes in the palate, detected relatively larger amounts of change local to the anterior neurocranium compared to the posterior neurocranium, and demonstrate a greater amount of basicranial growth along a mediolateral axis than previously reported. Cranial sexual dimorphism is also examined. A. geoffroyi is noted for being monomorphic, and we found a general similarity between male and female cranial forms at all developmental ages. However, differences in overall cranial size between the sexes were found in the oldest subadult age group but not between male and female adults. This difference suggests that A. geoffroyi females attain their adult cranial form slightly before males and implies a pattern of earlier onset of female maturity relative to males. © 1993 Wiley-Liss, Inc.     

Polypeptide growth factors in embryogenesis and tumor growth

Polypeptide growth factors, which belong to different families (epidermal growth factors, insulin-like growth factors, fibroblast growth factors, transforming growth factors-beta, and some others), were characterized regarding their specific role in embryogenesis and tumor growth. Differences and parallels of the functioning of growth factors in these processes have been noted. Potential significance of the described characteristics of growth factors for directed modulation of embryogenesis and tumor growth is discussed.     

Dosing of growth hormone in growth hormone deficiency

Growth hormone (GH) treatment of GH-deficient (GHD) children is to a certain extent standardized worldwide. Recombinant 22 kDa GH is injected once daily by the subcutaneous route, mostly in the evening. The amount of GH injected (calculated per kg body weight or body surface area, expressed in terms of IU or mg) in prepubertal children mimics the known production rate (approximately 0.02 mg [0. 06 IU]/kg body weight per day). However, there is a wide variation in dosage, the reasons for which are partly unknown and partly due to national traditions and regimes imposed by authorities regulating reimbursement. The situation during puberty is less standardized, with most clinicians still not increasing the dosage according to known production rates. The results of these approaches in terms of adult height outcome are not always satisfactory. In order to achieve optimal height development during childhood, puberty and adulthood, strategies must be developed to individualize GH dosing according to set therapeutical goals taking into account efficacy, safety and cost. The implementation of prediction algorithms will help us to reach these goals. In addition, other response variables will have to be monitored during treatment in order to correct for deficits resulting from GHD.     

Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth

To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only approximately 17% of normal and, in absolute magnitude ( approximately 5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants.     

The growth of growth

Over a 40-year period, 1940 through the present, human growth research has increased from a minimal to a major part of physical anthropology. Such research, originally conducted at the major American growth centers, has become more diverse and more specialized, extending to National Probability Samplings, nutritional surveys, studies of twins, investigations restricted to the craniofacial complex, and studies of the growth and development of various primate species. Besides extending knowledge of growth and development in general and control mechanisms in particular, there has been major feedback into physical anthropology affording far greater understanding of human variability, of taxonomic differences, and of changes previously believed to be phylogenetic in nature. To the larger extent, all physical anthropologists have some degree of growth awareness.     

Insulin-like growth factors,hepatocyte growth factor and transforming growth factor-alpha in mouse tongue myogenesis

Many reports have shown that tongue striated muscles have several unique characteristics not found in other skeletal muscles such as limb and trunk. Several peptide growth factors are reported to play important roles in skeletal myogenesis. In this article, the roles of insulin-like growth factors (IGF), hepatocyte growth factor (HGF) and transforming growth factor (TGF)-alpha in mouse tongue myogenesis were studied using an organ culture system of the mandible or tongue obtained from mouse embryos. It was found that IGF-I promotes the differentiation of tongue myoblasts. HGF plays an essential role in the migration and proliferation of tongue myogenic cells, and inhibits the differentiation of tongue myoblasts. TGF-alpha does not play an essential role in the proliferation of tongue myogenic cells, but does promote the early differentiation of tongue myoblasts. The role of IGF-I in the differentiation of tongue myoblasts, and that of HGF in the migration, proliferation and differentiation of tongue myogenic cells appear to be almost identical to their roles in the myogenesis of limb and cultured myogenic cell lines. However, the role of TGF-alpha in the proliferation and differentiation of tongue myogenic cells appears to be different from its role in the myogenesis of limb and cultured myogenic cell lines such as C2 and L6.     

Serum zinc and somatic growth in children with growth retardation

A possible role for zinc deficiency in some cases of growth retardation in southern France was investigated. Control values for zinc for 160 children (age=12.5±2.4 yr) are 0.85±0.22 mg/L (mean ±2 SD). Twenty-five children with low serum zinc values (<0.63 mg/L) and 25 matched short children with normal serum zinc values (>0.63 mg/L) were studied. Children in the two groups did not differ significantly in age, pubertal development, stature, and weight. For the 25 children whose serum values were low, we found significantly lower values for bone age delay, growth velocity in mm/month, as well as the ratio between calculated growth velocity and theoretical growth velocity for the bone age (so that zincemia was correlated to these parameters in the whole sample of 50 subjects). Nevertheless, no significant difference could be found between the two groups for serum somatomedin C, serum osteocalcin values, and GH responses to the GH stimulatory tests (exercise test, overnight sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc is associated with a retardation in both somatic growth and pubertal maturation.     

Parabolic growth patterns in 96-well plate cell growth experiments

Summary In preparing for the routine use of the ubiquitous in vitro cell growth inhibition assay for the study of anticancer agents, we characterized the statistical properties of the assay and found some surprising results. Parabolic well-to-well cell growth patterns were discovered, which could profoundly affect the results of routine growth inhibition studies of anticancer and other agents. Four human ovarian cell lines, A2780/WT, A2780/DX5, A2780/DX5B, and A121, and one human ileocecal adenocarcinoma cell line, HCT-8, were seeded into plastic 96-well plates with a 12-channel pipette, without drugs, and grown from 1–5 d. The wells were washed with a plate washer, cells stained with sulforhodamine B (SRB), and dye absorbance measured with a plate reader. Variance models were fit to the data from replicates to determine the nature of the heteroscedastic error structure. Exponential growth models were fit to data to estimate doubling times for each cell line. Polynomial models were fit to data from 10-plate stacks of 96-well plates to explore nonuniformity of cell growth in wells in different regions of the stacks. Each separate step in the assay was examined for precision, patterns, and underlying causes of variation. Differential evaporation of water from wells is likely a major, but not exclusive, contributor to the systematic well-to-well cell growth patterns. Because the fundamental underlying causes of the parabolic growth patterns were not conclusively found, a randomization step for the growth assay was developed.     

Peptide growth factor interactions in embryonic and fetal growth.

Peptide growth factors are expressed by multiple tissues in the animal and human embryo and fetus. They undergo specific interactions which control the rate of cellular proliferation, tissue differentiation and the induction of specific morphogenic events such as mesoderm formation in the embryo. Biologic control may not only be exerted at the level of growth factor synthesis and receptor expression but by the sequestration and storage of growth factors by extracellular matrix molecules. In the case of insulin-like growth factors (IGFs), storage maybe mediated by attachment to specific IGF-binding proteins which may additionally modulate biological potency. Basic fibroblast growth factor (basic FGF) and transforming growth factor-beta (TGF beta) directly bind to glycosaminoglycan molecules. Release of growth factors from these stores may be by local proteolytic action. A sequential expression of basic FGF, IGF-II and TGF beta occurs in the ovine fetal epiphyseal growth plate as chondrocytes progress from a proliferative to a postmitotic, hypertrophic state. Cellular phenotype may be largely explained by the relative amounts of these autocrine growth factors within the growth plate.     

Light growth inhibition and growth inhibitors in Sakurajima radish seedlings

Growth of Sakurajima radish seedlings (Raphanus sativus var.hortensis f. gigantissimus Makino) was studied in relation tothe effects of light, the effectiveness of plant hormones, andthe variation in endogenous growth inhibitor content Externally applied GAs and IAA had no effect on the elongationof the hypocotyl in the light as well as in the dark. BA wasslightly promotive in the light, but was not so effective asto nullify the light-induced inhibition of elongation. ABA wasstrongly suppressive in the light as well as in the dark. Growth inhibitors in seedlings were extracted, analyzed by thin-layerchromatography and the Sakurajima radish hypocotyl elongationtest, and 3 acidic and 3 neutral inhibitors were detected. Amongthem all of the acidic and one of the neutral inhibitors increasedwith the time period of illumination, whereas the other 2 neutralsubstances remained almost unchanged in the light but decreasedin the dark. Thus the levels of all 6 inhibitors was higherin light-grown seedlings than in dark-grown ones. This suggeststhat light inhibition in Sakurajima radish hypocotyls may becontrolled by the variation in the inhibitor levels in the seedlings. (Received December 1, 1977; )     

Chelal growth in pseudoscorpions

There is a linear relationship between the successive positions of named trichobothria on the pedipalpal chelae during the course of post-embryonic development of five British pseudoscorpions belonging to the family Neobisiidae. Growth constants calculated from the trichobothrial data are higher than those calculated for the chelal axis. This discrepancy is resolved in terms of a model, based on growing and non-growing regions, which is a good approximation to the data. The extent of these regions is calculated for all stages and differences between the species are noted. The assumptions implicit in the model, its realism and its predictive value are discussed.     

Cognitive function in growth hormone deficiency and growth hormone replacement

There is converging evidence from neuropsychological studies that growth hormone (GH) is associated with cognitive function. The aim of the current study was to review the existing neuropsychological literature for studies in which cognitive assessment had been conducted in patients with GH deficiency (GHD), and where change in cognitive function had been assessed following treatment with GH. Studies that have investigated relationships between GH and cognitive function and those that have developed methodological and statistical approaches that could be useful in future GH studies were identified. In this review, GH levels were found to be associated with cognitive function. Untreated individuals with GHD showed reliable impairment in memory and attentional functions when compared with matched controls. Appropriately designed prospective studies also indicated that cognitive function improved with GH treatment. It was concluded that individuals with GHD do show cognitive impairment and that this is ameliorated to some extent by GH treatment. It is now important to establish the clinical importance of these findings, and further work is required to understand better the nature, magnitude and meaning of GH-related cognitive impairments and improvements.     

Polyamines in intestinal growth

The total cellular mass of the small intestine is well controlled and can adapt, with hypo- or hyperplasia, to a wide variety of stimuli. Luminal nutrients, hormonal factors and pancreatic and biliary secretions have all been implicated in the regulation of intestinal mucosal growth. The polyamines (putrescine, spermidine and spermine) and the key enzyme controlling their synthesis (ornithine decarboxylase. ODC) are critical for many cell growth processes and appear to play important roles in intestinal growth. During intestinal adaptation in response to jejunectomy, lactation. pancreatic-biliary diversion, starvation-refeeding and feeding with kidney bean lectin, intestinal contents of ODC and polyamines are increased, paralleling increases in mucosal proliferative indices and DNA synthesis. With administration of the specific inhibitor of ODC (difluoromethylornithine, DFMO) the increase in ODC and polyamines is inhibited and intestinal growth is suppressed. In addition, the oral administration of exogenous polyamines results in precocious maturation of the neonatal rat intestine. These results suggest that the polyamines are important for intestinal growth.     

Xenomorphic growth in ostreids

Attachment surfaces of ostreids preserve the (negative) imprint of the substrate morphology while the right (upper, free) valve may reflect its positive form (xenomorphism or xenomorphic sculpture). The substrate may be an invertebrate skeleton which is dissolved during diagenesis. The imprint of such skeletons on ostreid valves has often a greater biostratigraphic significance than the ostreid itself. Fossil examples are described.