Development of Mandarin spoken language after pediatric cochlear implantation.
Li, Bei; Soli, Sigfrid D; Zheng, Yun; Li, Gang; Meng, Zhaoli
2014-07-01
The purpose of this study was to evaluate early spoken language development in young Mandarin-speaking children during the first 24 months after cochlear implantation, as measured by receptive and expressive vocabulary growth rates. Growth rates were compared with those of normally hearing children and with growth rates for English-speaking children with cochlear implants. Receptive and expressive vocabularies were measured with the simplified short form (SSF) version of the Mandarin Communicative Development Inventory (MCDI) in a sample of 112 pediatric implant recipients at baseline, 3, 6, 12, and 24 months after implantation. Implant ages ranged from 1 to 5 years. Scores were expressed in terms of normal equivalent ages, allowing normalized vocabulary growth rates to be determined. Scores for English-speaking children were re-expressed in these terms, allowing direct comparisons of Mandarin and English early spoken language development. Vocabulary growth rates during the first 12 months after implantation were similar to those for normally hearing children less than 16 months of age. Comparisons with growth rates for normally hearing children 16-30 months of age showed that the youngest implant age group (1-2 years) had an average growth rate of 0.68 that of normally hearing children; while the middle implant age group (2-3 years) had an average growth rate of 0.65; and the oldest implant age group (>3 years) had an average growth rate of 0.56, significantly less than the other two rates. Growth rates for English-speaking children with cochlear implants were 0.68 in the youngest group, 0.54 in the middle group, and 0.57 in the oldest group. Growth rates in the middle implant age groups for the two languages differed significantly. The SSF version of the MCDI is suitable for assessment of Mandarin language development during the first 24 months after cochlear implantation. Effects of implant age and duration of implantation can be compared directly across languages using normalized vocabulary growth rates. These comparisons for Mandarin and English reveal comparable results, despite the diversity of these languages, underscoring the universal role of plasticity in the developing auditory system. Copyright © 2014. Published by Elsevier Ireland Ltd.
Growth and development after hematopoietic cell transplant in children.
Sanders, J E
2008-01-01
Hematopoietic cell transplantation (HCT) following high-dose chemotherapy or chemoradiotherapy for children with malignant or nonmalignant hematologic disorders has resulted in an increasing number of long-term disease-free survivors. The preparative regimens include high doses of alkylating agents, such as CY with or without BU, and may include TBI. These agents impact the neuroendocrine system in growing children and their subsequent growth and development. Children receiving high-dose CY or BUCY have normal thyroid function, but those who receive TBI-containing regimens may develop thyroid function abnormalities. Growth is not impacted by chemotherapy-only preparative regimens, but TBI is likely to result in growth hormone deficiency and decreased growth rates that need to be treated with synthetic growth hormone therapy. Children who receive high-dose CY-only have normal development through puberty, whereas those who receive BUCY have a high incidence of delayed pubertal development. Following fractionated TBI preparative regimens, approximately half of the patients have normal pubertal development. These data demonstrate that the growth and development problems after HCT are dependent upon the preparative regimen received. All children should be followed for years after HCT for detection of growth and development abnormalities that are treatable with appropriate hormone therapy.
Normal development and growth of the human neurocranium and cranial base.
Friede, H
1981-01-01
The literature on normal development and growth of certain areas of the human head is reviewed, starting with the early induction of the desmal neurocranium. the development of the brain capsule with its dural reinforcement bands and their connection with the basicranium is discussed, as is the primordial chondrocranium, including its bone replacement. Growth of the calvaria and the three cranial fossae is also analysed. Special interest is focused on the anterior fossa, as knowledge of the growth in this area is very important for an understanding of pathogenesis and possibilities of treating premature craniosynostosis. Finally it is stressed that close observation of the effects of treatment on this pathology may increase our knowledge of normal growth.
What Is a Growth Disorder? (For Parents)
... hormone, which is essential for normal bone growth. Turner syndrome , one of the most common genetic growth disorders, ... chromosome. In addition to short stature, girls with Turner syndrome usually don't undergo normal sexual development because ...
Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen
2013-08-01
Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.
Li, X; Velleman, S G
2009-02-01
During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation. The TGF-beta1 signal is carried by Smad proteins into the cell nucleus, inhibiting the expression of key myogenic regulatory factors including MyoD and myogenin. However, the molecular mechanism by which TGF-beta1 inhibits muscle cell proliferation and differentiation has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on in vivo skeletal muscle growth and development. A chicken line, Low Score Normal (LSN) with reduced muscling and upregulated TGF-beta1 expression, was used and compared to a normal chicken line. The injection of TGF-beta1 at embryonic day (ED) 3 significantly reduced the pectoralis major (p. major) muscle weight in the normal birds at 1 wk posthatch, whereas no significant difference was observed in the LSN birds. The difference between normal and LSN birds in response to TGF-beta1 is likely due to different levels of endogenous TGF-beta1 where the LSN birds have increased TGF-beta1 expression in their p. major muscle at both 17 ED and 6 wk posthatch. Smad3 expression was reduced by TGF-beta1 from 10 ED to 1 wk posthatch in normal p. major muscle. Unlike Smad3, Smad7 expression was not significantly affected by TGF-beta1 until posthatch in both normal and LSN p. major muscle. Expression of MyoD was reduced 35% by TGF-beta1 during embryonic development in normal p. major muscle, whereas LSN p. major muscle showed a delayed decrease at 1 d posthatch in MyoD expression in response to the TGF-beta1 treatment. Myogenin expression was reduced 29% by TGF-beta1 after hatch in normal p. major muscle. In LSN p. major muscle, TGF-beta1 treatment significantly decreased myogenin expression by 43% at 1 d posthatch and 32% at 1 wk posthatch. These data suggested that TGF-beta1 reduced p. major muscle growth by inhibiting MyoD and myogenin expression during both embryonic and posthatch development. Furthermore, TGF-beta1 also reduced the expression of the cell adhesion receptor beta1 integrin subunit during embryonic and posthatch muscle growth in normal and LSN chickens. Therefore, the reduction of beta1 integrin in response to TGF-beta1 is also associated with decreased posthatch muscle growth. The results from this study indicate that TGF-beta1 inhibits skeletal muscle growth by regulating MyoD and myogenin expression. These data also suggest that a beta1 integrin-mediated alternative pathway is likely involved in the TGF-beta1-induced reduction of muscle growth.
Growth and development issues in adolescents with ostomies: a primer for the WOC nurses.
Mohr, Lynn D
2012-01-01
Caring for the adolescent (13-18 years of age) with an ostomy presents multiple challenges. The purpose of this article is to provide strategies to assist the WOC nurse in minimizing the potential impact on growth and development for this age group with an ostomy. This is relevant to the WOC nurse since it is estimated that between 6% and 14% of all adolescents have symptoms of irritable bowel disease, and many will require an ostomy. Thus the WOC nurse will be called upon to provide care to this age group. This article discusses normal adolescent growth and development and provides strategies to support the normal growth and development.
Development of a Novel Tissue Specific Aromatase Activity Regulation Therapeutic Method
2009-09-01
Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Estrogen is essential for normal growth and development of the female ...the ovaries and other tissues of the body using an enzyme called aromatase. Once women have reached menopause, the ovaries no longer produce estrogen...Introduction Estrogen is essential for normal growth and development of the female reproductive system, including breast tissue, and lifetime
Link, Daphna; Braginsky, Michael B; Joskowicz, Leo; Ben Sira, Liat; Harel, Shaul; Many, Ariel; Tarrasch, Ricardo; Malinger, Gustavo; Artzi, Moran; Kapoor, Cassandra; Miller, Elka; Ben Bashat, Dafna
2018-01-01
Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). The developed method showed high correlation with manual segmentation (r2 = 0.9183, p < 0.001) as well as mean volume and volume overlap differences of 4.77 and 18.13%, respectively. New reference data on 199 normal fetuses were created, and all 9 IUGR fetuses were at or below the third percentile of the normal growth chart. The proposed method is fast, accurate, reproducible, user independent, applicable with retrospective data, and is suggested for use in routine clinical practice. © 2017 S. Karger AG, Basel.
Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.
Wang, H; Wang, A; Wang, D; Bright, A; Sency, V; Zhou, A; Xin, B
2016-05-01
Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GSD) causes a complete absence of GM3 and all downstream biosynthetic derivatives. The individuals affected by this disorder manifest severe irritability, intractable seizures and profound intellectual disability. However, we have found that most newborns seem symptom-free for a period of time after birth. In order to further understand the onset of the disease, we investigated the early growth and development of patients with this condition through this study. We compared 37 affected individuals with their normal siblings and revealed that all children with GSD had relatively normal intrauterine growth and development, as their weight, length and head circumference were similar to their normal siblings at birth. However, the disease progresses quickly after birth and causes significant constitutional impairments of growth and development by 6 months of age. Neither breastfeeding nor gastrostomy tube placement made significant difference on growth and development as all groups of patients showed the similar pattern. We conclude that GSD causes significant postnatal growth and developmental impairments and the amount of gangliosides in breast milk and general nutritional intervention do not seem to alter these outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.
Jin, Jing; De Ribaupierre, Sandrine; Eagleson, Roy
2016-01-01
This paper describes a simulation framework for a clinical application involving skull-brain co-development in infants, leading to a platform for craniosynostosis modeling. Craniosynostosis occurs when one or more sutures are fused early in life, resulting in an abnormal skull shape. Surgery is required to reopen the suture and reduce intracranial pressure, but is difficult without any predictive model to assist surgical planning. We aim to study normal brain-skull growth by computer simulation, which requires a head model and appropriate mathematical methods for brain and skull growth respectively. On the basis of our previous model, we further specified suture model into fibrous and cartilaginous sutures and develop algorithm for skull extension. We evaluate the resulting simulation by comparison with datasets of cases and normal growth.
van den Hondel, Desiree; Sloots, Cornelius E J; Gischler, Saskia J; Meeussen, Conny J H M; Wijnen, Rene M H; IJsselstijn, Hanneke
2013-04-01
To evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. Non-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5 years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. 108 children (59% male) were included. 49% had a high malformation, and 46% had ≥ 1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥ 1 additional major anomaly had lower height at all ages; at 5 years, mean (95% CI) height was -1.83 (-2.7 to -1.1) and -0.70 (-1.3 to -0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5 years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). Non-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems. Copyright © 2013 Elsevier Inc. All rights reserved.
Kim, Jeong Chul; Wang, Li; Shen, Dinggang; Lin, Weili
2016-12-02
The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.
Lafeber, H N; Rolph, T P; Jones, C T
1984-12-01
The effects of reduced maternal placental blood flow on the growth and development of the fetal guinea pig have been studied by unilateral ligation of the uterine artery at day 30 of pregnancy. Fetal guinea pigs were investigated about 20 or 30 days later. In about one-third of cases fetal death occurred, in another third fetuses less than 60% of normal weight were observed and in the remainder all fetuses were in the normal weight range. In the growth retarded fetuses prenatal growth occurred at about 50% of the rate in control. There was no postnatal 'catch up' as growth still remained lower than in controls. Restricted fetal growth affected particularly development of the visceral tissues in which case size declined in proportion to body weight. Brain and adrenal by comparison were less affected as their contribution to total body weight increased, but even so in the severely retarded fetuses the mass of both fell. The responses of the liver were in general consistent with a delay in the pattern of development. Thus DNA, RNA, protein and haematopoietic cell content changes occurred later than normal. In contrast an enhanced deposition of glycogen was apparent in the liver of the growth-retarded fetus. The results indicate some of the ways in which nutritional deprivation of the fetuses leads to reprogramming of growth and maturation of selected fetal tissues to allow non-essential changes to await more favourable times.
Evidence for altered placental blood flow and vascularity in compromised pregnancies
Reynolds, Lawrence P; Caton, Joel S; Redmer, Dale A; Grazul-Bilska, Anna T; Vonnahme, Kimberly A; Borowicz, Pawel P; Luther, Justin S; Wallace, Jacqueline M; Wu, Guoyao; Spencer, Thomas E
2006-01-01
The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can ‘rescue’ fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies. PMID:16469783
Rastogi, Rajeev; Sawhney, Vipen K.
1990-01-01
The floral organs of the male sterile stamenless-2 (sl-2/sl-2) mutant of tomato (Lycopersicon esculentum Mill.) contain significantly higher level of polyamines than those of the normal (R Rastogi, VK Sawhney [1990] Plant Physiol 93: 439-445). The effects of putrescine, spermidine and spermine, and three different inhibitors of polyamine biosynthesis on the in vitro development of floral buds of the normal and sl-2/sl-2 mutant were studied. The polyamines were inhibitory to the in vitro growth and development of both the normal and mutant floral buds and they induced abnormal stamen development in normal flowers. The inhibitors of polyamine biosynthesis also inhibited the growth and development of floral organs of the two genotypes, but the normal flowers showed greater sensitivity than the mutant. The inhibitors also promoted the formation of normal-looking pollen in stamens of some mutant flowers. The effect of the inhibitors on polyamine levels was not determined. The polyamine-induced abnormal stamen development in the normal, and the inhibitor-induced production of normal-looking pollen in mutant flowers support the suggestion that the elevated polyamine levels contribute to abnormal stamen development in the sl-2/sl-2 mutant of tomato. Images Figure 3 Figure 5 PMID:16667486
Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.
Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen
2013-09-01
Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.
Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds
Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen
2013-01-01
Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652
Abdeyazdan, Zahra; Ehsanpour, Soheila; Hemmati, Elahe
2014-01-01
Growth and development monitoring could lead to general judgment about children's health. With advances in NICUs establishment, the survival rate of very low birth weight (VLBW) neonates has increased in many countries including Iran. Because of the lack of studies about growth and development pattern of low birth weight (LBW) and VLBW neonates in Iran, the present study aimed to compare growth and development of normal, low and very low birth weight neonates at 18 months of age. In a cross- sectional descriptive study, 214 children with age 18 months were enrolled (90 LBW, 90 LBW and 34 VLBW) and their growth and development were assessed. Data gathering tool was a researcher made questionnaire including anthropometrics measures and developmental key points. Data analyzed by descriptive (mean and SD) and inferential (ANOVA) tests using SPSS version 15. There were significant differences in the mean of anthropometric indexes between three groups. Majority of subjects in three groups had normal weight growth trend. Mean scores of gross motor and fine motor development indexes had significant association with birth weight. Meanwhile, there was no significant association between mean scores of social/cognitive and also language developmental aspects and birth weight. Findings revealed that in LBW and VLBW children, growth indexes at the age of 18 months are so far from those of NBW neonates. Further nationwide prospective studies, with a longer period of time is needed to estimate when Iranian LBW children reach at the levels of NBW ones.
NASA Astrophysics Data System (ADS)
McBirney, Samantha E.; Trinh, Kristy; Wong-Beringer, Annie; Armani, Andrea M.
2017-02-01
One of the fundamental analytical measurements performed in microbiology is monitoring and characterizing cell concentration in culture media. Measurement error will give rise to reproducibility problems in a wide range of applications, from biomanufacturing to basic research. Therefore, it is critical that the generated results are consistent. Single wavelength optical density (OD) measurements have become the preferred approach. Here, we compare the conventional OD600 technique with a multi-wavelength normalized scattering optical spectroscopy method to measure the growth rates of Pseudomonas aeruginosa and Staphylococcus aureus, two of the leading nosocomial pathogens with proven abilities to develop resistance. The multi-wavelength normalization process minimizes the impact of bacteria byproducts and environmental noise on the signal, thereby accurately quantifying growth rates with high fidelity at low concentrations. In contrast, due to poor absorbance and scattering at 600 nm, the classic OD600 measurement method is able to detect bacteria but cannot quantify the growth rate reliably. Our wavelength-normalization protocol to detect bacteria growth rates can be readily and easily adopted by research labs, given that it only requires the use of a standard spectrophotometer and implementation of straightforward data analysis. Measuring and monitoring bacteria growth rates play a critical role in a wide range of settings, spanning from therapeutic design and development to diagnostics and disease prevention. Having a full understanding of the growth cycles of bacteria known to cause severe infections and diseases will lead to a better understanding of the pathogenesis of these illnesses, leading to better treatment and, ultimately, the development of a cure.
Normal growth and development in the absence of hepatic insulin-like growth factor I
Yakar, Shoshana; Liu, Jun-Li; Stannard, Bethel; Butler, Andrew; Accili, Domenici; Sauer, Brian; LeRoith, Derek
1999-01-01
The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I. PMID:10377413
Growth in pediatric renal transplant recipients.
Vasudevan, A; Phadke, K
2007-04-01
One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.
Schmucker, Hannah S; Park, Jang Pyo; Coissieux, Marie-May; Bentires-Alj, Mohamed; Feltus, F Alex; Booth, Brian W
2017-05-01
Tumorigenic cells can be redirected to adopt a normal phenotype when transplanted into cleared mammary fat pads of juvenile female mice in specific ratios with normal epithelial cells. The redirected tumorigenic cells enter stem cell niches and provide progeny that differentiate into all mammary epithelial subtypes. We have developed an in vitro model that mimics the in vivo phenomenon. The shift in phenotype to redirection should be accomplished through a return to a normal gene expression state. To measure this shift, we interrogated the transcriptome of various in vitro model states in search for casual genes. For this study, expression of growth factors, cytokines, and their associated receptors was examined. In all, we queried 251 growth factor and cytokine-related genes. We found numerous growth factor and cytokine genes whose expression levels switched from expression levels seen in cancer cells to expression levels observed in normal cells. The comparisons of gene expression between normal mammary epithelial cells, tumor-derived cells, and redirected cancer cells have revealed insight into active and inactive growth factors and cytokines in cancer cell redirection.
NASA Astrophysics Data System (ADS)
Tvedt, Anette B. M.; Rotevatn, Atle; Jackson, Christopher A.-L.
2016-10-01
Normal faulting and the deep subsurface flow of salt are key processes controlling the structural development of many salt-bearing sedimentary basins. However, our detailed understanding of the spatial and temporal relationship between normal faulting and salt movement is poor due to a lack of natural examples constraining their geometric and kinematic relationship in three-dimensions. To improve our understanding of these processes, we here use 3D seismic reflection and borehole data from the Egersund Basin, offshore Norway, to determine the structure and growth of a normal fault array formed during the birth, growth and decay of an array of salt structures. We show that the fault array and salt structures developed in response to: (i) Late Triassic-to-Middle Jurassic extension, which involved thick-skinned, sub-salt and thin-skinned supra-salt faulting with the latter driving reactive diapirism; (ii) Early Cretaceous extensional collapse of the walls; and (iii) Jurassic-to-Neogene, active and passive diapirism, which was at least partly coeval with and occurred along-strike from areas of reactive diapirism and wall collapse. Our study supports physical model predictions, showcasing a three-dimensional example of how protracted, multiphase salt diapirism can influence the structure and growth of normal fault arrays.
Choline pathways during normal and stimulated renal growth in rats.
Bean, G H; Lowenstein, L M
1978-01-01
Cellular membrane synthesis occurs during normal and stimulated renal growth. Choline in the kidney is utilized as a precursor for membrane synthesis via the choline kinase reaction. We investigated choline phosphorylation during normal and stimulated renal growth. Rapidly growing neonatal rat kidneys contained relatively high levels of choline kinase activity (61 pmol phosphorylcholine/min per mg protein). Choline kinase activity and phosphorylcholine production then fell gradually over the 1st mo of life; by 1 mo phosphorylcholine production was 34 pmol phosphorylcholine/min per mg protein. Choline kinase activity increased by 27% (P less than 0.001) in 28-day-old rats when renal growth was stimulated by contralateral nephrectomy; the increase occurred within 2 h after surgery. Thus, changes in the activity of this important enzyme in the initiation of membrane synthesis is associated both with normal renal development and with adaptation to nephron loss. The findings further suggest that the cell membrane may be involved in the initiation of compensatory renal growth. PMID:659614
Growth and development of British vegan children.
Sanders, T A
1988-09-01
The growth and development of children born of vegan mothers and reared on a vegan diet has been studied longitudinally: All of the children were breast-fed for the first 6 mo of life and in most cases well into the second year of life. The majority of children grew and developed normally but they did tend to be smaller in stature and lighter in weight than standards for the general population. Energy, calcium, and vitamin D intakes were usually below the recommended amounts. Their diets, however, were generally adequate but a few children had low intakes of riboflavin and vitamin B-12. Most parents were aware of the need to supplement the diet with vitamin B-12. It is concluded that provided sufficient care is taken, a vegan diet can support normal growth and development.
NASA Technical Reports Server (NTRS)
Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.
2003-01-01
Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.
Growth hormone therapy in hypochondroplasia.
Ramaswami, U; Hindmarsh, P C; Brook, C G
1999-02-01
Patients with hypochondroplasia present with variable phenotypes. Children with severe short stature and disproportion of the body segments usually have the mutation Asn540Lys. They respond to growth hormone (GH) therapy with an increase in spinal length and, coupled with a surgical leg-lengthening procedure, it is possible for some patients to achieve adult heights within the normal range. Some children who present with proportionate short stature and hypochondroplasia fail to increase their growth rate at puberty, although the growth spurt can be restored by GH therapy. Others, with an identical presentation, seem to grow normally during puberty. At present, there is no way of predicting who will undergo a normal pubertal growth spurt. We therefore monitor all patients during childhood and give GH treatment only to those patients who fail to develop a growth spurt at puberty. Severe cases may occasionally need treatment before puberty if their growth velocity is compromised, but these will probably also be candidates for a surgical leg-lengthening procedure.
A frozen-thawed in vitro-matured bovine oocyte derived calf with normal growth and fertility.
Otoi, T; Yamamoto, K; Koyama, N; Tachikawa, S; Suzuki, T
1996-08-01
The growth and fertility of a female calf obtained from a frozen-thawed bovine oocyte was assessed. The birth weight of the calf was lower than the mean birth weight of calves from in vitro fertilized embryos (IVF-controls) and calves obtained by artificial insemination (AI-controls). The growth rate of the calf up to 6 months was slower than that of the IVF-controls, but similar to that of the AI-controls. When the calf developed into a heifer (200 kg), she was inseminated with frozen semen and 280 days later delivered a male calf. The chromosoms of this cow were normal. These findings suggest that the growth and fertility of the calf derived from the frozen oocyte are normal.
Optical aberrations, retinal image quality and eye growth: Experimentation and modeling
NASA Astrophysics Data System (ADS)
Tian, Yibin
2007-12-01
Retinal image quality is important for normal eye growth. Optical aberrations are of interest for two reasons: first, they degrade retinal images; second, they might provide some cues to defocus. Higher than normal ocular aberrations have been previously associated with human myopia. However, these studies were cross-sectional in design, and only reported aberrations in terms of root mean square (RMS) errors of Zernike coefficients, a poor metric of optical quality. This dissertation presents results from investigations of ocular optical aberrations, retinal image quality and eye growth in chicks and humans. A number of techniques were utilized, including Shack-Hartmann aberrometry, high-frequency A-scan ultrasonography, ciliary nerve section (CNX), photorefractive keratectomy (PRK) as well as computer simulations and modeling. A technique to extract light scatter information from Shack-Hartmann images was also developed. The main findings of the dissertation are summarized below. In young chicks, most ocular aberrations decreased with growth in both normal and CNX eyes, and there were diurnal fluctuations in some aberrations. Modeling suggested active reduction in higher order aberrations (HOAs) during early development. Although CNX eyes manifested greater than normal HOAs, they showed near normal growth. Retinal image degradation varied greatly among individual eyes post-PRK in young chicks. Including light scatter information into analyses of retinal image quality better estimated the latter. Albino eyes showed more severe retinal image degradation than normal eyes, due to increased optical aberrations and light scatter, but their growth was similar to those of normal eyes, implying that they are relatively insensitive to retina image quality. Although the above results questioned the influence of optical aberrations on early ocular growth, some optical quality metrics, derived from optical aberrations data, could predict how much the eyes of young chicks subsequently elongated. The performance of some focus measures was very poor when non-defocus aberrations exceeded a certain level; presumably, these non-defocus aberrations might interfere with the eye's ability to interpret defocus. In anisomyopic human adults, more myopic eyes had larger anterior and vitreous chambers, greater astigmatism, and more positive spherical aberration. However, compared to isometropes, only interocular differences in spherical equivalent refractive errors were significantly increased.
Circulating levels of IGF-1 directly regulate bone growth and density
Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek
2002-01-01
IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108
The origin and development of malocclusions. When, where and how dental malocclusions develop.
Loudon, Merle E
2013-01-01
This article describes the forces of the muscles from the stomatonathic system and how they interact in many children to change the normal forces of growth. Because of this change in muscle forces there is a change from normal teeth and bone growth positions to abnormal positions. These normal and/or abnormal changes in muscle forces are the basis for development into class one, class two and class three occlusions. This is very valuable information for the orthodontic clinician because these muscle forces are the fundamental basis for all orthodontic treatment. By knowing this an orthodontic clinician will be more able to diagnose and treat a malocclusion. This is exceptionally important for the dentist who is just starting to learn diagnosis, treatment planning, functional and fixed orthodontic treatment.
Red alder stand development and dynamics.
R.L. Deal
2006-01-01
This paper synthesizes information on the development of natural pure red alder stands and dynamics of mixed alder-conifer stands. Early research on red alder growth and yield focused on developing stand volume and normal yield. tables for alder in the Pacific Northwest. Recent site-index estimation and height-growth curves were developed on a 20-year site base age....
Placental angiogenesis in sheep models of compromised pregnancy
Reynolds, Lawrence P; Borowicz, Pawel P; Vonnahme, Kimberly A; Johnson, Mary Lynn; Grazul-Bilska, Anna T; Redmer, Dale A; Caton, Joel S
2005-01-01
Because the placenta is the organ that transports nutrients, respiratory gases and wastes between the maternal and fetal systems, development of its vascular beds is essential to normal placental function, and thus in supporting normal fetal growth. Compromised fetal growth and development have adverse health consequences during the neonatal period and throughout adult life. To establish the role of placental angiogenesis in compromised pregnancies, we first evaluated the pattern of placental angiogenesis and expression of angiogenic factors throughout normal pregnancy. In addition, we and others have established a variety of sheep models to evaluate the effects on fetal growth of various factors including maternal nutrient excess or deprivation and specific nutrients, maternal age, maternal and fetal genotype, increased numbers of fetuses, environmental thermal stress, and high altitude (hypobaric) conditions. Although placental angiogenesis is altered in each of these models in which fetal growth is adversely affected, the specific effect on placental angiogenesis depends on the type of ‘stress’ to which the pregnancy is subjected, and also differs between the fetal and maternal systems and between genotypes. We believe that the models of compromised pregnancy and the methods described in this review will enable us to develop a much better understanding of the mechanisms responsible for alterations in placental vascular development. PMID:15760944
Zhong, Ruiqin; Kays, Stanley J; Schroeder, Betty P; Ye, Zheng-Hua
2002-01-01
Chitinase-like proteins have long been proposed to play roles in normal plant growth and development, but no mutations in chitinase-like genes have been obtained previously to support this hypothesis. In this study, we have shown that the gene responsible for the elp1 mutation in Arabidopsis encodes a chitinase-like protein (AtCTL1). Mutation of this chitinase-like gene caused ectopic deposition of lignin and aberrant shapes of cells with incomplete cell walls in the pith of inflorescence stems. The AtCTL1 gene was expressed in all organs during normal plant growth and development, but it was not induced by wounding, salicylic acid, pectin fragments, or ethylene. Consistent with its ubiquitous expression pattern, mutation of the AtCTL1 gene affected many aspects of plant growth and development, including exaggerated hook curvature, reduced length and increased diameter of hypocotyls in dark-grown seedlings, and reduced root length and increased number of root hairs in light-grown seedlings. The mutant phenotypes could be rescued partially by ethylene inhibitors, and ethylene production in the mutant was significantly greater than in the wild type. Together, these results suggest that AtCTL1, a chitinase-like gene, is essential for normal plant growth and development in Arabidopsis.
The hormone prolactin (PRL) plays a critical role in normal breast development by stimulating the proliferation of mammary cells, the production of milk proteins, and the formation of new mammary blood vessels. Unfortunately, the same cell and vessel growth pathways controlled by PRL in normal cells also operate in breast cancer cells, and elevated plasma PRL is a risk factor
Weiss, S; Schaeffel, F
1993-04-01
1. If the eyes of young chickens are deprived of clear vision by translucent occluders, they develop considerable amounts of axial myopia within days. At the same time, the day time retinal dopamine levels drop by about 30%. Because the retinal dopamine levels of normally sighted chicks also differ diurnally and are low at night, we expected that the rate of axial eye growth might also differ during this time. 2. Unexpectedly, eyes grew in length only during the day (about 0.13 mm/day) and even shrank during the night (about -0.04 mm/night, average net growth +0.09 mm in 24 h). 3. If the eyes were occluded, they grew both during the day and also at night (average net growth: +0.16 mm in 24 h). Therefore, development of deprivation myopia was a result of the lack of growth inhibition at night rather than of excessive growth during the day when the actual deprivation occurred. 4. Suppression of dopaminergic retinal pathways by intravitreal injections of the neurotoxin 6-hydroxy-dopamine (6-OHDA) also suppressed development of deprivation myopia and it restored the growth inhibition at night. With normal visual experience, the drug had no effect on axial eye growth and refractive state. 5. Diurnal growth rhythms of the eyes disappeared under continuous light.(ABSTRACT TRUNCATED AT 250 WORDS)
Zahmatkeshan, Mozhghan; Karamizadeh, Zohre; Geramizadeh, Bita; Eshraghian, Ahad
2014-03-01
We report a patient with growth hormone deficiency that developed cholestatic hepatitis during treatment with recombinant human growth hormone (HGH). The patient developed jaundice and pruritus during treatment with growth hormone. She did not use any other medications. Her jaundice and pruritus were disappeared and liver enzyme disturbances were normalized after HGH discontinuation. Clinician should be aware of this potential adverse drug reaction and frequent checking of liver enzymes is recommended in patients treating with HGH.
Wang, Yuanxiao; Zhang, Lili; Zhou, Genlai; Liao, Zhiyong; Ahmad, Hussain; Liu, Wenbin; Wang, Tian
2012-10-28
Intra-uterine growth retardation (IUGR) impairs postnatal growth and development of the small intestine (SI) in neonatal pigs and infants. L-Arginine (Arg), a critical amino acid involved in promoting growth and metabolism in young mammals, is more deficient in IUGR fetuses. However, little is known whether dietary Arg supplementation would accelerate the impaired development of the SI induced by IUGR in piglets. In the present study, a total of six litters of newborn piglets were used. In each litter, one normal and two IUGR littermates were obtained. Piglets were fed milk-based diets supplemented with 0 (Normal), 0 (IUGR) and 0·60% Arg (IUGR+Arg) from 7 to 14 d of age, respectively. Compared with Normal piglets at 14 d of age, IUGR decreased (P < 0·05) the growth performance, entire SI weight, and villus height in the jejunum and ileum. IUGR piglets had lower (P < 0·05) mucosal concentrations of Arg, insulin, insulin growth factor 1, as well as phosphorylated Akt, mammalian target of rapamycin (mTOR) and p70 S6 kinase but higher (P < 0·05) enterocyte apoptosis index (AI). After Arg treatment in IUGR piglets, the growth performance, weight of entire SI and mucosa, and villus height in the jejunum and ileum were increased (P < 0·05). Diet supplemented with Arg also increased (P < 0·05) the levels of Arg, insulin, phosphorylated Akt and mTOR in SI mucosa of IUGR piglets, and decreased (P < 0·05) the AI and caspase-3 activity. In conclusion, Arg has a beneficiary effect in improving the impaired SI development in IUGR piglets via regulating cell apoptosis and activating Akt and mTOR signals in SI mucosa.
Antenatal glucocorticoid treatment of the growth-restricted fetus: benefit or cost?
Morrison, Janna L; Orgeig, Sandra
2009-06-01
Women at risk of preterm labor are commonly treated with antenatal glucocorticoids to reduce neonatal complications, including respiratory distress syndrome. Despite the benefits of antenatal glucocorticoid for neonatal lung function, they are associated with negative cardiovascular outcomes. Among this population, there is a group of intrauterine growth-restricted fetuses in which substrate supply is reduced and these fetuses must undergo a range of cardiovascular adaptations to survive. Interestingly, the cardiovascular changes caused by antenatal glucocorticoid in normally grown fetuses are contrary to the cardiovascular adaptations that the intrauterine growth-restricted fetus must make to survive. Hence, the possibility exists that antenatal glucocorticoid in intrauterine growth-restricted infants may compromise cardiovascular development. This review first provides an overview of general antenatal glucocorticoid effects, before outlining the effects on cardiorespiratory development in normally grown fetuses, the cardiovascular adaptations that occur in the intrauterine growth-restricted fetus and finally integrating this with the very limited evidence for the effect of antenatal glucocorticoid in intrauterine growth-restricted infants.
NASA Astrophysics Data System (ADS)
Sachs, Leo
1980-10-01
Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.
Growth and development of children with congenital heart disease.
Chen, Chi-Wen; Li, Chung-Yi; Wang, Jou-Kou
2004-08-01
Children with congenital heart disease (CHD) commonly experience delayed growth. Because growth and development are closely related, both should be considered when a child's progress is examined. This paper reports a study to evaluate and compare the growth and development of preschool children with CHD to those of normal preschool children. The heights and weights of 42 preschool children with CHD and 116 normal preschool children were compared with standard growth curves. Differences in development of personal and social skills, fine motor skills and adaptability, language, and gross motor skills were evaluated. Developmental skills were assessed using the Denver Developmental Screening Test II. A significant difference was found in both body height (P < 0.05) and weight (P < 0.05) between the two groups. More preschoolers with congenital hear disease were below the 50th percentile in height (P < 0.05) and weight (P < 0.001). Preschoolers with CHD had more suspicious interpretations than non-CHD preschoolers, specifically in the language (P < 0.01) and gross motor sections (P < 0.001). Nevertheless, there were two items in the personal-social section and one in the language section on which the children with heart disease passed in the range of 55.6-63.2%. Problems were encountered with the Denver II test because of differences in language, culture and childrearing methods between Taiwanese and Western societies. These cultural differences must be considered when the test is used to assess development. Learning about the growth and developmental differences between children with CHD and normal children may help parents of the former to detect problems associated with delayed growth and development earlier. These children and their families should have the opportunity to participate in a long-term, follow-up programme that provides information and encourages developmental progress. The results could serve as a reference for those in both clinical and community workers who provide nursing care to children with CHD.
Morphologic differentiation of colon carcinoma cell lines HT-29 and HT-29KM in rotating-wall vessels
NASA Technical Reports Server (NTRS)
Goodwin, T. J.; Jessup, J. M.; Wolf, D. A.
1992-01-01
A new low shear stress microcarrier culture system has been developed at NASA's Johnson Space Center that permits three-dimensional tissue culture. Two established human colon adenocarcinoma cell lines, HT-29, an undifferentiated, and HT-29KM, a stable, moderately differentiated subline of HT-29, were grown in new tissue culture bioreactors called Rotating-Wall Vessels (RWVs). RWVs are used in conjunction with multicellular cocultivation to develop a unique in vitro tissue modeling system. Cells were cultivated on Cytodex-3 microcarrier beads, with and without mixed normal human colonic fibroblasts, which served as the mesenchymal layer. Culture of the tumor lines in the absence of fibroblasts produced spheroidlike growth and minimal differentiation. In contrast, when tumor lines were co-cultivated with normal colonic fibroblasts, initial growth was confined to the fibroblast population until the microcarriers were covered. The tumor cells then commenced proliferation at an accelerated rate, organizing themselves into three-dimensional tissue masses that achieved 1.0- to 1.5-cm diameters. The masses displayed glandular structures, apical and internal glandular microvilli, tight intercellular junctions, desmosomes, cellular polarity, sinusoid development, internalized mucin, and structural organization akin to normal colon crypt development. Differentiated samples were subjected to transmission and scanning electron microscopy and histologic analysis, revealing embryoniclike mesenchymal cells lining the areas around the growth matrices. Necrosis was minimal throughout the tissue masses. These data suggest that the RWV affords a new model for investigation and isolation of growth, regulatory, and structural processes within neoplastic and normal tissue.
Preneoplastic lesion growth driven by the death of adjacent normal stem cells
Chao, Dennis L.; Eck, J. Thomas; Brash, Douglas E.; Maley, Carlo C.; Luebeck, E. Georg
2008-01-01
Clonal expansion of premalignant lesions is an important step in the progression to cancer. This process is commonly considered to be a consequence of sustaining a proliferative mutation. Here, we investigate whether the growth trajectory of clones can be better described by a model in which clone growth does not depend on a proliferative advantage. We developed a simple computer model of clonal expansion in an epithelium in which mutant clones can only colonize space left unoccupied by the death of adjacent normal stem cells. In this model, competition for space occurs along the frontier between mutant and normal territories, and both the shapes and the growth rates of lesions are governed by the differences between mutant and normal cells' replication or apoptosis rates. The behavior of this model of clonal expansion along a mutant clone's frontier, when apoptosis of both normal and mutant cells is included, matches the growth of UVB-induced p53-mutant clones in mouse dorsal epidermis better than a standard exponential growth model that does not include tissue architecture. The model predicts precancer cell mutation and death rates that agree with biological observations. These results support the hypothesis that clonal expansion of premalignant lesions can be driven by agents, such as ionizing or nonionizing radiation, that cause cell killing but do not directly stimulate cell replication. PMID:18815380
Sakagami, Nobutada; Umeki, Hidenobu; Nishino, Osamu; Uchiyama, Hiroko; Ichikawa, Kyoko; Takeshita, Kazuhisa; Kaneko, Etsushi; Akiyama, Kiyoshi; Kobayashi, Shuji; Tamada, Hiromichi
2012-01-01
The objective of this study was to examine whether high concentrations of epidermal growth factor (EGF) and/or insulin-like growth factor I (IGF-I) would have a beneficial effect on bovine embryo development in vitro and to obtain normal calves by using an ovum pick up method and embryo culture in a chemically defined medium. When compared with controls, EGF (100 or 200 ng/ml) or IGF-I (50 or 100 ng/ml) significantly increased the rate of embryos that developed into blastocysts during an 8-day culture after the in vitro fertilization of oocytes obtained from ovaries from a slaughterhouse. IGF-I induced a dose-dependent increase in cell number in both the inner cell mass and the trophectoderm, whereas EGF stimulated proliferation only in the inner cell mass. A combination of EGF (100 ng/ml) and IGF-I (50 ng/ml) produced an additive effect, and embryos developed into blastocysts at a comparatively high rate (27.9%) compared with controls (12.0%). A similar rate of development was achieved using a combination of EGF and IGF-I in the culture of embryos following ovum pick up by ultrasound-guided transvaginal follicular aspiration and in vitro fertilization, and 5 blastocysts that developed after the culture were transferred into uteri; two embryos implanted, and normal calves were born. These results suggest that the combined use of EGF and IGF-I makes bovine embryo culture in a chemically defined medium a practical and useful procedure for producing blastocysts, and its application to embryo culture following ovum pick up and in vitro fertilization could be useful for producing normal calves.
Genetics Home Reference: Netherton syndrome
... stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and ... Loss of LEKT1 function also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma, ...
USDA-ARS?s Scientific Manuscript database
Vascular endothelial growth factor (VEGF) is essential for normal vascular growth and development during wound repair. VEGF is estrogen responsive and capable of regulating its own receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). Several agricultural pesticides (e.g., methoxychlor)...
Extrinsic Factors Influencing Fetal Deformations and Intrauterine Growth Restriction
Moh, Wendy; Graham, John M.; Wadhawan, Isha; Sanchez-Lara, Pedro A.
2012-01-01
The causes of intrauterine growth restriction (IUGR) are multifactorial with both intrinsic and extrinsic influences. While many studies focus on the intrinsic pathological causes, the possible long-term consequences resulting from extrinsic intrauterine physiological constraints merit additional consideration and further investigation. Infants with IUGR can exhibit early symmetric or late asymmetric growth abnormality patterns depending on the fetal stage of development, of which the latter is most common occurring in 70–80% of growth-restricted infants. Deformation is the consequence of extrinsic biomechanical factors interfering with normal growth, functioning, or positioning of the fetus in utero, typically arising during late gestation. Biomechanical forces play a critical role in the normal morphogenesis of most tissues. The magnitude and direction of force impact the form of the developing fetus, with a specific tissue response depending on its pliability and stage of development. Major uterine constraining factors include primigravida, small maternal size, uterine malformation, uterine fibromata, early pelvic engagement of the fetal head, aberrant fetal position, oligohydramnios, and multifetal gestation. Corrective mechanical forces similar to those that gave rise to the deformation to reshape the deformed structures are often used and should take advantage of the rapid postnatal growth to correct form. PMID:22888434
Gibberellins Are Required for Seed Development and Pollen Tube Growth in Arabidopsis
Singh, Davinder P.; Jermakow, Angelica M.; Swain, Stephen M.
2002-01-01
Gibberellins (GAs) are tetracyclic diterpenoids that are essential endogenous regulators of plant growth and development. GA levels within the plant are regulated by a homeostatic mechanism that includes changes in the expression of a family of GA-inactivating enzymes known as GA 2-oxidases. Ectopic expression of a pea GA 2-oxidase2 cDNA caused seed abortion in Arabidopsis, extending and confirming previous observations obtained with GA-deficient mutants of pea, suggesting that GAs have an essential role in seed development. A new physiological role for GAs in pollen tube growth in vivo also has been identified. The growth of pollen tubes carrying the 35S:2ox2 transgene was reduced relative to that of nontransgenic pollen, and this phenotype could be reversed partially by GA application in vitro or by combining with spy-5, a mutation that increases GA response. Treatment of wild-type pollen tubes with an inhibitor of GA biosynthesis in vitro also suggested that GAs are required for normal pollen tube growth. These results extend the known physiological roles of GAs in Arabidopsis development and suggest that GAs are required for normal pollen tube growth, a physiological role for GAs that has not been established previously. PMID:12468732
The hormone prolactin (PRL) plays a critical role in normal breast development by stimulating the proliferation of mammary cells, the production of milk proteins, and the formation of new mammary blood vessels. Unfortunately, the same cell and vessel growth pathways controlled by PRL in normal cells also operate in breast cancer cells, and elevated plasma PRL is a risk factor for breast cancer, especially in post-menopausal women.
Genetics of Isolated Growth Hormone Deficiency
2010-01-01
When a child is not following the normal, predicted growth curve, an evaluation for underlying illnesses and central nervous system abnormalities is required, and appropriate consideration should be given to genetic defects causing growth hormone (GH) deficiency (GHD). Because Insulin−like Growth Factor−I (IGF−I) plays a pivotal role, GHD could also be considered as a form of IGF−I deficiency (IGFD). Although IGFD can develop at any level of the GH−releasing hormone (GHRH)−GH−IGF axis, a differentiation should be made between GHD (absent to low GH in circulation) and IGFD (normal to high GH in circulation). The main focus of this review is on the GH gene, the various gene alterations and their possible impact on the pituitary gland. However, although transcription factors regulating the pituitary gland development may cause multiple pituitary hormone deficiency, they may present initially as GHD. Conflict of interest:None declared. PMID:21274339
Physical Development: What's Normal? What's Not?
... Normal? What’s Not? Page Content Article Body Two boys or girls exactly the same age can start or end ... in Girls: What to Expect . Growth in both boys and girls slows considerably soon after puberty is complete. Having ...
Rogol, Alan D; Roemmich, James N; Clark, Pamela A
2002-12-01
Somatic growth and maturation are influenced by a number of factors that act independently or in concert to modify an individual's genetic potential. The secular trend in height and adolescent development is further evidence for the significant influence of environmental factors on an individual's genetic potential for linear growth. Nutrition, including energy and specific nutrient intake, is a major determinant of growth. Paramount to normal growth is the general health and well-being of an individual; in fact, normal growth is a strong testament to the overall good health of a child. More recently the effect of physical activity and fitness on linear growth, especially among teenage athletes, has become a topic of interest. Puberty is a dynamic period of development marked by rapid changes in body size, shape, and composition, all of which are sexually dimorphic. One of the hallmarks of puberty is the adolescent growth spurt. Body compositional changes, including the regional distribution of body fat, are especially large during the pubertal transition and markedly sexually dimorphic. The hormonal regulation of the growth spurt and the alterations in body composition depend on the release of the gonadotropins, leptin, the sex-steroids, and growth hormone. It is very likely that interactions among these hormonal axes are more important than their main effects, and that alterations in body composition and the regional distribution of body fat actually are signals to alter the neuroendocrine and peripheral hormone axes. These processes are merely magnified during pubertal development but likely are pivotal all along the way from fetal growth to the aging process.
Adolescent growth and pubertal progression in the Silver-Russell syndrome.
Davies, P S; Valley, R; Preece, M A
1988-01-01
The pattern of growth and development of 18 adolescent children with the Silver-Russell syndrome was studied. Mature height was about -3.6 standard deviation scores in both sexes. This is comparable to the height reduction at diagnosis, which has been reported previously. The pattern of puberty and adolescent growth was essentially normal and occurred at a marginally earlier time than normal, although in this small series the differences were not significant. In the girls there was a tendency to gain subcutaneous fat after puberty. This trend was not apparent in the boys. PMID:3348659
Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development.
Lange, Clemens A K; Luhmann, Ulrich F O; Mowat, Freya M; Georgiadis, Anastasios; West, Emma L; Abrahams, Sabu; Sayed, Haroon; Powner, Michael B; Fruttiger, Marcus; Smith, Alexander J; Sowden, Jane C; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B
2012-07-01
Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature.
Regulation of early human growth: impact on long-term health.
Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina
2014-01-01
Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. © 2014 S. Karger AG, Basel.
Diagnosis and treatment of pulmonary hypertension in infancy
Steinhorn, Robin H.
2013-01-01
Normal pulmonary vascular development in infancy requires maintenance of low pulmonary vascular resistance after birth, and is necessary for normal lung function and growth. The developing lung is subject to multiple genetic, pathological and/or environmental influences that can adversely affect lung adaptation, development, and growth, leading to pulmonary hypertension. New classifications of pulmonary hypertension are beginning to account for these diverse phenotypes, and or pulmonary hypertension in infants due to PPHN, congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most effective pharmacotherapeutic strategies for infants with PPHN are directed at selective reduction of PVR, and take advantage of a rapidly advancing understanding of the altered signaling pathways in the remodeled vasculature. PMID:24083892
Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N; Toole, Bryan P; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A
2009-08-01
The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.
Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth
DOE Office of Scientific and Technical Information (OSTI.GOV)
Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.
Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less
Morphometric analysis of the developing pediatric cervical spine.
Johnson, Kyle T; Al-Holou, Wajd N; Anderson, Richard C E; Wilson, Thomas J; Karnati, Tejas; Ibrahim, Mohannad; Garton, Hugh J L; Maher, Cormac O
2016-09-01
OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.
Wang, Guang-Long; Sun, Sheng; Xing, Guo-Ming; Wu, Xue-Jun; Wang, Feng; Xiong, Ai-Sheng
2015-01-01
Cytokinins have been implicated in normal plant growth and development. These bioactive molecules are essential for cell production and expansion in higher plants. Carrot is an Apiaceae vegetable with great value and undergoes significant size changes over the process of plant growth. However, cytokinin accumulation and its potential roles in carrot growth have not been elucidated. To address this problem, carrot plants at five stages were collected, and morphological and anatomical characteristics and expression profiles of cytokinin-related genes were determined. During carrot growth and development, cytokinin levels were the highest at the second stage in the roots, whereas relatively stable levels were observed in the petioles and leaves. DcCYP735A2 showed high expression at stage 2 in the roots, which may contribute largely to the higher cytokinin level at this stage. However, expression of most metabolic genes did not follow a pattern similar to that of cytokinin accumulation, indicating that cytokinin biosynthesis was regulated through a complex network. Genes involved in cytokinin signal perception and transduction were also integrated to normal plant growth and development. The results from the present work suggested that cytokinins may regulate plant growth in a stage-dependent manner. Our work would shed novel insights into cytokinin accumulation and its potential roles during carrot growth. Further studies regarding carrot cytokinins may be achieved by modification of the genes involved in cytokinin biosynthesis, inactivation, and perception.
Wang, Guang-Long; Sun, Sheng; Xing, Guo-Ming; Wu, Xue-Jun; Wang, Feng; Xiong, Ai-Sheng
2015-01-01
Cytokinins have been implicated in normal plant growth and development. These bioactive molecules are essential for cell production and expansion in higher plants. Carrot is an Apiaceae vegetable with great value and undergoes significant size changes over the process of plant growth. However, cytokinin accumulation and its potential roles in carrot growth have not been elucidated. To address this problem, carrot plants at five stages were collected, and morphological and anatomical characteristics and expression profiles of cytokinin-related genes were determined. During carrot growth and development, cytokinin levels were the highest at the second stage in the roots, whereas relatively stable levels were observed in the petioles and leaves. DcCYP735A2 showed high expression at stage 2 in the roots, which may contribute largely to the higher cytokinin level at this stage. However, expression of most metabolic genes did not follow a pattern similar to that of cytokinin accumulation, indicating that cytokinin biosynthesis was regulated through a complex network. Genes involved in cytokinin signal perception and transduction were also integrated to normal plant growth and development. The results from the present work suggested that cytokinins may regulate plant growth in a stage-dependent manner. Our work would shed novel insights into cytokinin accumulation and its potential roles during carrot growth. Further studies regarding carrot cytokinins may be achieved by modification of the genes involved in cytokinin biosynthesis, inactivation, and perception. PMID:26218147
Roadway lighting's impact on altering soybean growth : volume 1.
DOT National Transportation Integrated Search
2017-01-01
The impact of roadway lighting on soybean plant growth and development was measured in situ at seven locations in the state of : Illinois. The plant data collection included periodic height, reproductive-stage, and Normalized Difference Vegetation In...
Compartmentalization, resource allocation, and wood quality
Kevin T. Smith
2015-01-01
The concept of a trade-off of tree resources between growth and defense is readily grasped. The most detailed development of the concept is for the growth-differentiation balance hypothesis that predicts that resources for normal growth and primary metabolism are diverted to support plant defense and secondary or stress metabolism. This hypothesis has been applied to...
McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R
2016-03-01
Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met the criteria for preeclampsia, of which 199 met inclusion criteria, 139 (69%) with normal growth, and 60 (31%) with fetal growth restriction. Interval to delivery was significantly shorter in women with fetal growth restriction, median (interquartile range) of 3 (1.6) days vs normal growth, 5 (2.12) days, P < .001. The association between fetal growth restriction and latency less than 7 days remained significant, even after post hoc analysis controlling for confounding variables (adjusted odds ratio, 1.66 [95% confidence interval, 1.12-2.47]). There were no differences in the development of severe disease (85.9 vs 91.7%, P = .26), need for intravenous antihypertensive medications (47.1 vs 46.7%, P = .96), and the development of severe complications of preeclampsia (51.1 vs 42.9%, P = .30) in normally grown and growth-restricted fetuses, respectively. Fewer women with fetal growth restriction attained their scheduled delivery date, 3 of 60 (5.0%), compared with normally grown fetuses,12 of 139 (15.7%), P = .03. Admission to the neonatal intensive care unit, neonatal length of stay, and neonatal mortality were higher when there was fetal growth restriction; however, after a logistic regression analysis, these associations were no longer significant. Fetal growth restriction is associated with a shortened interval to delivery in women undergoing expectant management of preeclampsia when disease is diagnosed prior to 34 weeks. These data may be helpful in counseling patients regarding the expected duration of pregnancy, guiding decision making regarding administration of steroids and determining the need for maternal transport. Copyright © 2016 Elsevier Inc. All rights reserved.
In vitro cholesteatoma growth and secretion of cytokines.
Helgaland, Tore; Engelen, Bart; Olsnes, Carla; Aarstad, Hans Jørgen; Vassbotn, Flemming S
2010-07-01
Our results show a significant difference between skin and cholesteatoma biology in vitro. Cholesteatoma disease is a process of destruction characterized by uncontrolled growth of squamous epithelial cells in the middle ear or temporal bone. The pathophysiology behind the cholesteatoma development is controversial, and the mechanisms driving the cholesteatoma growth, migration and destructive properties is still unclear. We aimed to provide a method to study the effect of various compounds on cholesteatoma and skin tissue growth, as well as to further investigate the biological differences between normal skin and cholesteatoma tissue. We have established a method to study cholesteatoma biopsy tissue in vitro. Cholesteatoma tissues from patients undergoing surgery for chronic otitis were grown in culture medium and compared to growth patterns and behaviour of normal retroauricular skin. Conditioned medium was analysed for various secreted cytokines. We found a radial outgrowth of keratinocyte epithelium from the circular biopsies. After 5 days of culture we found a significant growth of both cholesteatoma and skin-derived cells. Cholesteatoma samples showed higher growth rate as compared with skin control cultures from the same patient. Moreover, the cholesteatoma cells showed higher production of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6 as compared with normal skin.
Growth velocity in constitutional delay of growth and development.
Butenandt, Otfrid; Kunze, Detlef
2010-01-01
Growth velocity was determined in 121 boys and 58 girls with constitutional delay of growth and development (CDGD) of familial origin. No data were included from patients suffering from growth hormone insufficiency (i.e. neurosecretory dysfunction for growth hormone) or any disease. From 479 values obtained in boys and 230 values obtained in girls the 25th, 50th and 75th percentiles were calculated. The mean growth velocity in children and adolescents with CDGD before the beginning of puberty was lower than the mean growth velocity of other European (British, German or Swiss) standards. Specific data of growth velocity should be used in patients with CDGD since population-based data may underestimate the normal growth velocity of these patients.
Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.
Garelli, Andres; Gontijo, Alisson M; Miguela, Veronica; Caparros, Esther; Dominguez, Maria
2012-05-04
Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginal discs autonomously activate DILP8, a Drosophila insulin-like peptide, to communicate abnormal growth and postpone maturation. DILP8 delays metamorphosis by inhibiting ecdysone biosynthesis, slowing growth in the imaginal discs, and generating normal-sized animals. Loss of dilp8 yields asymmetric individuals with an unusually large variation in size and a more varied time of maturation. Thus, DILP8 is a fundamental element of the hitherto ill-defined machinery governing the plasticity that ensures developmental stability and robustness.
Licausi, Francesco; Giorgi, Federico Manuel; Schmälzlin, Elmar; Usadel, Björn; Perata, Pierdomenico; van Dongen, Joost Thomas; Geigenberger, Peter
2011-11-01
The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.
Growth impairment due to transient hypercortisolism.
Armour, K; Chalew, S; Kowarski, A A
1986-01-01
Cushing's syndrome in childhood is generally recognized by classical features such as truncal obesity, striae, easy bruising, moon facies, hypertension and growth retardation. Exceptionally, Cushing's syndrome has been reported to present as growth failure alone. We diagnosed transient hypercortisolism in 6 children who had poor growth as their only presenting abnormality. The 6 children all had integrated concentrations of cortisols (IC-F) (14.1 +/- 1.7 micrograms/dl; mean +/- 1 SD) which exceeded the IC-F in healthy children and adults (5.7 +/- 1.5 micrograms/dl; P less than 0.001). The IC-F of these 6 index cases overlapped the range of IC-F in patients with pathologically proven Cushing's syndrome (20.2 +/- 4.7 micrograms/dl). Four of the 6 patients were treated with human growth hormone for 8 months and showed a marked improvement in their growth rates. Four patients have entered puberty and are growing at normal rates. Three of the 6 children had normal repeat IC-Fs, subsequently, at a time they had normal growth rates. In 1-1/2 to 3 years of follow-up, none of the patients developed any other stigmata of Cushing's syndrome. We conclude that transient hypercortisolism, documented by the IC-F, may cause growth failure without other symptoms of Cushing's syndrome. Growth hormone therapy may improve the growth rate of these children at the time of their poor growth.
Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth
Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis
2014-01-01
Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667
Yu, Xiaoming; Jiang, Lili; Wu, Rui; Meng, Xinchao; Zhang, Ai; Li, Ning; Xia, Qiong; Qi, Xin; Pang, Jinsong; Xu, Zheng-Yi; Liu, Bao
2016-12-05
ATP-dependent chromatin remodeling complexes play essential roles in the regulation of diverse biological processes by formulating a DNA template that is accessible to the general transcription apparatus. Although the function of chromatin remodelers in plant development has been studied in A. thaliana, how it affects growth and development of major crops (e.g., maize) remains uninvestigated. Combining genetic, genomic and bioinformatic analyses, we show here that the maize core subunit of chromatin remodeling complex, ZmCHB101, plays essential roles in growth and development of maize at both vegetative and reproductive stages. Independent ZmCHB101 RNA interference plant lines displayed abaxially curling leaf phenotype due to increase of bulliform cell numbers, and showed impaired development of tassel and cob. RNA-seq-based transcriptome profiling revealed that ZmCHB101 dictated transcriptional reprogramming of a significant set of genes involved in plant development, photosynthesis, metabolic regulation, stress response and gene expressional regulation. Intriguingly, we found that ZmCHB101 was required for maintaining normal nucleosome density and 45 S rDNA compaction. Our findings suggest that the SWI3 protein, ZmCHB101, plays pivotal roles in maize normal growth and development via regulation of chromatin structure.
CLIC4 Moves Into Nucleus to Stabilize Anti-Growth Signal | Center for Cancer Research
In cancer, the delicate balance of signaling pathways that control cell growth and function is disrupted. One signaling pathway commonly altered in cancer is the TGF-beta pathway. TGF-beta significantly inhibits growth of normal cells, particularly epithelial cells. Many cancer cells have developed ways to bypass one or more steps of this pathway in order to achieve uncontrolled growth.
Wu, Yong; Chen, Ping; Huang, Hui-Fang; Huang, Mei-Juan; Chen, Yuan-Zhong
2012-01-01
The expression of transforming growth factor-β1 (TGF-β1) in leukemic cells and sera from patients with leukemia and its possible role in leukemia development were studied. TGF-β1 levels in culture supernatants from leukemic cells were significantly lower than those from normal bone marrow mononuclear cells. Serum TGF-β1 levels in leukemic patients were significantly lower compared with healthy controls, but returned to normal in patients achieving complete remission, and decreased when patients relapsed. TGF-β1 mRNA expression levels were significantly higher in normal bone marrow mononuclear cells but lower in leukemic cells compared with normal CD34 + cells. After transfection of the TGF-β1 gene to HL-60 cells, cell apoptosis was detected. Moreover, by flow cytometry analysis, cells arrested in G1 phase were 62% for TGF-β1 transfected cells and 44% for controls. Transfection of exogenous TGF-β1 gene inhibited HL60 cells xenograft growth in nude mice, and prolonged survival of tumor-bearing mice compared with the controls. Decreased endogenous TGF-β1 expression in leukemia cells may be involved in leukemia development, Transfection of exogenous TGF-B1 gene to HL60 can inhibit the proliferation of the cells and induce cell apoptosis by down regulating bcl-2, hTERT (human telomerase reverse transcriptase) and c-myc expression.
Piairo, Paulina; Moura, Rute S; Baptista, Maria João; Correia-Pinto, Jorge; Nogueira-Silva, Cristina
2018-01-01
Congenital diaphragmatic hernia (CDH) is a life-threatening developmental anomaly, intrinsically combining severe pulmonary hypoplasia and hypertension. During development, signal transducers and activators of transcription (STAT) are utilized to elicit cell growth, differentiation, and survival. We used the nitrofen-induced CDH rat model. At selected gestational time points, lungs were divided into two experimental groups, i.e., control or CDH. We performed immunohistochemistry and western blotting analysis to investigate the developmental expression profile of the complete family of STATs (STAT1-6), plus specific STATs activation (p-STAT3, p-STAT6) and regulation by SOCS (SOCS3) in normal lungs against those of diseased lungs. The normal fetal lung explants were treated with piceatannol (STAT3 inhibitor) in vitro followed by morphometrical analysis. Molecular profiling of STATs during the lung development revealed distinct early and late expression signatures. Experimental CDH altered the STATs expression, activation, and regulation in the fetal lungs. In particular, STAT3 and STAT6 were persistently over-expressed and early over-activated. Piceatannol treatment dose-dependently stimulated the fetal lung growth. These findings suggest that STATs play an important role during normal fetal lung development and CDH pathogenesis. Moreover, functionally targeting STAT signaling modulates fetal lung growth, which highlights that STAT3 and STAT6 signaling might be promising therapeutic targets in reducing or preventing pulmonary hypoplasia in CDH. © 2018 The Author(s). Published by S. Karger AG, Basel.
Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G
2017-10-01
Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.
Catch-up Growth: Cellular and Molecular Mechanisms
Finkielstain, GP; Lui, JC; Baron, J
2012-01-01
In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687
Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia.
Soliman, A T; Alsalmi, I; Darwish, A; Asfour, M G
1996-01-01
Seven children, with a mean (SD) age of 4.6 (2.1) years, who as infants (21 (7.5) days) underwent near total (95-98%) pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) were studied. At birth all the infants were macrosomic. Four infants had been born after a difficult labour, of whom three had moderate birth asphyxia and respiratory distress. All had normal thyroid function. After surgery transient hyperglycaemia was manifest in six of the children and required insulin treatment for 5.8 (3.8) weeks, and transient hypoglycaemia was encountered in one child and responded well to increased carbohydrate intake and diazoxide for three weeks. Six of the children rapidly crossed down their length and weight centiles during the first year after surgery. At the end of the first year these children were at or below the 5th centile of height and weight for their age and gender. After a period of 4.6 (2.1) years, their mean (SD) height score was -2.57 (0.5), growth velocity 3.9 (0.75) cm/year, and growth velocity SD score -2.1 (0.55)l these were significantly low and denoted significant growth retardation. The growth hormone peak responses to provocation with clonidine were normal (13.5 (2.8) micrograms/l). However, the circulating insulin-like growth factor-I (IGF-I) concentrations were significantly decreased (79 (34) ng/ml). Three of the children developed diabetes at two and a half, five, and seven years after surgery, two others had impaired oral glucose tolerance and six out of the seven children had an impaired C peptide response to glucagon. Defective insulin secretion in these children might directly inhibit IGF-I synthesis in the liver. The body mass index of the pancreatectomised children was 14.9 (0.5) and was normal for age and gender; they had a normal 72 hour faecal fat content and normal serum albumin concentration. These data indicated grossly adequate exocrine pancreatic function. It appears that children requiring near total pancreatectomy for PHHI have normal developmental milestones but defective linear growth with impaired insulin secretion and low IGF-I production despite normal growth hormone response to provocation. PMID:8669952
The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice
Dickins, Ross A.; Frew, Ian J.; House, Colin M.; O'Bryan, Moira K.; Holloway, Andrew J.; Haviv, Izhak; Traficante, Nadia; de Kretser, David M.; Bowtell, David D. L.
2002-01-01
The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including β-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division. PMID:11884614
Szentpéteri, Imre; Rab, Attila; Kornya, László; Kovács, Péter; Joó, József Gábor
2013-07-01
In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)β-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α)< 33 weeks: 1.09; Ln 2(α)33-37 weeks: 1.27; Ln 2(α)> 37 weeks: 1.35). Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.
Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N.; Toole, Bryan P.; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A.
2009-01-01
Summary The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb. PMID:19633173
Regional gray matter growth, sexual dimorphism, and cerebral asymmetry in the neonatal brain.
Gilmore, John H; Lin, Weili; Prastawa, Marcel W; Looney, Christopher B; Vetsa, Y Sampath K; Knickmeyer, Rebecca C; Evans, Dianne D; Smith, J Keith; Hamer, Robert M; Lieberman, Jeffrey A; Gerig, Guido
2007-02-07
Although there has been recent interest in the study of childhood and adolescent brain development, very little is known about normal brain development in the first few months of life. In older children, there are regional differences in cortical gray matter development, whereas cortical gray and white matter growth after birth has not been studied to a great extent. The adult human brain is also characterized by cerebral asymmetries and sexual dimorphisms, although very little is known about how these asymmetries and dimorphisms develop. We used magnetic resonance imaging and an automatic segmentation methodology to study brain structure in 74 neonates in the first few weeks after birth. We found robust cortical gray matter growth compared with white matter growth, with occipital regions growing much faster than prefrontal regions. Sexual dimorphism is present at birth, with males having larger total brain cortical gray and white matter volumes than females. In contrast to adults and older children, the left hemisphere is larger than the right hemisphere, and the normal pattern of fronto-occipital asymmetry described in older children and adults is not present. Regional differences in cortical gray matter growth are likely related to differential maturation of sensory and motor systems compared with prefrontal executive function after birth. These findings also indicate that whereas some adult patterns of sexual dimorphism and cerebral asymmetries are present at birth, others develop after birth.
Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone
Ascenzi, Maria-Grazia; Du, Xia; Harding, James I; Beylerian, Emily N; de Silva, Brian M; Gross, Ben J; Kastein, Hannah K; Wang, Weiguang; Lyons, Karen M; Schaeffer, Hayden
2014-01-01
Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image’s plane of focus, and lack of cell-specific features, interfered with identification of cell. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes’ number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth. PMID:25525552
A comparative study of the characterization of miR-155 in knockout mice
Zhang, Dong; Cui, Yongchun; Li, Bin; Luo, Xiaokang; Li, Bo; Tang, Yue
2017-01-01
miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models. PMID:28278287
7 CFR 51.1868 - Well developed.
Code of Federal Regulations, 2011 CFR
2011-01-01
... shows normal growth. Tomatoes which are ridged and peaked at the stem end, contain dry tissue, and usually contain open spaces below the level of the stem scar, are not considered well developed. ...
7 CFR 51.1868 - Well developed.
Code of Federal Regulations, 2012 CFR
2012-01-01
... shows normal growth. Tomatoes which are ridged and peaked at the stem end, contain dry tissue, and usually contain open spaces below the level of the stem scar, are not considered well developed. ...
7 CFR 51.1868 - Well developed.
Code of Federal Regulations, 2010 CFR
2010-01-01
... shows normal growth. Tomatoes which are ridged and peaked at the stem end, contain dry tissue, and usually contain open spaces below the level of the stem scar, are not considered well developed. ...
Serafin, J.A.
1981-01-01
Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.
Partial hypopituitarism and Langerhans cell histiocytosis
Balaguruswamy, S; Chattington, P D
2011-01-01
A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201
NASA Technical Reports Server (NTRS)
Bula, R. J.
1997-01-01
The ASTROCULTURE(trademark) plant growth unit flown as part on the STS-63 mission in February 1995, represented the first time plants were flown in microgravity in a enclosed controlled environment plant growth facility. In addition to control of the major environmental parameters, nutrients were provided to the plants with the ZEOPONICS system developed by NASA Johnson Space Center scientists. Two plant species were included in this space experiment, dwarf wheat (Triticum aestivum) and a unique mustard called "Wisconsin Fast Plants" (Brassica rapa). Extensive post-flight analyses have been performed on the plant material and it has been concluded that plant growth and development was normal during the period the plants were in the microgravity environment of space. However, adequate plant growth and development control data were not available for direct comparisons of plant responses to the microgravity environment with those of plants grown at 1 g. Such data would allow for a more complete interpretation of the extent that microgravity affects plant growth and development.
ERIC Educational Resources Information Center
Fujisawa, Keiko K.; Ozaki, Koken; Suzuki, Kunitake; Yamagata, Shinji; Kawahashi, Ikko; Ando, Juko
2012-01-01
Although growth in head circumference (HC) during infancy is known to predict later childhood outcomes, the mechanisms underlying this association with later sociocognitive abilities remain undetermined. Thus, using a sample of 241 pairs of normally developing Japanese twins, this study investigated the underpinnings of the association between HC…
Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing.
Kuo, Anderson H; Li, Cun; Li, Jinqi; Huber, Hillary F; Nathanielsz, Peter W; Clarke, Geoffrey D
2017-02-15
Rodent models of intrauterine growth restriction (IUGR) successfully identify mechanisms that can lead to short-term and long-term detrimental cardiomyopathies but differences between rodent and human cardiac physiology and placental-fetal development indicate a need for models in precocial species for translation to human development. We developed a baboon model for IUGR studies using a moderate 30% global calorie restriction of pregnant mothers and used cardiac magnetic resonance imaging to evaluate offspring heart function in early adulthood. Impaired diastolic and systolic cardiac function was observed in IUGR offspring with differences between male and female subjects, compared to their respective controls. Aspects of cardiac impairment found in the IUGR offspring were similar to those found in normal controls in a geriatric cohort. Understanding early cardiac biomarkers of IUGR using non-invasive imaging in this susceptible population, especially taking into account sexual dimorphisms, will aid recognition of the clinical presentation, development of biomarkers suitable for use in humans and management of treatment strategies. Extensive rodent studies have shown that reduced perinatal nutrition programmes chronic cardiovascular disease. To enable translation to humans, we developed baboon offspring cohorts from mothers fed ad libitum (control) or 70% of the control ad libitum diet in pregnancy and lactation, which were growth restricted at birth. We hypothesized that intrauterine growth restriction (IUGR) offspring hearts would show impaired function and a premature ageing phenotype. We studied IUGR baboons (8 male, 8 female, 5.7 years), control offspring (8 male, 8 female, 5.6 years - human equivalent approximately 25 years), and normal elderly (OLD) baboons (6 male, 6 female, mean 15.9 years). Left ventricular (LV) morphology and systolic and diastolic function were evaluated with cardiac MRI and normalized to body surface area. Two-way ANOVA by group and sex (with P < 0.05) indicated ejection fraction, 3D sphericity indices, cardiac index, normalized systolic volume, normalized LV wall thickness, and average filling rate differed by group. Group and sex differences were found for normalized LV wall thickening and normalized myocardial mass, without interactions. Normalized peak LV filling rate and diastolic sphericity index were not correlated in control but strongly correlated in OLD and IUGR baboons. IUGR programming in baboons produces myocardial remodelling, reduces systolic and diastolic function, and results in the emergence of a premature ageing phenotype in the heart. To our knowledge, this is the first demonstration of the specific characteristics of cardiac programming and early life functional decline with ageing in an IUGR non-human primate model. Further studies across the life span will determine progression of cardiac dysfunction. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.
Taste bud cell dynamics during normal and sodium-restricted development.
Hendricks, Susan J; Brunjes, Peter C; Hill, David L
2004-04-26
Taste bud volume increases over the postnatal period to match the number of neurons providing innervation. To clarify age-related changes in fungiform taste bud volume, the current study investigated developmental changes in taste bud cell number, proliferation rate, and life span. Taste bud growth can largely be accounted for by addition of cytokeratin-19-positive taste bud cells. Examination of taste bud cell kinetics with 3H-thymidine autoradiography revealed that cell life span and turnover periods were not altered during normal development but that cells were produced more rapidly in young rats, a prominent modification that could lead to increased taste bud size. By comparison, dietary sodium restriction instituted during pre- and postnatal development results in small taste buds at adulthood as a result of fewer cytokeratin-19-positive cells. The dietary manipulation also had profound influences on taste bud growth kinetics, including an increased latency for cells to enter the taste bud and longer life span and turnover periods. These studies provide fundamental, new information about taste bud development under normal conditions and after environmental manipulations that impact nerve/target matching. Copyright 2004 Wiley-Liss, Inc.
[Study of the growth and development of Chlorella on "Kosmos-1887"].
Sychev, V N; Levinskikh, M A; Livanskaia, O G
1989-01-01
The growth, development and population characteristics of Chlorella cells flown for 13 days in space were investigated during their postflight cultivation. The growth rate of flown algae did not differ from that of ground-based controls in terms of increases in the cell number and biomass. All basic parameters of the specimens (generation time, number of developing autospores, time ratio of developmental phases) were ontogentically normal. Exposure of the algae to space flight as a component of the algobacterial cenosis--fish autotrophic-heterotrophic system produced no significant effect of the population or individual specimens during their postflight cultivation.
Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment
Butler, Merlin G.; Lee, Jaehoon; Cox, Devin M.; Manzardo, Ann M.; Gold, June-Anne; Miller, Jennifer L.; Roof, Elizabeth; Dykens, Elisabeth; Kimonis, Virginia; Driscoll, Daniel J.
2018-01-01
The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone–treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non–growth hormone–treated PWS individuals. Growth chart implications and recommended usage are discussed. PMID:26842920
Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco
2015-07-01
Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular schwannoma. Further studies are necessary to confirm the involvement of these factors in the growth of neoplasms and to develop inhibitors of pro-inflammatory cytokines as a potential treatment option in the future.
Volumetric study in the development of paranasal sinuses by CT imaging in Asian: a pilot study.
Park, Il-Ho; Song, Jong Seok; Choi, Hyuk; Kim, Tae Hoon; Hoon, Seung; Lee, Sang Hag; Lee, Heung-Man
2010-12-01
The volume of the air cavities in the paranasal sinuses is not only the simplest, but also the most important index for paranasal sinus evaluation. However, few volumetric studies have been performed in all age groups. The purpose of the current study was to outline the normal development of paranasal sinuses in all age groups, and to determine normal adult volumetric values by means of computed tomographic (CT) scan of paranasal sinus using volumetric procedures. A prospective volumetric CT study was conducted with 260 patients (520 sides) <25 years of age by means of three-dimensional reconstruction. The frontal sinuses began to pneumatize at 2 years of age, exhibited a faster growth pattern between 6 and 19 years of age, and the mean volume after full growth was 3.46±0.78 cm(3). The maxillary sinuses were pneumatized at birth in all cases, exhibited a monomodal growth pattern increasing until 15 years of age, and the mean volume after full growth was 14.83±1.36 cm(3). The floor of the sinus was the same level as the floor of the nasal cavity was between 7 and 15 years of age. The ethmoid sinuses exhibited a faster initial tendency to increase until 7 years of age, were completed by 15-16 years of age, and the mean volume after full growth was 4.51±0.92 cm(3). The sphenoid sinuses exhibited a growth spurt between 6 and 10 years of age, were completed by 15 years of age, and the mean volume after full growth was 3.47±0.93 cm(3). The results of this study are presented to provide the basis for an objective normal volume of sinus development and for studies involving diseases of the sinuses. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Molecular concept in human oral cancer.
Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U S
2015-01-01
The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy.
Molecular concept in human oral cancer
Krishna, Akhilesh; Singh, Shraddha; Kumar, Vijay; Pal, U. S.
2015-01-01
The incidence of oral cancer remains high in both Asian and Western countries. Several risk factors associated with development of oral cancer are now well-known, including tobacco chewing, smoking, and alcohol consumption. Cancerous risk factors may cause many genetic events through chromosomal alteration or mutations in genetic material and lead to progression and development of oral cancer through histological progress, carcinogenesis. Oral squamous carcinogenesis is a multistep process in which multiple genetic events occur that alter the normal functions of proto-oncogenes/oncogenes and tumor suppressor genes. Furthermore, these gene alterations can deregulate the normal activity such as increase in the production of growth factors (transforming growth factor-α [TGF-α], TGF-β, platelet-derived growth factor, etc.) or numbers of cell surface receptors (epidermal growth factor receptor, G-protein-coupled receptor, etc.), enhanced intracellular messenger signaling and mutated production of transcription factors (ras gene family, c-myc gene) which results disturb to tightly regulated signaling pathways of normal cell. Several oncogenes and tumor suppressor genes have been implicated in oral cancer especially cyclin family, ras, PRAD-1, cyclin-dependent kinase inhibitors, p53 and RB1. Viral infections, particularly with oncogenic human papilloma virus subtype (16 and 18) and Epstein-Barr virus have tumorigenic effect on oral epithelia. Worldwide, this is an urgent need to initiate oral cancer research programs at molecular and genetic level which investigates the causes of genetic and molecular defect, responsible for malignancy. This approach may lead to development of target dependent tumor-specific drugs and appropriate gene therapy. PMID:26668446
Chang, Guo-ying; Dong, Zhi-ya; Wang, Wei; Wang, De-fen
2010-12-01
To elucidate the curative and adverse effect of recombinant human growth hormone (rhGH) in 2 patients with isolated-growth hormone deficiency type IA (IGHDIA), to track sexual development and pregnancy, and reassess the quality of life in the adulthood. The authors summarized the data of 2-sister cases with IGHDIA; followed up for assessment of height, weight, blood pressure and sexual development; detected fasting blood lipids, glucose, insulin, insulin growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3); made an investigation of education and occupation, and so on. After 6.2 and 7.3 years treatment with rhGH, the two sisters had considerably improved height from -7.8 SDS, -8.8 SDS to -2.6 SDS and -1.3 SDS respectively. No evident side effect was observed. They had normal sexual development and pregnancy. The levels of IGF-1 and IGFBP-3 were still low, in the elder sister they were 46.6 µg/L, 2460 µg/L, and in the younger 52.4 µg/L, 2430 µg/L. No hyperlipidemia, diabetes or obesity occurred. Long term therapy with rhGH may improve final adult height of individuals with IGHDIA. They can have normal sexual development and pregnancy. Metabolic syndrome did not occur during the follow-up period.
Tse, J Y; Lao, T T; Chan, C C; Chiu, P M; Cheung, A N
2001-01-01
Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.
Zeng, Huihui; Cai, Haodong; Wang, Ying; Shen, Ying
2015-04-01
We studied the growth and development of children prenatally exposed to telbivudine used to treat chronic hepatitis B virus (HBV) infection in their mothers. Maternal abnormalities during pregnancy and delivery and infant congenital anomalies, physical development status, developmental quotient (DQ), HBV vertical transmission status, and HBV vaccination outcomes of 54 infants were evaluated (2010-2013). No fetal abnormalities were observed during pregnancy or delivery. Postpartum, three infants (5.56%) had abnormalities: ankyloglossia, cutaneous hemangioma, and vaginal canal leak. Height and weight were within the normal range at birth and at 6 weeks, but were higher than the reference at 12 months (p<0.05). Body mass index increased gradually with age (p<0.05). DQ scores were normal (84.81%, 229/270) in 37 children (68.52%), abnormal or suspicious for a developmental delay (15.19%, 41/270) in 17 children (31.48%), and indicated a developmental delay (4.07%, 11/270) in seven children (12.96%). There were no significant differences in developmental delay between children prenatally exposed to telbivudine and controls (p>0.05). HBV vertical transmission was successfully blocked in all infants. The effective HBV vaccination rate was 98.15% (53/54). The growth and development of children prenatally exposed to telbivudine was normal, indicating that telbivudine treatment during pregnancy is safe and effective. Copyright © 2015. Published by Elsevier Ltd.
Uauy, R; Casanello, P; Krause, B; Kuzanovic, J P; Corvalan, C
2013-09-01
Healthy growth in utero and after birth is fundamental for lifelong health and wellbeing. The World Health Organization (WHO) recently published standards for healthy growth from birth to 6 years of age; analogous standards for healthy fetal growth are not currently available. Current fetal growth charts in use are not true standards, since they are based on cross-sectional measurements of attained size under conditions that do not accurately reflect normal growth. In most cases, the pregnant populations and environments studied are far from ideal; thus the data are unlikely to reflect optimal fetal growth. A true standard should reflect how fetuses and newborns 'should' grow under ideal environmental conditions. The development of prescriptive intrauterine and newborn growth standards derived from the INTERGROWTH-21(st) Project provides the data that will allow us for the first time to establish what is 'normal' fetal growth. The INTERGROWTH-21(st) study centres provide the data set obtained under pre-established standardised criteria, and details of the methods used are also published. Multicentre study with sites in all major geographical regions of the world using a standard evaluation protocol. These standards will assess risk of abnormal size at birth and serve to evaluate potentially effective interventions to promote optimal growth beyond securing survival. The new normative standards have the potential to impact perinatal and neonatal survival and beyond, particularly in developing countries where fetal growth restriction is most prevalent. They will help us identify intrauterine growth restriction at earlier stages of development, when preventive or corrective strategies might be more effective than at present. These growth standards will take us one step closer to effective action in preventing and potentially reversing abnormal intrauterine growth. Achieving 'optimal' fetal growth requires that we act not only during pregnancy but that we optimize the maternal uterine environment from the time before conception, through embryonic development until fetal growth is complete. The remaining challenge is how 'early' will we be able to act, now that we can better monitor fetal growth. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.
D'Antonio, Maurizio; Droggiti, Anna; Feltri, M Laura; Roes, Jürgen; Wrabetz, Lawrence; Mirsky, Rhona; Jessen, Kristján R
2006-08-16
During development, Schwann cell numbers are precisely adjusted to match the number of axons. It is essentially unknown which growth factors or receptors carry out this important control in vivo. Here, we tested whether the type II transforming growth factor (TGF) beta receptor has a role in this process. We generated a conditional knock-out mouse in which the type II TGFbeta receptor is specifically ablated only in Schwann cells. Inactivation of the receptor, evident at least from embryonic day 18, resulted in suppressed Schwann cell death in normally developing and injured nerves. Notably, the mutants also showed a strong reduction in Schwann cell proliferation. Consequently, Schwann cell numbers in wild-type and mutant nerves remained similar. Lack of TGFbeta signaling did not appear to affect other processes in which TGFbeta had been implicated previously, including myelination and response of adult nerves to injury. This is the first in vivo evidence for a growth factor receptor involved in promoting Schwann cell division during development and the first genetic evidence for a receptor that controls normal developmental Schwann cell death.
Development of the preterm infant gut microbiome: A research priority
DOE Office of Scientific and Technical Information (OSTI.GOV)
Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.
The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role ofmore » the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.« less
Development of the preterm infant gut microbiome: A research priority
Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; ...
2014-10-13
The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role ofmore » the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.« less
CLIC4 Moves Into Nucleus to Stabilize Anti-Growth Signal | Center for Cancer Research
In cancer, the delicate balance of signaling pathways that control cell growth and function is disrupted. One signaling pathway commonly altered in cancer is the TGF-beta pathway. TGF-beta significantly inhibits growth of normal cells, particularly epithelial cells. Many cancer cells have developed ways to bypass one or more steps of this pathway in order to achieve
Vandewalle, Sara; Van Caenegem, Eva; Craen, Margarita; Taes, Youri; Kaufman, Jean-Marc; T'Sjoen, Guy
2018-03-28
Sex steroids are essential for sexual maturation, linear growth and bone development. However, there is no consensus on the optimal timing, dosage and dosage interval of testosterone therapy to induce pubertal development and achieve a normal adult height and bone mass in children with hypogonadism. A monozygotic monochorial male twin pair, of which one boy was diagnosed with anorchia at birth due to testicular regression syndrome was followed from the age of 3 until the age of 18 years. Low dose testosterone substitution (testosterone esters 25 mg/2 weeks) was initiated in the affected twin based on the start of pubertal development in the healthy twin and then gradually increased accordingly. Both boys were followed until age 18 and were compared as regards to linear growth, sexual maturation, bone maturation and bone development. Before puberty induction both boys had a similar weight and height. During puberty, a slightly faster weight and height gain was observed in the affected twin. Both boys ended up however, with a similar and normal (near) adult height and weight and experienced a normal development of secondary sex characteristics. At the age of 17 and 18 years, bone mineral density, body composition and volumetric bone parameters at the forearm and calf were evaluated in both boys. The affected boy had a higher lean mass and muscle cross-sectional area. The bone mineral density at the lumbar spine and whole body was similar. Trabecular and cortical volumetric bone parameters were comparable. At one cortical site (proximal radius), however, the affected twin had a smaller periosteal and endosteal circumference with a thicker cortex. In conclusion, a low dose testosterone substitution in bilateral anorchia led to a normal onset of pubertal development and (near) adult height. Furthermore, there was no difference in bone mineral density at the age of 17 and 18 years.
Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E
2012-11-15
To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.
McKelvey, Laura; Gutierrez, Humberto; Nocentini, Giuseppe; Crampton, Sean J.; Davies, Alun M.; Riccardi, Carlo R.; O’keeffe, Gerard W.
2012-01-01
Summary NF-κB transcription factors play a key role in regulating the growth of neural processes in the developing PNS. Although several secreted proteins have been shown to activate NF-κB to inhibit the growth of developing sympathetic neurons, it is unknown how the endogenous level of NF-κB activity present in these neurons is restricted to allow neurite growth to occur during their normal development. Here we show that activation of the glucocorticoid-induced tumour necrosis factor receptor (GITR) inhibits NF-κB activation while promoting the activation of Erk in developing sympathetic neurons. Conversely, inhibition of GITR results in an increase in NF-κB dependent gene transcription and a decrease in Erk activation leading to a reduction in neurite growth. These findings show that GITR signalling can regulate the extent of sympathetic neurite growth through an inverse modulation of Erk and NF-κB signalling, which provides an optimal environment for NGF-promoted growth. PMID:23213379
Modeling error distributions of growth curve models through Bayesian methods.
Zhang, Zhiyong
2016-06-01
Growth curve models are widely used in social and behavioral sciences. However, typical growth curve models often assume that the errors are normally distributed although non-normal data may be even more common than normal data. In order to avoid possible statistical inference problems in blindly assuming normality, a general Bayesian framework is proposed to flexibly model normal and non-normal data through the explicit specification of the error distributions. A simulation study shows when the distribution of the error is correctly specified, one can avoid the loss in the efficiency of standard error estimates. A real example on the analysis of mathematical ability growth data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99 is used to show the application of the proposed methods. Instructions and code on how to conduct growth curve analysis with both normal and non-normal error distributions using the the MCMC procedure of SAS are provided.
Survival and growth of trees and shrubs on different lignite minesoils in Louisiana
James D. Haywood; Allan E. Tiarks; James P. Barnett
1993-01-01
In 1980, an experimental opencast lignite mine was developed to compare redistributed A horizon with three minesoil mixtures as growth media for woody plants. The three minesoil mixtures contained different amounts and types of overburden materials, and normal reclamation practices were followed. Loblolly pine (Pinus taeda, L.), sawtooth oak (
Vuralli, Dogus; Gonc, E Nazli; Ozon, Z Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun
2017-06-01
We aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Two hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. Sixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. Early reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or 'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development. Copyright © 2017. Published by Elsevier Ltd.
7 CFR 51.1868 - Well developed.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 2 2013-01-01 2013-01-01 false Well developed. 51.1868 Section 51.1868 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Fresh Tomatoes 1 Definitions § 51.1868 Well developed. Well developed means that the tomatoe shows normal growth. Tomatoes which are ridged and peaked at the...
7 CFR 51.1908 - Well developed.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 7 Agriculture 2 2013-01-01 2013-01-01 false Well developed. 51.1908 Section 51.1908 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Fresh Tomatoes Definitions § 51.1908 Well developed. Well developed means that the tomato shows normal growth. Tomatoes which are ridged and peaked at...
7 CFR 51.1868 - Well developed.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 2 2014-01-01 2014-01-01 false Well developed. 51.1868 Section 51.1868 Agriculture..., CERTIFICATION, AND STANDARDS) United States Standards for Fresh Tomatoes 1 Definitions § 51.1868 Well developed. Well developed means that the tomatoe shows normal growth. Tomatoes which are ridged and peaked at the...
7 CFR 51.1908 - Well developed.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 7 Agriculture 2 2014-01-01 2014-01-01 false Well developed. 51.1908 Section 51.1908 Agriculture..., CERTIFICATION, AND STANDARDS) United States Consumer Standards for Fresh Tomatoes Definitions § 51.1908 Well developed. Well developed means that the tomato shows normal growth. Tomatoes which are ridged and peaked at...
Modeling Error Distributions of Growth Curve Models through Bayesian Methods
ERIC Educational Resources Information Center
Zhang, Zhiyong
2016-01-01
Growth curve models are widely used in social and behavioral sciences. However, typical growth curve models often assume that the errors are normally distributed although non-normal data may be even more common than normal data. In order to avoid possible statistical inference problems in blindly assuming normality, a general Bayesian framework is…
Parkinson, Eric Kenneth
2013-01-01
The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603
Interrelationship between growth and development in low and middle income countries.
Martorell, Reynaldo; Nguyen, Phuong
2010-01-01
Early childhood growth failure is a significant public health problem in developing countries. We examine relationships between low birthweight and stunting with child development. Compared to children born with normal birthweight, low birth-weight children have substantially poorer cognitive and schooling outcomes later in life. Linear growth failure leading to stunting mostly occurs before age 2 years, with stunting in older children reflecting growth failure in early life. Many studies show that stunting is associated with poor mental and motor development in infants and with low scores in cognitive tests, increased frequency of behavioral problems and poor school achievement in older children. Very few studies have assessed the relative importance for development of prenatal vs. postnatal growth failure and even fewer have done so using appropriate statistical techniques. The limited evidence to date suggests growth during the first 2 years of life is more important than growth at any other time, including the prenatal period, for predicting later cognitive development, schooling and educational achievement. In conclusion, children in settings of poverty who experience growth failure prior to age 2 years have reduced potential to succeed in school and to be productive members of society. Copyright (c) 2010 S. Karger AG, Basel.
The Effect of Radiation on the Normal and Oestrone-treated Mouse Vagina Grown in vitro
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lasnitzki, Ilse
1961-06-01
The effect of radiation on the differentiation of normal and oestrone- treated organ cultures of the mouse vagina was studied during growth in natural and in chemically defined medium. After explanation into either type of medium without addition of the hormone the vaginal epithelium spontaneously forms new squamous keratinising epithelium which displaces the original secretory epithelium. Addition of oestrone to the medium stimulates the growth of the new cells and hastens and increases keratin synthesis. Exposure to 200 r of x rays given one day after explanation inhibits the squamous development, suppresses keratin formation and preserves the original epithelium inmore » both normal and oestrone-treated explants grown in natural medium. Radiation of cultures kept in defined medium fails to influence the normal squamous differentiation and keratinisation. The mechanism of radiation action is discussed in the light of the differnet results obtained under the two conditions. (auth)« less
Lewis, John D.; Elman, Jeffrey L.
2009-01-01
Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory – as occurs in autism – should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth – indicating a reduced reliance on long-distance connections – for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects. PMID:18171375
Deletion of OTX2 in neural ectoderm delays anterior pituitary development
Mortensen, Amanda H.; Schade, Vanessa; Lamonerie, Thomas; Camper, Sally A.
2015-01-01
OTX2 is a homeodomain transcription factor that is necessary for normal head development in mouse and man. Heterozygosity for loss-of-function alleles causes an incompletely penetrant, haploinsufficiency disorder. Affected individuals exhibit a spectrum of features that range from developmental defects in eye and/or pituitary development to acephaly. To investigate the mechanism underlying the pituitary defects, we used different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. Mice homozygous for Otx2 deficiency in early head development and pituitary oral ectoderm exhibit craniofacial defects and pituitary gland dysmorphology, but normal pituitary cell specification. The morphological defects mimic those observed in humans and mice with OTX2 heterozygous mutations. Mice homozygous for Otx2 deficiency in the pituitary neural ectoderm exhibited altered patterning of gene expression and ablation of FGF signaling. The posterior pituitary lobe and stalk, which normally arise from neural ectoderm, were extremely hypoplastic. Otx2 expression was intact in Rathke's pouch, the precursor to the anterior lobe, but the anterior lobe was hypoplastic. The lack of FGF signaling from the neural ectoderm was sufficient to impair anterior lobe growth, but not the differentiation of hormone-producing cells. This study demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe and pituitary stalk, and it has significant extrinsic effects on anterior pituitary growth. Otx2 expression early in head development is important for establishing normal craniofacial features including development of the brain, eyes and pituitary gland. PMID:25315894
DEVELOPMENT AND DISORDERS OF SPEECH IN CHILDHOOD.
ERIC Educational Resources Information Center
KARLIN, ISAAC W.; AND OTHERS
THE GROWTH, DEVELOPMENT, AND ABNORMALITIES OF SPEECH IN CHILDHOOD ARE DESCRIBED IN THIS TEXT DESIGNED FOR PEDIATRICIANS, PSYCHOLOGISTS, EDUCATORS, MEDICAL STUDENTS, THERAPISTS, PATHOLOGISTS, AND PARENTS. THE NORMAL DEVELOPMENT OF SPEECH AND LANGUAGE IS DISCUSSED, INCLUDING THEORIES ON THE ORIGIN OF SPEECH IN MAN AND FACTORS INFLUENCING THE NORMAL…
Characterization of crack growth under combined loading
NASA Technical Reports Server (NTRS)
Feldman, A.; Smith, F. W.; Holston, A., Jr.
1977-01-01
Room-temperature static and cyclic tests were made on 21 aluminum plates in the shape of a 91.4x91.4-cm Maltese cross with 45 deg flaws to develop crack growth and fracture toughness data under mixed-mode conditions. During cyclic testing, it was impossible to maintain a high proportion of shear-mode deformation on the crack tips. Cracks either branched or turned. Under static loading, cracks remained straight if shear stress intensity exceeded normal stress intensity. Mixed-mode crack growth rate data compared reasonably well with published single-mode data, and measured crack displacements agreed with the straight and branched crack analyses. Values of critical strain energy release rate at fracture for pure shear were approximately 50% higher than for pure normal opening, and there was a large reduction in normal stress intensity at fracture in the presence of high shear stress intensity. Net section stresses were well into the inelastic range when fracture occurred under high shear on the cracks.
Bhadada, Sanjay K; Palnitkar, Saroj; Qiu, Shijing; Parikh, Nayana; Talpos, Gary B; Rao, Sudhaker D
2013-11-01
Tumor-induced osteomalacia (TIO) is an acquired hypophosphatemic metabolic bone disorder that can be cured by removing or ablating the offending tumor. However, when the tumor cannot be localized, lifelong therapy with oral phosphate and calcitriol or cinacalcet with close monitoring is required. A 56-year-old man was diagnosed with TIO in 1990. Initial therapy consisted of oral phosphate and calcitriol with symptomatic and biochemical improvement and healing of osteomalacia. Eight years later, hypercalcemic hyperparathyroidism developed, requiring subtotal parathyroidectomy with a transient increase in serum phosphate and normalization of serum calcium and PTH. Recurrent hypercalcemic hyperparathyroidism developed after 10 years of medical therapy. A deliberate total parathyroidectomy produced a prompt rise in serum phosphate into the normal range > 3.0 mg/dL and remained normal during the next 4 years of follow-up, despite continued very high serum fibroblast growth factor-23 levels throughout the 23-year follow-up. We report an unusual case of a TIO patient with long-term follow-up who developed recurrent hypercalcemic hyperparathyroidism on long-term oral phosphate therapy. Deliberate total parathyroidectomy normalized serum phosphate despite persistently elevated fibroblast growth factor-23 levels. Total parathyroidectomy offers a potentially novel therapy in some patients with TIO in whom medical therapy is not feasible or the tumor is unresectable.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim
Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6),more » who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.« less
MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network.
Samad, Abdul F A; Sajad, Muhammad; Nazaruddin, Nazaruddin; Fauzi, Izzat A; Murad, Abdul M A; Zainal, Zamri; Ismail, Ismanizan
2017-01-01
Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions.
Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants.
Hay, William W; Brown, Laura D; Denne, Scott C
2014-01-01
Energy is necessary for all vital functions of the body at molecular, cellular, organ, and systemic levels. Preterm infants have minimum energy requirements for basal metabolism and growth, but also have requirements for unique physiology and metabolism that influence energy expenditure. These include body size, postnatal age, physical activity, dietary intake, environmental temperatures, energy losses in the stool and urine, and clinical conditions and diseases, as well as changes in body composition. Both energy and protein are necessary to produce normal rates of growth. Carbohydrates (primarily glucose) are principle sources of energy for the brain and heart until lipid oxidation develops over several days to weeks after birth. A higher protein/energy ratio is necessary in most preterm infants to approximate normal intrauterine growth rates. Lean tissue is predominantly produced during early gestation, which continues through to term. During later gestation, fat accretion in adipose tissue adds increasingly large caloric requirements to the lean tissue growth. Once protein intake is sufficient to promote net lean body accretion, additional energy primarily produces more body fat, which increases almost linearly at energy intakes >80-90 kcal/kg/day in normal, healthy preterm infants. Rapid gains in adiposity have the potential to produce later life obesity, an increasingly recognized risk of excessive energy intake. In addition to fundamental requirements for glucose, protein, and fat, a variety of non-glucose carbohydrates found in human milk may have important roles in promoting growth and development, as well as production of a gut microbiome that could protect against necrotizing enterocolitis. © 2014 S. Karger AG, Basel.
Development of disease-specific growth charts in Turner syndrome and Noonan syndrome.
Isojima, Tsuyoshi; Yokoya, Susumu
2017-12-01
Many congenital diseases are associated with growth failure, and patients with these diseases have specific growth patterns. As the growth patterns of affected individuals differ from those of normal populations, it is challenging to detect additional conditions that can influence growth using standard growth charts. Disease-specific growth charts are thus very useful tools and can be helpful for understanding the growth pattern and pathogenesis of congenital diseases. In addition, disease-specific growth charts allow doctors to detect deviations from the usual growth patterns for early diagnosis of an additional condition and can be used to evaluate the effects of growth-promoting treatment for patients. When developing these charts, factors that can affect the reliability of the charts should be considered. These factors include the definition of the disease with growth failure, selection bias in the measurements used to develop the charts, secular trends of the subjects, the numbers of subjects of varying ages and ethnicities, and the statistical method used to develop the charts. In this review, we summarize the development of disease-specific growth charts for Japanese individuals with Turner syndrome and Noonan syndrome and evaluate the efforts to collect unbiased measurements of subjects with these diseases. These charts were the only available disease-specific growth charts of Turner syndrome and Noonan syndrome for Asian populations and were developed using a Japanese population. Therefore, when these charts are adopted for Asian populations other than Japanese, different growth patterns should be considered.
The Ornithine Decarboxylase Gene Is Essential for Cell Survival during Early Murine Development
Pendeville, Hélène; Carpino, Nick; Marine, Jean-Christophe; Takahashi, Yutaka; Muller, Marc; Martial, Joseph A.; Cleveland, John L.
2001-01-01
Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODC-deficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation. PMID:11533243
2013-01-01
Background A co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth. Results We conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth – infancy, childhood, puberty and final height. Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor – Hyper-geometric test, q < 0.05). The greatest degree of network ‘connectivity’ and hence functional significance was present in infancy (Wilcoxon test, p < 0.05), which then decreased through to adulthood. These observations were confirmed in a separate validation data set from lymphoid tissue. Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation. Conclusions Similar evolutionarily conserved pathways have been associated with gene expression and child growth in multiple tissues. These expression profiles associate with the developmental phases of growth including the return to active long bone growth in puberty, a distinctly human event. These observations also have direct medical relevance to pathological changes that induce disease in children. Taking into account development-dependent gene expression profiles for normal children will be key to the appropriate selection of genes and pathways as potential biomarkers of disease or as drug targets. PMID:23941278
Disordered follicle development
Chang, R. Jeffrey; Cook-Andersen, Heidi
2013-01-01
Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072
Dioxin inhibition of swim bladder development in zebrafish: is it secondary to heart failure?
Yue, Monica S; Peterson, Richard E; Heideman, Warren
2015-05-01
The swim bladder is a gas-filled organ that is used for regulating buoyancy and is essential for survival in most teleost species. In zebrafish, swim bladder development begins during embryogenesis and inflation occurs within 5 days post fertilization (dpf). Embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) before 96 h post fertilization (hpf) developed swim bladders normally until the growth/elongation phase, at which point growth was arrested. It is known that TCDD exposure causes heart malformations that lead to heart failure in zebrafish larvae, and that blood circulation is a key factor in normal development of the swim bladder. The adverse effects of TCDD exposure on the heart occur during the same period of time that swim bladder development and growth occurs. Based on this coincident timing, and the dependence of swim bladder development on proper circulatory development, we hypothesized that the adverse effects of TCDD on swim bladder development were secondary to heart failure. We compared swim bladder development in TCDD-exposed embryos to: (1) silent heart morphants, which lack cardiac contractility, and (2) transiently transgenic cmlc2:caAHR-2AtRFP embryos, which mimic TCDD-induced heart failure via heart-specific, constitutive activation of AHR signaling. Both of these treatment groups, which were not exposed to TCDD, developed hypoplastic swim bladders of comparable size and morphology to those found in TCDD-exposed embryos. Furthermore, in all treatment groups swim bladder development was arrested during the growth/elongation phase. Together, these findings support a potential role for heart failure in the inhibition of swim bladder development caused by TCDD. Copyright © 2015 Elsevier B.V. All rights reserved.
Jesudason, E. C.
2002-01-01
Lung hypoplasia is central to the poor prognosis of babies with congenital diaphragmatic hernia (CDH). Prolapse of abdominal organs through a diaphragmatic defect has traditionally been thought to impair lung growth by compression. The precise developmental biology of CDH remains unresolved. Refractory to fetal correction, lung hypoplasia in CDH may instead originate during embryogenesis and before visceral herniation. Resolving these conflicting hypotheses may lead to reappraisal of current clinical strategies. Genetic studies in murine models and the fruitfly, Drosophila melanogaster are elucidating the control of normal respiratory organogenesis. Branchless and breathless are Drosophila mutants lacking fibroblast growth factor (FGF) and its cognate receptor (FGFR), respectively. Sugarless and sulphateless mutants lack enzymes essential for heparan sulphate (HS) biosynthesis. Phenotypically, all these mutants share abrogated airway branching. Mammalian organ culture and transgenic models confirm the essential interaction of FGFs and HS during airway ramification. Embryonic airway development (branching morphogenesis) occurs in a defined spatiotemporal sequence. Unlike the surgically-created lamb model, the nitrofen rat model permits investigation of embryonic lung growth in CDH. Microdissecting embryonic lung primordia from the nitrofen CDH model and normal controls, we demonstrated that disruption of stereotyped airway branching correlates with and precedes subsequent CDH formation. To examine disturbed branching morphogenesis longitudinally, we characterised a system that preserves lung hypoplasia in organ culture. We tested FGFs and heparin (an HS analogue) as potential therapies on normal and hypoplastic lungs. Observing striking differences in morphological response to FGFs between normal and hypoplastic lung primordia, we postulated abnormalities of FGF/HS signalling in the embryonic CDH lung. Evaluating this hypothesis further, we examined effects of an HS-independent growth factor (epidermal growth factor, EGF) on hypoplastic lung development. Visible differences in morphological response indicate an intrinsic abnormality of hypoplastic lung primordia that may involve shared targets of FGFs and EGE. These studies indicate that lung hypoplasia precedes diaphragmatic hernia and may involve disturbances of mitogenic signalling pathways fundamental to embryonic lung development. What does this imply for human CDH? Fetal surgery may be 'too little, too late' to correct an established lung embryopathy. In utero growth factor therapy may permit antenatal lung rescue. Prevention of the birth defect by preconceptual prophylaxis may represent the ultimate solution. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 6 PMID:12215028
Neufeld, Stanley J.; Wang, Fan; Cobb, John
2014-01-01
The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. PMID:25217052
Neufeld, Stanley J; Wang, Fan; Cobb, John
2014-11-01
The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. Copyright © 2014 by the Genetics Society of America.
Disturbances of bone growth and development
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ledesma-Medina, J.; Newman, B.; Oh, K.S.
1988-03-01
''What is growth anyway. Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age. Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but themore » early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability. 116 references.« less
Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R
2010-06-01
Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.
Pappenheimer, A. M.; McCann, G. F.; Zucker, T. F.
1922-01-01
1. Casein phosphorus does not completely prevent the development of rickets when substituted in Diet 84 in amount equivalent to a protective dose of basic potassium phosphate. 2. The protection given by lecithin is equivalent to its phosphorus content. 3. The protection given by yeast is at least proportional to its phosphorus content. An amount carrying sufficient vitamine B to promote growth, but insufficient to provide adequate phosphorus, does not prevent rickets. 4. Vitamine A, in the form of butter or butter fat to the amount of 10 per cent of the diet, neither prevents nor cures rickets. 5. The substitution of 10 per cent of egg albumin in Diet 84 improves the nutrition, but does not prevent rickets. 6. The addition of meat to Diet 84, thereby supplying an abundance of phosphorus, promotes normal growth and normal bone formation. A diet consisting solely of meat and flour is inadequate for proper growth, and leads to changes in the bones comparable with those observed on a diet low in calcium, but rich in phosphorus. 7. A diet has been found which contains the necessary food elements for approximately normal growth, and in which the only known deficiency is phosphorus. This leads regularly to the production of rickets. PMID:19868618
NASA Technical Reports Server (NTRS)
Goodwin, Thomas J. (Inventor)
1998-01-01
Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue. The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.
NASA Technical Reports Server (NTRS)
Goodwin, Thomas J. (Inventor)
1998-01-01
Normal mammalian tissue and the culturing process has been developed for the three groups of organ, structural and blood tissue.The cells are grown in vitro under microgravity culture conditions and form three dimensional cells aggregates with normal cell function. The microgravity culture conditions may be microgravity or simulated microgravity created in a horizontal rotating wall culture vessel.
Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.
Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming
2015-06-03
Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor. Copyright © 2015 the authors 0270-6474/15/358384-10$15.00/0.
Divergent roles of growth factors in the GnRH regulation of puberty in mice
DiVall, Sara A.; Williams, Tameeka R.; Carver, Sarah E.; Koch, Linda; Brüning, Jens C.; Kahn, C. Ronald; Wondisford, Fredric; Radovick, Sally; Wolfe, Andrew
2010-01-01
Pubertal onset, initiated by pulsatile gonadotropin-releasing hormone (GnRH), only occurs in a favorable, anabolic hormonal milieu. Anabolic factors that may signal nutritional status to the hypothalamus include the growth factors insulin and IGF-1. It is unclear which hypothalamic neuronal subpopulation these factors affect to ultimately regulate GnRH neuron function in puberty and reproduction. We examined the direct role of the GnRH neuron in growth factor regulation of reproduction using the Cre/lox system. Mice with the IR or IGF-1R deleted specifically in GnRH neurons were generated. Male and female mice with the IR deleted in GnRH neurons displayed normal pubertal timing and fertility, but male and female mice with the IGF-1R deleted in GnRH neurons experienced delayed pubertal development with normal fertility. With IGF-1 administration, puberty was advanced in control females, but not in females with the IGF-1R deleted in GnRH neurons, in control males, or in knockout males. These mice exhibited developmental differences in GnRH neuronal morphology but normal number and distribution of neurons. These studies define the role of IGF-1R signaling in the coordination of somatic development with reproductive maturation and provide insight into the mechanisms regulating pubertal timing in anabolic states. PMID:20628204
Gravistimulus Production in Roots of Corn
NASA Technical Reports Server (NTRS)
Feldman, L. J.
1985-01-01
Because of the similarities in structure of known growth regulators, specifically abscisic acid and xanthoxin, with portions of the violaxanthin molecule, it was suggested that these growth substances normally arise from the breakdown or turnover of carotenoid. The light-induced disappearance of violaxanthin occurs in a time frame coincident with an increase in the levels in cap tissue of substances with growth inhibitor properties. One of the ways by which light may regulate root development, including aspects of gravitropism, is through the production of inhibitory growth substances arising from the turnover of carotenoids.
Embryonic essential myosin light chain regulates fetal lung development in rats.
Santos, Marta; Moura, Rute S; Gonzaga, Sílvia; Nogueira-Silva, Cristina; Ohlmeier, Steffen; Correia-Pinto, Jorge
2007-09-01
Congenital diaphragmatic hernia (CDH) is currently the most life-threatening congenital anomaly the major finding of which is lung hypoplasia. Lung hypoplasia pathophysiology involves early developmental molecular insult in branching morphogenesis and a late mechanical insult by abdominal herniation in maturation and differentiation processes. Since early determinants of lung hypoplasia might appear as promising targets for prenatal therapy, proteomics analysis of normal and nitrofen-induced hypoplastic lungs was performed at 17.5 days after conception. The major differentially expressed protein was identified by mass spectrometry as myosin light chain 1a (MLC1a). Embryonic essential MLC1a and regulatory myosin light chain 2 (MLC2) were characterized throughout normal and abnormal lung development by immunohistochemistry and Western blot. Disruption of MLC1a expression was assessed in normal lung explant cultures by antisense oligodeoxynucleotides. Since early stages of normal lung development, MLC1a was expressed in vascular smooth muscle (VSM) cells of pulmonary artery, and MLC2 was present in parabronchial smooth muscle and VSM cells of pulmonary vessels. In addition, early smooth muscle differentiation delay was observed by immunohistochemistry of alpha-smooth muscle actin and transforming growth factor-beta1. Disruption of MLC1a expression during normal pulmonary development led to significant growth and branching impairment, suggesting a role in branching morphogenesis. Both MLC1a and MLC2 were absent from hypoplastic fetal lungs during pseudoglandular stage of lung development, whereas their expression partially recovered by prenatal treatment with vitamin A. Thus, a deficiency in contractile proteins MLC1a and MLC2 might have a role among the early molecular determinants of lung hypoplasia in the rat model of nitrofen-induced CDH.
Gascoyne, Duncan M; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E; Croucher, Peter I; Banham, Alison H
2015-01-01
Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology.
Gascoyne, Duncan M.; Spearman, Hayley; Lyne, Linden; Puliyadi, Rathi; Perez-Alcantara, Marta; Coulton, Les; Fisher, Simon E.; Croucher, Peter I.; Banham, Alison H.
2015-01-01
Mutations of the forkhead transcription factor FOXP2 gene have been implicated in inherited speech-and-language disorders, and specific Foxp2 expression patterns in neuronal populations and neuronal phenotypes arising from Foxp2 disruption have been described. However, molecular functions of FOXP2 are not completely understood. Here we report a requirement for FOXP2 in growth arrest of the osteosarcoma cell line 143B. We observed endogenous expression of this transcription factor both transiently in normally developing murine osteoblasts and constitutively in human SAOS-2 osteosarcoma cells blocked in early osteoblast development. Critically, we demonstrate that in 143B osteosarcoma cells with minimal endogenous expression, FOXP2 induced by growth arrest is required for up-regulation of p21WAF1/CIP1. Upon growth factor withdrawal, FOXP2 induction occurs rapidly and precedes p21WAF1/CIP1 activation. Additionally, FOXP2 expression could be induced by MAPK pathway inhibition in growth-arrested 143B cells, but not in traditional cell line models of osteoblast differentiation (MG-63, C2C12, MC3T3-E1). Our data are consistent with a model in which transient upregulation of Foxp2 in pre-osteoblast mesenchymal cells regulates a p21-dependent growth arrest checkpoint, which may have implications for normal mesenchymal and osteosarcoma biology. PMID:26034982
Vitamins are substances that your body needs to grow and develop normally. Vitamin A plays a role in your Vision Bone growth Reproduction Cell functions Immune system Vitamin A is an antioxidant. It can come from ...
Tank, Jigna G; Thaker, Vrinda S
2014-01-01
Molecular mechanism regulated by auxin and cytokinin during endoreduplication, cell division, and elongation process is studied by using Allium cepa roots as a model system. The activity of CDK genes modulated by auxin and cytokinin during cell division, elongation, and endoreduplication process is explained in this research work. To study the significance of auxin and cytokinin in the management of cell division and endoreduplication process in plant meristematic cells at molecular level endoreduplication was developed in root tips of Allium cepa by giving colchicine treatment. There were inhibition of vegetative growth, formation of c-tumor at root tip, and development of endoreduplicated cells after colchicine treatment. This c-tumor was further treated with NAA and BAP to reinitiate vegetative growth in roots. BAP gave positive response in reinitiation of vegetative growth of roots from center of c-tumor. However, NAA gave negative response in reinitiation of vegetative growth of roots from c-tumor. Further, CDKs gene expression analysis from normal, endoreduplicated, and phytohormone (NAA or BAP) treated root tip was done and remarkable changes in transcription level of CDK genes in normal, endoreduplicated, and phytohormones treated cells were observed.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rodriguez-Concepcion, M.; Gruissem, W.
Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression ofmore » HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.« less
Tank, Jigna G.; Thaker, Vrinda S.
2014-01-01
Molecular mechanism regulated by auxin and cytokinin during endoreduplication, cell division, and elongation process is studied by using Allium cepa roots as a model system. The activity of CDK genes modulated by auxin and cytokinin during cell division, elongation, and endoreduplication process is explained in this research work. To study the significance of auxin and cytokinin in the management of cell division and endoreduplication process in plant meristematic cells at molecular level endoreduplication was developed in root tips of Allium cepa by giving colchicine treatment. There were inhibition of vegetative growth, formation of c-tumor at root tip, and development of endoreduplicated cells after colchicine treatment. This c-tumor was further treated with NAA and BAP to reinitiate vegetative growth in roots. BAP gave positive response in reinitiation of vegetative growth of roots from center of c-tumor. However, NAA gave negative response in reinitiation of vegetative growth of roots from c-tumor. Further, CDKs gene expression analysis from normal, endoreduplicated, and phytohormone (NAA or BAP) treated root tip was done and remarkable changes in transcription level of CDK genes in normal, endoreduplicated, and phytohormones treated cells were observed. PMID:24955358
... they do not eat a good breakfast. The relationship between breakfast and improved learning has been clearly ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...
REFORESTATION AND SEEDLING SYMBIONTS
Tree seedlings are dependent on symbiotic associations with microorganisms including bacteria, fungi, and actinomycetes for normal growth and development. itrogen fixing leguminous and non-leguminous trees form symbiotic relationships with Rhizobium (bacteria) and Frankia (actino...
Growth factors and chronic wound healing: past, present, and future.
Goldman, Robert
2004-01-01
Growth substances (cytokines and growth factors) are soluble signaling proteins affecting the process of normal wound healing. Cytokines govern the inflammatory phase that clears cellular and extracellular matrix debris. Wound repair is controlled by growth factors (platelet-derived growth factor [PDGF], keratinocyte growth factor, and transforming growth factor beta). Endogenous growth factors communicate across the dermal-epidermal interface. PDGF is important for most phases of wound healing. Becaplermin (PDGF-BB), the only growth factor approved by the Food and Drug Administration, requires daily application for neuropathic wound healing. Gene therapy is under development for more efficient growth factor delivery; a single application will induce constitutive growth factor expression for weeks. Based on dramatic preclinical animal studies, a phase 1 clinical trial planned on a PDGF genetic construct appears promising.
Critical role of the axonal guidance cue EphrinB2 in lung growth, angiogenesis, and repair.
Vadivel, Arul; van Haaften, Tim; Alphonse, Rajesh S; Rey-Parra, Gloria-Juliana; Ionescu, Lavinia; Haromy, Al; Eaton, Farah; Michelakis, Evangelos; Thébaud, Bernard
2012-03-01
Lung diseases characterized by alveolar damage currently lack efficient treatments. The mechanisms contributing to normal and impaired alveolar growth and repair are incompletely understood. Axonal guidance cues (AGC) are molecules that guide the outgrowth of axons to their targets. Among these AGCs, members of the Ephrin family also promote angiogenesis, cell migration, and organogenesis outside the nervous system. The role of Ephrins during alveolar growth and repair is unknown. We hypothesized that EphrinB2 promotes alveolar development and repair. We used in vitro and in vivo manipulation of EphrinB2 signaling to assess the role of this AGC during normal and impaired lung development. In vivo EphrinB2 knockdown using intranasal siRNA during the postnatal stage of alveolar development in rats arrested alveolar and vascular growth. In a model of O(2)-induced arrested alveolar growth in newborn rats, air space enlargement, loss of lung capillaries, and pulmonary hypertension were associated with decreased lung EphrinB2 and receptor EphB4 expression. In vitro, EphrinB2 preserved alveolar epithelial cell viability in O(2), decreased O(2)-induced alveolar epithelial cell apoptosis, and accelerated alveolar epithelial cell wound healing, maintained lung microvascular endothelial cell viability, and proliferation and vascular network formation. In vivo, treatment with intranasal EphrinB2 decreased alveolar epithelial and endothelial cell apoptosis, preserved alveolar and vascular growth in hyperoxic rats, and attenuated pulmonary hypertension. The AGC EphrinB2 may be a new therapeutic target for lung repair and pulmonary hypertension.
Olfactory granule cell development in normal and hyperthyroid rats.
Brunjes, P C; Schwark, H D; Greenough, W T
1982-10-01
Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.
Hanlon, R T; Bidwell, J P; Tait, R
1989-01-01
When cephalopod eggs were incubated in artificial sea water it was found that they sometimes resulted in hatchlings with defects of the statocyst suprastructure, leading to the severe behavioural defect of uncontrolled swimming. Experiments in defined media (seven basic salts mixed in deionized water) with seven species of cephalopods demonstrated clearly that there is 100% normal development of the aragonite statoliths when strontium levels were 8 mg l-1. Conversely, statoliths did not develop when strontium was absent. In cuttlefish, the growth of the cuttlebone was also affected adversely when strontium was absent. In mariculture production tanks, supplementing commercial artificial sea water with strontium to normal levels of 8 mg l-1 almost eliminated the occurrence of abnormal hatchlings. Circumstantial evidence indicates that there is a critical window in development during which strontium is required for normal development. The role of strontium in biomineralization during embryogenesis is unknown, but it appears to be important in the Mollusca.
Review: Neuroinflammation in intrauterine growth restriction.
Wixey, Julie A; Chand, Kirat K; Colditz, Paul B; Bjorkman, S Tracey
2017-06-01
Disruption to the maternal environment during pregnancy from events such as hypoxia, stress, toxins, inflammation, and reduced placental blood flow can affect fetal development. Intrauterine growth restriction (IUGR) is commonly caused by chronic placental insufficiency, interrupting supply of oxygen and nutrients to the fetus resulting in abnormal fetal growth. IUGR is a major cause of perinatal morbidity and mortality, occurring in approximately 5-10% of pregnancies. The fetal brain is particularly vulnerable in IUGR and there is an increased risk of long-term neurological disorders including cerebral palsy, epilepsy, learning difficulties, behavioural difficulties and psychiatric diagnoses. Few studies have focused on how growth restriction interferes with normal brain development in the IUGR neonate but recent studies in growth restricted animal models demonstrate increased neuroinflammation. This review describes the role of neuroinflammation in the progression of brain injury in growth restricted neonates. Identifying the mediators responsible for alterations in brain development in the IUGR infant is key to prevention and treatment of brain injury in these infants. Copyright © 2016 Elsevier Ltd. All rights reserved.
Yan, Jing; Charles, Julia F
2018-04-01
Microbiota and their hosts have coevolved for millions of years. Microbiota are not only critical for optimal development of the host under normal physiological growth, but also important to ensure proper host development during nutrient scarcity or disease conditions. A large body of research has begun to detail the mechanism(s) of how microbiota cooperate with the host to maintain optimal health status. One crucial host pathway recently demonstrated to be modulated by microbiota is that of the growth factor insulin like growth factor 1 (IGF-1). Gut microbiota are capable of dynamically modulating circulating IGF-1 in the host, with the majority of data suggesting that microbiota induce host IGF-1 synthesis to influence growth. Microbiota-derived metabolites such as short chain fatty acids are sufficient to induce IGF-1. Whether microbiota induction of IGF-1 is mediated by the difference in growth hormone expression or the host sensitivity to growth hormone is still under investigation. This review summarizes the current data detailing the interaction between gut microbiota, IGF-1 and host development.
Targeting the fibroblast growth factor receptors for the treatment of cancer.
Lemieux, Steven M; Hadden, M Kyle
2013-06-01
Receptor tyrosine kinases (RTKs) are transmembrane proteins that play a critical role in stimulating signal transduction cascades to influence cell proliferation, growth, and differentiation and they have also been shown to promote angiogenesis when they are up-regulated or mutated. For this reason, their dysfunction has been implicated in the development of human cancer. Over the past decade, much attention has been devoted to developing inhibitors and antibodies against several classes of RTKs, including vascular endothelial growth factor receptors (VEGFRs), epidermal growth factor receptors (EGFRs), and platelet-derived growth factor receptors (PDGFRs). More recently, interest in the fibroblast growth factor receptor (FGFR) class of RTKs as a drug target for the treatment of cancer has emerged. Signaling through FGFRs is critical for normal cellular function and their dysregulation has been linked to various malignancies such as breast and prostate cancer. This review will focus on the current state of both small molecules and antibodies as FGFR inhibitors to provide insight into their development and future potential as anti-cancer agents.
Genetics Home Reference: acrocallosal syndrome
... callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum ) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth ...
MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network
Samad, Abdul F. A.; Sajad, Muhammad; Nazaruddin, Nazaruddin; Fauzi, Izzat A.; Murad, Abdul M. A.; Zainal, Zamri; Ismail, Ismanizan
2017-01-01
Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions. PMID:28446918
Knowledge Cannot Explain the Developmental Growth of Working Memory Capacity
Cowan, Nelson; Ricker, Timothy J.; Clark, Katherine M.; Hinrichs, Garrett A.; Glass, Bret A.
2014-01-01
According to some views of cognitive growth, the development of working memory capacity can account for increases in the complexity of cognition. It has been difficult to ascertain, though, that there actually is developmental growth in capacity that cannot be attributed to other developing factors. Here we assess the role of item familiarity. We document developmental increases in working memory for visual arrays of English letters versus unfamiliar characters. Although letter knowledge played a special role in development between the ages of 6 to 8 years, children with adequate letter knowledge showed practically the same developmental growth in normalized functions for letters and unfamiliar characters. The results contribute to a growing body of evidence that the developmental improvement in working memory does not wholly stem from supporting processes such as encoding, mnemonic strategies, and knowledge. PMID:24942111
Randolph, J F; Miller, C L; Cummings, J F; Lothrop, C D
1990-01-01
Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.
Hox11 genes regulate postnatal longitudinal bone growth and growth plate proliferation.
Pineault, Kyriel M; Swinehart, Ilea T; Garthus, Kayla N; Ho, Edward; Yao, Qing; Schipani, Ernestina; Kozloff, Kenneth M; Wellik, Deneen M
2015-10-23
Hox genes are critical regulators of skeletal development and Hox9-13 paralogs, specifically, are necessary for appendicular development along the proximal to distal axis. Loss of function of both Hoxa11 and Hoxd11 results in severe malformation of the forelimb zeugopod. In the radius and ulna of these mutants, chondrocyte development is perturbed, growth plates are not established, and skeletal growth and maturation fails. In compound mutants in which one of the four Hox11 alleles remains wild-type, establishment of a growth plate is preserved and embryos develop normally through newborn stages, however, skeletal phenotypes become evident postnatally. During postnatal development, the radial and ulnar growth rate slows compared to wild-type controls and terminal bone length is reduced. Growth plate height is decreased in mutants and premature growth plate senescence occurs along with abnormally high levels of chondrocyte proliferation in the reserve and proliferative zones. Compound mutants additionally develop an abnormal curvature of the radius, which causes significant distortion of the carpal elements. The progressive bowing of the radius appears to result from physical constraint caused by the disproportionately slower growth of the ulna than the radius. Collectively, these data are consistent with premature depletion of forelimb zeugopod progenitor cells in the growth plate of Hox11 compound mutants, and demonstrate a continued function for Hox genes in postnatal bone growth and patterning. © 2015. Published by The Company of Biologists Ltd.
Differential Regulation of Mouse B Cell Development by Transforming Growth Factor β1
Kaminski, Denise A.; Letterio, John J.; Burrows, Peter D.
2002-01-01
Transforming growth factor β (TGFβ) can inhibit the in vitro proliferation, survival and differentiation of B cell progenitors, mature B lymphocytes and plasma cells. Here we demonstrate unexpected, age-dependent reductions in the bone marrow (BM) B cell progenitors and immature B cells in TGFβ1-/- mice. To evaluate TGFβ responsiveness during normal B lineage development, cells were cultured in interleukin 7 (IL7)±TGFβ. Picomolar doses of TGFβ1 reduced pro-B cell recoveries at every timepoint. By contrast, the pre-B cells were initially reduced in number, but subsequently increased compared to IL7 alone, resulting in a 4-fold increase in the growth rate for the pre-B cell population. Analysis of purified BM sub-populations indicated that pro-B cells and the earliest BP1- pre-B cells were sensitive to the inhibitory effects of TGFβ1. However, the large BP1+ pre-B cells, although initially reduced, were increased in number at days 5 and 7 of culture. These results indicate that TGFβ1 is important for normal B cell development in vivo, and that B cell progenitors are differentially affected by the cytokine according to their stage of differentiation. PMID:12739785
Empirical analyses on the development trend of non-ferrous metal industry under China’s new normal
NASA Astrophysics Data System (ADS)
Li, C. X.; Liu, C. X.; Zhang, Q. L.
2017-08-01
The CGE model of Yunnan’s macro economy was constructed based on the input-output data of Yunnan in 2012, and the development trend of the non-ferrous metals industry (NMI) under the China’s new normal was simulated. In view of this, according to different expected economic growth, and optimized economic structure, the impact on development of Yunnan NMI was simulated. The results show that the NMI growth rate is expected to decline when the economic growth show a downward trend, but the change of the proportion is relatively small. Moreover, the structure in proportion was adjusted to realize the economic structure optimization, while the proportion of NMI in GDP will decline. In contrast, the biggest influence on the NMI is the change of economic structure. From the statistics of last two years, we can see that NMI is growing, and at the same time, its proportion is declining, which is consistent with the results of simulation. But the adjustment of economic structure will take a long time. It is need to improve the proportion of deep-processing industry, extend the industrial chain, enhance the value chain, so as to be made good use of resource advantage.
Control of continuous irradiation injury on potatoes with daily temperature cycling
NASA Technical Reports Server (NTRS)
Tibbitts, T. W.; Bennett, S. M.; Cao, W.
1990-01-01
Two controlled-environment experiments were conducted to determine the effects of temperature fluctuations under continuous irradiation on growth and tuberization of two potato (Solanum tuberosum L.) cultivars, Kennebec and Superior. These cultivars had exhibited chlorotic and stunted growth under continuous irradiation and constant temperatures. The plants were grown for 4 weeks in the first experiment and for 6 weeks in the second experiment. Each experiment was conducted under continuous irradiation of 400 micromoles per square meter per second of photosynthetic photon flux and included two temperature treatments: constant 18 degrees C and fluctuating 22 degrees C/14 degrees C on a 12-hour cycle. A common vapor pressure deficit of 0.62 kilopascal was maintained at all temperatures. Plants under constant 18 degrees C were stunted and had chlorotic and abscised leaves and essentially no tuber formation. Plants grown under the fluctuating temperature treatment developed normally, were developing tubers, and had a fivefold or greater total dry weight as compared with those under the constant temperature. These results suggest that a thermoperiod can allow normal plant growth and tuberization in potato cultivars that are unable to develop effectively under continuous irradiation.
NASA Technical Reports Server (NTRS)
Hardman, P.; Spooner, B. S.
1992-01-01
It is important to know whether microgravity will adversely affect developmental processes. Collagens are macromolecular structural components of the extracellular matrix (ECM) which may be altered by perturbations in gravity. Interstitial collagens have been shown to be necessary for normal growth and morphogenesis in some embryonic organs, and in the mouse salivary gland, the biosynthetic pattern of these molecules changes during development. Determination of the effects of microgravity on epithelial organ development must be preceded by crucial ground-based studies. These will define control of normal synthesis, secretion, and deposition of ECM macromolecules and the relationship of these processes to morphogenesis.
Crimmins, Sarah; Mo, Cecilia; Nassar, Yomna; Kopelman, Jerome N; Turan, Ozhan M
2018-01-01
This study aims to investigate the perinatal outcome of fetuses with polyhydramnios and/or accelerated growth among women with a normal oral glucose challenge test (oGCT). Singleton, nonanomalous pregnancies with an oGCT(< 130 mg/dL) at 24 to 28 weeks, who subsequently demonstrate polyhydramnios (amniotic fluid index > 24 cm or maximum vertical pocket > 8 cm) and/or accelerated growth (abdominal circumference > 95th percentile) on two-third trimester examinations were studied. Maternal demographics, delivery, and neonatal information were recorded. Cases were compared with a reference group (normal oGCT with neither abnormal third-trimester growth nor polyhydramnios). A total of 282 pregnancies were in the study group, and 663 were in the reference group. Deliveries in the study group were at a higher risk for birth weight (BW)% > 90%, standard deviation, and postpartum hemorrhage when compared with the reference group (adjusted odds ratio: 2.3-5.6). Pregnancies complicated by both polyhydramnios and accelerated fetal growth were significantly more likely to result in a BW% > 90% (odds ratio [OR]: 18.5; 95% confidence interval [CI]: 8.9-38.6) and PPH (OR: 4.2; 95% CI: 2.4-7.6). Pregnancies with normal oGCT that develop polyhydramnios and accelerated growth are at higher risk for maternal and neonatal complications. Isolated polyhydramnios without accelerated growth increases the risk for delivery complications but not neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Thyroid Hormones and Growth in Health and Disease
Tarım, Ömer
2011-01-01
Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631
WANG, WEI; WANG, HONG; WANG, CHUN-MEI; GOU, SI; CHEN, ZHONG-HUA; GUO, JIE
2014-01-01
The aim of this study was to investigate whether Huisheng oral solution (HSOS) has an inhibitory effect on the development of pulmonary thrombosis and metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible mechanisms involved. A mouse model of LLC was developed, and model mice were divided into either a treatment group or a control group to undergo treatment with HSOS or normal saline. Normal mice treated with saline were used as normal controls. On day 25 after treatment, blood samples were drawn from the eyes of half the mice in each group to determine blood cell counts and plasma levels of D-Dimer and vascular endothelial growth factor (VEGF), while heart blood samples were collected from the remaining mice to measure the rate of thrombin-induced platelet aggregation. For all mice, pathological analyses of the cerebrum, lung, mesentery, femoral vein, external iliac vein and spleen were performed. Tumors were weighed to assess the impact of HSOS treatment on tumor growth, and the number of thrombi, metastatic nodules and neovessels in the tumor tissue were counted. In addition, 24 normal New Zealand rabbits were divided into two groups and treated with either HSOS or normal saline to determine the rates of ADP-, collagen- or thrombin-induced platelet aggregation. Compared with the model group, HSOS treatment decreased the incidence of pulmonary thromboembolism and metastasis, the number of metastatic nodules, the plasma levels of D-dimer and VEGF, the rate of collagen-induced platelet aggregation in rabbits and the numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the thymus and spleen coefficients and the number of platelets (P<0.05 for all), but had no significant effect on thrombin-induced platelet aggregation in mice and rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS treatment effectively reduced the development of pulmonary thromboembolism and metastasis in mice bearing LLC via mechanisms possibly associated with ameliorating a blood hypercoagulable state, decreasing tumor angiogenesis and enhancing immunity. PMID:24348827
Overexpression of c-jun, junB, or junD affects cell growth differently.
Castellazzi, M; Spyrou, G; La Vista, N; Dangy, J P; Piu, F; Yaniv, M; Brun, G
1991-10-15
The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth.
Overexpression of c-jun, junB, or junD affects cell growth differently.
Castellazzi, M; Spyrou, G; La Vista, N; Dangy, J P; Piu, F; Yaniv, M; Brun, G
1991-01-01
The coding sequences of murine c-jun, junB, or junD, which code for proteins with practically identical dimerization and DNA binding properties, were introduced into a nondefective retroviral vector, and the phenotype of primary avian fibroblasts chronically infected with each of these viruses was studied. Cells expressing c-jun grew in low-serum medium and developed into colonies in agar, two properties characteristic of in vitro transformation. Cells expressing junB grew in agar, with a reduced efficiency as compared to c-jun, but did not grow in low-serum medium. Finally, no effect of junD expression on cell growth was observed. These different phenotypes suggest that these three closely related transcription factors play distinct roles during normal cell growth. Analysis of c-jun deletion mutants and of c-jun/junB and c-jun/junD chimeric genes showed that the N-terminal portion (amino acids 2-168) of the c-Jun protein that is involved in transcriptional activation is required for efficient transformation. On the contrary, cells expressing a truncated mouse c-Jun lacking this N-terminal domain grew slower than normal embryo fibroblasts. The reduced growth rate may be related to the finding that expression of the intact or the truncated mouse c-jun repressed the endogenous avian c-Jun homologue, suggesting that functional c-Jun product is required for normal cell growth. Images PMID:1924349
Hung, T-H; Chen, S-F; Lo, L-M; Li, M-J; Yeh, Y-L; Hsieh, T-T
2012-04-01
Myeloperoxidase (MPO) is a heme protein produced and released by activated neutrophils and monocytes, and increased MPO is considered important in the pathophysiology of cardiovascular diseases (CVD). Accumulating evidence suggests that preeclampsia (PE), idiopathic intrauterine growth restriction (IUGR), and CVD share many similar metabolic disturbances, including an enhanced systemic inflammatory response and endothelial dysfunction. We hypothesized that MPO plays an important role in the development of PE and IUGR. Plasma samples were collected mid-gestation and at delivery from women with normal pregnancies (n = 40) and those who subsequently developed PE (n = 20), IUGR (n = 11) or both (PE + IUGR, n = 8). Placental samples were obtained immediately after delivery from 22 women with normal pregnancies, 19 women with PE, 14 women with IUGR, and 14 women with PE + IUGR. The MPO concentrations were measured using ELISA. Women with PE + IUGR had significantly higher plasma MPO before delivery than normal pregnant women. There was no difference in plasma levels at mid-gestation or the placental concentrations between women with normal pregnancies and those who developed PE, IUGR, or PE + IUGR. Using explants prepared from the placentas of 8 women with normal pregnancies and 8 women with PE, we found no difference in the levels of MPO in the tissue homogenates and culture media between these two groups of women. Together, these results indicate that increased maternal circulating MPO in women with PE + IUGR is likely a result of enhanced systemic inflammation caused by the established disease rather than a primary pathophysiological factor. Copyright © 2012 Elsevier Ltd. All rights reserved.
Jerman, Urška Dragin; Veranič, Peter; Kreft, Mateja Erdani
2014-04-01
The amniotic membrane (AM) is a naturally derived biomaterial that possesses biological and mechanical properties of great importance for tissue engineering. The aim of our study was to determine whether the AM enables the formation of a normal urinary bladder epithelium-urothelium--and to reveal any differences in the urothelial cell (UC) growth and differentiation when using different AM scaffolds. Cryopreserved human AM was used as a scaffold in three different ways. Normal porcine UCs were seeded on the AM epithelium (eAM), denuded AM (dAM), and stromal AM (sAM) and were cultured for 3 weeks. UC growth on AM scaffolds was monitored daily. By using electron microscopy, histochemical and immunofluorescence techniques, we here provide evidence that all three AM scaffolds enable the development of the urothelium. The fastest growth and the highest differentiation of UCs were demonstrated on the sAM scaffold, which enables the development of tissue-engineered urothelium with molecular and ultrastructural properties comparable to that of the native urothelium. Most importantly, the highly differentiated urothelia on the sAM scaffolds provide important experimental models for future drug delivery studies and developing tissue engineering strategies considering that subtle differences are identified before translation to the clinical settings.
Maintained larval growth in mussel larvae exposed to acidified under-saturated seawater.
Ventura, Alexander; Schulz, Sabrina; Dupont, Sam
2016-03-29
Ocean acidification (OA) is known to affect bivalve early life-stages. We tested responses of blue mussel larvae to a wide range of pH in order to identify their tolerance threshold. Our results confirmed that decreasing seawater pH and decreasing saturation state increases larval mortality rate and the percentage of abnormally developing larvae. Virtually no larvae reared at average pHT 7.16 were able to feed or reach the D-shell stage and their development appeared to be arrested at the trochophore stage. However larvae were capable of reaching the D-shell stage under milder acidification (pHT ≈ 7.35, 7.6, 7.85) including in under-saturated seawater with Ωa as low as 0.54 ± 0.01 (mean ± s. e. m.), with a tipping point for normal development identified at pHT 7.765. Additionally growth rate of normally developing larvae was not affected by lower pHT despite potential increased energy costs associated with compensatory calcification in response to increased shell dissolution. Overall, our results on OA impacts on mussel larvae suggest an average pHT of 7.16 is beyond their physiological tolerance threshold and indicate a shift in energy allocation towards growth in some individuals revealing potential OA resilience.
Maintained larval growth in mussel larvae exposed to acidified under-saturated seawater
NASA Astrophysics Data System (ADS)
Ventura, Alexander; Schulz, Sabrina; Dupont, Sam
2016-03-01
Ocean acidification (OA) is known to affect bivalve early life-stages. We tested responses of blue mussel larvae to a wide range of pH in order to identify their tolerance threshold. Our results confirmed that decreasing seawater pH and decreasing saturation state increases larval mortality rate and the percentage of abnormally developing larvae. Virtually no larvae reared at average pHT 7.16 were able to feed or reach the D-shell stage and their development appeared to be arrested at the trochophore stage. However larvae were capable of reaching the D-shell stage under milder acidification (pHT ≈ 7.35, 7.6, 7.85) including in under-saturated seawater with Ωa as low as 0.54 ± 0.01 (mean ± s. e. m.), with a tipping point for normal development identified at pHT 7.765. Additionally growth rate of normally developing larvae was not affected by lower pHT despite potential increased energy costs associated with compensatory calcification in response to increased shell dissolution. Overall, our results on OA impacts on mussel larvae suggest an average pHT of 7.16 is beyond their physiological tolerance threshold and indicate a shift in energy allocation towards growth in some individuals revealing potential OA resilience.
Maintained larval growth in mussel larvae exposed to acidified under-saturated seawater
Ventura, Alexander; Schulz, Sabrina; Dupont, Sam
2016-01-01
Ocean acidification (OA) is known to affect bivalve early life-stages. We tested responses of blue mussel larvae to a wide range of pH in order to identify their tolerance threshold. Our results confirmed that decreasing seawater pH and decreasing saturation state increases larval mortality rate and the percentage of abnormally developing larvae. Virtually no larvae reared at average pHT 7.16 were able to feed or reach the D-shell stage and their development appeared to be arrested at the trochophore stage. However larvae were capable of reaching the D-shell stage under milder acidification (pHT ≈ 7.35, 7.6, 7.85) including in under-saturated seawater with Ωa as low as 0.54 ± 0.01 (mean ± s. e. m.), with a tipping point for normal development identified at pHT 7.765. Additionally growth rate of normally developing larvae was not affected by lower pHT despite potential increased energy costs associated with compensatory calcification in response to increased shell dissolution. Overall, our results on OA impacts on mussel larvae suggest an average pHT of 7.16 is beyond their physiological tolerance threshold and indicate a shift in energy allocation towards growth in some individuals revealing potential OA resilience. PMID:27020613
Killer, Monika; Arthur, Adam; Al-Schameri, Abdul Rahman; Barr, John; Elbert, Donald; Ladurner, Gunther; Shum, Julie; Cruise, Gregory
2010-10-01
To better understand the development of hydrocephalus of different origins, we evaluated cytokine and growth factor concentration in cerebrospinal fluid from patients with hydrocephalus. CSF was collected from patients developing hydrocephalus following hemorrhage (n = 15), patients with normal pressure hydrocephalus (n = 10), and following the embolization of unruptured intracranial aneurysms (n = 9). Myelography patients (n = 15) served as controls. Quantification of 11 molecules relating angiogenesis, inflammation, and wound healing in the CSF was performed using ELISA. All three hydrocephalus groups had decreased concentration of TIMP-4 compared to the normal group. The hemorrhage group showed increased concentration of IL-6, IL-8, MCP-1, MMP-9, and TIMP-1 compared to the control group. The unruptured aneurysm group had increased concentration of IL-6 and decreased concentration of TIMP-2 compared to the control group. Compared to the normal patients, increased concentrations of wound healing molecules were evident in all three groups. Increased inflammation was evident in the hemorrhage and unruptured aneurysm groups.
Association between growth stunting with dental development and skeletal maturation stage.
Flores-Mir, Carlos; Mauricio, Franco Raul; Orellana, Maria Fernanda; Major, Paul William
2005-11-01
The aim of this study was to determine the influence of growth stunting on the maturation stage of the medium phalanx of the third finger (MP3) and the dental development of the left mandibular canine in 280 high school children (140 stunted and 140 normal controls; equally distributed by sex) between 9.5 and 16.5 years of age, from a representative Peruvian school. Periapical radiographs of the MP3 from the left hand were used to determine the skeletal maturity stage, according to an adaptation of the Hägg and Taranger method. Panoramic radiographs were used to determine the dental maturity stage of the lower left canine, according to Demirjian method. Stunting was determined by relating height and age, according to the World Health Organization recommendations. There was no statistically significant difference in the skeletal maturation stage (P = .134) and the dental development stage (P = .497) according to nutritional status, even when considering different age groups (P > .183). A high correlation (r = 0.85) was found between both maturity indicators regardless of the nutritional status (growth stunted, r = 0.855 and normal controls, r = 0.863) or sex (boys, r = 0.809 and girls, r = 0.892). When skeletal level was considered, correlations values were similar between advanced (r = 0.903) and average (r = 0.895) maturers but lower (r = 0.751) for delayed maturers. Growth stunting was not associated with dental development and skeletal maturity stages in Peruvian school children.
Multiplicative Modeling of Children's Growth and Its Statistical Properties
NASA Astrophysics Data System (ADS)
Kuninaka, Hiroto; Matsushita, Mitsugu
2014-03-01
We develop a numerical growth model that can predict the statistical properties of the height distribution of Japanese children. Our previous studies have clarified that the height distribution of schoolchildren shows a transition from the lognormal distribution to the normal distribution during puberty. In this study, we demonstrate by simulation that the transition occurs owing to the variability of the onset of puberty.
ERIC Educational Resources Information Center
SCOTT, ROLAND B.; AND OTHERS
THIS ARTICLE PRESENTS SIZE AND GROWTH VELOCITY DATA COLLECTED DURING A LONGITUDINAL STUDY OF 111 NORMAL, HEALTHY NEGRO INFANTS FROM LOWER-MIDDLE-CLASS FAMILIES. DATA WERE OBTAINED FROM BIRTH RECORDS AND MEASUREMENTS TAKEN DURING ROUTINE PHYSICAL EXAMINATIONS. WHEN THIS NEGRO SAMPLE WAS COMPARED WITH WHITE INFANTS IN SIMILAR STUDIES IT WAS FOUND…
Congenital isolated thyrotrophin releasing hormone deficiency
Niimi, H; Inomata, H; Sasaki, N; Nakajima, H
1982-01-01
A 4⅓-year-old girl with congenital thyrotrophin-releasing hormone (TRH) deficiency is described. Oral TRH administration led to normal thyroid hormone and TRH levels in the blood; favourable growth and development was achieved. PMID:6816148
Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu
2017-01-01
Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260
Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu
2017-03-01
Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.
Health Instruction Packages: Consumer--Child Care.
ERIC Educational Resources Information Center
Wojcik, Bonnie; And Others
Text, illustrations, and exercises are utilized in these four learning modules to instruct parents and nursing students in topics related to child care and development. The first module, "Growth and Development: Let's Test Your Baby's Reflexes" by Bonnie Wojcik, describes the behavioral signs that are indicative of eight normal primitive…
Top 10 Research Questions Related to Body Composition
ERIC Educational Resources Information Center
Going, Scott; Lee, Vinson; Blew, Rob; Laddu, Deepika; Hetherington-Rauth, Megan
2014-01-01
An understanding of body composition is crucial to understanding human health, disease, and function. Research in body composition has focused on the development of assessment methods, description of normal changes in body composition with growth and development and aging, and the changes that occur in body composition in response to challenges…
Development of Databases with Iodine in Foods and Dietary Supplements
USDA-ARS?s Scientific Manuscript database
Iodine is an essential micronutrient required for normal growth and development, thus an adequate intake of iodine is particularly important in pregnant and lactating women, and throughout childhood. Low levels of iodine in the soil and groundwater are common in many parts of the world, often leadi...
Infant and Newborn Development
... During their first year, babies start to develop skills they will use for the rest of their lives. The normal growth of babies can be broken down into the following areas: Gross motor - controlling the head, sitting, crawling, maybe even starting to walk Fine motor - holding a spoon, picking up a piece ...
Seed-to-seed growth of Arabidopsis thaliana on the International Space Station
NASA Technical Reports Server (NTRS)
Link, B. M.; Durst, S. J.; Zhou, W.; Stankovic, B.
2003-01-01
The assembly of the International Space Station (ISS) as a permanent experimental outpost has provided the opportunity for quality plant research in space. To take advantage of this orbital laboratory, engineers and scientists at the Wisconsin Center for Space Automation and Robotics (WCSAR), University of Wisconsin-Madison, developed a plant growth facility capable of supporting plant growth in the microgravity environment. Utilizing this Advanced Astroculture (ADVASC) plant growth facility, an experiment was conducted with the objective to grow Arabidopsis thaliana plants from seed-to-seed on the ISS. Dry Arabidopsis seeds were anchored in the root tray of the ADVASC growth chamber. These seeds were successfully germinated from May 10 until the end of June 2001. Arabidopsis plants grew and completed a full life cycle in microgravity. This experiment demonstrated that ADVASC is capable of providing environment conditions suitable for plant growth and development in microgravity. The normal progression through the life cycle, as well as the postflight morphometric analyses, demonstrate that Arabidopsis thaliana does not require the presence of gravity for growth and development. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.
Restrain of bone growth by estrogen-mimetic peptide-1 (EMP-1): a micro-computed tomographic study.
Kasher, Roni; Bajayo, Alon; Gabet, Yankel; Nevo, Nava; Fridkin, Mati; Katchalski-Katzir, Ephraim; Kohen, Fortune; Bab, Itai
2009-06-01
Estrogen has a key role in the regulation of skeletal growth and maintenance of bone mass. Recently, we developed peptides having estrogen-like activity as potential estrogen-based new drugs. The aim of the present study was to evaluate the influence of long-term administration of the most efficacious of these peptides, the hexapeptide EMP-1 (VSWFFE), on bone mass and development. EMP-1 was injected daily to ovariectomized (OVX) and intact young, sexually mature female mice for 10 weeks. Whole femora, including the cartilaginous growth plates were analyzed by micro-computed tomography (microCT). We found that peptide EMP-1 restrains bone growth in OVX mice: it inhibited dramatically bone longitudinal growth (40%), and decreased femoral diaphyseal diameter. Peptide EMP-1 had no effect on bone growth in normal mice, and did not influence the OVX-induced bone loss. We then developed a new microCT methodology to evaluate uncalcified and calcified growth plate parameters. In the OVX mice, peptide EMP-1 reduced volume and thickness of the uncalcified growth plate, a possible cause for the inhibition of bone longitudinal growth. Peptide EMP-1 may be used as a lead compound for the development of drugs to treat acromegalic patients.
Principles of Bobath neuro-developmental therapy in cerebral palsy.
Klimont, L
2001-01-01
The purpose of this article is to present the basics of Bobath Neurodevelopment Therapy (NDT) for the rehabilitation of patients with cerebral palsy, based on the fundamentals of neurophysiology.
Two factors are continually stressed in therapy: first, postural tension, whose quality provides the foundation for the development of motor coordination, both normal and pathological, and plays a role in shaping the mechanism of the normal postural reflex; and secondly, the impact of damage to the central nervous system on the process of its growth and development.
The practical application of the theoretical assumptions includes the use of inhibition, facilitation, and stimulation by key points of control, preparatory to evoking more nearly normal motor responses.
Growth hormone deficiency: an unusual presentation of floating harbor syndrome.
Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos
2011-01-01
Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.
Loudness growth in 1/2-octave bands (LGOB)--a procedure for the assessment of loudness.
Allen, J B; Hall, J L; Jeng, P S
1990-08-01
In this paper, a method that has been developed for the assessment and quantification of loudness perception in normal-hearing and hearing-impaired persons is described. The method has been named LGOB, which stands for loudness growth in 1/2-octave bands. The method uses 1/2-octave bands of noise, centered at 0.25, 0.5, 1.0, 2.0, and 4.0 kHz, with subjective levels between a subject's threshold of hearing and the "too loud" level. The noise bands are presented to the subject, randomized over frequency and level, and the subject is asked to respond with a loudness rating (one of: VERY SOFT, SOFT, OK, LOUD, VERY LOUD, TOO LOUD). Subject responses (normal and hearing-impaired) are then compared to the average responses of a group of normal-hearing subjects. This procedure allows one to estimate the subject's loudness growth relative to normals, as a function of frequency and level. The results may be displayed either as isoloudness contours or as recruitment curves. In its present form, the measurements take less than 30 min. The signal presentation and analysis is done using a PC and a PC plug-in board having a digital to analog converter.
Differential Role of Poly(ADP-ribose) polymerase in D. discoideum growth and development
2011-01-01
Background Poly(ADP-ribose) polymerase is evolutionarily conserved as a responder to various forms of stress. Though PARP's role in cell death is well addressed, its role in development and multicellularity is still an enigma. We have previously reported the role of PARP in oxidative stress induced delayed development of D. discoideum. Results In the current study we highlight the involvement of PARP during D. discoideum development. Oxidative stress affects expression of aca and cAR1 thus affecting aggregation. Although parp expression is not affected during oxidative stress but it is involved during normal development as confirmed by our PARP down-regulation studies. Constitutive PARP down-regulation resulted in blocked development while no effect was observed on D. discoideum growth. Interestingly, stage specific PARP down-regulation arrested development at the slug stage. Conclusion These results emphasize that PARP is essential for complex differentiation and its function may be linked to multicellularity. This is the first report where the involvement of PARP during normal multicellular development in D. discoideum, an ancient eukaryote, is established which could be of evolutionary significance. Thus our study adds one more role to the multitasking function of PARP. PMID:21385463
High-protein formulas: evidence for use in preterm infants.
Brown, Laura D; Hendrickson, Kendra; Masor, Marc L; Hay, William W
2014-06-01
Relatively high amounts of protein are required to achieve normal fractional protein synthetic rates during the late second through early third trimester of fetal growth. Once preterm infants achieve higher protein intakes for sustained periods, growth begins to approximate that of the normally growing fetus and long-term neurodevelopmental outcomes are improved. Preterm formulas have been developed that are enriched in protein. This review discusses several factors when using standard preterm formulas and high-protein preterm formulas in the neonatal intensive care unit, with an emphasis on quantity and quality of enteral protein delivery and risks to insufficient and/or excess protein administration. Copyright © 2014 Elsevier Inc. All rights reserved.
Delayed cerebral development in twins with congenital hyperthyroidism.
Kopelman, A E
1983-09-01
Twins had congenital hyperthyroidism and delayed cerebral development manifested as ventriculomegaly, increased space in the interhemispheric fissure, and an exaggerated gyral pattern on cranial computed tomographic scans. At 3 1/2 years of age, both children had delayed development. Fetal and neonatal hyperthyroidism may interfere with normal brain growth and maturation with both neuranatomic and developmental sequelae.
Liu, Xiaojun; Ferguson, Richard B.; Zheng, Hengbiao; Cao, Qiang; Tian, Yongchao; Cao, Weixing; Zhu, Yan
2017-01-01
The successful development of an optimal canopy vegetation index dynamic model for obtaining higher yield can offer a technical approach for real-time and nondestructive diagnosis of rice (Oryza sativa L) growth and nitrogen (N) nutrition status. In this study, multiple rice cultivars and N treatments of experimental plots were carried out to obtain: normalized difference vegetation index (NDVI), leaf area index (LAI), above-ground dry matter (DM), and grain yield (GY) data. The quantitative relationships between NDVI and these growth indices (e.g., LAI, DM and GY) were analyzed, showing positive correlations. Using the normalized modeling method, an appropriate NDVI simulation model of rice was established based on the normalized NDVI (RNDVI) and relative accumulative growing degree days (RAGDD). The NDVI dynamic model for high-yield production in rice can be expressed by a double logistic model: RNDVI=(1+e−15.2829×(RAGDDi−0.1944))−1−(1+e−11.6517×(RAGDDi−1.0267))−1 (R2 = 0.8577**), which can be used to accurately predict canopy NDVI dynamic changes during the entire growth period. Considering variation among rice cultivars, we constructed two relative NDVI (RNDVI) dynamic models for Japonica and Indica rice types, with R2 reaching 0.8764** and 0.8874**, respectively. Furthermore, independent experimental data were used to validate the RNDVI dynamic models. The results showed that during the entire growth period, the accuracy (k), precision (R2), and standard deviation of RNDVI dynamic models for the Japonica and Indica cultivars were 0.9991, 1.0170; 0.9084**, 0.8030**; and 0.0232, 0.0170, respectively. These results indicated that RNDVI dynamic models could accurately reflect crop growth and predict dynamic changes in high-yield crop populations, providing a rapid approach for monitoring rice growth status. PMID:28338637
Liu, Xiaojun; Ferguson, Richard B; Zheng, Hengbiao; Cao, Qiang; Tian, Yongchao; Cao, Weixing; Zhu, Yan
2017-03-24
The successful development of an optimal canopy vegetation index dynamic model for obtaining higher yield can offer a technical approach for real-time and nondestructive diagnosis of rice (Oryza sativa L) growth and nitrogen (N) nutrition status. In this study, multiple rice cultivars and N treatments of experimental plots were carried out to obtain: normalized difference vegetation index (NDVI), leaf area index (LAI), above-ground dry matter (DM), and grain yield (GY) data. The quantitative relationships between NDVI and these growth indices (e.g., LAI, DM and GY) were analyzed, showing positive correlations. Using the normalized modeling method, an appropriate NDVI simulation model of rice was established based on the normalized NDVI (RNDVI) and relative accumulative growing degree days (RAGDD). The NDVI dynamic model for high-yield production in rice can be expressed by a double logistic model: RNDVI = ( 1 + e - 15.2829 × ( R A G D D i - 0.1944 ) ) - 1 - ( 1 + e - 11.6517 × ( R A G D D i - 1.0267 ) ) - 1 (R2 = 0.8577**), which can be used to accurately predict canopy NDVI dynamic changes during the entire growth period. Considering variation among rice cultivars, we constructed two relative NDVI (RNDVI) dynamic models for Japonica and Indica rice types, with R2 reaching 0.8764** and 0.8874**, respectively. Furthermore, independent experimental data were used to validate the RNDVI dynamic models. The results showed that during the entire growth period, the accuracy (k), precision (R2), and standard deviation of RNDVI dynamic models for the Japonica and Indica cultivars were 0.9991, 1.0170; 0.9084**, 0.8030**; and 0.0232, 0.0170, respectively. These results indicated that RNDVI dynamic models could accurately reflect crop growth and predict dynamic changes in high-yield crop populations, providing a rapid approach for monitoring rice growth status.
Novel Antimicrobial Peptides That Inhibit Gram Positive Bacterial Exotoxin Synthesis
Merriman, Joseph A.; Nemeth, Kimberly A.; Schlievert, Patrick M.
2014-01-01
Gram-positive bacteria, such as Staphylococcus aureus, cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin and signal transduction inhibitors glycerol monolaurate and α-globin and β-globin chains of hemoglobin indicate that their abilities to inhibit exotoxin production by S. aureus are separable from abilities to inhibit growth of the organism. Additionally, our previous studies suggest that inhibition of exotoxin production, in absence of ability to kill S. aureus and normal flora lactobacilli, will prevent colonization by pathogenic S. aureus, while not interfering with lactobacilli colonization. These disparate activities may be important in development of novel anti-infective agents that do not alter normal flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity of hemoglobin peptides further to develop potential agents to prevent S. aureus infections. We tested synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, and two human defensins for ability to inhibit exotoxin production without significantly inhibiting S. aureus growth. All of these peptides were weakly or not inhibitory to bacterial growth. However, the peptides were inhibitory to exotoxin production with increasing activity dependent on increasing numbers of positively-charged amino acids. Additionally, the peptides could be immobilized on agarose beads or have amino acid sequences scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not toxic to human vaginal epithelial cells and do not inhibit growth of normal flora L. crispatus. These peptides may interfere with plasma membrane signal transduction in S. aureus due to their positive charges. PMID:24748386
BAD-mediated apoptotic pathway is associated with human cancer development.
Stickles, Xiaomang B; Marchion, Douglas C; Bicaku, Elona; Al Sawah, Entidhar; Abbasi, Forough; Xiong, Yin; Bou Zgheib, Nadim; Boac, Bernadette M; Orr, Brian C; Judson, Patricia L; Berry, Amy; Hakam, Ardeshir; Wenham, Robert M; Apte, Sachin M; Berglund, Anders E; Lancaster, Johnathan M
2015-04-01
The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, p<0.001), breast (n=185, p<0.0008; n=61, p=0.04), colon (n=22, p<0.001) and endometrial (n=33, p<0.001) cancers, as well as with ovarian endometriosis (n=20, p<0.001). Higher pBAD protein levels were observed in the cancer cells compared to the immortalized normal cells, whereas PP2C gene expression was lower in the cancer compared to the ovarian tumor tissue samples (n=76, p<0.001). The increased pBAD protein levels after the depletion of PP2C conferred a growth advantage to the immortalized normal and cancer cells. The BAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.
NASA Technical Reports Server (NTRS)
Brittnacher, M.; Quest, K. B.; Karimabadi, H.
1995-01-01
We have developed the linear theory of collisionless ion tearing in a two-dimensional magnetotail equilibrium for a single resonant species. We have solved the normal mode problem for tearing instability by an algorithm that employs particle-in-cell simulation to calculate the orbit integrals in the Maxwell-Vlasov eigenmode equation. The results of our single-species tearing analysis can be applied to ion tearing where electron effects are not included. We have calculated the tearing growth rate as a function of the magnetic field component B(sub n) normal to the current sheet for thick and thin current sheets, and we show that marginal stability occurs when the normal gyrofrequency Omega(sub n) is comparable to the Harris neutral sheet growth rate. A cross-tail B(sub y) component has little effect on the growth rate for B(sub y) approximately = B(sub n). Even in the limit B(sub y) much greater than B(sub n), the mode is strongly stabilized by B(sub n). We report than random pitch angle scattering can overcome the stabilizing effect of B(sub n) and drive the growth rate up toward the Harris neutral sheet (B(sub n) = 0) value when the pitch angle diffusion rate is comparable to Omega(sub n).
Placental gene expression of the placental growth factor (PlGF) in intrauterine growth restriction.
Joó, József Gábor; Rigó, János; Börzsönyi, Balázs; Demendi, Csaba; Kornya, László
2017-06-01
We analyzed changes in gene expression of placental growth factor (PIGF) in human placental samples obtained postpartum from pregnancies with IUGR. During a twelve-month study period representing the calendar year of 2012 placental samples from 101 pregnancies with IUGR and from 140 normal pregnancies were obtained for analysis of a potential difference in PIGF gene expression. There was no significant difference in gene activity of the PIGF gene between the IUGR versus normal pregnancy groups (Ln2 α : 0.92; p < 0.06). Within the IUGR group, no fetal gender-dependent differences were seen in placental PIGF gene expression (Ln2 α : 0.72; p = 0.05). Placental PIGF gene activity was significantly lower in fetuses with more severe IUGR versus less severe cases (Ln2 α : -1.49; p < 0.03). We found no difference in gene expression of PIGF in placental samples obtained from IUGR pregnancies versus normal pregnancy suggesting the absence of a direct role of PIGF gene activity in the development of defective angiogenesis in IUGR during the later stages of gestation. However, in more severe cases of intrauterine growth restriction PIGF expression does show a significant decrease indicating its potential role in the profound defect in angiogenesis in these cases.
Normal bacterial flora from vaginas of Criollo Limonero cows.
Zambrano-Nava, Sunny; Boscán-Ocando, Julio; Nava, Jexenia
2011-02-01
In order to describe the normal bacterial flora in vaginas of Criollo Limonero cows, 51 healthy multiparous cows, at least 90-day postpartum, were selected. Duplicated swabs (N = 102) were taken from the vaginal fornix of cows to perform aerobic and anaerobic cultures as well as conventional biochemical tests. Out of 102 swabs, bacterial growth was obtained in 55 (53.9%) while the remaining 47 (46.1%) did not exhibited any bacterial growth. Of the 55 bacterial growths, 23 (41.8%) were aerobic whereas 32 (58.1%) were anaerobic. Likewise, 29 (52.72%) of bacterial growths were pure and 26 (47.27%) were mixed. Under both aerobic and anaerobic conditions, Gram positive bacteria were predominant (81.82% and 73.08%, respectively) over Gram negative bacteria (18.18% and 26.92%, respectively). Isolated bacteria were Arcanobacterium pyogenes (22.92%), Staphylococcus aureus (15.63%), Staphylococcus coagulase negative (17.71%), Erysipelothrix rhusiopathiae (6.25%), Bacteroides spp. (13.54%), and Peptostreptococcus spp. (7.29%). In conclusion, normal vaginal bacterial flora of Criollo Limonero cows was predominantly Gram positive and included A. pyogenes, S. aureus, coagulase negative Staphylococcus, E. rhusiopathiae, Bacteroides spp., and Peptostreptococcus spp. In Criollo Limonero cattle, adaptive aspects such as development of humoral and physical mechanisms for defense, and bacterial adaptation to host deserve research attention.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hsiao, Susan J; Poitras, Marc; Cook, Brandoch
Regulation of telomere length maintenance and capping are a critical cell functions in both normal and tumor cells. Tankyrase 2 (Tnks2) is a poly(ADP-ribose) polymerase (PARP) that has been shown to modify itself and TRF1, a telomere-binding protein. We show here by overexpression studies that tankyrase 2, like its closely related homolog tankyrase 1, can function as a positive regulator of telomere length in human cells, dependent on its catalytic PARP activity. To study the role of Tnks2 in vivo, we generated mice with the Tnks2 PARP domain deleted. These mice are viable and fertile but display a growth retardationmore » phenotype. Telomere analysis by quantitative fluorescence in situ hybridization (FISH), flow-FISH, and restriction fragment analysis showed no change in telomere length or telomere capping in these mice. To determine the requirement foTnks2 in long-term maintenance of telomeres, we generated embryonic stem cells with the Tnks2 PARP domain deleted and observed no change, even upon prolonged growth, in telomere length or telomere capping. Together these results suggest that Tnkjs2 has a role in normal growth and development but is not essential for telomere length maintenance or telomere capping in mice.« less
[Studies on the role of silicic acid in the development of higher plants].
Werner, D
1967-03-01
Germanium acid, a specific inhibitor of the silicic acid metabolism in diatoms, inhibits the growth of Sinapis alba, Lemna minor, Wolffia arrhiza, Nicotiana tabacum, Tradescantia spec, Zinnia elegans, and Secale cereale when applied in the same concentrations as those used in the case of diatoms (15-75 μg GeO2/ml medium). The growth of Aspergillus niger, Phycomyces blakesleanus, Escherichia coli K 12, Euglena gracilis and Pandorina morum is not influenced by these and higher concentrations of Germanium acid. By application of high concentrations of silicic acid, the growth inhibition produced by germanium acid in Lemna minor is partially reduced. Plants of Lemna minor which have been inhibited by germanium acid are essentially smaller than plants grown in a normal medium; their chlorophyll content is significantly decreased. The growth of the roots in Lemna is particularly inhibited. Isolated growing roots of Lycopersicon pimpinellifolium MILL. are inhibited by small concentrations of Ge(OH)4 (ca. 1,5×10(-4) M/l). In contrast to the growth of older plants, the germination of Secale cereale and Sinapis alba is not influenced by Ge(OH)4. The effects of germanium acid are discussed in relation to the physiological role of silicic acid. The results suggest that the element silicon, in the form of silicic acid, is generally essential for the normal development of higher plants.
The role of fire in shaping avian communities in sagebrush ecosystems
Holmes, Aaron; Knick, Steven T.; Miller, R.F.
2005-01-01
Four experiments were conducted to examine the riboflavin, niacin, pantothenic acid and choline requirements of young Bobwhite quail. Quail fed purified diets deficient in either riboflavin, niacin, pantothenic acid or choline grew poorly and high mortality occurred by 5 weeks of age. Under the conditions of these experiments, it was found that: (1) young quail require approximately 3.8 mg. riboflavin/kg. diet for satisfactory growth and survival; (2) no more than 31 mg. niacin/kg. diet are required for normal growth and survival of young quail; (3) the requirement for pantothenic acid is higher than has previously been reported, quail in these studies requiring 12.6 mg. pantothenic acid/kg. feed for growth and survival; and (4) the requirement for choline for reducing mortality is approximately 1000 mg./kg., while the amount necessary for normal growth of young quail is no greater than 1500 mg./kg. when the diet contains ample amounts of methionine. Quail fed a niacin-deficient diet developed stiff, shortened feathers and an erythema about the head; those receiving a riboflavin-deficient ration developed enlarged hocks and bowed legs, as did quail fed diets low or devoid of choline. Aside from slow growth, poor feathering was the only other indication that a deficient diet was being fed when quail were placed on a basal ration without pantothenic acid for five weeks.
Studies on the riboflavin, niacin, pantothenic acid and choline requirements of young bobwhite quail
Serafin, J.A.
1974-01-01
Four experiments were conducted to examine the riboflavin, niacin, pantothenic acid and choline requirements of young Bobwhite quail. Quail fed purified diets deficient in either riboflavin, niacin, pantothenic acid or choline grew poorly and high mortality occurred by 5 weeks of age. Under the conditions of these experiments, it was found that: (1) young quail require approximately 3.8 mg. riboflavin/kg. diet for satisfactory growth and survival; (2) no more than 31 mg. niacin/kg. diet are required for normal growth and survival of young quail; (3) the requirement for pantothenic acid is higher than has previously been reported, quail in these studies requiring 12.6 mg. pantothenic acid/kg. feed for growth and survival; and (4) the requirement for choline for reducing mortality is approximately 1000 mg./kg., while the amount necessary for normal growth of young quail is no greater than 1500 mg./kg. when the diet contains ample amounts of methionine. Quail fed a niacin-deficient diet developed stiff, shortened feathers and an erythema about the head; those receiving a riboflavin-deficient ration developed enlarged hocks and bowed legs, as did quail fed diets low or devoid of choline. Aside from slow growth, poor feathering was the only other indication that a deficient diet was being fed when quail were placed on a basal ration without pantothenic acid for five weeks.
Effects of real or simulated microgravity on plant cell growth and proliferation
NASA Astrophysics Data System (ADS)
Medina, Francisco Javier; Manzano, Ana Isabel; Herranz, Raul; Dijkstra, Camelia; Larkin, Oliver; Hill, Richard; Carnero-Díaz, Eugénie; van Loon, Jack J. W. A.; Anthony, Paul; Davey, Michael R.; Eaves, Laurence
Experiments on seed germination and seedling growth performed in real microgravity on the International Space Station and in different facilities for simulating microgravity in Earth-based laboratories (Random Positioning Machine and Magnetic Levitation), have provided evidence that the absence of gravity (or the artificial compensation of the gravity vector) results in the uncoupling of cell growth and proliferation in root meristematic cells. These are two essential cellular functions that support plant growth and development, which are strictly coordinated under normal ground gravity conditions. Under conditions of altered gravity, we observe that cell proliferation is enhanced, whereas cell growth is reduced, according to different morphometric, cytological and immunocytochemical parameters. Since coordination of cell growth and proliferation are major features of meristematic cells, this observed uncoupling represents a major stress condition for these cells, inducing major alterations in the pattern of plant development. Moreover, the expression of the cyclin B1 gene, a regulator of the entry into mitosis and normally used as an indicator of cell proliferation, appears reduced in the smaller and more actively proliferating cells of samples grown under the conditions of our experiments. These results are compatible with an alteration of the regulation of the cell cycle, producing a shorter G2 period. Interestingly, while cyclin B1 expression is depleted in these conditions in root meristematic cells, it is enhanced in cotyledons of the same seedlings, as shown by qPCR and by the expression of the gus reporter gene. It is known that regulation of root growth (including regulation of root meristematic activity) is driven mainly by auxin, whereas cytokinin is the key hormone regulating cotyledon growth. Therefore, our results indicate a major role of auxin in the sensitivity to altered gravity of root meristematic cells. Auxin is crucial in maintaining the coupling of cell growth and proliferation under normal conditions and it should have a decisive influence in the uncoupling of these processes under altered gravity. Experiments to detect auxin distribution in roots under altered gravity produced by diamagnetic levitation have shown that the lateral balanced distribution of the growth regulator in the root cap is altered slightly and that the total concentration of the auxin detected in root tips is somewhat reduced. These effects are independent of the orientation of statoliths in columella cells.
Large-scale grain growth in the solid-state process: From "Abnormal" to "Normal"
NASA Astrophysics Data System (ADS)
Jiang, Minhong; Han, Shengnan; Zhang, Jingwei; Song, Jiageng; Hao, Chongyan; Deng, Manjiao; Ge, Lingjing; Gu, Zhengfei; Liu, Xinyu
2018-02-01
Abnormal grain growth (AGG) has been a common phenomenon during the ceramic or metallurgy processing since prehistoric times. However, usually it had been very difficult to grow big single crystal (centimeter scale over) by using the AGG method due to its so-called occasionality. Based on the AGG, a solid-state crystal growth (SSCG) method was developed. The greatest advantages of the SSCG technology are the simplicity and cost-effectiveness of the technique. But the traditional SSCG technology is still uncontrollable. This article first summarizes the history and current status of AGG, and then reports recent technical developments from AGG to SSCG, and further introduces a new seed-free, solid-state crystal growth (SFSSCG) technology. This SFSSCG method allows us to repeatedly and controllably fabricate large-scale single crystals with appreciable high quality and relatively stable chemical composition at a relatively low temperature, at least in (K0.5Na0.5)NbO3(KNN) and Cu-Al-Mn systems. In this sense, the exaggerated grain growth is no longer 'Abnormal' but 'Normal' since it is able to be artificially controllable and repeated now. This article also provides a crystal growth model to qualitatively explain the mechanism of SFSSCG for KNN system. Compared with the traditional melt and high temperature solution growth methods, the SFSSCG method has the advantages of low energy consumption, low investment, simple technique, composition homogeneity overcoming the issues with incongruent melting and high volatility. This SFSSCG could be helpful for improving the mechanical and physical properties of single crystals, which should be promising for industrial applications.
IGF2 DNA methylation is a modulator of newborn's fetal growth and development.
St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi
2012-10-01
The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity.
IGF2 DNA methylation is a modulator of newborn’s fetal growth and development
St-Pierre, Julie; Hivert, Marie-France; Perron, Patrice; Poirier, Paul; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi
2012-01-01
The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn’s fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn’s weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn’s fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. PMID:22907587
Hegazi, Moustafa A; Sehlo, Mohammad G; Al-Jasir, Albandari; El-Deek, Basem S
2015-09-01
This study was conducted to assess development and cognitive functions in relation to growth in Saudi pre-school children with feeding problems (FPs) without underlying medical disorders. Three hundred fifteen pre-school children with FPs (221 with normal growth (FP-N), 62 with failure to thrive (FTT) (FP-FTT), 32 with overweight (FP-OW)) and 100 healthy children (Ref group) underwent in-depth assessment by anthropometric measurements, dietetic history, Behavioral Pediatrics Feeding Assessment Scale, Denver Developmental Screening test (DDST) and Stanford Binet fifth edition intelligence scales (SB-5). The main FPs detected in Saudi children were picky eating in 85.5% of FP-N group, infantile anorexia and poor eating in more than 90% of FP-FTT group and overeating in 53% of FP-OW group. FPs were not due to evident psychosocial factors but were mostly related to unhealthy feeding behaviours. FP-N children were still having normal growth parameters, but they had significantly lower growth parameters than healthy children. Failed screening with DDST was only more significantly recorded in FP-FTT children than in Ref children (P = 0.04). The overall IQ value by SB-5 was significantly lower in FP-FTT group compared with FP-N group (P = 0.01), in FP-FTT group compared with Ref group (P < 0.001) as well as in FP-OW group compared with Ref group (P < 0.001). Persistent FPs resulted in significant negative impact not only on growth status but also on developmental milestones and cognitive functions of pre-school children. Healthy feeding habits are mandatory to prevent serious consequences of FPs on growth and development of Saudi pre-school children. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
de Zegher, Francis; Reynaert, Nele; De Somer, Lien; Wouters, Carine; Roelants, Mathieu
2018-06-25
Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature. © 2018 S. Karger AG, Basel.
Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent
Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.
2015-01-01
Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897
DOE Office of Scientific and Technical Information (OSTI.GOV)
Howlett, Anthony R; Petersen, Ole W; Steeg, Patricia S
1994-01-01
We have developed a culture system using reconstituted basement membrane components in which normal human mammary epithelial cells exhibit several aspects of the development and differentiation process, including formation of acinar-like structures, production and basal deposition of basement membrane components, and production and apical secretion of sialomucins. Cell lines and cultures from human breast carcinomas failed to recapitulate this process. The data indicate the importance of cellular interactions with the basement membrane in the regulation of normal breast differentiation and, potentially, its loss in neoplasia. Our purpose was to use this assay to investigate the role of the putative metastasismore » suppressor gene nm23-H1 in mammary development and differentiation. The metastatic human breast carcinoma cell line MDA-MB-435, clones transfected with a control pCMVBamneo vector, and clones transfected with pCMVBamneo vector containing nm23-H1 complementary DNA (the latter of which exhibited a substantial reduction in spontaneous metastatic potential in vivo) were cultured within a reconstituted basement membrane. Clones were examined for formation of acinus-like spheres, deposition of basement membrane components, production of sialomucin, polarization, and growth arrest. In contrast to the parental cell line and control transfectants, MDA-MB-435 breast carcinoma cells overexpressing Nm23-H1 protein regained several aspects of the normal phenotype within reconstituted basement membrane. Nm23-H1 protein-positive cells formed organized acinus-like spheres, deposited the basement membrane components type IV collagen and, to some extent, laminin to the outside of the spheres, expressed sialomucin, and growth arrested. Growth arrest of Nm23-H1 protein-positive cells was preceded by and correlated with formation of a basement membrane, suggesting a causal relationship. The data indicate a previously unidentified cause-and-effect relationship between nm23-H1 gene expression and morphological-biosynthetic-growth aspects of breast differentiation in this model system. While the basement membrane microenvironment is capable of directing the differentiation of normal human breast cells, neoplastic transformation abrogates this relationship, suggesting that intrinsic cellular events are also critical to this process. The data identify nm23-H1 gene expression as one of these events, suggesting an important role in the modulation of cellular responsiveness to the microenvironment. The data also identify previously unknown growth inhibitory effects of nm23-H1 gene overexpression.« less
... too much of it. Vitamin C is a water-soluble vitamin that supports normal growth and development and helps ... Dec. 12, 2017. Pazirandeh S, et al. Overview of water-soluble vitamins. https://www.uptodate.com/contents/search. Accessed Dec. ...
An extra-uterine system to physiologically support the extreme premature lamb
Partridge, Emily A.; Davey, Marcus G.; Hornick, Matthew A.; McGovern, Patrick E.; Mejaddam, Ali Y.; Vrecenak, Jesse D.; Mesas-Burgos, Carmen; Olive, Aliza; Caskey, Robert C.; Weiland, Theodore R.; Han, Jiancheng; Schupper, Alexander J.; Connelly, James T.; Dysart, Kevin C.; Rychik, Jack; Hedrick, Holly L.; Peranteau, William H.; Flake, Alan W.
2017-01-01
In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed ‘amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination. PMID:28440792
Diagnostic workstation for digital hand atlas in bone age assessment
NASA Astrophysics Data System (ADS)
Cao, Fei; Huang, H. K.; Pietka, Ewa; Gilsanz, Vicente; Ominsky, Steven
1998-06-01
Bone age assessment by a radiological examination of a hand and wrist image is a procedure frequently performed in pediatric patients to evaluate growth disorders, determine growth potential in children and monitor therapy effects. The assessment method currently used in radiological diagnosis is based on atlas matching of the diagnosed hand image with the reference set of atlas patterns, which was developed in 1950s and is not fully applicable for children of today. We intent to implement a diagnostic workstation for creating a new reference set of clinically normal images which will serve as a digital atlas and can be used for a computer-assisted bone age assessment. In this paper, we present the initial data- collection and system setup phase of this five-year research program. We describe the system design, user interface implementation and software tool development for collection, visualization, management and processing of clinically normal hand and wrist images.
Bandura, Marzena; Opalko, Krystyna
2005-01-01
The objective of this study was to determine the content of fluorides and magnesium in permanent teeth of children and adolescents with constitutional delay of growth and development (CDGD) and to correlate the findings with susceptibility to caries. Our study group consisting of 20 patients with CDGD, aged 11 to 20 years, was compared with an age-matched control group of 20 normal subjects. Dentition status was assessed according to the average DMFs score. Acid biopsy of enamel on the labial surface of incisors was done to measure the content of calcium, magnesium, and fluorides. CDGD patients demonstrated a higher average DFs value and less permanent teeth than their normal counterparts. Microanalyses of enamel showed that the depth of the acid biopsy was similar in all subjects. The content of fluorides and magnesium in enamel was lower in patients with CDGD.
An extra-uterine system to physiologically support the extreme premature lamb
NASA Astrophysics Data System (ADS)
Partridge, Emily A.; Davey, Marcus G.; Hornick, Matthew A.; McGovern, Patrick E.; Mejaddam, Ali Y.; Vrecenak, Jesse D.; Mesas-Burgos, Carmen; Olive, Aliza; Caskey, Robert C.; Weiland, Theodore R.; Han, Jiancheng; Schupper, Alexander J.; Connelly, James T.; Dysart, Kevin C.; Rychik, Jack; Hedrick, Holly L.; Peranteau, William H.; Flake, Alan W.
2017-04-01
In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed `amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.
Bilateral carpal valgus deformity in hand-reared cheetah cubs (Acinonyx jubatus).
Bell, Katherine M; van Zyl, Malan; Ugarte, Claudia E; Hartman, Angela
2011-01-01
Four hand-reared cheetah cubs (Acinonyx jubatus) exhibited progressively severe bilateral valgus deformity of the carpi (CV) during the weaning period. Radiographs of the thoracic limbs suggested normal bone ossification, and serum chemistry was unremarkable. All affected cubs developed CV shortly after the onset of gastroenteritis, which was treated medically, and included use of a prescription diet. A sudden decrease in growth rate was associated with gastrointestinal disease. Before gastroenteritis and CV, affected cubs had higher growth rates than unaffected cubs, despite similar mean daily energy intake. Return to normal thoracic limb conformation was consequent to dietary manipulation (including a reduction in energy intake and vitamin and mineral supplementation), as well as decreased growth rates and recovery from gastroenteritis. The cause of the CV is likely to have been multi-factorial with potentially complex physiological interactions involved. © 2010 Wiley-Liss, Inc.
LUO, BAO; TANG, LIPING; WANG, ZHISHAN; ZHANG, JUNLAN; LING, YIQUN; FENG, WENGUANG; SUN, JU-ZHONG; STOCKARD, CECIL R.; FROST, ANDRA R.; CHEN, YIU-FAI; GRIZZLE, WILLIAM E.; FALLON, MICHAEL B.
2010-01-01
Background & Aims Hepatic production and release of endothelin 1 plays a central role in experimental hepatopulmonary syndrome after common bile duct ligation by stimulating pulmonary endothelial nitric oxide production. In thioacetamide-induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not occur, and hepatopulmonary syndrome does not develop. However, the source and regulation of hepatic endothelin 1 after common bile duct ligation are not fully characterized. We evaluated the sources of hepatic endothelin 1 production after common bile duct ligation in relation to thioacetamide cirrhosis and assessed whether transforming growth factor β1 regulates endothelin 1 production. Methods Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were evaluated after common bile duct ligation or thioacetamide administration. Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser capture microdissection of cholangiocytes. Transforming growth factor β1 expression and signaling were assessed by using immunohistochemistry and Western blotting and by evaluating normal rat cholangiocytes. Results Hepatic and plasma endothelin 1 levels increased and hepatopulmonary syndrome developed only after common bile duct ligation. Hepatic endothelin 1 and transforming growth factor β1 levels increased over a similar time frame, and cholangiocytes were a major source of each peptide. Transforming growth factor β1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor β1 and phosphorylated Smad2 levels. Transforming growth factor β1 also stimulated endothelin 1 promoter activity, expression, and production in normal rat cholangiocytes. Conclusions Cholangiocytes are a major source of hepatic endothelin 1 production during the development of hepatopulmonary syndrome after common bile duct ligation, but not in thioacetamide-induced cirrhosis. Transforming growth factor β1 stimulates cholangiocyte endothelin 1 expression and production. Cholangiocyte-derived endothelin 1 may be an important endocrine mediator of experimental hepatopulmonary syndrome. PMID:16083721
Niu, Longjian; Tao, Yan-Bin; Chen, Mao-Sheng; Fu, Qiantang; Li, Chaoqiong; Dong, Yuling; Wang, Xiulan; He, Huiying; Xu, Zeng-Fu
2015-06-03
Real-time quantitative PCR (RT-qPCR) is a reliable and widely used method for gene expression analysis. The accuracy of the determination of a target gene expression level by RT-qPCR demands the use of appropriate reference genes to normalize the mRNA levels among different samples. However, suitable reference genes for RT-qPCR have not been identified in Sacha inchi (Plukenetia volubilis), a promising oilseed crop known for its polyunsaturated fatty acid (PUFA)-rich seeds. In this study, using RT-qPCR, twelve candidate reference genes were examined in seedlings and adult plants, during flower and seed development and for the entire growth cycle of Sacha inchi. Four statistical algorithms (delta cycle threshold (ΔCt), BestKeeper, geNorm, and NormFinder) were used to assess the expression stabilities of the candidate genes. The results showed that ubiquitin-conjugating enzyme (UCE), actin (ACT) and phospholipase A22 (PLA) were the most stable genes in Sacha inchi seedlings. For roots, stems, leaves, flowers, and seeds from adult plants, 30S ribosomal protein S13 (RPS13), cyclophilin (CYC) and elongation factor-1alpha (EF1α) were recommended as reference genes for RT-qPCR. During the development of reproductive organs, PLA, ACT and UCE were the optimal reference genes for flower development, whereas UCE, RPS13 and RNA polymerase II subunit (RPII) were optimal for seed development. Considering the entire growth cycle of Sacha inchi, UCE, ACT and EF1α were sufficient for the purpose of normalization. Our results provide useful guidelines for the selection of reliable reference genes for the normalization of RT-qPCR data for seedlings and adult plants, for reproductive organs, and for the entire growth cycle of Sacha inchi.
Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects
Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying
2013-01-01
Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635
USDA-ARS?s Scientific Manuscript database
The present study was designed to determine if normal birth weight pigs that grow poorly during the pre-weaning period have altered skeletal muscle metabolism, as previously reported for intrauterine growth retarded pigs relative to littermates with normal growth rates. Eight pairs of average birth...
[Evaluation of growth and development of institutionalized children].
Chaves, Caroline Magna Pessoa; Lima, Francisca Elisângela Teixeira; Mendonça, Larissa Bento de Araújo; Custódio, Ires Lopes; Matias, Erica Oliveira
2013-01-01
The study aimed to evaluate the growth and development of institutionalized children from 0-6 years old. It had a descriptive, transversal and quantitative approach, and was held in a shelter from the Bureau of Labor and Social Development of the Government of the State of Ceará, in the months of March and April 2011. The sample comprised 44 children. It the sample prevailed male children (59.1%), aged 24 to 72 months (56.8%) and with time of sheltering more than one year (72.7%). It was found that the children were in the normal range of nutrition; however, 65.9% of children did not achieve at least one of the development milestones proposed by the Ministry of Health. The study suggests a reflection on how children living in shelters are being assisted by the health team, making it necessary follow up their growth and development, in order to intervene on the alterations.
NASA Astrophysics Data System (ADS)
Beier, M.; Anken, R.; Rahmann, H.
It has been shown earlier that hypergravity slows down inner ear otolith growth in developing fish. Otolith growth in terms of mineralisation mainly depends on the enzyme carboanhydrase (CAH), which is responsible for the provision of the pH- value necessary for calcium carbonate deposition and thus also is presumed to play a prominent role in Ménière's disease (a sensory - motor disorder inducing vertigo and kinetosis). Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (3g; 6 hours) during development and separated into normally and kinetotically swimming individuals following the transfer to 1g (i.e., stopping the centrifuge; kinetotically behaving fish performed spinning movements). Subsequently, CAH was histochemically demonstrated in inner ear ionocytes (cells involved in the endolymphatic ion exchange) and enzyme reactivity was determined densitometrically. The results showed that CAH-reactivity was significantly increased in normally behaving hyper-g specimens as compared to controls kept at 1g, whereas no difference in enzyme reactivity was evident between the controls and kinetotically behaving fish. On the background of earlier studies, according to which (1) hypergravity induces a decrease of otolith growth and (2) the otolithic calcium incorporation (visualized using the calcium -tracer alizarin complexone) of kinetotically swimming hyper - g fish was lower as compared to normally behaving hyper - g animals, the present study strongly supports the concept that an increase in CAH-reactivity may result in a decrease of otolithic calcium deposition. The mechanism regulating CAH-activity hitherto remains to be determined. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).
Gravitational Effects on Reproduction, Growth, and Development of Mammals
NASA Technical Reports Server (NTRS)
Oyama, J.
1985-01-01
The broad objective of this research program is to determine the role which gravity plays in the growth and development of mammalian animals. Current studies are focused on the effects of graded hypergravitatinal field intensities on mice, rats and other small sized laboratory animals using the chronic centrifugation technique. They include studies on reproduction and prenatal and postnatel growth and development. Among the important questions addressed are: (1) what stage or stages in animal development are affected by hypergravity and what are the effects? (2) is there a minimum or critical body size for hypergravity to produce a significant effect on growth and development? (3) are there field intensity thresholds for the preceding questions? From analysis of the body masses at birth of rats conceived and allowed to undergo gestation under 2.1G and under normal gravity (1G), it was found that there was no significant difference between the two groups. Futhermore, their growth rates postnatally were the same until they reached a body mass of approximately 50 grams when the 2.1G group showed a significantly slower rate. Results from these studies support the conclusion that prenatal as well as the early postnatal stages of growth and development of the rat are refractory to hyper-G.
Minireview: The Androgen Receptor in Breast Tissues: Growth Inhibitor, Tumor Suppressor, Oncogene?
Hickey, T. E.; Robinson, J. L. L.; Carroll, J. S.
2012-01-01
Androgen receptor (AR) signaling exerts an antiestrogenic, growth-inhibitory influence in normal breast tissue, and this role may be sustained in estrogen receptor α (ERα)-positive luminal breast cancers. Conversely, AR signaling may promote growth of a subset of ERα-negative, AR-positive breast cancers with a molecular apocrine phenotype. Understanding the molecular mechanisms whereby androgens can elicit distinct gene expression programs and opposing proliferative responses in these two breast cancer phenotypes is critical to the development of new therapeutic strategies to target the AR in breast cancer. PMID:22745190
The Effects of Macroglossia on Speech: A Case Study
ERIC Educational Resources Information Center
Mekonnen, Abebayehu Messele
2012-01-01
This article presents a case study of speech production in a 14-year-old Amharic-speaking boy. The boy had developed secondary macroglossia, related to a disturbance of growth hormones, following a history of normal speech development. Perceptual analysis combined with acoustic analysis and static palatography is used to investigate the specific…
Biology and biotechnology of follicle development.
Palma, Gustavo Adolfo; Argañaraz, Martin Eduardo; Barrera, Antonio Daniel; Rodler, Daniela; Mutto, Adrian Ángel; Sinowatz, Fred
2012-01-01
Growth and development of ovarian follicles require a series of coordinated events that induce morphological and functional changes within the follicle, leading to cell differentiation and oocyte development. The preantral early antral follicle transition is the stage of follicular development during which gonadotropin dependence is obtained and the progression into growing or atresia of the follicle is made. Follicular growth during this period is tightly regulated by oocyte-granulosatheca cell interactions. A cluster of early expressed genes is required for normal folliculogenesis. Granulosa cell factors stimulate the recruitment of theca cells from cortical stromal cells. Thecal factors promote granulosa cell proliferation and suppress granulosa cell apoptosis. Cell-cell and cell-extracellular matrix interactions influence the production of growth factors in the different follicular compartments (oocyte, granulosa, and theca cells). Several autocrine and paracrine factors are involved in follicular growth and differentiation; their activity is present even at the time of ovulation, decreasing the gap junction communication, and stimulating the theca cell proliferation. In addition, the identification of the factors that promote follicular growth from the preantral stage to the small antral stage may provide important information for the identification for assisted reproduction techniques.
2D Process-based Microbialite Growth Model
NASA Astrophysics Data System (ADS)
Airo, A.; Smith, A.
2007-12-01
A 2D process-based microbialite growth model (MGM) has been developed that integrates the coupled effects of the microbialite growth and sediment distribution within a two-dimensional cross-section of a subaqueous bedrock profile. Sediment transport is realized through particle erosion and deposition that are a function of local wave energy which is computed on the basis of linear wave theory. Surface-normal microbialite growth is directly correlated to light intensity, which is computed for every point of the microbialite surface by using a Henyey- Greenstein-type relation for scattering and the Beer's Law for absorption in the water column. Shadowing effects by surrounding obstacles and/or overlying sediment are also considered. Sediment particles can be incorporated into the microbialite framework if growth occurs in the presence of sediment. The resulting meter-size microbialite constructs develop morphologies that correspond well to natural microbialites. Furthermore, changes of environmental factors such as light intensity, wave energy, and bedrock profile result in morphological variations of the microbialites that would be expected on the basis of the current understanding of microbialite growth and development.
Redox control of plant growth and development.
Kocsy, Gábor; Tari, Irma; Vanková, Radomíra; Zechmann, Bernd; Gulyás, Zsolt; Poór, Péter; Galiba, Gábor
2013-10-01
Redox changes determined by genetic and environmental factors display well-organized interactions in the control of plant growth and development. Diurnal and seasonal changes in the environmental conditions are important for the normal course of these physiological processes and, similarly to their mild irregular alterations, for stress adaptation. However, fast or large-scale environmental changes may lead to damage or death of sensitive plants. The spatial and temporal redox changes influence growth and development due to the reprogramming of metabolism. In this process reactive oxygen and nitrogen species and antioxidants are involved as components of signalling networks. The control of growth, development and flowering by reactive oxygen and nitrogen species and antioxidants in interaction with hormones at organ, tissue, cellular and subcellular level will be discussed in the present review. Unsolved problems of the field, among others the need for identification of new components and interactions in the redox regulatory network at various organization levels using systems biology approaches will be also indicated. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Regulation of microglial development: a novel role for thyroid hormone.
Lima, F R; Gervais, A; Colin, C; Izembart, M; Neto, V M; Mallat, M
2001-03-15
The postnatal development of rat microglia is marked by an important increase in the number of microglial cells and the growth of their ramified processes. We studied the role of thyroid hormone in microglial development. The distribution and morphology of microglial cells stained with isolectin B4 or monoclonal antibody ED1 were analyzed in cortical and subcortical forebrain regions of developing rats rendered hypothyroid by prenatal and postnatal treatment with methyl-thiouracil. Microglial processes were markedly less abundant in hypothyroid pups than in age-matched normal animals, from postnatal day 4 up to the end of the third postnatal week of life. A delay in process extension and a decrease in the density of microglial cell bodies, as shown by cell counts in the developing cingulate cortex of normal and hypothyroid animals, were responsible for these differences. Conversely, neonatal rat hyperthyroidism, induced by daily injections of 3,5,3'-triiodothyronine (T3), accelerated the extension of microglial processes and increased the density of cortical microglial cell bodies above physiological levels during the first postnatal week of life. Reverse transcription-PCR and immunological analyses indicated that cultured cortical ameboid microglial cells expressed the alpha1 and beta1 isoforms of nuclear thyroid hormone receptors. Consistent with the trophic and morphogenetic effects of thyroid hormone observed in situ, T3 favored the survival of cultured purified microglial cells and the growth of their processes. These results demonstrate that thyroid hormone promotes the growth and morphological differentiation of microglia during development.
Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen
2009-04-14
The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.
Hay, W W
2006-07-01
Normal fetal nutrition is a useful guide for understanding postnatal nutrition of infants born very preterm. Fetal lipid uptake gradually increases towards term and is primarily used to produce fat in adipose tissue, with essential fatty acid uptake providing necessary structural and functional elements in membranes of cells in the central nervous system. Fetal glucose uptake and utilization rates are nearly twice as high at 23-26 weeks gestation as they are at term, contributing primarily to energy production and glycogen formation. Amino-acid uptake by the fetus is two-to threefold greater at 23-26 weeks gestation than at term and is required to meet the very high fractional protein synthesis and growth rates at this gestational period; amino acids also contribute significantly to fetal energy production. In contrast, after birth most of the very preterm infants are fed more lipid and glucose and less amino acids and protein than they need. Not surprisingly, therefore, very preterm infants accumulate fat but remain relatively growth restricted at term gestational age compared to those infants who grew normally in utero, and this postnatal growth restriction has long-term adverse growth, development, and health consequences. More thorough understanding of the unique nutritional, metabolic, and growth requirements of the normally growing fetus and the very preterm infant, once born, are needed to determine optimal nutritional strategies to improve the outcome of preterm infants.
Steinman, Gary
2013-07-01
The amounts of at least three biochemical factors are more often abnormal in autistic people than neurologically normal ones. They include insulin-like growth factor, anti-myelin basic protein, and serotonin. This may explain why processes initiated in utero which hinder normal neurogenesis, especially myelination, continue after delivery. Quantitation of these parameters may make possible the calculation of an autism index, anticipating at birth which children will ultimately develop overt autism. Copyright © 2013 Elsevier Ltd. All rights reserved.
Asian G6PD-Mahidol Reticulocytes Sustain Normal Plasmodium Vivax Development
Bancone, Germana; Malleret, Benoit; Suwanarusk, Rossarin; Chowwiwat, Nongnud; Chu, Cindy S; McGready, Rose; Rénia, Laurent; Nosten, François
2017-01-01
Abstract Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the recent selection of G6PD alleles. We use an experimental approach to determine whether G6PD-MahidolG487A variant, a widespread cause of severe G6PD deficiency in Southeast Asia, provides a barrier against vivax malaria. Our results show that the immature reticulocytes (CD71+) targeted by P. vivax invasion are enzymatically normal, even in hemizygous G6PD-Mahidol G487A mutants; thus, allowing the normal growth, development, and high parasite density in severely deficient samples. PMID:28591790
Airway growth and development: a computerized 3-dimensional analysis.
Schendel, Stephen A; Jacobson, Richard; Khalessi, Sadri
2012-09-01
The present study was undertaken to investigate the changes in the normal upper airway during growth and development using 3-dimensional computer analysis from cone-beam computed tomography (CBCT) data to provide a normative reference. The airway size and respiratory mode are known to have a relationship to facial morphology and the development of a malocclusion. The use of CBCT, 3-dimensional imaging, and automated computer analysis in treatment planning allows the upper airway to be precisely evaluated. In the present study, we evaluated the growth of the airway using 3-dimensional analysis and CBCT data from age 6 through old age, in 1300 normal individuals. The airway size and length increase until age 20 at which time a variable period of stability occurs. Next, the airway at first decreases slowly in size and then, after age 40, more rapidly. Normative data are provided in the present study for age groups from 6 to 60 years in relation to the airway total volume, smallest cross-sectional area and vertical length of the airway. This 3-dimensional data of the upper airway will provide a normative reference as an aid in the early understanding of respiration and dentofacial anatomy, which will help in early treatment planning. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Ebrahimi, Aziz; Zarei, Abdolkarim; Zamani Fardadonbeh, Mojtaba; Lawson, Shaneka
2017-01-01
Limiting the juvenile phase and reducing tree size are the two main challenges for breeders to improve most fruit crops. Early maturation and dwarf cultivars have been reported for many fruit species. "Early mature" and low vigor walnut genotypes were found among seedlings of Persian walnut. Nine microsatellite markers were used to evaluate genetic diversity among "Early Mature" Persian walnut accessions and provide a comparison with "normal growth" accessions. Six maturation related characteristics were also measured in "Early Mature" samples. Phenotypic traits and diversity indices showed relatively high levels of genetic diversity in "Early Mature" seedlings and indicated high differentiation between individuals. Seedling height, the most diverse phenotypic trait, has an important role in the clustering of "Early Mature" accessions. The "Early Mature" type had higher number of alleles, number of effective allele, and Shannon index compared to the "Normal Growth" group. The two types of studied walnuts had different alleles, with more than half of produced alleles specific to a specific group. "Early Mature" and "Normal Growth" walnuts had 27 and 17 private alleles, respectively. Grouping with different methods separated "Early Mature" and "Normal Growth" samples entirely. The presence of moderate to high genetic diversity in "Early Mature" walnuts and high genetic differentiation with "Normal Growth" walnuts, indicated that "Early Mature" walnuts were more diverse and distinct from "Normal Growth" samples. Moreover, our results showed SSR markers were useful for differentiating between "Early Mature" and "Normal Growth" walnuts. A number of identified loci have potential in breeding programs for identification of "Early Mature" walnuts at the germination phase.
Molinari, E; Sartori, A; Ceccarelli, A; Marchi, S
2002-04-01
It is well established that children with short stature frequently have problems in cognitive development, personality, self-esteem and social relations. This is partly due to the fact that many parents view them as more vulnerable than other children of normal stature and do not allow them to face the normal experiences that correspond to their actual age. The aim of the present study was to assess, through the administration of appropriate psychological tools, a series of psychological and cognitive characteristics [i.e. anxiety, depression, good adjustment, social functioning, feeling of guilt, interpersonal relationship, intelligence quotient (IQ)], as well as variables linked to development of body image, in a group of children suffering from normal growth variants [familial short stature (FSS), no. 10, 4 males/6 females; with constitutional growth delay (CGD), no. 4,4 males; height standard deviation score (HSDS) ranging between -2.4 and -1.9] and in a control group children of normal stature (HSDS between -0.1 and +0.1). Children with short stature significantly differed from normal statured controls as far as Colored Progressive Matrices (CPMs, centiles), IQ (IQ, obtained using the Goodenough test), "Good Adjustment" (Draw-a-Person index, DAP), "Feelings of Guilt" (DAP index), "Height" (as emerges from drawings of the body) are concerned. Significant relationships were found between the height of the subjects (in centiles) and cognitive skills, measured both using CPMs (r=0.408; p=0.017) and Draw-a-Man (DAM) (r=0.359; p=0.037) and between height and feelings of guilt (r=0.325; p=0.027), measured using DAP. CPM scores correlated positively with the "Good Adjustment" index of DAP (r=0.354; p=0.05) and negatively with Children's Depression Inventory (CDI) (r=-0.609; p=0.01), "School Anxiety" index (r=-0.427; p=0.05) and "Total Anxiety" index (r=-0.436; p=0.05) of the Anxiety Scale Questionnaire for the Age of Development, and with 2 indices of DAP, namely, "Feelings of Guilt" (r=-0.461; p=0.01) and "Interpersonal Relationships (Difficulty in Establishing)" (r=-0.455; p=0.01). A significant positive correlation was found between the height of the subject and both the measurement of the "Body of Drawing 3" (r=0.450, p=0.01) and the measurement of the "Body of Drawing 4" (r=0.461, p=0.01), as well as the with the "Total Height of Drawing 4" (r=0.464, p=0.01). Higher indices for anxiety, depression, feelings of guilt and difficulty in establishing interpersonal relationships and lower indices for good adjustment were found in children with CGD as compared to subjects with FSS or normal statured children. Although further additional studies on larger samples are needed to confirm these preliminary observations, the present study underlines the importance of psychological support also during the growth and development in short normal children.
Gene Profiling in Experimental Models of Eye Growth: Clues to Myopia Pathogenesis
Stone, Richard A.; Khurana, Tejvir S.
2010-01-01
To understand the complex regulatory pathways that underlie the development of refractive errors, expression profiling has evaluated gene expression in ocular tissues of well-characterized experimental models that alter postnatal eye growth and induce refractive errors. Derived from a variety of platforms (e.g. differential display, spotted microarrays or Affymetrix GeneChips), gene expression patterns are now being identified in species that include chicken, mouse and primate. Reconciling available results is hindered by varied experimental designs and analytical/statistical features. Continued application of these methods offers promise to provide the much-needed mechanistic framework to develop therapies to normalize refractive development in children. PMID:20363242
Role of growth differentiation factor 11 in development, physiology and disease
Zhang, Yonghui; Wei, Yong; Liu, Dan; Liu, Feng; Li, Xiaoshan; Pan, Lianhong; Pang, Yi; Chen, Dilong
2017-01-01
Growth differentiation factor (GDF11) is a member of TGF-β/BMP superfamily that activates Smad and non-Smad signaling pathways and regulates expression of its target nuclear genes. Since its discovery in 1999, studies have shown the involvement of GDF11 in normal physiological processes, such as embryonic development and erythropoiesis, as well as in the pathophysiology of aging, cardiovascular disease, diabetes mellitus, and cancer. In addition, there are contradictory reports regarding the role of GDF11 in aging, cardiovascular disease, diabetes mellitus, osteogenesis, skeletal muscle development, and neurogenesis. In this review, we describe the GDF11 signaling pathway and its potential role in development, physiology and disease. PMID:29113418
Dell'Agnolo, Cátia Millene; Cyr, Caroline; de Montigny, Francine; de Barros Carvalho, Maria Dalva; Pelloso, Sandra Marisa
2015-11-01
Several outcomes of pregnancy after bariatric surgery are currently being studied. This cross-sectional, retrospective study evaluated the obstetric and perinatal outcomes of pregnancies in 19 women who underwent bariatric surgery, as well as the growth and development of their children, in the Southern Brazil. Among these women, 11 children were born prior to surgery and 32 were born post-surgery. The mean time between the surgery and the first pregnancy was 42.96 months. Preterm newborns were more common among the pre-surgery childbirths. Regarding growth, normal weights were observed in 27.3 % of the children in the pre-surgery births and obesity was observed in 54.5 %. In contrast, normal weights were observed in 59.4 % of the children born during the postoperative period and obesity was observed in 31.2 %. The average excess weight that the women lost prior to pregnancy was 64.88. Speech delays were found in three male children evaluated using the Denver Developmental Screening Test II. A statistical association was found between the interval from the surgery to the pregnancy and the outcome of the questionable Denver II test results (p = 0.011). Except for the large index of low birth weight, it can be concluded that pregnancy after bariatric surgery is safe. The growth rate was found to be adequate in the children born after the surgery, with reduced obesity. Although changes in speech development were detected, no factors were supported an association with pregnancy after bariatric surgery.
Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A.; Löfqvist, Chatarina; Smith, Lois E. H.; Hård, Anna-Lena
2018-01-01
The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina. Glucose metabolism in the developing brain is controlled by IGF-1 which also stimulates differentiation and prevents apoptosis. Serum concentrations of IGF-1 decrease to very low levels after very preterm birth and remain low for most of the perinatal development. Strong correlations have been found between low neonatal serum concentrations of IGF-1 and poor brain and retinal growth as well as poor general growth with multiorgan morbidities, such as intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis. Experimental and clinical studies indicate that early supplementation with IGF-1 can improve growth in catabolic states and reduce brain injury after hypoxic/ischemic events. A multicenter phase II study is currently underway to determine whether intravenous replacement of human recombinant IGF-1 up to normal intrauterine serum concentrations can improve growth and development and reduce prematurity-associated morbidities. PMID:27603537
Role of Growth Hormone in Breast Cancer.
Subramani, Ramadevi; Nandy, Sushmita B; Pedroza, Diego A; Lakshmanaswamy, Rajkumar
2017-06-01
Breast cancer is one of the most common cancers diagnosed in women. Approximately two-thirds of all breast cancers diagnosed are classified as hormone dependent, which indicates that hormones are the key factors that drive the growth of these breast cancers. Ovarian and pituitary hormones play a major role in the growth and development of normal mammary glands and breast cancer. In particular, the effect of the ovarian hormone estrogen has received much attention in regard to breast cancer. Pituitary hormones prolactin and growth hormone have also been associated with breast cancer. Although the role of these pituitary hormones in breast cancers has been studied, it has not been investigated extensively. In this review, we attempt to compile basic information from most of the currently available literature to understand and demonstrate the significance of growth hormone in breast cancer. Based on the available literature, it is clear that growth hormone plays a significant role in the development, progression, and metastasis of breast cancer by influencing tumor angiogenesis, stemness, and chemoresistance. Copyright © 2017 Endocrine Society.
Regulation of cellular growth by the Drosophila target of rapamycin dTOR
Zhang, Hongbing; Stallock, James P.; Ng, Joyce C.; Reinhard, Christoph; Neufeld, Thomas P.
2000-01-01
The TOR protein kinases (TOR1 and TOR2 in yeast; mTOR/FRAP/RAFT1 in mammals) promote cellular proliferation in response to nutrients and growth factors, but their role in development is poorly understood. Here, we show that the Drosophila TOR homolog dTOR is required cell autonomously for normal growth and proliferation during larval development, and for increases in cellular growth caused by activation of the phosphoinositide 3-kinase (PI3K) signaling pathway. As in mammalian cells, the kinase activity of dTOR is required for growth factor-dependent phosphorylation of p70 S6 kinase (p70S6K) in vitro, and we demonstrate that overexpression of p70S6K in vivo can rescue dTOR mutant animals to viability. Loss of dTOR also results in cellular phenotypes characteristic of amino acid deprivation, including reduced nucleolar size, lipid vesicle aggregation in the larval fat body, and a cell type-specific pattern of cell cycle arrest that can be bypassed by overexpression of the S-phase regulator cyclin E. Our results suggest that dTOR regulates growth during animal development by coupling growth factor signaling to nutrient availability. PMID:11069888
Trophic and neurotrophic factors in human pituitary adenomas (Review).
Spoletini, Marialuisa; Taurone, Samanta; Tombolini, Mario; Minni, Antonio; Altissimi, Giancarlo; Wierzbicki, Venceslao; Giangaspero, Felice; Parnigotto, Pier Paolo; Artico, Marco; Bardella, Lia; Agostinelli, Enzo; Pastore, Francesco Saverio
2017-10-01
The pituitary gland is an organ that functionally connects the hypothalamus with the peripheral organs. The pituitary gland is an important regulator of body homeostasis during development, stress, and other processes. Pituitary adenomas are a group of tumors arising from the pituitary gland: they may be subdivided in functional or non-functional, depending on their hormonal activity. Some trophic and neurotrophic factors seem to play a key role in the development and maintenance of the pituitary function and in the regulation of hypothalamo-pituitary-adrenocortical axis activity. Several lines of evidence suggest that trophic and neurotrophic factors may be involved in pituitary function, thus suggesting a possible role of the trophic and neurotrophic factors in the normal development of pituitary gland and in the progression of pituitary adenomas. Additional studies might be necessary to better explain the biological role of these molecules in the development and progression of this type of tumor. In this review, in light of the available literature, data on the following neurotrophic factors are discussed: ciliary neurotrophic factor (CNTF), transforming growth factors β (TGF‑β), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), vascular endothelial growth inhibitor (VEGI), fibroblast growth factors (FGFs) and epidermal growth factor (EGF) which influence the proliferation and growth of pituitary adenomas.
Transforming Growth Factor-B Receptors in Human Breast Cancer.
1998-05-01
I., Polyak, K., Iavarone, A., and Massagud, J. Kip/ Cip and Ink4 cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-ß. Genes Dev...specimens. Thirdly, we have developped transient transfection assays to determine how specific TßR mutations affect affect receptor function. Using...Growth Factor-ß (TGFß) is the most potent known inhibitor of cell cycle progression of normal mammary epithelial cells; in addition, it causes cells
NASA Technical Reports Server (NTRS)
Patel, Zarana S.; Wettergreen, Matthew A.; Huff, Janice L.
2014-01-01
We are developing a novel, autonomous bioreactor that can provide for the growth and maintenance in microgravity of 3-D organotypic epithelial-stromal cultures that require an air-liquid interface. These complex 3-D tissue models accurately represent the morphological features, differentiation markers, and growth characteristics observed in normal human epithelial tissues, including the skin, esophagus, lung, breast, pancreas, and colon. However, because of their precise and complex culture requirements, including that of an air-liquid interface, these 3-D models have yet to be utilized for life sciences research aboard the International Space Station. The development of a bioreactor for these cultures will provide the capability to perform biological research on the ISS using these realistic, tissue-like human epithelial-stromal cell models and will contribute significantly to advances in fundamental space biology research on questions regarding microgravity effects on normal tissue development, aging, cancer, and other disease processes. It will also allow for the study of how combined stressors, such as microgravity with radiation and nutritional deficiencies, affect multiple biological processes and will provide a platform for conducting countermeasure investigations on the ISS without the use of animal models. The technology will be autonomous and consist of a cell culture chamber that provides for air-liquid, liquid-liquid, and liquid-air exchanges within the chambers while maintaining the growth and development of the biological samples. The bioreactor will support multiple tissue types and its modular design will provide for incorporation of add-on capabilities such as microfluidics drug delivery, media sampling, and in situ biomarker analysis. Preliminary flight testing of the hardware will be conducted on a parabolic platform through NASA's Flight Opportunities Program.
A sharp interface model for void growth in irradiated materials
NASA Astrophysics Data System (ADS)
Hochrainer, Thomas; El-Azab, Anter
2015-03-01
A thermodynamic formalism for the interaction of point defects with free surfaces in single-component solids has been developed and applied to the problem of void growth by absorption of point defects in irradiated metals. This formalism consists of two parts, a detailed description of the dynamics of defects within the non-equilibrium thermodynamic frame, and the application of the second law of thermodynamics to provide closure relations for all kinetic equations. Enforcing the principle of non-negative entropy production showed that the description of the problem of void evolution under irradiation must include a relationship between the normal fluxes of defects into the void surface and the driving thermodynamic forces for the void surface motion; these thermodynamic forces are identified for both vacancies and interstitials and the relationships between these forces and the normal point defect fluxes are established using the concepts of transition state theory. The latter theory implies that the defect accommodation into the surface is a thermally activated process. Numerical examples are given to illustrate void growth dynamics in this new formalism and to investigate the effect of the surface energy barriers on void growth. Consequences for phase field models of void growth are discussed.
Normative biometry of the fetal brain using magnetic resonance imaging.
Kyriakopoulou, Vanessa; Vatansever, Deniz; Davidson, Alice; Patkee, Prachi; Elkommos, Samia; Chew, Andrew; Martinez-Biarge, Miriam; Hagberg, Bibbi; Damodaram, Mellisa; Allsop, Joanna; Fox, Matt; Hajnal, Joseph V; Rutherford, Mary A
2017-07-01
The fetal brain shows accelerated growth in the latter half of gestation, and these changes can be captured by 2D and 3D biometry measurements. The aim of this study was to quantify brain growth in normal fetuses using Magnetic Resonance Imaging (MRI) and to produce reference biometry data and a freely available centile calculator ( https://www.developingbrain.co.uk/fetalcentiles/ ). A total of 127 MRI examinations (1.5 T) of fetuses with a normal brain appearance (21-38 gestational weeks) were included in this study. 2D and 3D biometric parameters were measured from slice-to-volume reconstructed images, including 3D measurements of supratentorial brain tissue, lateral ventricles, cortex, cerebellum and extra-cerebral CSF and 2D measurements of brain biparietal diameter and fronto-occipital length, skull biparietal diameter and occipitofrontal diameter, head circumference, transverse cerebellar diameter, extra-cerebral CSF, ventricular atrial diameter, and vermis height, width, and area. Centiles were constructed for each measurement. All participants were invited for developmental follow-up. All 2D and 3D measurements, except for atrial diameter, showed a significant positive correlation with gestational age. There was a sex effect on left and total lateral ventricular volumes and the degree of ventricular asymmetry. The 5th, 50th, and 95th centiles and a centile calculator were produced. Developmental follow-up was available for 73.1% of cases [mean chronological age 27.4 (±10.2) months]. We present normative reference charts for fetal brain MRI biometry at 21-38 gestational weeks. Developing growth trajectories will aid in the better understanding of normal fetal brain growth and subsequently of deviations from typical development in high-risk pregnancies or following premature delivery.
Steinbacher, Peter; Wanzenböck, Josef; Brandauer, Magdalena; Holper, Raphael; Landertshammer, Jasmin; Mayr, Magdalena; Platzl, Christian; Stoiber, Walter
2017-01-01
Ecotype pairs provide well-suited model systems for study of intraspecific phenotypical diversification of animals. However, little is still known about the processes that account for the development of different forms and sizes within a species, particularly in teleosts. Here, embryos of a normal-growing 'large' form and a dwarf form of whitefish Coregonus lavaretus were incubated at two temperatures that are usually experienced at their own spawning sites (2°C for the normal and 6°C for the dwarf form). All fish were subjected to similar thermal treatment after hatching. The present data demonstrate for the first time that different thermal experience in embryonic life has lasting effects on body and muscle growth of this ecotype pair and contributes to the development of the dwarf form. Thus, juvenile fish of the regular form are much smaller and have less muscle mass when pre-hatching thermal conditions were similar to those typical for the spawning sites of the dwarf form (6°C) than when subjected to conditions of their own spawning sites (2°C). Surprisingly, fish of the dwarf form exhibit a similar pattern of response to thermal history (2°-fish much larger than 6°-fish), indicating that in their case, normal spawning site temperature (6°C) is indeed likely to act as a growth limiting factor. Results also demonstrate that the hypertrophic and hyperplastic muscle growth modes are similarly affected by thermal history. Immunolabelling experiments for Pax7, H3P and Mef2 provide evidence that the cellular mechanisms behind the increased growth rates after cold incubation in both ecotypes are increased proliferation and reduced differentiation rates of muscle precursor cells. This is of major significance to aspects of ecological and developmental biology and from the evolutionary perspective.
Wan, Haifeng; Zhu, Jiatao; Su, Guoqi; Liu, Yan; Hua, Lun; Hu, Liang; Wu, Caimei; Zhang, Ruinan; Zhou, Pan; Shen, Yong; Lin, Yan; Xu, Shengyu; Fang, Zhengfeng; Che, Lianqiang; Feng, Bin; Wu, De
2016-04-01
Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7-28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.
Pollock, Claire B; McDonough, Sara; Wang, Victor S; Lee, Hyojung; Ringer, Lymor; Li, Xin; Prandi, Cristina; Lee, Richard J; Feldman, Adam S; Koltai, Hinanit; Kapulnik, Yoram; Rodriguez, Olga C; Schlegel, Richard; Albanese, Christopher; Yarden, Ronit I
2014-03-30
Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Treatment of cancer cells with strigolactone analogues was hallmarked by activation of the stress-related MAPKs: p38 and JNK and induction of stress-related genes; cell cycle arrest and apoptosis evident by increased percentages of cells in the sub-G1 fraction and Annexin V staining. In addition, we tested the response of patient-matched conditionally reprogrammed primary prostate normal and cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis confirmed by PARP1 cleavage compared to their normal counterpart cells. Thus, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.
Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.
2010-01-01
Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609
Eye Growth in Term- And Preterm-Born Eyes Modeled From Magnetic Resonance Images
Munro, Robert J.; Fulton, Anne B.; Chui, Toco Y. P.; Moskowitz, Anne; Ramamirtham, Ramkumar; Hansen, Ronald M.; Prabhu, Sanjay P.; Akula, James D.
2015-01-01
Purpose. We generated a model of eye growth and tested it against an eye known to develop abnormally, one with a history of retinopathy of prematurity (ROP). Methods. We reviewed extant magnetic resonance images (MRIs) from term and preterm-born patients for suitable images (n = 129). We binned subjects for analysis based upon postmenstrual age at birth (in weeks) and ROP history (“Term” ≥ 37, “Premature” ≤ 32 with no ROP, “ROP” ≤ 32 with ROP). We measured the axial positions and curvatures of the cornea, anterior and posterior lens, and inner retinal surface. We fit anterior chamber depth (ACD), posterior segment depth (PSD), axial length (AL), and corneal and lenticular curvatures with logistic growth curves that we then evaluated for significant differences. We also measured the length of rays from the centroid to the surface of the eye at 5° intervals, and described the length versus age relationship of each ray, Lray(x), using the same logistic growth curve. We determined the rate of ray elongation, Eray(x), from Lray dy/dx. Then, we estimated the scleral growth that accounted for Eray(x), G(x), at every age and position. Results. Relative to Term, development of ACD, PSD, AL, and corneal and lenticular curvatures was delayed in ROP eyes, but not Premature eyes. In Term infants, G(x) was fast and predominantly equatorial; in age-matched ROP eyes, maximal G(x) was offset by approximately 90°. Conclusions. We produced a model of normal eye growth in term-born subjects. Relative to normal, the ROP eye is characterized by delayed, abnormal growth. PMID:26024095
Vickers, Mark H; Guan, Jian; Gustavsson, Malin; Krägeloh, Christian U; Breier, Bernhard H; Davison, Michael; Fong, Bertram; Norris, Carmen; McJarrow, Paul; Hodgkinson, Steve C
2009-06-01
Alterations in nutritional factors during early development can exert long-term effects on growth, neural function, and associated behaviors. The lipid component of milk provides a critical nutritional source for generating both energy and essential nutrients for the growth of the newborn. The present study, therefore, investigated the hypothesis that nutritional supplementation with a complex milk lipid (CML) preparation, derived from the milk fat globule membrane rich in phospholipids and gangliosides from young rats, has beneficial effects on learning behavior and postnatal growth and development. Male Wistar rat offspring from normal pregnancies were treated from neonatal day 10 until postnatal day 80 with either vehicle or CML at a dose of 0.2% (low) and 1.0% (high) based on total food intake (n = 16 per group). Neonatal dosing was via daily oral gavage, while postweaning dosing was via gel supplementation to a standard chow diet. Animals underwent behavioral tasks related to spatial memory, learning, and cognitive function. Complex milk lipid supplementation significantly increased linear growth rate (P < .05), and the improved growth trajectory was not related to changes in body composition as quantified by dual-energy x-ray absorptiometry scanning or altered plasma lipid profiles. Moreover, this effect was not dose dependent and not attributable to the contribution to total energy intake of the CML composition. Supplementation of the CML to growing rats resulted in statistically significant improvements in parameters related to novelty recognition (P < .02) and spatial memory (P < .05) using standard behavioral techniques, but operant testing showed no significant differences between treatment groups. Supplementation with a CML containing gangliosides had positive growth and learning behavioral effects in young normal growing rats.
Merialdi, Mario; Widmer, Mariana; Gülmezoglu, Ahmet Metin; Abdel-Aleem, Hany; Bega, George; Benachi, Alexandra; Carroli, Guillermo; Cecatti, Jose Guilherme; Diemert, Anke; Gonzalez, Rogelio; Hecher, Kurt; Jensen, Lisa N; Johnsen, Synnøve L; Kiserud, Torvid; Kriplani, Alka; Lumbiganon, Pisake; Tabor, Ann; Talegawkar, Sameera A; Tshefu, Antoinette; Wojdyla, Daniel; Platt, Lawrence
2014-05-02
In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/- 1 week) to be performed by trained ultrasonographers.The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards.
Ultrasound evaluation of cortical brain development in fetuses with intrauterine growth restriction.
Businelli, Caterina; de Wit, Charlotte; Visser, Gerard H A; Pistorius, Lourens R
2014-09-10
Abstract Objective: We evaluated the ultrasound appearance of brain volume and cortical development in fetuses with early growth restriction and placental insufficiency. Methods: We examined a cohort of 20 fetuses with severe intrauterine growth restriction (IUGR) and evidence of placental insufficiency by three-dimensional (3D) ultrasound between 24 and 34 weeks. We graded cortical development and measured the supratentorial intracranial volume. The cortical grading and volume were compared to data obtained from a reference population of 28 adequate for gestational age (AGA) fetuses. Results: Ultrasound examinations were performed in 20 fetuses with IUGR. The biometry and brain volume were significantly reduced in IUGR fetuses. There was evidence of accelerated cortical development in IUGR fetuses. Conclusion: This study confirms that the smaller brain volume in IUGR fetuses, with normal or accelerated cortical maturation as previously depicted with postnatal MRI examination, can be demonstrated by prenatal 3D ultrasound.
Early recognition of growth abnormalities permitting early intervention
USDA-ARS?s Scientific Manuscript database
Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height. This rev...
Tanajak, Pongpan; Pongkan, Wanpitak; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2018-05-01
Propose: To investigate the temporal relationship between plasma fibroblast growth factor 21 levels, insulin resistance, metabolic dysfunction and cardiac fibroblast growth factor 21 resistance in long-term high-fat diet-induced obese rats. In total, 36 male Wistar rats were fed with either a normal diet or high-fat diet for 12 weeks. Blood was collected from the tail tip, and plasma was used to determine metabolic profiles and fibroblast growth factor 21 levels. Rats were sacrificed at weeks 4, 8 and 12, and the hearts were rapidly removed for the determination of cardiac fibroblast growth factor 21 signalling pathways. Body weight and plasma fibroblast growth factor 21 levels were increased after 4 weeks of consumption of a high-fat diet. At weeks 8 and 12, high-fat diet rats had significantly increased body weight and plasma fibroblast growth factor 21 levels, together with increased plasma insulin, HOMA index, area under the curve of glucose, plasma total cholesterol, plasma low-density lipoprotein cholesterol, serum malondialdehyde and cardiac malondialdehyde levels. However, plasma high-density lipoprotein cholesterol levels and cardiac fibroblast growth factor 21 signalling proteins (p-FGFR1 Tyr 154 , p-ERK1/2 Thr 202 /Tyr 204 and p-Akt Ser 473 ) were decreased, compared with normal diet rats. These findings suggest that plasma fibroblast growth factor 21 levels could be an early predictive biomarker prior to the development of insulin resistance, metabolic disturbance and cardiac fibroblast growth factor 21 resistance.
NASA Technical Reports Server (NTRS)
Hatfield, J. L.; Asrar, G.; Kanemasu, E. T.
1982-01-01
The interception of photosynthetically active radiation (PAR) was evaluated relative to greenness and normalized difference (MSS 7-5/7+5) for five planting dates of wheat for 1978-79 and 1979-80 in Phoenix. Intercepted PAR was calculated from a model driven by leaf area index and stage of growth. Linear relationships were found between greenness and normalized difference with a separate model representing growth and senescence of the crop. Normalized difference was a significantly better model and would be easier to apply than the empirically derived greenness parameter. For the leaf area growth portion of the season the model between PAR interception and normalized difference was the same over years, however, for the leaf senescence the models showed more variability due to the lack of data on measured interception in sparse canopies. Normalized difference could be used to estimate PAR interception directly for crop growth models.
Immediate metabolic consequences of intrauterine growth restriction and low birthweight.
Bhatia, Jatinder; Gates, Amy
2013-01-01
Optimal fetal growth resulting in a 'normally grown' term infant is of paramount importance for assuring a healthy start for postnatal growth and development. Fetal, infant and childhood growth restriction is an important clinical problem for obstetricians, neonatologists, pediatricians and globally, for public health. Worldwide, an estimated 20 million infants are born with low birthweight and a substantial proportion are small for gestational age. Many advances have been made in defining growth restriction by prenatal techniques, thus allowing the recognition of intrauterine growth restriction. Distinguishing infants who are small but have appropriate growth potential from those with growth restriction is important in order to apply obstetric surveillance, anticipate neonatal problems and plan for postneonatal guidance. It is clear that the fetus in growth-restricted pregnancies has limited supply of nutrients and oxygen. The resultant changes, if involving the placenta as well, can lead to circulatory and metabolic changes affecting both short- and long-term survival and development. In this paper, the causes and immediate consequence of being born with low birthweight, intrauterine growth restriction or small for gestational age will be discussed. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.
Cerebellar granule cells (CGC) provide a homogenous population of cells which can be used as an in vitro model for studying the cellular processes involved in the normal development of the CNS. They may also be useful for hazard identification as in vitro screens fo...
Tanner, J M; Whitehouse, R H
1976-01-01
New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls. PMID:952550
Neural-Thyroid Interaction on Skeletal Isomyosin in Zero Gravity
NASA Technical Reports Server (NTRS)
Baldwin, Kenneth M.
2000-01-01
The primary goal of the project was to develop a ground based model to first study the role of the nerve and of thyroid hormone (T3) in the regulation of body growth and skeletal muscle growth and differentiation in rodents. A primary objective was to test the hypothesis that normal weight bearing activity is essential for the development of antigravity, slow twitch skeletal muscle and the corresponding slow myosin heavy chain (MHC) gene; whereas, T3 was obligatory for general body and muscle growth and the establishment of fast MHC phenotype in typically fast locomoter muscles. These ground based experiments would provide both the efficacy and background for a spaceflight experiment (referred to as the Neurolab Mission) jointly sponsored by the NIH and NASA.
Growth and development of overweight and obese girls.
Wronka, Iwona
2011-01-01
The pattern of development of obesity during childhood and adolescence is unclear, hindering preventive strategies. The aim of this study was to investigate the differences in growth and tempo of maturation between overweight or obese and normal weight girls. The data were obtained from 1008 schoolgirls aged 16-18 years for whom earlier data on weight and height were available. The height and body mass were measured and the BMI was calculated. Height and weight in early life were assessed by medical records review. Underweight, overweight and obesity were assessed using the international BMI cut points, defined by Cole et al. Girls in higher BMI categories at 7 years had significantly higher values of BMI at 9, 14 and 16-18 years of age, however only 10% of them were also overweight or obese at youth. Overweight and obese girls tend to lose body weight after the puberty period, whereas normal weight children tend to gain body weight. Overweight and obese children were significantly taller than their peers at 7, 9 and 14 years. Those differences vanished after the puberty period. The rate of height gain between ages 7 and 16-18 years was lower in girls with higher BMI values at childhood. Girls, those who were overweight or obese at young age experience menarche at a younger age than normal weight girls. The obtained data show that overweight and obesity in childhood is associated with rapid tempo of growth and maturity.
The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats.
Yanagida, M; Ide, Y; Imai, A; Toriyama, M; Aoki, T; Harada, K; Izumi, H; Uzumaki, H; Kusaka, M; Tokiwa, T
1997-12-01
Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.
NASA Astrophysics Data System (ADS)
Contreras, J.; Vega-Ramirez, L. A.; Spelz, R. M.; Portner, R. A.; Clague, D. A.
2017-12-01
The Monterey Bay Aquarium Research Institute collected in 2012 and 2015 high-resolution (1 m horizontal/0.2 m vertical) bathymetry data in the southern Gulf of California using an autonomous underwater vehicle (AUV) that bring to light an extensive array of normal faults and fissures cutting lava domes and smaller volcanic cones, pillow mounds and lava sheet flows of variable compositions along the Alarcon rise. Active faulting and fissure growth in the transition between the neovolcanic zone and adjacent axial summit trough, in a 6.9 x 1.5 km2 area at the NE segment of the rise, developed at some point between 6 Ka B.P. (14C) and the present time. We performed a population analysis of fracture networks imaged by the AUV that reveal contrasting scaling attributes between mode I (opening) and mode III (shearing) extensional structures. Opening-mode fractures are spatially constrained to narrow bands 400 m wide. The youngest set developed on pillow lavas 800 yr old (14C) of the neovolcanic zone. Regions of normal fault propagation by anti-plane shearing alternate with the tensile-fracture growth areas. This provides evidence for permutations in space of the stress field across the ridge axis. Moreover, fault-length frequency plots for both fracture networks show that opening-mode fractures are best fit using an exponential relationship whereas normal faults are best fit using a power-law relationship. These size distributions indicate tensile fractures rapidly reached a saturated state in which large fractures (102 m) accommodate most of the strain and appear to be constrained to a thin mechanical/thermal layer. Faults, by contrast, have slowly evolved to a state of self-organization characterized by growth by linkage with neighboring faults in the strike direction forming fault arrays with a maximum length of 2km. We also analyzed the development of faults in the vicinity of an off-axis rhyolitic dome. We find that faults have asymmetric, half-restricted slip profiles with abrupt displacement gradients towards the dome. We further document a strain deficit in normal faulting near the dome. We suggest that these observations reflect the control that changes in mechanical properties and rheology may exert on fault slip localization by effectively suppressing fault nucleation and propagation.
ERIC Educational Resources Information Center
Yoches, Betty; Luera, Margarita
The purpose of this training manual is to assist parents and professionals in understanding how a child's temperament, sensorimotor system, and communication system support each other in helping the child develop a solid foundation for normal growth and development. Training is based on the premise that awareness of the interaction and integration…
CXCR4(+) dendritic cells promote angiogenesis during embryo implantation in mice.
Barrientos, Gabriela; Tirado-González, Irene; Freitag, Nancy; Kobelt, Peter; Moschansky, Petra; Klapp, Burghard F; Thijssen, Victor L J L; Blois, Sandra M
2013-04-01
Early pregnancy is characterized by decidual adaption to the developing embryo involving angiogenesis and vascular growth. Failure of decidual vascular expansion is linked to diseases of pregnancy. Dendritic cells (DC) have been associated with vascular growth during early gestation, though it is unknown whether their capacity to modulate angiogenesis is ubiquitous to all DC subsets. Here, we show that DC normally found associated with the decidual vasculature co-express the C-X-C chemokine receptor type 4 (CXCR4). In addition, we demonstrate that impaired homing of CXCR4(+)DC during early gestation provoked a disorganized decidual vasculature with impaired spiral artery remodeling later in gestation. In contrast, adoptive transfer experiments provided evidence that CXCR4(+)DC are able to rescue early pregnancy by normalizing decidual vascular growth and delivery of pro-angiogenic factors, which results in adequate remodeling of the spiral arteries during placental development. Taken together, our results indicate an important role of CXCR4(+)DC in the regulation of decidual angiogenesis and highlight the importance of the CXCL12/CXCR4 pathway during this process, suggesting that this may represent a key pathway to evaluate during pregnancy pathologies associated with impaired vascular expansion.
Bartmann, M; Schaeffel, F; Hagel, G; Zrenner, E
1994-01-01
Chickens were raised with either translucent occluders or lenses, both under normal light cycles (12-h light/12-h dark) and in constant light (CL). Under normal light cycles, eyes with occluders became very myopic, and eyes with lenses became either relatively hyperopic (positive lenses) or myopic (negative lenses). After the treatment, retinal dopamine (DA), DOPAC, and serotonin levels were measured by high-pressure liquid chromatography (HPLC-EC). A significant drop in daytime retinal DOPAC (-20%) was observed after 1 week of deprivation, and in both DOPAC (-40%) and DA (-30%) after 2 weeks of deprivation. No changes in retinal serotonin levels were found. Retinal DA or DOPAC content remained unchanged after 2 or 4 days of lens wearing even though the lenses had already exerted their maximal effect on axial eye growth. When the chickens were raised in CL, development of deprivation myopia was reduced (8 days CL) or entirely blocked (13 days CL). Lens-induced changes in eye growth were not different after either 6 or 11 days in CL, compared to animals raised in a normal light cycle. Thirteen days of CL resulted in a dramatic reduction of DA and DOPAC levels, but serotonin levels were also lowered. The results suggest that lens-induced changes in refraction may not be dependent on dopaminergic pathways whereas deprivation myopia requires normal diurnal DA rhythms to develop.
Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans
Chauhan, Nitin M; Shinde, Ravikumar B; Karuppayil, S. Mohan
2013-01-01
In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation. PMID:24688528
Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans.
Chauhan, Nitin M; Shinde, Ravikumar B; Karuppayil, S Mohan
2013-12-01
In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Murdock, L.L.; Shade, R.E.; Pomeroy, M.A.
1988-06-01
E-64, a specific inhibitor of cysteine proteinases, was incorporated into artificial seeds at low levels (0.01-0.25% by weight). It prolonged developmental time and increased mortality of the larval cowpea weevil, Callosobruchus maculatus (F.), in direct proportion to its concentration in the artificial seeds. The fecundity of females emerging from the artificial seeds was significantly decreased by E-64 concentrations of 0.06% and higher. These observations are compatible with the hypothesis that the midgut cysteine proteinase in C. maculatus is essential for normal growth and development.
USDA-ARS?s Scientific Manuscript database
The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, the nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in normal individuals are not well-defined. The purpose of this study was to determine the ...
... puberty too soon, resulting in faster than normal bone growth and development of sexual characteristics) in girls usually between 2 and 8 years of age and in boys usually between 2 and 9 years of age. ... It works by decreasing the amount of certain hormones in the body.
2017-06-01
Most children born with low weight or intrauterine growth restriction develop catch-up growth that allows them to reach a final height according to their genetic target height. However, in about 15% of children this growth is insufficient. In both, children who have adequate compensatory growth and therefore normal height and children who remain low in childhood, it is necessary to take into account that if puberty starts early, the final height could be compromised. Timely and appropriate intervention could improve it. Control of body weight is also important, as an excessive gain in childhood is associated with metabolic complications in adolescence and adult life. Sociedad Argentina de Pediatría.
Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma
Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.
2016-01-01
Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781
Uterine artery blood flow, fetal hypoxia and fetal growth
Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.
2015-01-01
Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072
Diagnosis and management of congenital hypothyroidism.
Harrell, G B; Murray, P D
1998-03-01
Thyroid hormones are integral to the development and maturation of the central nervous system as well as normal growth and development. Comprehensive knowledge of the maturation and function of the thyroid gland is essential to understanding the pathophysiology of thyroid dysfunction. Early diagnosis and appropriate treatment in thyroid disease are imperative for normalization of thyroid hormone ratios. Optimal management includes early introduction and strict adherence to a regimen of L-thyroxine and routine monitoring of thyroid levels throughout life. Parents need to understand the importance of consistent medication administration and daily assessment of well-being because these actions are crucial to the attainment of an optimal level of development for infants with congenital hypothyroidism.
Bianchi, E; Scarinci, F; Grande, C; Plateroti, R; Plateroti, P; Plateroti, A M; Fumagalli, L; Capozzi, P; Feher, J; Artico, M
2012-01-01
Human pterygium is made up of chronic proliferative fibro-vascular tissue growing on the ocular surface. This disease exhibits both degenerative and hyperplastic properties. Some fibroangiogenic factors have recently been shown to play a potential role in fibrovascular diseases via the angiogenesis process. The aim of this study is to evaluate VEGF, TGF-β and PGE₂ expression in the epithelial, endothelial and stromal cells of human pterygium and normal conjunctiva in order to determine whether these factors participate in the development of pterygium. Ten specimens from patients with pterygium and two normal conjunctivas (cadavers) were analyzed by immunohistochemistry using specific antibodies against these growth factors. The technique used was ABC/HRP (Avidin complexed with biotinylated peroxidase). Immunoreactivity of VEGF was significantly increased in the epithelium, vascular endothelium and stromal cells in primary pterygium as compared with normal conjunctiva. A moderate expression of TGF-β in the pterygium was observed in the epithelial and stromal layers. On the contrary, immunolabeling of this growth factor in the human normal conjunctiva was weak. PGE₂ was strongly expressed in the epithelium of patients with pterygium, as in control conjunctival tissues, and the immunolabeling was moderate in the stroma from the same patients. Our results suggest that these growth factors may contribute to the progression of primary pterygium by increasing angiogenesis, thus leading to the formation of new blood vessels from the pre-existing vasculature. We conclude that VEGF, TGF-β and PGE₂ may be potential therapeutic targets in the treatment of this disease although proof of this evidence requires further studies.
Fetal body weight and the development of the control of the cardiovascular system in fetal sheep.
Frasch, M G; Müller, T; Wicher, C; Weiss, C; Löhle, M; Schwab, K; Schubert, H; Nathanielsz, P W; Witte, O W; Schwab, M
2007-03-15
Reduced birth weight predisposes to cardiovascular diseases in later life. We examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether spontaneously occurring variations in fetal weight affect maturation of autonomic control of cardiovascular function. Fetal weights at both gestational ages were grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses were within the normal weight span showing minor growth dysproportionality at 0.76 gestation favouring heart and brain, with a primary growth of carcass between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW fetuses, weight differences between singletons and twins were absent at 0.76 and modest at 0.87 gestation, underscoring the fact that twins belong to normality in fetal sheep not constituting a major malnutritive condition. Mean fetal blood pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76 but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex sensitivity were increased in LW fetuses (P < 0.05), suggesting increased sympathetic activity and immaturity of circulatory control. Development of vagal modulation of fetal heart rate depended on fetal weight (P < 0.01). These functional associations were largely independent of twin pregnancies. We conclude, low fetal weight within the normal weight span is accompanied by a different trajectory of development of sympathetic blood pressure and vagal heart rate control. This may contribute to the development of elevated blood pressure in later life. Examination of the underlying mechanisms and consequences may contribute to the understanding of programming of cardiovascular diseases.
Drosophila Growth and Development in the Absence of dMyc and dMnt
Pierce, Sarah B.; Yost, Cynthia; Anderson, Sarah A. R.; Flynn, Erin M.; Delrow, Jeffrey; Eisenman, Robert N.
2008-01-01
Myc oncoproteins are essential regulators of the growth and proliferation of mammalian cells. In Drosophila the single ortholog of Myc (dMyc), encoded by the dm gene, influences organismal size and the growth of both mitotic and endoreplicating cells. A null mutation in dm results in attenuated endoreplication and growth arrest early in larval development. Drosophila also contains a single ortholog of the mammalian Mad/Mnt transcriptional repressor proteins (dMnt), which is thought to antagonize dMyc function. Here we show that animals lacking both dMyc and dMnt display increased viability and grow significantly larger and develop further than dMyc single mutants. We observe increased endoreplication and growth of larval tissues in these double mutants and disproportionate growth of the imaginal discs. Gene expression analysis indicates that loss of dMyc leads to decreased expression of genes required for ribosome biogenesis and protein synthesis. The additional loss of dMnt partially rescues expression of a small number of dMyc and dMnt genes that are primarily involved in rRNA synthesis and processing. Our results indicate that dMnt repression is normally overridden by dMyc activation during larval development. Therefore the severity of the dm null phenotype is likely due to unopposed repression by dMnt on a subset of genes critical for cell and organismal growth. Surprisingly, considerable growth and development can occur in the absence of both dMyc and dMnt. PMID:18241851
Martini, M; Schulz, M; Röhrig, A; Nadal, J; Messing-Jünger, M
2015-10-01
Frontoorbital advancement (FOA) in patients with non-syndromic craniosynostosis mainly addresses the aesthetic and functional correction of the frontoorbital region. To help define the operative strategy and any follow-up assessments after surgical correction, objective parameters describing the critical regions of skull deformity are essential. Based on 3D morphometric analysis, new parameters for the documentation of changes of the frontoorbital bandeau were developed in a prospective study. In a prospective series, 13 children with non-syndromic craniosynostosis (seven metopic, four unilateral coronal, and two bilateral coronal) treated with frontoorbital advancement, underwent detailed morphometric and volumetric evaluation using a 3D light optical scan system (3D-Shape, Erlangen, Germany). Measurements were obtained preoperatively and at 3, 6 and 12 months postoperatively with newly developed parameters generated by cephalometric analysis software (Onyx Ceph, Image Instruments, Chemnitz, Germany). In most patients, frontoorbital advancement resulted in stable long-term results without growth inhibition and with normalization or improvement of ongoing skull development. The mean frontal angle was 145° and the frontoparietal angle 137-140°. The cephalic index was normalized or markedly improved. Head circumference and head height increased significantly (p = 0.001 and p = 0.002, respectively). These changes were confirmed in all postoperative measurements. During the 12-month follow-up period all angle parameters proved to be stable and no major impairment of normal skull growth was observed after FOA. The frontoorbital angle is a useful parameter in evaluating long-term outcome. The frontoparietal angle is important for the stability of the frontoparietal region, in which a certain growth inhibition may be observed postoperatively. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.
Aerts, Peter; Prims, Sara; Ayuso, Miriam; Van Cruchten, Steven; Van Ginneken, Chris
2018-01-01
In polytocous species, such as pigs, the growth of an individual fetus is affected by competition from its littermates and the sow. This intrauterine competition greatly influences postnatal traits such as birth weight and vitality (physical strength). A lowered vitality is most often observed among low birth weight piglets. Since it has been argued that locomotion might be key to unraveling vitality-related differences, we compared gait development in piglets with a low birth weight and low vitality (L piglets) with piglets with a normal birth weight and normal vitality (N piglets) by means of spatio-temporal gait analysis during locomotion at self-selected speed. Video recordings of L and N piglets walking along a corridor at ten time points (between birth and 96 h after birth) were made and the footfalls were digitized. Hence, self-selected speed, spatio-temporal characteristics and gait symmetry were analyzed to compare motor performance, neuromotor maturation (motor task, interlimb and intralimb coordination) and gait variability for L and N piglets. The analysis included both absolute and normalized data (according to the dynamic similarity concept), to distinguish neuromotor maturation from effects caused by growth. Results indicate that intrauterine crowding affects locomotion, mainly by impairing growth in utero, with a lowered motor performance during the first 96 h of age as a consequence. A difference in neuromotor skills was also visible, though only for swing and stance duration, implying a difference in neuromotor development in utero. However, further maturation during the first days after birth does not seem to be affected by intrauterine crowding. We can therefore conclude that L piglets might be considered a smaller and fictitious younger version of N piglets. PMID:29689084
Simon, Laure; Nusinovici, Simon; Flamant, Cyril; Cariou, Bertrand; Rouger, Valérie; Gascoin, Géraldine; Darmaun, Dominique; Rozé, Jean-Christophe; Hanf, Matthieu
2017-01-01
While the effects of growth from birth to expected term on the subsequent development of preterm children has attracted plentiful attention, less is known about the effects of post-term growth. We aimed to delineate distinct patterns of post-term growth and to determine their association with the cognitive development of preterm children. Data from a prospective population-based cohort of 3,850 surviving infants born at less than 35 weeks of gestational age were used. Growth was assessed as the Body Mass Index (BMI) Z-scores at 3, 9, 18, 24, 36, 48, and 60 months. Cognitive development at five years of age was evaluated by the Global School Adaptation score (GSA). Latent class analysis was implemented to identify distinct growth patterns and logistic regressions based on propensity matching were used to evaluate the relationship between identified growth trajectories and cognitive development. Four patterns of post-term growth were identified: a normal group with a Z-score consistently around zero during childhood (n = 2,469; 64%); a group with an early rapid rise in the BMI Z-score, but only up to 2 years of age (n = 195; 5%); a group with a slow yet steady rise in the BMI Z-score during childhood (n = 510; 13%); and a group with a negative Z-score growth until 3 years of age (n = 676; 18%). The group with a slow yet steady rise in the BMI Z-score was significantly associated with low GSA scores. Our findings indicate heterogeneous post-term growth of preterm children, with potential for association with their cognitive development.
Simulation of Gravity Effects on Bulk Crystal Growth with Effects on undercooling
NASA Astrophysics Data System (ADS)
Chuang, S.-H.; Lu, M.-F.
For the production of a perfect single crystal by Bridgman, it is important to acquire the correct information about the heat transfer mechanism and to control the heat transfer in the Bridgman furnace. Because the quality of the crystal is closely related to its thermal history and the transport phenomena in the furnace. Ma et al. (2004) presented that faceting simulation of bulk crystal growth with undercooling method. Lan et al. (2003) developed a new model to study heat flow and facet formation in Bridgman growth with the undercooling satisfied the given growth mechanism. Considering the gravity effects added kinetic undercooling is thus developed. Heat conduction, convection and radiation are considered and coupled with the two-dimensional transient undercooling simulation. The solidification interface temperature is related to the undercooling along the interface and the melting temperature. In this investigation, we are going to apply the developed model to simulate interface in vertical Bridgman crystal growth process for yttrium aluminum garnet subjected to the normal gravity to microgravity. Also, it discusses the effect upon the shape and the propagation of the solidification crystal front.
Kuchma, V R; Sukhareva, L M; Iampol'skaia, Iu A
2009-01-01
The presented materials are the result of many years' observations of the growth and development of Moscow senior adolescent schoolchildren, by revealing main trends in their physical development. By using the representative material (more than 2.5 thousand persons), the authors consider the trend in the physical development of 16-17-year-old adolescents examined in 1960-2007 by the strictly unified program. The physical development of Moscow adolescents has been recently characterized by: 1) neither increment in size signs no cardinal changes in the level of biological maturity; 2) a fall in the proportion of persons with normal physical development and a rise in the number of deviations (particularly in young males due to overweight); 3) a progressive reduction in strength capacities.
Martha, P M; Rogol, A D; Carlsson, L M; Gesundheit, N; Blizzard, R M
1993-08-01
Previous studies have provided compelling evidence that GH secretion increases transiently during midpuberty in normally growing children. Although it is likely that the increase in GH production serves a primary role in generating the pubertal growth spurt, such a conclusion necessarily assumes that other essential "down-stream" components of the GH axis responsible for mediating the effects of GH remain unchanged. To investigate this concept, we assessed longitudinally another important component of the endogenous GH axis, the serum GH-binding protein (GHBP)/receptor system, in a cohort of 11 normal boys as they matured through normal puberty. At 4-month intervals over 4.0-5.1 yr, 24-h serum GH concentration profiles and serum GHBP activity were evaluated. Serum GHBP levels varied over a more than 12-fold range (40-504 pmol/L) among all subjects. However, the values for individual subjects consistently varied within more narrow limits. The coefficient of variation for values from all subjects was 51% compared to the mean intrasubject coefficient of variation of only 30% (P < 0.05). Although the highest GHBP level (all subjects) was 12.6-fold greater than the lowest, the mean intrasubject range was only 3.1 +/- 0.5-fold (P < 0.05). The overall mean serum GHBP level correlated directly with the overall mean body mass index (r = 0.69; P = 0.018), but correlated inversely with the mean 24-h GH concentration (r = -0.61; P < 0.05). There was no significant increase in the GHBP level during puberty. However, because mean 24-h GH concentrations did increase during midpuberty, the data suggest that an increase in the relative amounts of free vs. bound GH develops during the period of the pubertal growth spurt. These data indicate that serum GHBP levels are regulated in individual children within much more narrow limits than those present in the larger population and do not undergo the dramatic changes during puberty typical of GH secretion and linear growth velocity. As a consequence, alterations may develop in the relative amounts of free vs. bound GH present in serum during the midpubertal years compared to those present during either the prepubertal or postpubertal periods. The majority of the known age-related increase in serum GHBP levels probably occurs before the period of active pubertal development. These findings strengthen further the concept that the midpubertal changes in GH secretion serve a primary role in generating the growth spurt.(ABSTRACT TRUNCATED AT 400 WORDS)
Knowledge cannot explain the developmental growth of working memory capacity.
Cowan, Nelson; Ricker, Timothy J; Clark, Katherine M; Hinrichs, Garrett A; Glass, Bret A
2015-01-01
According to some views of cognitive growth, the development of working memory capacity can account for increases in the complexity of cognition. It has been difficult to ascertain, though, that there actually is developmental growth in capacity that cannot be attributed to other developing factors. Here we assess the role of item familiarity. We document developmental increases in working memory for visual arrays of English letters versus unfamiliar characters. Although letter knowledge played a special role in development between the ages of 6 and 8 years, children with adequate letter knowledge showed practically the same developmental growth in normalized functions for letters and unfamiliar characters. The results contribute to a growing body of evidence that the developmental improvement in working memory does not wholly stem from supporting processes such as encoding, mnemonic strategies, and knowledge. A video abstract is available at: https://www.youtube.com/watch?v=LJdqErLR2Hs&feature=youtu.be. © 2014 John Wiley & Sons Ltd.
Rempel, Gwen R; Harrison, Margaret J; Williamson, Deanna L
2009-04-01
Developing technology affords children with complex congenitally malformed hearts a chance for survival. Parents gratefully pursue life-saving options on behalf of their children, despite the risks to the life of their child, and uncertainty about outcomes. Little is known about how mothers and fathers experience parenting a child whose new state as a survivor may include less than optimal developmental sequels. Our study involved multiple interactive interviews with 9 mothers and 7 fathers of infants and preschool children with hypoplastic left heart syndrome who had survived the Norwood surgical approach. Qualitative methodology included grounded theory methods of simultaneous collection and analysis of data, and we used open and selective coding of transcribed interviews. Parents used normalization in the context of uncertainty regarding the ongoing survival of their child. Parents described their underweight children as being on their own growth curve, and viewed their developmental progress, however delayed, as reason for celebration, as they had been prepared for their child to die. There is growing evidence that children with congenitally malformed hearts who require surgical intervention during the first year of life may experience developmental delay. The use of normalization by their parents may be effective in decreasing their worry regarding the uncertain future faced by their child, but may negatively affect the developmental progress of the child if they do not seek resources to assist development. Advice from paediatric specialists for parents to view their children as normal needs to be balanced with assistance for parents to access services to support optimal growth and development of their child.
Growth hormone and early treatment.
Antoniazzi, F; Cavarzere, P; Gaudino, R
2015-06-01
Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.
Xing, Lianping; Chen, Di; Boyce, Brendan F
2013-12-01
NF-κBp50/p52 double knockout (dKO) and RANK KO mice have no osteoclasts and develop severe osteopetrosis associated with dwarfism. In contrast, Op/Op mice, which form few osteoclasts, and Src KO mice, which have osteoclasts with defective resorptive function, are osteopetrotic, but they are not dwarfed. Here, we compared the morphologic features of long bones from p50/p52 dKO, RANK KO, Op/Op and Src KO mice to attempt to explain the differences in their long bone lengths. We found that growth plates in p50/p52 dKO and RANK KO mice are significantly thicker than those in WT mice due to a 2-3-fold increase in the hypertrophic chondrocyte zone associated with normal a proliferative chondrocyte zone. This growth plate abnormality disappears when animals become older, but their dwarfism persists. Op/Op or Src KO mice have relatively normal growth plate morphology. In-situ hybridization study of long bones from p50/p52 dKO mice showed marked thickening of the growth plate region containing type 10 collagen-expressing chondrocytes. Treatment of micro-mass chondrocyte cultures with RANKL did not affect expression levels of type 2 collagen and Sox9, markers for proliferative chondrocytes, but RANKL reduced the number of type 10 collagen-expressing hypertrophic chondrocytes. Thus, RANK/NF-κB signaling plays a regulatory role in post-natal endochondral ossification that maintains hypertrophic conversion and prevents dwarfism in normal mice.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Romshe, C.A.; Zipf, W.B.; Miser, A.
1984-02-01
We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significantmore » differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.« less
Clinical growth charts for pre-school children.
Al-Amoud, Maysoon M; Al-Mazrou, Yagob Y; El-Gizouli, Sirrag E; Khoja, Tawfik A; Al-Turki, Khalid A
2004-11-01
Growth standards are indicators for normal growth of the children and growth charts are important tools for their growth monitoring. Children from different populations are different in their growth pattern, it is important to create national standards for the growth of children in each population to develop local growth charts, and since these were not available in the Kingdom of Saudi Arabia (KSA), the aim of this study was to construct national growth standards and to develop growth charts for 0-5-years Saudi children. A cross-sectional study following World Health Organization (WHO) criteria in determining sample size was adopted, where by 24000 children from 5 regions in the KSA were selected during the period 1992 to 1995 to be the desired sample. One hundred and two Primary Health Care centers (PHCCs) were selected randomly from the 5 regions, from where the sample was drawn, and a special questionnaire was designed. Weight, height and head circumference were measured by standard procedures. The total number of children examined was 23821 (11913 boys and 11908 girls). Saudi (0-5-years) boys weight and height for age measurements were significantly different from girls. The same difference was found between urban and rural boys and girls and between boys and girls from the different regions of the country (p<0.05). These national standards derived from this study were used to develop national growth charts that are currently utilized to monitor growth in all Saudi health institutes.
Biology and Biotechnology of Follicle Development
Palma, Gustavo Adolfo; Argañaraz, Martin Eduardo; Barrera, Antonio Daniel; Rodler, Daniela; Mutto, Adrian Ángel; Sinowatz, Fred
2012-01-01
Growth and development of ovarian follicles require a series of coordinated events that induce morphological and functional changes within the follicle, leading to cell differentiation and oocyte development. The preantral early antral follicle transition is the stage of follicular development during which gonadotropin dependence is obtained and the progression into growing or atresia of the follicle is made. Follicular growth during this period is tightly regulated by oocyte-granulosatheca cell interactions. A cluster of early expressed genes is required for normal folliculogenesis. Granulosa cell factors stimulate the recruitment of theca cells from cortical stromal cells. Thecal factors promote granulosa cell proliferation and suppress granulosa cell apoptosis. Cell-cell and cell-extracellular matrix interactions influence the production of growth factors in the different follicular compartments (oocyte, granulosa, and theca cells). Several autocrine and paracrine factors are involved in follicular growth and differentiation; their activity is present even at the time of ovulation, decreasing the gap junction communication, and stimulating the theca cell proliferation. In addition, the identification of the factors that promote follicular growth from the preantral stage to the small antral stage may provide important information for the identification for assisted reproduction techniques. PMID:22666170
Three-Dimensional Coculture Of Human Small-Intestine Cells
NASA Technical Reports Server (NTRS)
Wolf, David; Spaulding, Glen; Goodwin, Thomas J.; Prewett, Tracy
1994-01-01
Complex three-dimensional masses of normal human epithelial and mesenchymal small-intestine cells cocultured in process involving specially designed bioreactors. Useful as tissued models for studies of growth, regulatory, and differentiation processes in normal intestinal tissues; diseases of small intestine; and interactions between cells of small intestine and viruses causing disease both in small intestine and elsewhere in body. Process used to produce other tissue models, leading to advances in understanding of growth and differentiation in developing organisms, of renewal of tissue, and of treatment of myriad of clinical conditions. Prior articles describing design and use of rotating-wall culture vessels include "Growing And Assembling Cells Into Tissues" (MSC-21559), "High-Aspect-Ratio Rotating Cell-Culture Vessel" (MSC-21662), and "In Vitro, Matrix-Free Formation Of Solid Tumor Spheroids" (MSC-21843).
Basu, Debarati; Showalter, Allan M.
2015-01-01
Hydroxyproline-O-galactosyltransferase (GALT) initiates O-glycosylation of arabinogalactan-proteins (AGPs). We previously characterized GALT2 (At4g21060), and now report on functional characterization of GALT5 (At1g74800). GALT5 was identified using heterologous expression in Pichia and an in vitro GALT assay. Product characterization showed GALT5 specifically adds galactose to hydroxyproline in AGP protein backbones. Functions of GALT2 and GALT5 were elucidated by phenotypic analysis of single and double mutant plants. Allelic galt5 and galt2 mutants, and particularly galt2 galt5 double mutants, demonstrated lower GALT activities and reductions in β-Yariv-precipitated AGPs compared to wild type. Mutant plants showed pleiotropic growth and development phenotypes (defects in root hair growth, root elongation, pollen tube growth, flowering time, leaf development, silique length, and inflorescence growth), which were most severe in the double mutants. Conditional mutant phenotypes were also observed, including salt-hypersensitive root growth and root tip swelling as well as reduced inhibition of pollen tube growth and root growth in response to β-Yariv reagent. These mutants also phenocopy mutants for an AGP, SOS5, and two cell wall receptor-like kinases, FEI1 and FEI2, which exist in a genetic signaling pathway. In summary, GALT5 and GALT2 function as redundant GALTs that control AGP O-glycosylation, which is essential for normal growth and development. PMID:25974423
Basu, Debarati; Wang, Wuda; Ma, Siyi; DeBrosse, Taylor; Poirier, Emily; Emch, Kirk; Soukup, Eric; Tian, Lu; Showalter, Allan M
2015-01-01
Hydroxyproline-O-galactosyltransferase (GALT) initiates O-glycosylation of arabinogalactan-proteins (AGPs). We previously characterized GALT2 (At4g21060), and now report on functional characterization of GALT5 (At1g74800). GALT5 was identified using heterologous expression in Pichia and an in vitro GALT assay. Product characterization showed GALT5 specifically adds galactose to hydroxyproline in AGP protein backbones. Functions of GALT2 and GALT5 were elucidated by phenotypic analysis of single and double mutant plants. Allelic galt5 and galt2 mutants, and particularly galt2 galt5 double mutants, demonstrated lower GALT activities and reductions in β-Yariv-precipitated AGPs compared to wild type. Mutant plants showed pleiotropic growth and development phenotypes (defects in root hair growth, root elongation, pollen tube growth, flowering time, leaf development, silique length, and inflorescence growth), which were most severe in the double mutants. Conditional mutant phenotypes were also observed, including salt-hypersensitive root growth and root tip swelling as well as reduced inhibition of pollen tube growth and root growth in response to β-Yariv reagent. These mutants also phenocopy mutants for an AGP, SOS5, and two cell wall receptor-like kinases, FEI1 and FEI2, which exist in a genetic signaling pathway. In summary, GALT5 and GALT2 function as redundant GALTs that control AGP O-glycosylation, which is essential for normal growth and development.
The effect of flurbiprofen on the development of anencephaly in early stage chicken embryos.
Özeren, Ersin; Er, Uygur; Güvenç, Yahya; Demirci, Adnan; Arıkök, Ata Türker; Şenveli, Engin; Ergün, Rüçhan Behzat
2015-04-01
The study investigated the effect of flurbiprofen on the development of anencephaly in early stage chicken embryos. We looked at four groups with a total of 36 embryos. There was a control group, a normal saline group, a normal-dose group and a high-dose group with ten, ten, eight and eight eggs with embryo respectively. Two embryos in the control group, studied with light microscopy at 48 h, were consistent with 28-29 hours' incubation in the Hamburger-Hamilton System. They had open neural tubes. The other embryos in this group were considered normal. One embryo in the normal saline group was on the occlusion stage at 48 h. One embryo showed an open neural tube. They were compatible with 28-29 hours' incubation in the Hamburger-Hamilton system. The remaining eight embryos showed normal development. In the normal dose group, one embryo showed underdevelopment of the embryonic disc and the embryo was dead. In four embryos, the neural tubes were open. One cranial malformation was found that was complicated with anencephaly in one embryo. In two embryos the neural tubes were closed, as they showed normal development, and they reached their expected stages according to the Hamburger-Hamilton classification. There was no malformation or growth retardation. Four experimental embryos were anencephalic in the high dose group, and three embryos had open neural tubes. One embryo exhibited both anencephaly and a neural tube closure defect. None of the embryos in this group showed normal development. Even the usual therapeutic doses of flurbiprofen increased the risk of neural tube defect. Flurbiprofen was found to significantly increase the risk of anencephaly. The provision of improved technical materials and studies with larger sample sizes will reveal the stage of morphological disruption during the development of embryos.
Bone marrow fat: linking adipocyte-induced inflammation with skeletal metastases
Hardaway, Aimalie L.; Herroon, Mackenzie K.; Rajagurubandara, Erandi
2014-01-01
Adipocytes are important but underappreciated components of bone marrow microenvironment, and their numbers greatly increase with age, obesity, and associated metabolic pathologies. Age and obesity are also significant risk factors for development of metastatic prostate cancer. Adipocytes are metabolically active cells that secrete adipokines, growth factors, and inflammatory mediators; influence behavior and function of neighboring cells; and have a potential to disturb local milleu and dysregulate normal bone homeostasis. Increased marrow adiposity has been linked to bone marrow inflammation and osteoporosis of the bone, but its effects on growth and progression of prostate tumors that have metastasized to the skeleton are currently not known. This review focuses on fat-bone relationship in a context of normal bone homeostasis and metastatic tumor growth in bone. We discuss effects of marrow fat cells on bone metabolism, hematopoiesis, and inflammation. Special attention is given to CCL2- and COX-2-driven pathways and their potential as therapeutic targets for bone metastatic disease. PMID:24398857
6-Hydroxy dopamine does not affect lens-induced refractive errors but suppresses deprivation myopia.
Schaeffel, F; Hagel, G; Bartmann, M; Kohler, K; Zrenner, E
1994-01-01
Degradation of the retinal image by translucent occluders during postnatal development induces axial myopia in chickens, tree shrews and monkeys. Local visual deprivation produces myopia even in local regions of the eye and neither accommodation nor intact connection between the eye and the brain are necessary. Therefore, it is an important question whether a similar local-retinal pathway translating visual information into growth or stretch signals to the underlying sclera is acting to emmetropize the growing eye. It is not known until now whether occluder deprivation triggers similar eye growth (or scleral stretch) mechanisms that are also responsible for visual guidance of normal refractive development. We here report that, in chickens, 6-hydroxy dopamine suppresses deprivation-induced myopia but has no effect on the magnitude of changes in axial eye elongation that are induced by spectacle lenses. The result suggests that, in chickens with normal accommodation, two pharmacologically different feedback loops may be responsible for deprivation myopia and lens-induced refractive errors.
Jopp, Eilin; Scheffler, Christiane; Hermanussen, Michael
2014-01-01
Screening is an important issue in medicine and is used to early identify unrecognised diseases in persons who are apparently in good health. Screening strongly relies on the concept of "normal values". Normal values are defined as values that are frequently observed in a population and usually range within certain statistical limits. Screening for obesity should start early as the prevalence of obesity consolidates already at early school age. Though widely practiced, measuring BMI is not the ultimate solution for detecting obesity. Children with high BMI may be "robust" in skeletal dimensions. Assessing skeletal robustness and in particularly assessing developmental tempo in adolescents are also important issues in health screening. Yet, in spite of the necessity of screening investigations, appropriate reference values are often missing. Meanwhile, new concepts of growth diagrams have been developed. Stage line diagrams are useful for tracking developmental processes over time. Functional data analyses have efficiently been used for analysing longitudinal growth in height and assessing the tempo of maturation. Convenient low-cost statistics have also been developed for generating synthetic national references.
Maternal amino acid supplementation for intrauterine growth restriction
Brown, Laura D; Green, Alice S; Limesand, Sean W; Rozance, Paul J
2011-01-01
Maternal dietary protein supplementation to improve fetal growth has been considered as an option to prevent or treat intrauterine growth restriction. However, in contrast to balanced dietary supplementation, adverse perinatal outcomes in pregnant women who received high amounts of dietary protein supplementation have been observed. The responsible mechanisms for these adverse outcomes are unknown. This review will discuss relevant human and animal data to provide the background necessary for the development of explanatory hypotheses and ultimately for the development therapeutic interventions during pregnancy to improve fetal growth. Relevant aspects of fetal amino acid metabolism during normal pregnancy and those pregnancies affected by IUGR will be discussed. In addition, data from animal experiments which have attempted to determine mechanisms to explain the adverse responses identified in the human trials will be presented. Finally, we will suggest new avenues for investigation into how amino acid supplementation might be used safely to treat and/or prevent IUGR. PMID:21196387
Interactions between the thyroid hormones and the hormones of the growth hormone axis.
Laron, Zvi
2003-12-01
The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.
SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice
Ding, Feng; Li, Hong Hua; Zhang, Shengwen; Solomon, Nicola M.; Camper, Sally A.; Cohen, Pinchas; Francke, Uta
2008-01-01
Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a ∼4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a ∼150 kb deletion of the >40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation. PMID:18320030
Khodabakhshi, A; Ghayour-Mobarhan, M; Rooki, H; Vakili, R; Hashemy, S-I; Mirhafez, S R; Shakeri, M-T; Kashanifar, R; Pourbafarani, R; Mirzaei, H; Dahri, M; Mazidi, M; Ferns, G; Safarian, M
2015-05-01
Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants. In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10 < weight for length percentile < 85) who were between 2 and 5 months of age were enrolled. Anthropometric indices of infants and mothers were measured by routine methods. Breast milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods. The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50 pg/ml, than in mothers with obese infants, 132.00 pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04 ng/ml) and without (0/038 ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P > 0.05). There was also a significant positive correlation between EGF and ghrelin in both groups. This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.
Nishida, Kazuhiko; Yamaguchi, Osamu; Hirotani, Shinichi; Hikoso, Shungo; Higuchi, Yoshiharu; Watanabe, Tetsuya; Takeda, Toshihiro; Osuka, Soh; Morita, Takashi; Kondoh, Gen; Uno, Yoshihiro; Kashiwase, Kazunori; Taniike, Masayuki; Nakai, Atsuko; Matsumura, Yasushi; Miyazaki, Jun-ichi; Sudo, Tatsuhiko; Hongo, Kenichi; Kusakari, Yoichiro; Kurihara, Satoshi; Chien, Kenneth R.; Takeda, Junji; Hori, Masatsugu; Otsu, Kinya
2004-01-01
The molecular mechanism for the transition from cardiac hypertrophy, an adaptive response to biomechanical stress, to heart failure is poorly understood. The mitogen-activated protein kinase p38α is a key component of stress response pathways in various types of cells. In this study, we attempted to explore the in vivo physiological functions of p38α in hearts. First, we generated mice with floxed p38α alleles and crossbred them with mice expressing the Cre recombinase under the control of the α-myosin heavy-chain promoter to obtain cardiac-specific p38α knockout mice. These cardiac-specific p38α knockout mice were born normally, developed to adulthood, were fertile, exhibited a normal life span, and displayed normal global cardiac structure and function. In response to pressure overload to the left ventricle, they developed significant levels of cardiac hypertrophy, as seen in controls, but also developed cardiac dysfunction and heart dilatation. This abnormal response to pressure overload was accompanied by massive cardiac fibrosis and the appearance of apoptotic cardiomyocytes. These results demonstrate that p38α plays a critical role in the cardiomyocyte survival pathway in response to pressure overload, while cardiac hypertrophic growth is unaffected despite its dramatic down-regulation. PMID:15572667
Expression of the le Mutation in Young Ovaries of Pisum sativum and Its Effect on Fruit Development.
Santes, C. M.; Hedden, P.; Sponsel, V. M.; Reid, J. B.; Garcia-Martinez, J. L.
1993-01-01
The effect of the le mutation on the growth and gibberellin (GA) content of developing fruits was investigated using the near-isogenic lines of Pisum sativum L. 205+ (LeLe) and 205- (lele). Although stem elongation is known to be reduced in 205- plants by approximately 65%, the growth of pods and seeds was unaffected by the le mutation. GA1, GA3, and GA20 stimulated parthenocarpic development of unpollinated ovaries on both 205+ and 205- plants. GA20 was less active on 205- ovaries than on 205+, whereas GA1 had similar, high activity in both lines. The activity of GA3 was even higher than that of GA1 in both lines. Decapitation of 205+ plants induced parthenocarpic development of unpollinated ovaries, but this treatment was much less effective on 205- plants. The contents of GA1 and GA8 in entire ovaries 6 d after anthesis, as well as in the pod and fertilized ovules, were substantially lower in 205- than in 205+ plants, whereas the reverse was true for the levels of GA20 and GA29. These results suggest that 3[beta]-hydroxylation of GA20 to GA1 is reduced in ovaries as well as in vegetative tissues. Thus, the le mutation appears to be expressed in young reproductive organs of the 205- line, even though it does not affect the fruit phenotype. Because the content of GA3 in the ovary was similar in the two lines, one explanation for the normal fruit size in the 205- line is that GA3 is the native regulator of pod growth. Alternatively, sufficient GA1 may still be produced in 205- fruits to maintain normal pod growth. PMID:12231727
Sunday, M E; Hua, J; Torday, J S; Reyes, B; Shipp, M A
1992-12-01
The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth.
Pulungan, Sri Imriani; Yano, Ryoichi; Okabe, Yoshihiro; Ichino, Takuji; Kojima, Mikiko; Takebayashi, Yumiko; Sakakibara, Hitoshi; Ariizumi, Tohru; Ezura, Hiroshi
2018-06-01
Leaves are the major plant organs with a primary function for photosynthesis. Auxin controls various aspects of plant growth and development, including leaf initiation, expansion and differentiation. Unique and intriguing auxin features include its polar transport, which is mainly controlled by the AUX1/LAX and PIN gene families as influx and efflux carriers, respectively. The role of AUX1/LAX genes in root development is well documented, but the role of these genes in leaf morphogenesis remains unclear. Moreover, most studies have been conducted in the plant model Arabidopsis thaliana, while studies in tomato are still scarce. In this study, we isolated six lines of the allelic curly leaf phenotype 'curl' mutants from a γ-ray and EMS (ethyl methanesulfonate) mutagenized population. Using a map-based cloning strategy combined with exome sequencing, we observed that a mutation occurred in the SlLAX1 gene (Solyc09g014380), which is homologous to an Arabidopsis auxin influx carrier gene, AUX1 (AtAUX1). Characterization of six alleles of single curl mutants revealed the pivotal role of SlLAX1 in controlling tomato leaf flatness by balancing adaxial and abaxial pavement cell growth, which has not been reported in tomato. Using TILLING (Targeting Induced Local Lesions IN Genome) technology, we isolated an additional mutant allele of the SlLAX1 gene and this mutant showed a curled leaf phenotype similar to other curl mutants, suggesting that Solyc09g014380 is responsible for the curl phenotype. These results showed that SlLAX1 is required for normal leaf development mediated by balanced adaxial and abaxial pavement cell growth in tomato.
Lu, Zhi Hong; Books, Jason T.; Ley, Timothy J.
2005-01-01
Proteins containing “cold shock” domains belong to the most evolutionarily conserved family of nucleic acid-binding proteins known among bacteria, plants, and animals. One of these proteins, YB-1, is widely expressed throughout development and has been implicated as a cell survival factor that regulates the transcription and/or translation of many cellular growth and death-related genes. For these reasons, YB-1 deficiency has been predicted to be incompatible with cell survival. However, the majority of YB-1−/− embryos develop normally up to embryonic day 13.5 (E13.5). After E13.5, YB-1−/− embryos exhibit severe growth retardation and progressive mortality, revealing a nonredundant role of YB-1 in late embryonic development. Fibroblasts derived from YB-1−/− embryos displayed a normal rate of protein synthesis and minimal alterations in the transcriptome and proteome but demonstrated reduced abilities to respond to oxidative, genotoxic, and oncogene-induced stresses. YB-1−/− cells under oxidative stress expressed high levels of the G1-specific CDK inhibitors p16Ink4a and p21Cip1 and senesced prematurely; this defect was corrected by knocking down CDK inhibitor levels with specific small interfering RNAs. These data suggest that YB-1 normally represses the transcription of CDK inhibitors, making it an important component of the cellular stress response signaling pathway. PMID:15899865
Tissue Architecture and Microenvironment Sustain Hormone Signaling | Center for Cancer Research
Cells interact with their environments in part through protein receptors embedded in the cell membrane. Activation of a receptor by external signaling molecules sets off a complex chain of events within the cell that can result in alterations in protein structure and function and/or changes in gene expression. Proper integration of these signals is crucial for normal cell growth and development. A more complete understanding of these normal processes will help elucidate how aberrant signaling results in diseases such as cancer.
Johnson, W; Stovitz, S D; Choh, A C; Czerwinski, S A; Towne, B; Demerath, E W
2012-04-01
To estimate differences in skeletal maturity and stature from birth to age 18 years between individuals who are overweight vs normal weight in young adulthood. Weight, length and height, and relative skeletal age (skeletal-chronological age) were assessed annually from birth to age 18 years in 521 subjects (255 women) in the Fels Longitudinal Study who were overweight or obese (body mass index (BMI) >25 kg m(-2), n=131) or normal weight (n=390) in young adulthood (18-30 years). Generalized estimating equations were used to test for skeletal maturity and stature differences by young adult BMI status. Differences in height increased during puberty, being significant for girls at ages 10 to 12 years, and for boys at ages 11 to 13 years (P-values<0.001), with overweight or obese adults being ∼3 cm taller at those ages than normal weight adults. These differences then diminished so that by age 18 years, overweight or obese adults were not significantly different in stature to their normal weight peers. Differences in skeletal maturity were similar, but more pervasive; overweight or obese adults were more skeletally advanced throughout childhood. Skeletal maturity differences peaked at chronological age 12 in boys and 14 in girls (P-values<0.001), with overweight or obese adults being ∼1 year more advanced than normal weight adults. This descriptive study is the first to track advanced skeletal maturity and linear growth acceleration throughout infancy, childhood and adolescence in individuals who become overweight, showing that differences occur primarily around the time of the pubertal growth spurt. Increased BMI in children on a path to becoming overweight adults precedes an advancement in skeletal development and subsequently tall stature during puberty. Further work is required to assess the predictive value of accelerated pubertal height growth for assessing obesity risk in a variety of populations.
ERIC Educational Resources Information Center
Andersson, Tommy; Magnusson, David
1990-01-01
The relationship between biological maturation, as evidenced by skeletal growth, during adolescence and the development of drinking habits and alcohol abuse was studied for a representative group of Swedish males (N=88). Early and late maturers had more advanced drinking habits at age 14 years than did normally maturing subjects. (TJH)
USDA-ARS?s Scientific Manuscript database
Maternal low protein diets during prenatal development contribute to the development of obesity and insulin resistance in offspring. In this study, obese-prone Sprague -Dawley rats were fed diets having either 8% (low protein, LP) or 20% (normal protein, NP) protein for 3-wk prior to conception and...
Sawarkar, Ritwick; Visweswariah, Sandhya S; Nellen, Wolfgang; Nanjundiah, Vidyanand
2009-09-04
Epigenetic modifications of histones regulate gene expression and lead to the establishment and maintenance of cellular phenotypes during development. Histone acetylation depends on a balance between the activities of histone acetyltransferases and histone deacetylases (HDACs) and influences transcriptional regulation. In this study, we analyse the roles of HDACs during growth and development of one of the cellular slime moulds, the social amoeba Dictyostelium discoideum. The inhibition of HDAC activity by trichostatin A results in histone hyperacetylation and a delay in cell aggregation and differentiation. Cyclic AMP oscillations are normal in starved amoebae treated with trichostatin A but the expression of a subset of cAMP-regulated genes is delayed. Bioinformatic analysis indicates that there are four genes encoding putative HDACs in D. discoideum. Using biochemical, genetic and developmental approaches, we demonstrate that one of these four genes, hdaB, is dispensable for growth and development under laboratory conditions. A knockout of the hdaB gene results in a social context-dependent phenotype: hdaB(-) cells develop normally but sporulate less efficiently than the wild type in chimeras. We infer that HDAC activity is important for regulating the timing of gene expression during the development of D. discoideum and for defining aspects of the phenotype that mediate social behaviour in genetically heterogeneous groups.
Coen, Enrico; Rolland-Lagan, Anne-Gaëlle; Matthews, Mark; Bangham, J. Andrew; Prusinkiewicz, Przemyslaw
2004-01-01
Although much progress has been made in understanding how gene expression patterns are established during development, much less is known about how these patterns are related to the growth of biological shapes. Here we describe conceptual and experimental approaches to bridging this gap, with particular reference to plant development where lack of cell movement simplifies matters. Growth and shape change in plants can be fully described with four types of regional parameter: growth rate, anisotropy, direction, and rotation. A key requirement is to understand how these parameters both influence and respond to the action of genes. This can be addressed by using mechanistic models that capture interactions among three components: regional identities, regionalizing morphogens, and polarizing morphogens. By incorporating these interactions within a growing framework, it is possible to generate shape changes and associated gene expression patterns according to particular hypotheses. The results can be compared with experimental observations of growth of normal and mutant forms, allowing further hypotheses and experiments to be formulated. We illustrate these principles with a study of snapdragon petal growth. PMID:14960734
Hellström, Ann; Smith, Lois E H; Dammann, Olaf
2015-01-01
The immature retinas of preterm neonates are susceptible to insults that disrupt neurovascular growth, leading to retinopathy of prematurity. Suppression of growth factors due to hyperoxia and loss of the maternal–fetal interaction result in an arrest of retinal vascularisation (phase 1). Subsequently, the increasingly metabolically active, yet poorly vascularised, retina becomes hypoxic, stimulating growth factor-induced vasoproliferation (phase 2), which can cause retinal detachment. In very premature infants, controlled oxygen administration reduces but does not eliminate retinopathy of prematurity. Identification and control of factors that contribute to development of retinopathy of prematurity is essential to prevent progression to severe sight-threatening disease and to limit comorbidities with which the disease shares modifiable risk factors. Strategies to prevent retinopathy of prematurity will depend on optimisation of oxygen saturation, nutrition, and normalisation of concentrations of essential factors such as insulin-like growth factor 1 and ω-3 polyunsaturated fatty acids, as well as curbing of the effects of infection and inflammation to promote normal growth and limit suppression of neurovascular development. PMID:23782686
Substrate flexibility regulates growth and apoptosis of normal but not transformed cells
NASA Technical Reports Server (NTRS)
Wang, H. B.; Dembo, M.; Wang, Y. L.
2000-01-01
One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.
Yan, Huaming; Konstorum, Anna; Lowengrub, John S
2018-05-01
We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies.
Yan, Huaming; Konstorum, Anna
2017-01-01
We develop a three-dimensional multispecies mathematical model to simulate the growth of colon cancer organoids containing stem, progenitor and terminally differentiated cells, as a model of early (prevascular) tumor growth. Stem cells (SCs) secrete short-range self-renewal promoters (e.g., Wnt) and their long-range inhibitors (e.g., Dkk) and proliferate slowly. Committed progenitor (CP) cells proliferate more rapidly and differentiate to produce post-mitotic terminally differentiated cells that release differentiation promoters, forming negative feedback loops on SC and CP self-renewal. We demonstrate that SCs play a central role in normal and cancer colon organoids. Spatial patterning of the SC self-renewal promoter gives rise to SC clusters, which mimic stem cell niches, around the organoid surface, and drive the development of invasive fingers. We also study the effects of externally applied signaling factors. Applying bone morphogenic proteins, which inhibit SC and CP self-renewal, reduces invasiveness and organoid size. Applying hepatocyte growth factor, which enhances SC self-renewal, produces larger sizes and enhances finger development at low concentrations but suppresses fingers at high concentrations. These results are consistent with recent experiments on colon organoids. Because many cancers are hierarchically organized and are subject to feedback regulation similar to that in normal tissues, our results suggest that in cancer, control of cancer stem cell self-renewal should influence the size and shape in similar ways, thereby opening the door to novel therapies. PMID:28681151
Lushnikov, Pavel M; Zubarev, Nikolay M
2018-05-18
Relative motion of the normal and superfluid components of helium II results in the quantum Kelvin-Helmholtz instability (KHI) at their common free surface. We found the integrability and exact growing solutions for the nonlinear stage of the development of that instability. Contrary to the usual KHI of the interface between two classical fluids, the dynamics of a helium II free surface allows reduction to the Laplace growth equation, which has an infinite number of exact solutions, including the generic formation of sharp cusps at the free surface in a finite time.
NASA Astrophysics Data System (ADS)
Lushnikov, Pavel M.; Zubarev, Nikolay M.
2018-05-01
Relative motion of the normal and superfluid components of helium II results in the quantum Kelvin-Helmholtz instability (KHI) at their common free surface. We found the integrability and exact growing solutions for the nonlinear stage of the development of that instability. Contrary to the usual KHI of the interface between two classical fluids, the dynamics of a helium II free surface allows reduction to the Laplace growth equation, which has an infinite number of exact solutions, including the generic formation of sharp cusps at the free surface in a finite time.
Auditory processing deficits in growth restricted fetuses affect later language development.
Kisilevsky, Barbara S; Davies, Gregory A L
2007-01-01
An increased risk for language deficits in infants born growth restricted has been reported in follow-up studies for more than 20 years, suggesting a relation between fetal auditory system development and later language learning. Work with animal models indicate that there are at least two ways in which growth restriction could affect the development of auditory perception in human fetuses: a delay in myelination or conduction and an increase in sensorineural threshold. Systematic study of auditory function in growth restricted human fetuses has not been reported. However, results of studies employing low-risk fetuses delivering as healthy full-term infants demonstrate that, by late gestation, the fetus can hear, sound properties modulate behavior, and sensory information is available from both inside (e.g., maternal vascular) and outside (e.g., noise, voices, music) of the maternal body. These data provide substantive evidence that the auditory system is functioning and that environmental sounds are available for shaping neural networks and laying the foundation for language acquisition before birth. We hypothesize that fetal growth restriction affects auditory system development, resulting in atypical auditory information processing in growth restricted fetuses compared to healthy, appropriately-grown-for-gestational-age fetuses. Speech perception that lays the foundation for later language competence will differ in growth restricted compared to normally grown fetuses and be associated with later language abilities.
It takes a tissue to make a tumor: epigenetics, cancer and the microenvironment
NASA Technical Reports Server (NTRS)
Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)
2001-01-01
How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises its ability to suppress carcinogenesis.
Larsen, Karen B
2017-01-01
Human fetal brain development is a complex process which is vulnerable to disruption at many stages. Although histogenesis is well-documented, only a few studies have quantified cell numbers across normal human fetal brain growth. Due to the present lack of normative data it is difficult to gauge abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples are unreliable due to unpredictable shrinking artifacts, and the fragility of the fetal brain requires particular care in handling and processing. The optical fractionator design offers a direct and robust estimate of total cell numbers in the fetal brain with a minimum of handling of the tissue. Bearing this in mind, we have used the optical fractionator to quantify the growth of total cell numbers as a function of fetal age. We discovered a two-phased development in total cell numbers in the human fetal forebrain consisting of an initial steep rise in total cell numbers between 13 and 20 weeks of gestation, followed by a slower linear phase extending from mid-gestation to 40 weeks of gestation. Furthermore, we have demonstrated a reduced total cell number in the forebrain in fetuses with Down syndome at midgestation and in intrauterine growth-restricted fetuses during the third trimester.
The axonal guidance cue semaphorin 3C contributes to alveolar growth and repair.
Vadivel, Arul; Alphonse, Rajesh S; Collins, Jennifer J P; van Haaften, Tim; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard
2013-01-01
Lung diseases characterized by alveolar damage such as bronchopulmonary dysplasia (BPD) in premature infants and emphysema lack efficient treatments. Understanding the mechanisms contributing to normal and impaired alveolar growth and repair may identify new therapeutic targets for these lung diseases. Axonal guidance cues are molecules that guide the outgrowth of axons. Amongst these axonal guidance cues, members of the Semaphorin family, in particular Semaphorin 3C (Sema3C), contribute to early lung branching morphogenesis. The role of Sema3C during alveolar growth and repair is unknown. We hypothesized that Sema3C promotes alveolar development and repair. In vivo Sema3C knock down using intranasal siRNA during the postnatal stage of alveolar development in rats caused significant air space enlargement reminiscent of BPD. Sema3C knock down was associated with increased TLR3 expression and lung inflammatory cells influx. In a model of O2-induced arrested alveolar growth in newborn rats mimicking BPD, air space enlargement was associated with decreased lung Sema3C mRNA expression. In vitro, Sema3C treatment preserved alveolar epithelial cell viability in hyperoxia and accelerated alveolar epithelial cell wound healing. Sema3C preserved lung microvascular endothelial cell vascular network formation in vitro under hyperoxic conditions. In vivo, Sema3C treatment of hyperoxic rats decreased lung neutrophil influx and preserved alveolar and lung vascular growth. Sema3C also preserved lung plexinA2 and Sema3C expression, alveolar epithelial cell proliferation and decreased lung apoptosis. In conclusion, the axonal guidance cue Sema3C promotes normal alveolar growth and may be worthwhile further investigating as a potential therapeutic target for lung repair.
Feng, Fan; Chen, Liang; Lian, Chaoqun; Xia, Hengchuan; Zhou, Yang; Yao, Qin; Chen, Keping
2014-08-28
The silkworm, Bombyx mori, is an important model of lepidoptera insect, and it has been used for several models of human diseases. In human being, long-term high-sugar diet can induce the occurrence of diabetes and other related diseases. Interestingly, our experiments revealed the high glucose diet also has a suppressive effect on the development of silkworms. To investigate the molecular mechanism by which high-glucose diet inhibited the midgut growth in silkworms, we employed comparative proteomic analysis to globally identify proteins differentially expressed in normal and high-glucose diet group silkworms. In all, 28 differently proteins were suppressed and 5 proteins induced in high-glucose diet group. Gene ontology analysis showed that most of these differently proteins are mainly involved in metabolic process, catalytic and cellular process. A development related protein, imaginal disk growth factor (IDGF), was further confirmed by western blot exclusively expressing in the normal diet group silkworms. Taken together, our data suggests that IDGF plays a critical role in impairing the development of silkworms by a high-glucose diet. Glucose has been thought to play essential roles in growth and development of silkworm. In this paper, we certified firstly that high-glucose diet can suppress the growth of silkworm, and comparative proteomic was employed to reveal the inhibition mechanism. Moreover, an important regulation related protein (IDGF) was found to involve in this inhibition process. These results will help us get a deeper understanding of the relationship between diet and healthy. Furthermore, IDGF may be the critical protein for reducing the blood sugar in silkworm, and it may be used for screening human hypoglycemic drug. The work has not been submitted elsewhere for publication, in whole or in part, and all the authors have approved the manuscript. Copyright © 2014 Elsevier B.V. All rights reserved.
Gab3-deficient mice exhibit normal development and hematopoiesis and are immunocompetent.
Seiffert, Martina; Custodio, Joseph M; Wolf, Ingrid; Harkey, Michael; Liu, Yan; Blattman, Joseph N; Greenberg, Philip D; Rohrschneider, Larry R
2003-04-01
Gab proteins are intracellular scaffolding and docking molecules involved in signaling pathways mediated by various growth factor, cytokine, or antigen receptors. Gab3 has been shown to act downstream of the macrophage colony-stimulating factor receptor, c-Fms, and to be important for macrophage differentiation. To analyze the physiological role of Gab3, we used homologous recombination to generate mice deficient in Gab3. Gab3(-/-) mice develop normally, are visually indistinguishable from their wild-type littermates, and are healthy and fertile. To obtain a detailed expression pattern of Gab3, we generated Gab3-specific monoclonal antibodies. Immunoblotting revealed a predominant expression of Gab3 in lymphocytes and bone marrow-derived macrophages. However, detailed analysis demonstrated that hematopoiesis in mice lacking Gab3 is not impaired and that macrophages develop in normal numbers and exhibit normal function. The lack of Gab3 expression during macrophage differentiation is not compensated for by increased levels of Gab1 or Gab2 mRNA. Furthermore, Gab3-deficient mice have no major immune deficiency in T- and B-lymphocyte responses to protein antigens or during viral infection. In addition, allergic responses in Gab3-deficient mice appeared to be normal. Together, these data demonstrate that loss of Gab3 does not result in detectable defects in normal mouse development, hematopoiesis, or immune system function.
Koontz, Laura M; Liu-Chittenden, Yi; Yin, Feng; Zheng, Yonggang; Yu, Jianzhong; Huang, Bo; Chen, Qian; Wu, Shian; Pan, Duojia
2013-05-28
The Hippo tumor suppressor pathway restricts tissue growth by inactivating the transcriptional coactivator Yki. Although Sd has been implicated as a DNA-binding transcription factor partner for Yki and can genetically account for gain-of-function Yki phenotypes, how Yki regulates normal tissue growth remains a long-standing puzzle because Sd, unlike Yki, is dispensable for normal growth in most Drosophila tissues. Here we show that the yki mutant phenotypes in multiple developmental contexts are rescued by inactivation of Sd, suggesting that Sd functions as a default repressor and that Yki promotes normal tissue growth by relieving Sd-mediated default repression. We further identify Tgi as a cofactor involved in Sd's default repressor function and demonstrate that the mammalian ortholog of Tgi potently suppresses the YAP oncoprotein in transgenic mice. These findings fill a major gap in Hippo-mediated transcriptional regulation and open up possibilities for modulating the YAP oncoprotein in cancer and regenerative medicine. Copyright © 2013 Elsevier Inc. All rights reserved.
Strand, Tor A; Ulak, Manjeswori; Chandyo, Ram K; Kvestad, Ingrid; Hysing, Mari; Shrestha, Merina; Basnet, Sudha; Ranjitkar, Suman; Shrestha, Laxman; Shrestha, Prakash S
2017-04-21
Vitamin B 12 deficiency is one of the most common micronutrient deficiencies and is associated with poor cognitive development and growth. Vitamin B 12 is crucial for normal cell division and differentiation, and it is necessary for the development and myelination of the central nervous system. The aim of the present study is to measure the effect of daily supplementation of vitamin B 12 on the neurodevelopment and growth of young children in Nepal. We are conducting an individually randomized, double-blind, placebo-controlled trial with 600 marginally stunted children 6-11 months old (length for age less than -1 z-score). Children are randomized to receive a lipid-based paste containing vitamin B 12 or placebo daily for 12 months. The main outcomes are changes in growth (z-scores) and in neurodevelopment measured by the Bayley Scales of Infant and Toddler Development, Third Edition, from baseline until the end of the study. If vitamin B 12 supplementation benefits early child development and growth, this will have consequences for dietary recommendations for malnourished children worldwide. ClinicalTrials.gov Identifier: NCT02272842 . Registered on 21 October 2014. Universal Trial Number: U1111-1161-5187. Registered on 8 September 2014.
Growth plate closure: Apex view on bone scan
DOE Office of Scientific and Technical Information (OSTI.GOV)
Giles, P.H.; Trochei, M.; Yeates, K.
1984-01-01
Angular deformities of the extremities in children following premature closure of the growth plate are well known. The deformities depend on the position of an osseus bridge which forms between the epiphysis and metaphysis. Several surgical procedures including resection of the osseus bridge have been described, however, delineation of the site of fusion is difficult to define. The commonest site of growth plate arrest is the distal femoral or proximal tibial growth plate. A new technique using the bone scan has been developed which accurately defines the area and position of these osseus bridges. Two hours after injection of technetiummore » 99m methylene diphosphonate apex views of the affected distal femoral growth plate were performed. The knee was flexed into its smallest angle. Using a pinhole collimator the gamma camera was angled to face the affected growth plate end on. The image was collected onto computer and analysed by: (I) regions of interest over segments of the growth plate to calculate the relative area of total growth plate affected: (II) generating histograms: (III) thresholding or performing isocontours to accentuate abnormal areas. The growth plate is normally uniformly increased when compared to the normal shaft of the bone. Fusion across the plate appears as an area of diminished uptake. The apex view gives a unique functional map of the growth plate such that abnormal areas are displayed, and the site, size and position of osseus fusion obtained. The technique has the potential for determining the metabolic activity of the growth plate before and after surgery. Serial studies will allow assessment of regneration of the plate and reformation of new osseus bridges.« less
Lee, Ji-Yeon; Kim, Lee-Han; Kim, Ha-Eun; Park, Jae-Sin; Han, Kap-Hoon; Han, Dong-Min
2013-12-01
The nsdD gene encoding a GATA type transcription factor positively controls sexual development in Aspergillus nidulans. According to microarray data, 20 genes that were upregulated by deleting nsdD during various life cycle stages were randomly selected and deleted for functional analysis. None of the mutants showed apparent changes in growth or development compared with those of the wild-type except the AN3154 gene that encodes a putative APSES transcription factor and is an ortholog of Saccharomyces cerevisiae swi4. Deleting AN3154 resulted in retarded growth and development, and the gene was named rgdA (retared growth and development). The rgdA deletion mutant developed a reduced number of conidia even under favorable conditions for asexual development. The retarded growth and development was partially suppressed by the veA1 mutation. The conidial heads of the mutant aborted, showing reduced and irregular shaped phialides. Fruiting body development was delayed compared with that in the wild-type. The mutant did not respond to various nutritional or environmental factors that affected the development patterns. The rgdA gene was expressed at low levels throughout the life cycle and was not significantly affected by several regulators of sexual and asexual development such as nsdD, veA, stuA, or brlA. However, the rgdA gene affected brlA and abaA expression, which function as key regulators of asexual sporulation, suggesting that rgdA functions upstream of those genes.
Adoption of multivariate copulae in prognostication of economic growth by means of interest rate
NASA Astrophysics Data System (ADS)
Saputra, Dewi Tanasia; Indratno, Sapto Wahyu, Dr.
2015-12-01
Inflation, at a healthy rate, is a sign of growing economy. Nonetheless, when inflation rate grows uncontrollably, it will negatively influence economic growth. Many tackle this problem by increasing interest rate to help protecting the value of money which is detained by inflation. There are few, however, who study the effects of interest rate in economic growth. The main purposes of this paper are to find how the change of interest rate affects economic growth and to use the relationship in prognostication of economic growth. By using expenditure model, a linear relationship between economic growth and interest rate is developed. The result is then used for prediction by normal copula and Vine Archimedean copula. It is shown that increasing interest rate to tackle inflation is a poor solution. Whereas implementation of copula in predicting economic growth yields an accurate result, with not more than 0.5% difference.
USDA-ARS?s Scientific Manuscript database
The gut represents a continuously evolving ecosystem where a dynamic interaction between host immune, neuroendocrine and entero-endocrine cells and the gut microbiota influences normal physiological development and homeostasis. New antibiotic regulatory policies and cage-free rearing systems in pou...
Robbins, C.S.
1990-01-01
In areas impacted by acid precipitation, water chemistry of acidic ponds and streams often changes, resulting in increased mobilization of aluminum and decreased concentration of calcium carbonate. Aluminum binds with phosphorus and inhibits its uptake by organisms. Thus, invertebrate food organisms used by waterfowl may have inadequate Ca and P or elevated Al for normal growth and development. Acid rain and its effects may be one of the factors negatively impacting American black ducks (Anas rubripes) in eastern North America. One-day old mallards (A. platyrhynchos) and black ducks were placed on one of three Ca:P regimens: low:low (LL), normal:normal (NN), and low:high (LH) with each regimen divided further into three or four Al levels for 10 weeks. Forty-five % of the black ducks died on nine different diets whereas only 28% of the mallards died on three different diets. Mortality was significantly related to diet in both species. Growth rates for body weight, culmens, wings, and tarsi of both species on control diets exceeded those on many treatment diets but the differences were less apparent for mallards than for black ducks. Differences among treatments were due to both Ca:P and Al levels.
Marzella, P L; Gillespie, L N; Clark, G M; Bartlett, P F; Kilpatrick, T J
1999-12-01
A number of growth factor families have been implicated in normal inner ear development, auditory neuron survival and protection. Several growth factors, including transforming growth factor-beta5 (TGF-beta5) and TGF-beta3, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were tested for their ability, individually or in combination, to promote auditory neuron survival in dissociated cell cultures of early rat post-natal spiral ganglion cells (SGCs). The results indicate that at discrete concentrations all growth factors act in an additive fashion and some in synergy when promoting neuronal survival. These findings support the hypothesis that growth factors from different families may be interdependent when sustaining neuronal integrity.
Jung, Susan; Boie, Gudrun; Doerr, Helmuth-Guenther; Trollmann, Regina
2017-04-01
Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O 2 , 6 h; postnatal day 7 , P7) at P14. Exposure to hypoxia led to reduced body weight ( P < 0.001) and length ( P < 0.04) compared with controls and was associated with significantly reduced plasma levels of mouse GH ( P < 0.01) and IGF-1 ( P < 0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared with controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain. Copyright © 2017 the American Physiological Society.
Raade, Merja; Hämäläinen, Esa; Sane, Timo
2015-01-01
Background Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up. Methods Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line. Results Tumor (n=69) size was similar before and after 5 years follow-up (19±6 mm vs. 20±7 mm). Mean tumor growth was 1±2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. Conclusion None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years. PMID:26354488
Schalin-Jäntti, Camilla; Raade, Merja; Hämäläinen, Esa; Sane, Timo
2015-12-01
Current guidelines for follow-up of adrenal incidentalomas are extensive and hampered by lack of follow-up studies. We tested the hypothesis that small lipid-rich adrenal incidentalomas, initially characterized by tumor size <40 mm and <10 Hounsfield units (HUs) on unenhanced computed tomography (CT) may not demonstrate excessive growth/hormonal hypersecretion on follow-up. Sixty-nine incidentalomas in 56 patients were restudied with unenhanced CT and screening for hypercortisolism (dexamethasone suppression test [DST], plasma adrenocorticotropic hormone) and pheochromocytoma (24-hour urinary metanephrines and normetanephrines) 5 years later. Primary hyperaldosteronism was excluded at base-line. Tumor (n=69) size was similar before and after 5 years follow-up (19±6 mm vs. 20±7 mm). Mean tumor growth was 1±2 mm. Largest increase in tumor size was 8 mm, this tumor was surgically removed and histopathology confirmed cortical adenoma. DST was normal in 54 patients and two patients (3.6%) were still characterized by subclinical hypercortisolism. Initial tumor size was >20 mm for the patient with largest tumor growth and those with subclinical hypercortisolism. All patients had normal 24-hour urinary metanephrines and normetanephrines. Low attenuation (<10 HU) was demonstrated in 97% of 67 masses re-evaluated with unenhanced CT. None of the patients developed clinically relevant tumor growth or new subclinical hypercortisolism. Biochemical screening for pheochromocytoma in incidentalomas demonstrating <10 HU on unenhanced CT is not needed. For such incidentalomas <40 mm, it seems sufficient to perform control CT and screen for hypercortisolism after 5 years.
Unbound (bioavailable) IGF1 enhances somatic growth
Elis, Sebastien; Wu, Yingjie; Courtland, Hayden-William; Cannata, Dara; Sun, Hui; Beth-On, Mordechay; Liu, Chengyu; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Basta-Pljakic, Jelena; Cardoso, Luis; Rosen, Clifford J.; Frystyk, Jan; Yakar, Shoshana
2011-01-01
SUMMARY Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or ‘free IGF1’. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions. PMID:21628395
Unbound (bioavailable) IGF1 enhances somatic growth.
Elis, Sebastien; Wu, Yingjie; Courtland, Hayden-William; Cannata, Dara; Sun, Hui; Beth-On, Mordechay; Liu, Chengyu; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Basta-Pljakic, Jelena; Cardoso, Luis; Rosen, Clifford J; Frystyk, Jan; Yakar, Shoshana
2011-09-01
Understanding insulin-like growth factor-1 (IGF1) biology is of particular importance because, apart from its role in mediating growth, it plays key roles in cellular transformation, organ regeneration, immune function, development of the musculoskeletal system and aging. IGF1 bioactivity is modulated by its binding to IGF-binding proteins (IGFBPs) and the acid labile subunit (ALS), which are present in serum and tissues. To determine whether IGF1 binding to IGFBPs is necessary to facilitate normal growth and development, we used a gene-targeting approach and generated two novel knock-in mouse models of mutated IGF1, in which the native Igf1 gene was replaced by Des-Igf1 (KID mice) or R3-Igf1 (KIR mice). The KID and KIR mutant proteins have reduced affinity for the IGFBPs, and therefore present as unbound IGF1, or 'free IGF1'. We found that both KID and KIR mice have reduced serum IGF1 levels and a concomitant increase in serum growth hormone levels. Ternary complex formation of IGF1 with the IGFBPs and the ALS was markedly reduced in sera from KID and KIR mice compared with wild type. Both mutant mice showed increased body weight, body and bone lengths, and relative lean mass. We found selective organomegaly of the spleen, kidneys and uterus, enhanced mammary gland complexity, and increased skeletal acquisition. The KID and KIR models show unequivocally that IGF1-complex formation with the IGFBPs is fundamental for establishing normal body and organ size, and that uncontrolled IGF bioactivity could lead to pathological conditions.
Mathematical modeling of solid cancer growth with angiogenesis
2012-01-01
Background Cancer arises when within a single cell multiple malfunctions of control systems occur, which are, broadly, the system that promote cell growth and the system that protect against erratic growth. Additional systems within the cell must be corrupted so that a cancer cell, to form a mass of any real size, produces substances that promote the growth of new blood vessels. Multiple mutations are required before a normal cell can become a cancer cell by corruption of multiple growth-promoting systems. Methods We develop a simple mathematical model to describe the solid cancer growth dynamics inducing angiogenesis in the absence of cancer controlling mechanisms. Results The initial conditions supplied to the dynamical system consist of a perturbation in form of pulse: The origin of cancer cells from normal cells of an organ of human body. Thresholds of interacting parameters were obtained from the steady states analysis. The existence of two equilibrium points determine the strong dependency of dynamical trajectories on the initial conditions. The thresholds can be used to control cancer. Conclusions Cancer can be settled in an organ if the following combination matches: better fitness of cancer cells, decrease in the efficiency of the repairing systems, increase in the capacity of sprouting from existing vascularization, and higher capacity of mounting up new vascularization. However, we show that cancer is rarely induced in organs (or tissues) displaying an efficient (numerically and functionally) reparative or regenerative mechanism. PMID:22300422
Yu, Shengqiang; Yeh, Chiuan-Ren; Niu, Yuanjie; Chang, Hong-Chiang; Tsai, Yu-Chieh; Moses, Harold L; Shyr, Chih-Rong; Chang, Chawnshang; Yeh, Shuyuan
2012-03-01
Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear. To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development. The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors. Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer. Copyright © 2011 Wiley Periodicals, Inc.
Bueters, Ruud R G; Jeronimus-Klaasen, Annelies; Brüggemann, Roger J M; van den Heuvel, Lambertus P; Schreuder, Michiel F
2017-09-01
Up to two-thirds of premature born neonates are treated for infections with aminoglycosides such as gentamicin. Although acute toxicities are well described, there is uncertainty on developmental changes after treatment of premature born neonates. We studied the effect of gentamicin and ceftazidime on kidney development in the rat. Additionally, we evaluated the modulating effect of extrauterine growth restriction. On postnatal day (PND) 2, Wistar rats were cross-fostered into normal sized litters (12 pups) or large litters (20 pups) to create normal food (NF) or food restricted (FR) litters to simulate growth restriction and dosed daily intraperitoneally with placebo, 4 mg/kg of gentamicin or 50 mg/kg ceftazidime until PND 8. Gentamicin pharmacokinetics were studied in a separate group of animals. Kidneys were weighed. Renal expression of 18 developmental genes was evaluated by quantitative PCR on PND 8. On PND 35, glomerular number was assessed by stereology and glomerular generations were counted. Food restricted litters showed 22% less body weight compared with controls by day 35 (p < 0.001), 1.4- to 1.5-fold down regulation of Renin, Oat1, and Agtr1a (p < 0.05) expression and a 12% reduction in glomerular numbers (mean 30841 vs. 35187, p < 0.001), whereas glomerular generation count was unaffected. Gentamicin pharmacokinetic parameters were found to be in a human clinical range (mean maximum concentration in plasma of 4.88 mg/L and mean area under the plasma-concentration time curve up to the last measured concentration after 4 hr of 10.71 mg.h/L for sexes combined) and all endpoints were unaffected. Ceftazidime reduced Renin expression by 1.7-fold (p < 0.01). Our experiments showed that gentamicin at clinical levels did not disturb kidney development, ceftazidime can affect Renin expression, and extrauterine growth restriction impairs kidney development, but did not modulate potential drug toxicity. Birth Defects Research 109:1228-1235, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
NASA Technical Reports Server (NTRS)
Hanely, Julia C.; Reinsch, Sigrid; Myers, Zachary A.; Freeman, John; Steele, Marianne K.; Sun, Gwo-Shing; Heathcote, David G.
2014-01-01
The European Modular Cultivation System, EMCS, was developed by ESA for plant experiments. To expand the use of flight verified hardware for various model organisms, we performed ground experiments to determine whether ARC EMCS Seed Cassettes could be adapted for use with cellular slime mold for future space flight experiments. Dictyostelium is a cellular slime mold that can exist both as a single-celled independent organism and as a part of a multicellular colony which functions as a unit (pseudoplasmodium). Under certain stress conditions, individual amoebae will aggregate to form multicellular structures. Developmental pathways are very similar to those found in Eukaryotic organisms, making this a uniquely interesting organism for use in genetic studies. Dictyostelium has been used as a genetic model organism for prior space flight experiments. Due to the formation of spores that are resistant to unfavorable conditions such as desiccation, Dictyostelium is also a good candidate for use in the EMCS Seed Cassettes. The growth substratum in the cassettes is a gridded polyether sulfone (PES) membrane. A blotter beneath the PES membranes contains dried growth medium. The goals of this study were to (1) verify that Dictyostelium are capable of normal growth and development on PES membranes, (2) develop a method for dehydration of Dictyostelium spores with successful recovery and development after rehydration, and (3) successful mock rehydration experiments in cassettes. Our results show normal developmental progression in two strains of Dictyostelium discoideum on PES membranes with a bacterial food source. We have successfully performed a mock rehydration of spores with developmental progression from aggregation to slug formation, and production of morphologically normal spores within 9 days of rehydration. Our results indicate that experiments on the ISS using the slime mold, Dictyostelium discoideum could potentially be performed in the flight verified hardware of the EMCS ARC Seed Cassettes.
Niu, Longjian; Tao, Yan-Bin; Chen, Mao-Sheng; Fu, Qiantang; Li, Chaoqiong; Dong, Yuling; Wang, Xiulan; He, Huiying; Xu, Zeng-Fu
2015-01-01
Real-time quantitative PCR (RT-qPCR) is a reliable and widely used method for gene expression analysis. The accuracy of the determination of a target gene expression level by RT-qPCR demands the use of appropriate reference genes to normalize the mRNA levels among different samples. However, suitable reference genes for RT-qPCR have not been identified in Sacha inchi (Plukenetia volubilis), a promising oilseed crop known for its polyunsaturated fatty acid (PUFA)-rich seeds. In this study, using RT-qPCR, twelve candidate reference genes were examined in seedlings and adult plants, during flower and seed development and for the entire growth cycle of Sacha inchi. Four statistical algorithms (delta cycle threshold (ΔCt), BestKeeper, geNorm, and NormFinder) were used to assess the expression stabilities of the candidate genes. The results showed that ubiquitin-conjugating enzyme (UCE), actin (ACT) and phospholipase A22 (PLA) were the most stable genes in Sacha inchi seedlings. For roots, stems, leaves, flowers, and seeds from adult plants, 30S ribosomal protein S13 (RPS13), cyclophilin (CYC) and elongation factor-1alpha (EF1α) were recommended as reference genes for RT-qPCR. During the development of reproductive organs, PLA, ACT and UCE were the optimal reference genes for flower development, whereas UCE, RPS13 and RNA polymerase II subunit (RPII) were optimal for seed development. Considering the entire growth cycle of Sacha inchi, UCE, ACT and EF1α were sufficient for the purpose of normalization. Our results provide useful guidelines for the selection of reliable reference genes for the normalization of RT-qPCR data for seedlings and adult plants, for reproductive organs, and for the entire growth cycle of Sacha inchi. PMID:26047338
TRAJECTORY AND CORRELATES OF GROWTH OF EXTREMELY LOW BIRTH WEIGHT ADOLESCENTS
Hack, Maureen; Schluchter, Mark; Margevicius, Seunghee; Andreias, Laura; Taylor, Gerry; Cuttler, Leona
2014-01-01
Background Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch-up among extremely low birth weight (ELBW, <1 kg) adolescents. Methods Cohort study of 148 neurologically normal ELBW children and 115 normal birth weight (NBW) controls born 1992 through 1995. Longitudinal measures of gender-specific growth of ELBW children from birth, and growth and measures of obesity of ELBW and NBW children at 14 years. Results Following neonatal growth failure, ELBW children had accelerated growth, but at 8 years they still had lower weight and height z scores than NBW children. By 14 years ELBW boys had caught up in growth to their NBW controls but ELBW girls remained significantly smaller. ELBW children however did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses only maternal BMI and weight gain during infancy and childhood predicted the ELBW children’s 14-year weight z scores, BMI z scores and abdominal circumference. Perinatal risk factors including intrauterine growth only predicted growth up to 20 months. Conclusion Maternal BMI and rate of growth, rather than perinatal factors, predict 14-year obesity among neurologically normal ELBW adolescents. PMID:24216539
Investigation of Mechanisms Associated with Nucleate Boiling Under Microgravity Conditions
NASA Technical Reports Server (NTRS)
Dhir, Vijay K.
1996-01-01
The focus of the present work is to experimentally study and to analytically/numerically model the mechanisms of growth of bubbles attached to, and sliding along, a heated surface. To control the location of the active cavities, the number, the spacing, and the nucleation superheat, artificial cavities will be formed on silicon wafers. In order to study the effect of magnitude of components of gravitational acceleration acting parallel to, and normal to the surface, experiments will be conducted on surfaces inclined at different angles including a downward facing surface. Information on the temperature field around bubbles, bubble shape and size, and bubble induced liquid velocities will be obtained through the use of holography, video/high speed photography and hydrogen bubble techniques, respectively. Analytical/numerical models will be developed to describe the heat transfer including that through the micro-macro layer underneath and around a bubble. In the micro layer model capillary and disjoining pressures will be included. Evolution of the interface along with induced liquid motion will be modelled. Subsequent to the world at normal gravity, experiments will be conducted in the KC-135 or the Lear jet especially to learn about bubble growth/detachment under low gravity conditions. Finally, an experiment will be defined to be conducted under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide microgravity data on bubble growth and detachment and will lead to a validation of the nucleate boiling heat transfer model developed from the preceding studies performed at normal and low gravity (KC-135 or Lear jet) conditions.
Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T
1983-05-01
A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.
Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang
2012-08-15
Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.
Asian G6PD-Mahidol Reticulocytes Sustain Normal Plasmodium Vivax Development.
Bancone, Germana; Malleret, Benoit; Suwanarusk, Rossarin; Chowwiwat, Nongnud; Chu, Cindy S; McGready, Rose; Rénia, Laurent; Nosten, François; Russell, Bruce
2017-07-15
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymatic disorder in humans and appears to be protective against falciparum severe malaria. Controversially, it is also thought that Plasmodium vivax has driven the recent selection of G6PD alleles. We use an experimental approach to determine whether G6PD-MahidolG487A variant, a widespread cause of severe G6PD deficiency in Southeast Asia, provides a barrier against vivax malaria. Our results show that the immature reticulocytes (CD71+) targeted by P. vivax invasion are enzymatically normal, even in hemizygous G6PD-Mahidol G487A mutants; thus, allowing the normal growth, development, and high parasite density in severely deficient samples. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
Hypoxia-inducible factors promote alveolar development and regeneration.
Vadivel, Arul; Alphonse, Rajesh S; Etches, Nicholas; van Haaften, Timothy; Collins, Jennifer J P; O'Reilly, Megan; Eaton, Farah; Thébaud, Bernard
2014-01-01
Understanding how alveoli and the underlying capillary network develop and how these mechanisms are disrupted in disease states is critical for developing effective therapies for lung regeneration. Recent evidence suggests that lung angiogenesis promotes lung development and repair. Vascular endothelial growth factor (VEGF) preserves lung angiogenesis and alveolarization in experimental O2-induced arrested alveolar growth in newborn rats, but combined VEGF+angiopoietin 1 treatment is necessary to correct VEGF-induced vessel leakiness. Hypoxia-inducible factors (HIFs) are transcription factors that activate multiple O2-sensitive genes, including those encoding for angiogenic growth factors, but their role during postnatal lung growth is incompletely understood. By inducing the expression of a range of angiogenic factors in a coordinated fashion, HIF may orchestrate efficient and safe angiogenesis superior to VEGF. We hypothesized that HIF inhibition impairs alveolarization and that HIF activation regenerates irreversible O2-induced arrested alveolar growth. HIF inhibition by intratracheal dominant-negative adenovirus (dnHIF-1α)-mediated gene transfer or chetomin decreased lung HIF-1α, HIF-2α, and VEGF expression and led to air space enlargement and arrested lung vascular growth. In experimental O2-induced arrested alveolar growth in newborn rats, the characteristic features of air space enlargement and loss of lung capillaries were associated with decreased lung HIF-1α and HIF-2α expression. Intratracheal administration of Ad.HIF-1α restored HIF-1α, endothelial nitric oxide synthase, VEGF, VEGFR2, and Tie2 expression and preserved and rescued alveolar growth and lung capillary formation in this model. HIFs promote normal alveolar development and may be useful targets for alveolar regeneration.
Alahakoon, Thushari I; Zhang, Weiyi; Arbuckle, Susan; Zhang, Kewei; Lee, Vincent
2018-05-01
To localize, quantify and compare angiogenic factors, vascular endothelial growth factor (VEGF), placental growth factor (PlGF), as well as their receptors fms-like tyrosine kinase receptor (Flt-1) and kinase insert domain receptor (KDR) in the placentas of normal pregnancy and complications of preeclampsia (PE), intrauterine fetal growth restriction (IUGR) and PE + IUGR. In a prospective cross-sectional case-control study, 30 pregnant women between 24-40 weeks of gestation, were recruited into four clinical groups. Representative placental samples were stained for VEGF, PlGF, Flt-1 and KDR. Analysis was performed using semiquantitative methods and digital image analysis. The overall VEGF and Flt-1 were strongly expressed and did not show any conclusive difference in the expression between study groups. PlGF and KDR were significantly reduced in expression in the placentas from pregnancies complicated by IUGR compared with normal and preeclamptic pregnancies. The lack of PlGF and KDR may be a cause for the development of IUGR and may explain the loss of vasculature and villous architecture in IUGR. Automated digital image analysis software is a viable alternative method to the manual reading of placental immunohistochemical staining. © 2018 Japan Society of Obstetrics and Gynecology.
Normal Skeletal Maturation and Imaging Pitfalls in the Pediatric Shoulder.
Zember, Jonathan S; Rosenberg, Zehava S; Kwong, Steven; Kothary, Shefali P; Bedoya, Maria A
2015-01-01
A growing number of magnetic resonance (MR) imaging studies of the shoulder are being performed as a result of greater and earlier participation of children and adolescents in competitive sports such as softball and baseball. However, scant information is available regarding the MR imaging features of the normal sequential development of the shoulder. The authors discuss the radiographic and MR imaging appearances of the normal musculoskeletal maturation patterns of the shoulder, with emphasis on (a) development of secondary ossification centers of the glenoid (including the subcoracoid and peripheral glenoid ossification centers); (b) development of preossification and secondary ossification centers of the humeral head and the variable appearance and number of the secondary ossification centers of the distal acromion, with emphasis on the formation of the os acromiale; (c) development of the growth plates, glenoid bone plates, glenoid bare area, and proximal humeral metaphyseal stripe; and (d) marrow signal alterations in the distal humerus, acromion, and clavicle. In addition, the authors discuss various imaging interpretation pitfalls inherent to the normal skeletal maturation of the shoulder, examining clues that may help distinguish normal development from true disease (eg, osteochondral lesions, labral tears, abscesses, fractures, infection, tendon disease, acromioclavicular widening, and os acromiale). Familiarity with the timing, location, and appearance of maturation patterns in the pediatric shoulder is crucial for correct image interpretation. ©RSNA, 2015.
Intelligence development of pre-lingual deaf children with unilateral cochlear implantation.
Chen, Mo; Wang, Zhaoyan; Zhang, Zhiwen; Li, Xun; Wu, Weijing; Xie, Dinghua; Xiao, Zi-An
2016-11-01
The present study aims to test whether deaf children with unilateral cochlear implantation (CI) have higher intelligence quotients (IQ). We also try to find out the predictive factors of intelligence development in deaf children with CI. Totally, 186 children were enrolled into this study. They were divided into 3 groups: CI group (N = 66), hearing loss group (N = 54) and normal hearing group (N = 66). All children took the Hiskey-Nebraska Test of Learning Aptitude to assess the IQ. After that, we used Deafness gene chip, Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) methods to evaluate the genotype, auditory and speech performance, respectively. At baseline, the average IQ of hearing loss group (HL), CI group, normal hearing (NH) group were 98.3 ± 9.23, 100.03 ± 12.13 and 109.89 ± 10.56, while NH group scored higher significantly than HL and CI groups (p < 0.05). After 12 months, the average IQ of HL group, CI group, NH group were99.54 ± 9.38,111.85 ± 15.38, and 112.08 ± 8.51, respectively. No significant difference between the IQ of the CI and NH groups was found (p > 0.05). The growth of SIR was positive correlated with the growth of IQ (r = 0.247, p = 0.046), while no significant correlation were found between IQ growth and other possible factors, i.e. gender, age of CI, use of hearing aid, genotype, implant device type, inner ear malformation and CAP growth (p > 0.05). Our study suggests that CI potentially improves the intelligence development in deaf children. Speech performance growth is significantly correlated with IQ growth of CI children. Deaf children accepted CI before 6 years can achieve a satisfying and undifferentiated short-term (12 months) development of intelligence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Poyatos-Pertíñez, Sandra; Quinet, Muriel; Ortíz-Atienza, Ana; Yuste-Lisbona, Fernando J; Pons, Clara; Giménez, Estela; Angosto, Trinidad; Granell, Antonio; Capel, Juan; Lozano, Rafael
2016-01-01
Floral organogenesis requires coordinated interactions between genes specifying floral organ identity and those regulating growth and size of developing floral organs. With the aim to isolate regulatory genes linking both developmental processes (i.e., floral organ identity and growth) in the tomato model species, a novel mutant altered in the formation of floral organs was further characterized. Under normal growth conditions, floral organ primordia of mutant plants were correctly initiated, however, they were unable to complete their development impeding the formation of mature and fertile flowers. Thus, the growth of floral buds was blocked at an early stage of development; therefore, we named this mutant as unfinished flower development ( ufd ). Genetic analysis performed in a segregating population of 543 plants showed that the abnormal phenotype was controlled by a single recessive mutation. Global gene expression analysis confirmed that several MADS-box genes regulating floral identity as well as other genes participating in cell division and different hormonal pathways were affected in their expression patterns in ufd mutant plants. Moreover, ufd mutant inflorescences showed higher hormone contents, particularly ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC) and strigol compared to wild type. Such results indicate that UFD may have a key function as positive regulator of the development of floral primordia once they have been initiated in the four floral whorls. This function should be performed by affecting the expression of floral organ identity and growth genes, together with hormonal signaling pathways.
Dendritic Growth of Hard-Sphere Crystals. Experiment 34
NASA Technical Reports Server (NTRS)
Russel, W. B.; Chaikin, P. M.; Zhu, Ji-Xiang; Meyer, W. V.; Rogers, R.
1998-01-01
Recent observations of the disorder-order transition for colloidal hard spheres under microgravity revealed dendritic crystallites roughly 1-2 mm in size for samples in the coexistence region of the phase diagram. Order-of-magnitude estimates rationalize the absence of large or dendritic crystals under normal gravity and their stability to annealing in microgravity. A linear stability analysis of the Ackerson and Schaetzel model for crystallization of hard spheres establishes the domain of instability for diffusion-limited growth at small supersaturations. The relationship between hard-sphere and molecular crystal growth is established and exploited to relate the predicted linear instability to the well-developed dendrites observed.
Pituitary gigantism causing diabetic ketoacidosis.
Alvi, N S; Kirk, J M
1999-01-01
Although growth hormone excess (acromegaly) in association with glucose intolerance and diabetes mellitus is well documented in adult medicine, it is much less common in the paediatric age group. We report the case of a 13 year-old boy who presented with tall stature secondary to a large growth hormone secreting adenoma of the pituitary gland. Random growth hormone was 630 mIU/l and did not suppress during an oral glucose tolerance test. Following debulking of the tumour, he developed diabetic ketoacidosis requiring insulin treatment, but after further surgery glucose handling returned to normal. He has been started on testosterone to arrest further increase in height.
Fire ant baits and biocontrol with pathogens update
USDA-ARS?s Scientific Manuscript database
The insect growth regulator (IGR) methoprene (isopropyl-(2E,4E,7R,S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate) has been shown to have deleterious effects on red imported fire ants, Solenopsis invicta. It interferes with normal development of worker caste brood and reduces queen egg production...
A Physiologically Based Kinetic Model of Rat and Mouse Gestation: Disposition of a Weak Acid
A physiologically based toxicokinetic model of gestation in the rat mouse has been developed. The model is superimposed on the normal growth curve for nonpregnant females. It describes the entire gestation period including organogenesis. The model consists of uterus, mammary tiss...
Ancient Dietary Wisdom for Tomorrow's Children.
ERIC Educational Resources Information Center
Fallon, Sally
1997-01-01
A review of Dr. Weston Price's work on the nutritional practices of "primitive" peoples and their subsequent levels of physical development shows that animal fats and cholesterol are not villains but vital factors in the diet, necessary for normal growth, proper functioning of the brain and nervous system, protection from disease, and…
Pasquini, Juana M; Barrantes, Francisco J; Quintá, Héctor R
2017-09-01
It was recently described that Galectin-1 (Gal-1) promotes axonal growth after spinal cord injury. This effect depends on protein dimerization, since monomeric Gal-1 fails to stimulate axonal re-growth. Gal-1 is expressed in vivo at concentrations that favor the monomeric species. The aim of the present study is to investigate whether endogenous Gal-1 is required for spinal axon development and normal locomotor behavior in mice. In order to characterize axonal development, we used a novel combination of 3-DISCO technique with 1-photon microscopy and epifluorescence microscopy under high power LED illumination, followed by serial image section deconvolution and 3-D reconstruction. Cleared whole lgals-1 -/- embryos were used to analyze the 3-D cytoarchitecture of motor, commissural, and sensory axons. This approach allowed us to evaluate axonal development, including the number of fibers, fluorescence density of the fiber tracts, fiber length as well as the morphology of axonal sprouting, deep within the tissue. Gal-1 deficient embryos did not show morphological/anatomical alterations in any of the axonal populations and parameters analyzed. In addition, specific guidance receptor PlexinA4 did not change its axonal localization in the absence of Gal-1. Finally, Gal-1 deficiency did not change normal locomotor activity in post-natal animals. Taken together, our results show that development of spinal axons as well as the locomotor abilities observed in adult mice are independent of Gal-1. Supporting our previous observations, the present study further validates the use of lgals-1 -/- mice to develop spinal cord- or traumatic brain injury models for the evaluation of the regenerative action of Gal-1. © 2017 Wiley Periodicals, Inc.
Costochondral grafts replacing the mandibular condyle.
Ross, R B
1999-07-01
The purpose of this study was to determine the success rate of costochondral bone grafts used to replace absent or nonfunctioning temporomandibular joints and the subsequent growth of these grafts when placed in young children. This is a retrospective study of all cases with adequate follow-up records that were treated at the Craniofacial Centre at Toronto's The Hospital for Sick Children from 1974-1986. A total of 55 patients were evaluated, of whom 13 were growing children. The findings suggest that there was increased success when surgery was performed at an early age. Poorer results were achieved when previous surgery had been performed or when pathology was present. Growth of the graft did not always equal the growth of the "normal" side, but in most cases a satisfactory symmetry was achieved. Several cases exhibited excessive overgrowth. Surgery at 4 to 5 years of age will alleviate the impact of a severe facial deformity on the child during the early school years, when self-esteem is fragile and patterns of social interactions are developing. Development of the dentition is better if the jaw relationship is close to normal at an early age. It would appear that early temporomandibular joint (TMJ) construction by costochondral grafting is, at present, the method of choice for severe hemifacial microsomia.
Rac1 Dosage Is Crucial for Normal Endochondral Bone Growth.
Suzuki, Dai; Bush, Jason R; Bryce, Dawn-Marie; Kamijo, Ryutaro; Beier, Frank
2017-10-01
Rac1, a member of the small Rho GTPase family, plays multiple cellular roles. Studies of mice conditionally lacking Rac1 have revealed essential roles for Rac1 in various tissues, including cartilage and limb mesenchyme, where Rac1 loss produces dwarfism and long bone shortening. To gain further insight into the role of Rac1 in skeletal development, we have used transgenic mouse lines to express a constitutively active (ca) Rac1 mutant protein in a Cre recombinase-dependent manner. Overexpression of caRac1 in limb bud mesenchyme or chondrocytes leads to reduced body weight and shorter bones compared with control mice. Histological analysis of growth plates showed that caRac1;Col2-Cre mice displayed ectopic hypertrophic chondrocytes in the proliferative zone and enlarged hypertrophic zones. These mice also displayed a reduced proportion of proliferating cell nuclear antigen-positive cells in the proliferative zone and nuclear β-catenin localization in the ectopic hypertrophic chondrocytes. Importantly, overexpression of caRac1 partially rescued the phenotypes of Rac1fl/fl;Col2-Cre and Rac1fl/fl;Prx1-Cre conditional knockout mice, including body weight, bone length, and growth plate disorganization. These results suggest that tight regulation of Rac1 activity is necessary for normal cartilage development. Copyright © 2017 Endocrine Society.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, S.; Kazim, D.; Kraveka, J.
Normal human fibroblast cells have not been reported to escape crisis--that is they die after about 24 doublings in culture. The authors have been studying the growth properties of skin fibroblast cells from persons in families with familial adenopolyposis of the colon (FAP). An individual hemizygous at the FAP locus will develop hyperplasia of the colonic epithelium followed by colonic polyps, both at an early age. Polyps themselves still retain a single functional FAP allele. A mutation or deletion in this allele in a polyp is hypothesized to lead to further loss of growth control; thus, a tumor is formed.more » They found that the in vitro life-span of skin fibroblast cells from FAP individuals and from some asymptomatic children were markedly extended when compared with normal individuals.« less
2014-01-01
Background In 2006 WHO presented the infant and child growth charts suggested for universal application. However, major determinants for perinatal outcomes and postnatal growth are laid down during antenatal development. Accordingly, monitoring fetal growth in utero by ultrasonography is important both for clinical and scientific reasons. The currently used fetal growth references are derived mainly from North American and European population and may be inappropriate for international use, given possible variances in the growth rates of fetuses from different ethnic population groups. WHO has, therefore, made it a high priority to establish charts of optimal fetal growth that can be recommended worldwide. Methods This is a multi-national study for the development of fetal growth standards for international application by assessing fetal growth in populations of different ethnic and geographic backgrounds. The study will select pregnant women of high-middle socioeconomic status with no obvious environmental constraints on growth (adequate nutritional status, non-smoking), and normal pregnancy history with no complications likely to affect fetal growth. The study will be conducted in centres from ten developing and industrialized countries: Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand. At each centre, 140 pregnant women will be recruited between 8 + 0 and 12 + 6 weeks of gestation. Subsequently, visits for fetal biometry will be scheduled at 14, 18, 24, 28, 32, 36, and 40 weeks (+/− 1 week) to be performed by trained ultrasonographers. The main outcome of the proposed study will be the development of fetal growth standards (either global or population specific) for international applications. Discussion The data from this study will be incorporated into obstetric practice and national health policies at country level in coordination with the activities presently conducted by WHO to implement the use of the Child Growth Standards. PMID:24886101
Wu, Yingjie; Sun, Hui; Yakar, Shoshana; LeRoith, Derek
2009-09-01
IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I.
The role of embryo movement in the development of the furcula.
Pollard, A S; Boyd, S; McGonnell, I M; Pitsillides, A A
2017-03-01
The pectoral girdle is a complex structure which varies in its morphology between species. A major component in birds is the furcula, which can be considered equivalent to a fusion of the paired clavicles found in many mammals, and the single interclavicle found in many reptiles. These elements are a remnant of the dermal skeleton and the only intramembranous bones in the trunk. Postnatally, the furcula plays important mechanical roles by stabilising the shoulder joint and acting as a mechanical spring during flight. In line with its mechanical role, previous studies indicate that, unlike many other intramembranous bones, furcula growth during development can be influenced by mechanical stimuli. This study investigated the response of individual aspects of furcula growth to both embryo immobilisation and hypermotility in the embryonic chicken. The impact of altered incubation temperature, which influences embryo motility, on crocodilian interclavicle development was also explored. We employed whole-mount bone and cartilage staining and 3D imaging by microCT to quantify the impact of rigid paralysis, flaccid paralysis and hypermobility on furcula growth in the chicken, and 3D microCT imaging to quantify the impact of reduced temperature (32-28 °C) and motility on interclavicle growth in the crocodile. This revealed that the growth rates of the clavicular and interclavicular components of the furcula differ during normal development. Total furcula area was reduced by total unloading produced by flaccid paralysis, but not by rigid paralysis which maintains static loading of embryonic bones. This suggests that dynamic loading, which is required for postnatal bone adaptation, is not a requirement for prenatal furcula growth. Embryo hypermotility also had no impact on furcula area or arm length. Furcula 3D shape did, however, differ between groups; this was marked in the interclavicular component of the furcula, the hypocleideum. Hypocleideum length was reduced by both methods of immobilisation, and interclavicle area was reduced in crocodile embryos incubated at 28 °C, which are less motile than embryos incubated at 32 °C. These data suggest that the clavicular and interclavicle components of the avian furcula respond differently to alterations in embryo movement, with the interclavicle requiring both the static and dynamic components of movement-related loading for normal growth, while static loading preserved most aspects of clavicle growth. Our data suggest that embryo movement, and the mechanical loading this produces, is important in shaping these structures during development to suit their postnatal mechanical roles. © 2016 Anatomical Society.
Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Hardy, Kate
2017-01-01
Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS. PMID:28324051
Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate
2017-04-01
Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.
Sizonenko, P C; Rabinovitch, A; Schneider, P; Paunier, L; Wollheim, C B; Zahnd, G
1975-09-01
The effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa. The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P less than 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four- to sixfold increases of plasma GH were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.05). Arginine infusion resulted in two- to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic beta cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa, pancreatic alpha cell responsiveness, to arginine at least, appears to be intact under these conditions.
Impact of skeletal unloading on bone formation: Role of systemic and local factors
NASA Astrophysics Data System (ADS)
Bikle, Daniel D.; Halloran, Bernard P.; Morey-Holton, Emily
We have developed a model of skeletal unloading using growing rats whose hindlimbs are unweighted by tail suspension. The bones in the hindlimbs undergo a transient cessation of bone growth; when reloaded bone formation is accelerated until bone mass is restored. These changes do not occur in the normally loaded bones of the forelimbs. Associated with the fall in bone formation is a fall in 1,25(OH) 2D 3 production and osteocalcin levels. In contrast, no changes in parathyroid hormone, calcium, or corticosterone levels are seen. To examine the role of locally produced growth factors, we have measured the mRNA and protein levels of insulin like growth factor-1 (IGF-1) in bone during tail suspension. Surprisingly, both the mRNA and protein levels of IGF-1 increase during tail suspension as bone formation is reduced. Furthermore, the bones in the hindlimbs of the suspended animals develop a resistance to the growth promoting effects of both growth hormone and IGF-1 when given parenterally. Thus, the cessation of bone growth with skeletal unloading is apparently associated with a resistance to rather than failure to produce local growth factors. The cause of this resistance remains under active investigation.
Zhang, Xiao Man; Shi, Jun; Meng, Guo Zhen; Chen, Hong Sai; Zhang, Li Na; Wang, Zhao Yan; Wu, Hao
2015-03-01
To explore the effects of obstructive sleep apnea syndrome (OSAS) on children's growth by the study of identical twins. Seventeen cases of nonobese children with OSAS were included in this study. The control group was their identical twin sibling, who had no signs of OSAS. Data including height, weight, and serum insulin-like growth factor 1 levels were analyzed before tonsillectomy and adenoidectomy (T&A) and at 3, 6, and 12 months after surgery. The mean apnea hyponea index was 3.9 times/hour in patients with OSAS and became normal after surgery. Minimum oxygen saturation gradually increased after T&A. The height and weight of the OSAS group before T&A was lower than the control group. During the follow-up period, height and weight increased but were lower than the control group. Serum insulin-like growth factor 1 levels in the OSAS group before T&A were lower than the control group. The level was significantly increased 3 months after T&A. OSAS impairs growth and development. Significant growth recovery occurs after T&A, and early surgical intervention is an important factor for improvement in growth. Copyright © 2015. Published by Elsevier Inc.
Alu-mediated recombination defect in IGF1R: haploinsufficiency in a patient with short stature.
Harmel, Eva-Maria; Binder, Gerhard; Barnikol-Oettler, Anja; Caliebe, Janina; Kiess, Wieland; Losekoot, Monique; Ranke, Michael B; Rappold, Gudrun A; Schlicke, Marina; Stobbe, Heike; Wit, Jan M; Pfäffle, Roland; Klammt, Jürgen
2013-01-01
The insulin-like growth factor (IGF) receptor (IGF1R) is essential for normal development and growth. IGF1R mutations cause IGF-1 resistance resulting in intrauterine and postnatal growth failure. The phenotypic spectrum related to IGF1R mutations remains to be fully understood. Auxological and endocrinological data of a patient identified previously were assessed. The patient's fibroblasts were studied to characterize the IGF1R deletion, mRNA fate, protein expression and signalling capabilities. The boy, who carries a heterozygous IGF1R exon 6 deletion caused by Alu element-mediated recombination and a heterozygous SHOX variant (p.Met240Ile), was born appropriate for gestational age but developed proportionate short stature postnatally. IGF-1 levels were low-normal. None of the stigmata associated with SHOX deficiency or sporadically observed in IGF1R mutation carriers were present. Nonsense-mediated mRNA decay led to a substantial decline of IGF1R dosage and IGF-1-dependent receptor autophosphorylation but not impaired downstream signalling. We present the first detailed report of an intragenic IGF1R deletion identified in a patient who, apart from short stature, deviates from all established markers that qualify a growth-retarded child for IGF1R analysis. Although such children will usually escape routine clinical mutation screenings, they can contribute to the understanding of factors and mechanisms that cooperate with the IGF1R. © 2013 S. Karger AG, Basel.
Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O
2000-09-28
Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.
Gut microbiota: puppeteer of the host juvenile growth.
Schwarzer, Martin
2018-05-01
This review focuses on the recent discoveries about the impact of intestinal microbiota on mammalian host juvenile growth. Intestinal microbiota is a powerful modulator of many facets of multicellular host's physiology. Recent results from human field studies and animal research have clearly shown that not only the nutrition, but also the intestinal microbiota impacts host postnatal growth kinetics. Absence of microbiome leads to stunted growth in mammalian gnotobiotic models and changes in the composition of the intestinal microbiota can impact the postnatal growth kinetics both positively and negatively under normal nutritional conditions as well as in undernutrition. Strikingly, specific bacterial strains are able to interact with GH/IGF-1 somatotropic axis activity, thus directly impacting host juvenile development. Intestinal microbiota dictates the pace of host postnatal growth. This newly described role envisages that therapy with specific bacterial strains, together with re-nutritional strategies, might successfully alleviate the long-term sequelae of undernutrition during childhood in humans.
Li, Yang; Wang, Guanghui; Xu, Jin-Rong; Jiang, Cong
2016-01-01
The hemibiotrophic pathogen Magnaporthe oryzae causes one of the most destructive diseases in cultivated rice. Complex infection-related morphogenesis and production of various effectors are known to be important for successful colonization and disease development. In this study, we characterized the activation of the MoGTI1 transcription factor and its role in infection-related morphogenesis and effector gene expression. The Mogti1 mutant was nonpathogenic, although it was normal in appressorium formation and turgor generation. Close examination showed that Mogti1 was defective in penetration and growth of normal invasive hyphae. Deletion of MoGTI1 affected the expression of the majority of effector genes. The expression of MoGti1 appeared to be controlled by the Mps1 but not Pmk1 mitogen-activated protein kinase (MAPK), and the mps1 and Mogti1 mutants had similar phenotypes in plant infection and cell wall integrity defects. However, lack of MAPK phosphorylation sites and dispensability of the putative MAPK docking site suggested that MoGti1 is not a direct target of Mps1. Site-specific mutagenesis analyses showed that the putative protein kinase A phosphorylation site was not essential for localization of MoGti1 to the nucleus but important for its normal function. Although the cyclin-dependent kinase (CDK) phosphorylation site of MoGti1 is dispensable during vegetative growth and appressorium formation, the S77A mutation affected penetration and invasive growth. Localization of MoGti1(S77A)-green fluorescent protein to the nucleus in late stages of appressorium formation and during invasive growth was not observed, suggesting a stage-specific CDK phosphorylation of MoGti1. Overall, our data indicate that Mps1 may indirectly regulate the expression of MoGti1 in maintaining cell wall integrity, conidiation, and plant infection. MoGti1 is likely a stage-specific target of CDK and plays a crucial role in effector gene expression and morphogenesis related to the development of penetration pegs and invasive hyphae.
[GHBP, IGF-1 and IGFBP-3 serum levels in familial short-statured and normal-statured children].
del Valle Núñez, Cristóbal Jorge; López-Siguero, Juan Pedro; López-Canti, Luis Fernando; Lechuga Campoy, José Luis; Espigares Martín, Rosa; Martínez-Aedo Ollero, María José
2004-10-09
Growth hormone binding protein (GHBP), insuline-like growth factor 1 (IGF-1) and insuline-like growth factor binding protein 3 (IGFBP-3) serum concentrations were studied in familial short-statured patients (FSS) and age-matched normal-statured subjects. The aim of the study was to ascertain whether differences in growth factors concentrations between groups could be shown and whether they may contribute to explaining the different patterns of growth in both groups. Serum samples of 38 FSS patients (20 boys) and 31 normal-statured subjects (15 boys) in Tanner I stage (prepubertal), were analysed in a central laboratory. All auxological parameters (height, growth velocity, target height, body mass index (BMI) and biochemical parameters (IGF-1 and IGFBP-3) were standardised for age and sex-matched subjects. GHBP values were expressed as percentage of specific binding. The studied populations were similar and no statistically-significant differences in chronological age, bone age and BMI were found. Height, growth velocity and target height were significantly lower in FSS patients compared with normal subjects (p < 0.0001). IGF-1, IGFBP-3 and GHBP concentrations were significantly lower in the FSS group (p < 0.01). Correlations were found between IGF-1 and IGFBP-3 (r = 0.56; p = 0.0004) and between IGF-1 and GHBP (r = 0.34; p = 0.03) in the FSS group. However, in the normal-statured group only BMI and GHBP were correlated (r = 0.5; p = 0.02). These results strongly support the importance of the GH/IGF-1 functional axis in the pattern of growth and probably contribute to understanding of the pathophysiologic basis of the auxological differences found between groups.
Wallace, Jacqueline M; Milne, John S; Aitken, Raymond P; Horgan, Graham W; Adam, Clare L
2018-05-22
Low birthweight is a risk factor for later adverse health. Here the impact of placentally-mediated prenatal growth-restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks). Dual-energy X-ray absorptiometry revealed lower bone mineral density in restricted versus normal lambs at 11, 41, 64 and 107 weeks, with males>females from 41 weeks onwards. Body fat percentage was higher in females versus males throughout, in restricted versus normal lambs at weaning (both sexes), and in restricted versus normal females at mid-adulthood. Insulin secretion after glucose-challenge was greater in restricted versus normal of both sexes at 7 weeks, and in restricted-males at 32 weeks. In both sexes fasting glucose concentrations were greater in restricted offspring across the life-course, while glucose area-under-the-curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance. Therefore prenatal growth-restriction has negative consequences for body composition and metabolism throughout the life-course with the effects modulated by sex differences in postnatal growth rates, fat deposition and bone mass accrual.
de Faria, Maria Estela Justamante; Carvalho, Luciani R; Rossetto, Shirley M; Amaral, Terezinha Sampaio; Berger, Karina; Arnhold, Ivo Jorge Prado; Mendonca, Berenice Bilharinho
2009-01-01
There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone (GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2-11 years. GH doses (0.1-0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur. Copyright 2009 S. Karger AG, Basel.
Changes in Polysome Association of mRNA Throughout Growth and Development in Arabidopsis thaliana.
Yamasaki, Shotaro; Matsuura, Hideyuki; Demura, Taku; Kato, Ko
2015-11-01
Translational control is a key regulatory step in the expression of genes as proteins. In plant cells, the translational efficiency of mRNAs differs for different mRNA species, and the efficiency dynamically changes in various conditions. To gain a global view of translational control throughout growth and development, we performed genome-wide analysis of polysome association of mRNA during growth and leaf development in Arabidopsis thaliana by subjecting the mRNAs in polysomes to DNA microarray. This analysis revealed that the degree of polysome association of mRNA was different depending on the mRNA species, and the polysome association changed greatly throughout growth and development for each. In the growth stage, transcripts showed varying changes in polysome association from strongly depressed to unchanged, with the majority of transcripts showing dissociation from ribosomes. On the other hand, during leaf development, the polysome association of transcripts showed a normal distribution from repressed to activated mRNAs when comparing expanding and expanded leaves. In addition, functional category analysis of the microarray data suggested that translational control has a physiological significance in the plant growth and development process, especially in the categories of signaling and protein synthesis. In addition to this, we compared changes in polysome association of mRNAs between various conditions and characterized translational controls in each. This result suggested that mRNA translation might be controlled by complicated mechanisms for response to each condition. Our results highlight the importance of dynamic changes in mRNA translation in plant development and growth. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Microenvironmental autophagy promotes tumour growth.
Katheder, Nadja S; Khezri, Rojyar; O'Farrell, Fergal; Schultz, Sebastian W; Jain, Ashish; Rahman, Mohammed M; Schink, Kay O; Theodossiou, Theodossis A; Johansen, Terje; Juhász, Gábor; Bilder, David; Brech, Andreas; Stenmark, Harald; Rusten, Tor Erik
2017-01-19
As malignant tumours develop, they interact intimately with their microenvironment and can activate autophagy, a catabolic process which provides nutrients during starvation. How tumours regulate autophagy in vivo and whether autophagy affects tumour growth is controversial. Here we demonstrate, using a well characterized Drosophila melanogaster malignant tumour model, that non-cell-autonomous autophagy is induced both in the tumour microenvironment and systemically in distant tissues. Tumour growth can be pharmacologically restrained using autophagy inhibitors, and early-stage tumour growth and invasion are genetically dependent on autophagy within the local tumour microenvironment. Induction of autophagy is mediated by Drosophila tumour necrosis factor and interleukin-6-like signalling from metabolically stressed tumour cells, whereas tumour growth depends on active amino acid transport. We show that dormant growth-impaired tumours from autophagy-deficient animals reactivate tumorous growth when transplanted into autophagy-proficient hosts. We conclude that transformed cells engage surrounding normal cells as active and essential microenvironmental contributors to early tumour growth through nutrient-generating autophagy.
Tumor-homing peptides as tools for targeted delivery of payloads to the placenta
King, Anna; Ndifon, Cornelia; Lui, Sylvia; Widdows, Kate; Kotamraju, Venkata R.; Agemy, Lilach; Teesalu, Tambet; Glazier, Jocelyn D.; Cellesi, Francesco; Tirelli, Nicola; Aplin, John D.; Ruoslahti, Erkki; Harris, Lynda K.
2016-01-01
The availability of therapeutics to treat pregnancy complications is severely lacking mainly because of the risk of causing harm to the fetus. As enhancement of placental growth and function can alleviate maternal symptoms and improve fetal growth in animal models, we have developed a method for targeted delivery of payloads to the placenta. We show that the tumor-homing peptide sequences CGKRK and iRGD bind selectively to the placental surface of humans and mice and do not interfere with normal development. Peptide-coated nanoparticles intravenously injected into pregnant mice accumulated within the mouse placenta, whereas control nanoparticles exhibited reduced binding and/or fetal transfer. We used targeted liposomes to efficiently deliver cargoes of carboxyfluorescein and insulin-like growth factor 2 to the mouse placenta; the latter significantly increased mean placental weight when administered to healthy animals and significantly improved fetal weight distribution in a well-characterized model of fetal growth restriction. These data provide proof of principle for targeted delivery of drugs to the placenta and provide a novel platform for the development of placenta-specific therapeutics. PMID:27386551
It takes a tissue to make a tumor: Epigenetics, cancer and the microenvironment
DOE Office of Scientific and Technical Information (OSTI.GOV)
Barcellos-Hoff, Mary Helen
How do normal tissues limit the development of cancer? This review discusses the evidence that normal cells effectively restrict malignant behavior, and that such tissue forces must be subjugated to establish a tumor. The action of ionizing radiation will be specifically discussed regarding the disruption of the microenvironment that promotes the transition from preneoplastic to neoplastic growth. Unlike the highly unpredictable nature of genetic mutations, the response of normal cells to radiation damage follows an epigenetic program similar to wound healing and other damage responses. Our hypothesis is that the persistent disruption of the microenvironment in irradiated tissue compromises itsmore » ability to suppress carcinogenesis.« less
Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim
2008-06-27
There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.
Cross-sectional growth changes in skeletal and soft tissue cephalometric landmarks of children.
Inada, Emi; Saitoh, Issei; Hayasaki, Haruaki; Yamada, Chiaki; Iwase, Yoko; Takemoto, Yoshihiko; Matsumoto, Yuko; Yamasaki, Youichi
2008-07-01
In order to provide standard values for craniofacial growth of normal children, we evaluated the growth changes of skeletal and soft tissue cephalometric landmarks from lateral cephalograms of 180 Japanese children. They were divided into three groups: primary dentition, mixed dentition, and permanent dentition. Specific skeletal angles and distances showed significant gender differences with increasing age. The only significant soft tissue gender difference was nose height in the oldest group. Upper pharynx dimension and nose height differed significantly among the groups in both genders. Positions of both the upper and lower lip changed significantly between the intermediate and oldest groups of both genders. Nasolabial angle did not change significantly with growth. The results of this study should be useful for predicting craniofacial growth and development or determining the effect of orthodontic treatment.
A study on causes and types of abnormal increase in infants' head circumference in kashan/iran.
Talebian, Ahmad; Soltani, Babak; Moravveji, Alireza; Salamati, Ladan; Davami, Majid
2013-01-01
Head circumference is a valuable index of brain growth and its disturbances can indicate different disorders of nervous system. Abnormal increased head circumference (macrocephaly) is common and observed in about 2% of infants. In this study, the causes and clinical types of abnormal increase in infants' head circumference were investigated in Kashan, Iran. This cross-sectional study was performed on 90 infants less than 2 years of age with abnormal increase in head circumference in Kashan, during 2009- 2011. The data were collected by history taking, physical examination, growth chart, and imaging. 65 (72%) cases out of 90 infants were male and 25 ( 28%) cases were female. Fifty-three (58.8%) cases had familial megalencephaly, 30 (33.4%) had hydrocephalus, and other causes were observed in 7 (7.8%) cases. Eighty-three percent of Infants with familial megalencephaly and 50% with hydrocephalus had normal fontanels. In 90.6% of cases with familial megalencephaly, family history for large head was positive. Motor development was normal in 100% of cases with familial megalencephaly and 76.7% of hydrocephalic infants. Familial megalencephaly was the most common cause of macrocephaly in the studied infants, and most of them had normal physical examination and development, so, parental head circumferences should be considered in the interpretation of infant's head circumference and in cases of abnormal physical examination or development, other diagnostic modalities, including brain imaging should be done.
Trajectory and correlates of growth of extremely-low-birth-weight adolescents.
Hack, Maureen; Schluchter, Mark; Margevicius, Seunghee; Andreias, Laura; Taylor, H Gerry; Cuttler, Leona
2014-02-01
Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch up among extremely-low-birth-weight (ELBW) (<1 kg) adolescents. A cohort study of 148 neurologically normal ELBW children and 115 normal-birth-weight (NBW) controls born during the period 1992-1995 was conducted. Longitudinal measures of gender-specific growth of ELBW children from birth, in addition to growth and measures of obesity of ELBW and NBW children at 14 y, were evaluated. Following neonatal growth failure, ELBW children had accelerated growth, but at 8 y, they still had lower weight and height z scores than NBW children. By 14 y, ELBW boys had caught up in growth to their NBW controls, but ELBW girls remained significantly smaller. ELBW children, however, did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses, only maternal BMI and weight gain during infancy and childhood predicted the ELBW children's 14-y weight z scores, BMI z scores, and abdominal circumference. Perinatal risk factors, including intrauterine growth, only predicted growth up to 20 mo. Maternal BMI and rate of growth, rather than perinatal factors, predict 14-y obesity among neurologically normal ELBW adolescents.
Long-wave theory for a new convective instability with exponential growth normal to the wall.
Healey, J J
2005-05-15
A linear stability theory is presented for the boundary-layer flow produced by an infinite disc rotating at constant angular velocity in otherwise undisturbed fluid. The theory is developed in the limit of long waves and when the effects of viscosity on the waves can be neglected. This is the parameter regime recently identified by the author in a numerical stability investigation where a curious new type of instability was found in which disturbances propagate and grow exponentially in the direction normal to the disc, (i.e. the growth takes place in a region of zero mean shear). The theory describes the mechanisms controlling the instability, the role and location of critical points, and presents a saddle-point analysis describing the large-time evolution of a wave packet in frames of reference moving normal to the disc. The theory also shows that the previously obtained numerical solutions for numerically large wavelengths do indeed lie in the asymptotic long-wave regime, and so the behaviour and mechanisms described here may apply to a number of cross-flow instability problems.
Crowe, Andrew; Jackaman, Connie; Beddoes, Katie M.; Ricciardo, Belinda; Nelson, Delia J.
2013-01-01
Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes. PMID:24013775
Abnormal Weight and Body Mass Index in Children with Juvenile Huntington's Disease.
Tereshchenko, Alexander; McHugh, Michael; Lee, Jessica K; Gonzalez-Alegre, Pedro; Crane, Kaitlin; Dawson, Jeffrey; Nopoulos, Peg
2015-01-01
The hallmark clinical manifestation of Huntington's disease (HD), namely lower weight and BMI has been reported in prodromal HD (PreHD) adults and also in PreHD children. Here, we aim to evaluate anthropometric measures of growth and development (height, weight, body mass index (BMI)) in a group of children, adolescents, and young adults diagnosed with Juvenile Onset Huntington's Disease (JHD). Growth measures for 18 JHD patients, documented prior to or shortly after diagnosis, were obtained through medical records. JHD growth measures were compared to a large sample (n = 274) of healthy children, as well as the Center for Disease Control (CDC) growth norms. After controlling for sex and age, the JHD subjects had no significant differences in height. However, they were an average of 10% lower than controls in weight and BMI. Using CDC norms, the JHD subjects had the same pattern of normal height but decrement in weight. Length of cytosine-adenine-guanine (CAG) repeat in the huntingtin gene was significantly correlated to measures of weight with longer CAG repeats being associated with more severe weight reduction. A subset of 4 subjects had measures that pre-dated onset of any symptom and were therefore prodromal JHD (preJHD). These subjects also had a significant decrement in BMI compared to CDC norms. Children with JHD have normal height, but significantly reduced weight and BMI, indicative of a specific deficit in body weight. As the preJHD subjects were also low in BMI, this suggests that these changes are directly due to the effect of the mutated gene on development, rather than symptom manifestation of the disease itself. Potential mechanisms of the weight decrement include energy deficiency due to mitochondrial dysfunction during development.
Body mass status of school children of Dera Ismail Khan, Pakistan.
Ramzan, Muhammad; Ali, Irshad; Khan, Abdus Salam
2008-01-01
Childhood obesity is a global epidemic involving both developed and developing countries. It is a stare of over-nutrition with long-term complications such as dyslipidemia, hypertension, and coronary artery disease and type-2 diabetes. Underweight is the result of under nutrition leading to reduction in growth and development of every body organ especially the Central Nervous System. Long-term under-nutrition causes failure in linear growth (height) of the child. Growth is further retarded by the repeated attacks of respiratory infections, diarrhea and anemia as a result of reduced immunity. This study was carried, out eight primary schools of Dera Ismail Khan (Private, semi government organizations, and welfare foundations) having mixed population with some of the wards belonging to high socioeconomic group. Thorough clinical examination excluded those suffering from chronic heath problems. Height and weight of each one was taken body mass index of determined according to 'Quatelet's' index. Body mass index number was plotted on the CDC S age and gender specific growth charts 2-20 years for BMI-for age percentile and body mass status (underweight, normal weight, overweight/at the risk of overweight and obese/overweight. Total 1338 school going children (6-11 years) were examined with 865 (67.75%) boys and 471 (35.25%) as girls. 13.39%, 72.15%, 8.83% and 5.61% as underweight, normal weight, overweight and obese respectively. Percentage of underweight was higher in girls (25%) than boys (13.22). Percentage of obesity was higher (5.17%) in boys than girls (1.39%). Awareness about balanced diet, improvement in the level of education and socioeconomic conditions, easy access to health facilities and prevention of the gender discrimination, are the remedial measures to be taken to redress the situation.
Ikenoue, T; Ikeda, T; Ibara, S; Otake, M; Schull, W J
1993-01-01
We performed two studies to investigate environmental factors in relation to neurological development in infants. The first, a field study, examined the elementary school performance of 929 children who were born from mothers exposed to the atomic bombing of Hiroshima, Japan, August 6, 1945. The most severe mental retardation was observed in the group exposed between 8 and 15 weeks following fertilization, and the second most severely damaged group was exposed between 16 and 25 weeks. The second, a clinical investigation, examined infants in the perinatal center who survived intrauterine growth retardation (IUGR). Those who survived with abnormal neurological development had a mean growth arrest corresponding to a uterine height of 27 weeks of gestation. This was at an earlier stage than those who survived with normal neurological development and had a mean growth arrest corresponding to 29-30 weeks of gestation. A smaller head circumference at birth was closely correlated with abnormal neurological sequelae. These results indicate that the brain development of the fetuses may have been affected by neurotoxic events similar to ionizing radiation. We emphasize the importance of avoiding neurotoxic stress to pregnant women when the fetus is in the critical period of neuronal development, before 27 weeks of gestational age. PMID:8243407
Kleinberg, David L.; Wood, Teresa L.; Furth, Priscilla A.; Lee, Adrian V.
2009-01-01
Adult female mammary development starts at puberty and is controlled by tightly regulated cross-talk between a group of hormones and growth factors. Although estrogen is the initial driving force and is joined by luteal phase progesterone, both of these hormones require GH-induced IGF-I in the mammary gland in order to act. The same group of hormones, when experimentally perturbed, can lead to development of hyperplastic lesions and increase the chances, or be precursors, of mammary carcinoma. For example, systemic administration of GH or IGF-I causes mammary hyperplasia, and overproduction of IGF-I in transgenic animals can cause the development of usual or atypical hyperplasias and sometimes carcinoma. Although studies have clearly demonstrated the transforming potential of both GH and IGF-I receptor in cell culture and in animals, debate remains as to whether their main role is actually instructive or permissive in progression to cancer in vivo. Genetic imprinting has been shown to occur in precursor lesions as early as atypical hyperplasia in women. Thus, the concept of progression from normal development to cancer through precursor lesions sensitive to hormones and growth factors discussed above is gaining support in humans as well as in animal models. Indeed, elevation of estrogen receptor, GH, IGF-I, and IGF-I receptor during progression suggests a role for these pathways in this process. New agents targeting the GH/IGF-I axis may provide a novel means to block formation and progression of precursor lesions to overt carcinoma. A novel somatostatin analog has recently been shown to prevent mammary development in rats via targeted IGF-I action inhibition at the mammary gland. Similarly, pegvisomant, a GH antagonist, and other IGF-I antagonists such as IGF binding proteins 1 and 5 also block mammary gland development. It is, therefore, possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations. PMID:19075184
Kim, Dae Won; Jeon, Su Jeong; Hwang, Sung Min; Hong, Jong Chan; Bahk, Jeong Dong
2016-09-01
Eukaryotic C3H-type zinc finger proteins (Znfs) comprise a large family of regulatory proteins involved in many aspects of plant stress response, growth and development. However, compared to mammalian, only a few plant Znfs have been functionally characterized. Here, T-DNA inserted gds1 (growth, development and splicing 1) mutant, displayed abnormal growth throughout the lifecycle owing to the reduction of cell size and number. Inverse PCR analysis revealed that the abnormal growth was caused by the disruption of At3g47120, which encodes a C3H42 protein belonging to the C-X7-C-X5-C-X3-H class of the Znf family. GDS1 was ubiquitously transcribed, but shows high levels of expression in young seedling and unexpanded new leaves. In gds1, the transcripts of many growth- and development-related genes were down-regulated, and the auxin response was dramatically reduced. A fluorescence-based assay revealed that the GDS1 protein was localized to the nucleus, prominently in the speckle compartments. Its arginine/serine dipeptide-rich-like (RS-like) domain was essential for nuclear localization. In addition, the SR1, SRm102 and U1-70K components of the U1 spliceosome interacted with GDS1 in the nuclear speckle compartments. Taken together, these suggest that GDS1, a nuclear-speckle-associated Znf, might play a significant role in splicing during plant growth and development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Tosti, Elisabetta; Gallo, Alessandra; Silvestre, Francesco
2011-01-01
Electrophysiological techniques were used to study the role of ion currents in the ascidian Ciona intestinalis oocyte plasma membrane during different stages of growth, meiosis, fertilization and early development. Three stages of immature oocytes were discriminated in the ovary, with the germinal vesicle showing specific different features of growth and maturation. Stage-A (pre-vitellogenic) oocytes exhibited the highest L-type calcium current activity and were incompetent for meiosis resumption. Stage-B (vitellogenic) oocytes showed a progressive disappearance of calcium currents and the first appearance of sodium currents that remained high during the maturation process, up to the post-vitellogenic stage-C oocytes. The latter had acquired meiotic competence, undergoing spontaneous in vitro maturation and interacting with the spermatozoon. However, fertilized oocytes did not produce normal larvae, suggesting that cytoplasmic maturation may affect embryo development. In mature oocytes at the metaphase I stage, sodium currents were present and remained high up to the zygote stage. Oocytes fertilized in the absence of sodium showed significant reduction of the fertilization current amplitude and high development of anomalous "rosette" embryos. Current amplitudes became negligible in embryos at the 2- and 4-cell stage, whereas resumption of all the current activities occurred at the 8-cell embryo. Taken together, these results suggest: (i) an involvement of L-type calcium currents in initial oocyte meiotic progression and growth; (ii) a role of sodium currents at fertilization; (iii) a role of the fertilization current in ensuring normal embryo development. Copyright © 2011 Wiley Periodicals, Inc.
Is Greulich and Pyle atlas still a good reference for bone age assessment?
NASA Astrophysics Data System (ADS)
Zhang, Aifeng; Tsao, Sinchai; Sayre, James W.; Gertych, Arkadiusz; Liu, Brent J.; Huang, H. K.
2007-03-01
The most commonly used method for bone age assessment in clinical practice is the book atlas matching method developed by Greulich and Pyle in the 1950s. Due to changes in both population diversity and nutrition in the United States, this atlas may no longer be a good reference. An updated data set becomes crucial to improve the bone age assessment process. Therefore, a digital hand atlas was built with 1,100 children hand images, along with patient information and radiologists' readings, of normal Caucasian (CAU), African American (BLK), Hispanic (HIS), and Asian (ASI) males (M) and females (F) with ages ranging from 0 - 18 years. This data was collected from Childrens' Hospital Los Angeles. A computer-aided-diagnosis (CAD) method has been developed based on features extracted from phalangeal regions of interest (ROIs) and carpal bone ROIs from this digital hand atlas. Using the data collected along with the Greulich and Pyle Atlas-based readings and CAD results, this paper addresses this question: "Do different ethnicities and gender have different bone growth patterns?" To help with data analysis, a novel web-based visualization tool was developed to demonstrate bone growth diversity amongst differing gender and ethnic groups using data collected from the Digital Atlas. The application effectively demonstrates a discrepancy of bone growth pattern amongst different populations based on race and gender. It also has the capability of helping a radiologist determine the normality of skeletal development of a particular patient by visualizing his or her chronological age, radiologist reading, and CAD assessed bone age relative to the accuracy of the P&G method.
Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.
McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C
2016-05-12
Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).
Short stature in carriers of recessive mutation causing familial isolated growth hormone deficiency.
Leiberman, E; Pesler, D; Parvari, R; Elbedour, K; Abdul-Latif, H; Brown, M R; Parks, J S; Carmi, R
2000-01-31
Isolated growth hormone deficiency (IGHD) IB is an autosomal recessive disorder characterized by a good response to exogenous growth hormone (GH) treatment without development of anti-GH antibodies. Patients with IGHD IB were found to be compound heterozygotes for deletion and frameshift mutations as well as homozygotes for splicing mutations in the GH-1 gene. Recently, a novel splicing mutation in the GH-1 gene was identified in an extended, consanguineous Arab-Bedouin family from Israel with IGHD IB. Prior to the identification of this mutation, a considerable number of children with short stature in this family were found normal on pharmacological stimulation for GH release. This observation prompted a genotype/phenotype correlation of potential heterozygotes in the family. Carriers of the mutant GH-1 allele were found as a group to have a significantly shorter stature than normal homozygote (mean standard deviation scores, 1.67 and -0.40, respectively, P<0.05). Moreover, 11 of 33 (33%) heterozygotes, but only 1 of 17 (5.9%) normal homozygotes, had their height at 2 or more SD below the mean. Overall, 48.5% of studied heterozygotes were found to be of appreciably short stature with height at or lower than the 5th centile (> or = -1.7 SD), whereas only 5.9% of the normal homozygotes did (P<0.004). This phenomenon of heterozygotes for a recessive mutation in the GH-1 gene manifesting short stature, might imply that some such mutations may account for non-GH deficiency reduced height in the general population.
Traeger, Stefanie; Nowrousian, Minou
2015-04-14
During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. Copyright © 2015 Traeger and Nowrousian.
Traeger, Stefanie; Nowrousian, Minou
2015-01-01
During sexual development, filamentous ascomycetes form complex, three-dimensional fruiting bodies for the generation and dispersal of spores. In previous studies, we identified genes with evolutionary conserved expression patterns during fruiting body formation in several fungal species. Here, we present the functional analysis of two developmentally up-regulated genes, chs7 and sec22, in the ascomycete Sordaria macrospora. The genes encode a class VII (division III) chitin synthase and a soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) protein, respectively. Deletion mutants of chs7 had normal vegetative growth and were fully fertile but showed sensitivity toward cell wall stress. Deletion of sec22 resulted in a reduced number of ascospores and in defects in ascospore pigmentation and germination, whereas vegetative growth was normal in the mutant. A SEC22-EGFP fusion construct under control of the native sec22 promoter and terminator regions was expressed during different stages of sexual development. Expression of several development-related genes was deregulated in the sec22 mutant, including three genes involved in melanin biosynthesis. Our data indicate that chs7 is dispensable for fruiting body formation in S. macrospora, whereas sec22 is required for ascospore maturation and germination and thus involved in late stages of sexual development. PMID:25873638
Dixit, A; Govil, S; Patel, N V
1992-03-01
In this cross sectional study, 2000 apparently normal children aged 0-6 years (1200 urban and 800 rural), were nutritionally and developmentally assessed and their environment scrutinized for possible risk factors. Measurement of mid upper arm circumference (MUAC) using standard techniques revealed malnutrition in 44% of the rural and 24% of the urban children especially in the 2-6 years of age group. Culture appropriate indicators of psycho-social development picked up gross delays in gross motor (GM), vision and fine motor (V&FM) and language skills. Self help, concept hearing (SHCH) skills were recorded as normal while social skills were advanced particularly in the 0-2 years old urban group. By the use of the family protocols, low socio-economic status, malnutrition and 9 other risks factors have been generated for the urban group. No risk factor could be identified for the rural group. Better income emerged as the only real protective factor for the sample showing a direct positive relationship with the 45 skills tested, especially in the 2-6 years age group. Nineteen developmental skills were identified as powerful predictors of development. A prototype home based screening record was constructed for monitoring of growth and development which can be even used by minimally trained primary care worker.
Matrix Disruptions, Growth, and Degradation of Cartilage with Impaired Sulfation*
Mertz, Edward L.; Facchini, Marcella; Pham, Anna T.; Gualeni, Benedetta; De Leonardis, Fabio; Rossi, Antonio; Forlino, Antonella
2012-01-01
Diastrophic dysplasia (DTD) is an incurable recessive chondrodysplasia caused by mutations in the SLC26A2 transporter responsible for sulfate uptake by chondrocytes. The mutations cause undersulfation of glycosaminoglycans in cartilage. Studies of dtd mice with a knock-in Slc26a2 mutation showed an unusual progression of the disorder: net undersulfation is mild and normalizing with age, but the articular cartilage degrades with age and bones develop abnormally. To understand underlying mechanisms, we studied newborn dtd mice. We developed, verified and used high-definition infrared hyperspectral imaging of cartilage sections at physiological conditions, to quantify collagen and its orientation, noncollagenous proteins, and chondroitin chains, and their sulfation with 6-μm spatial resolution and without labeling. We found that chondroitin sulfation across the proximal femur cartilage varied dramatically in dtd, but not in the wild type. Corresponding undersulfation of dtd was mild in most regions, but strong in narrow articular and growth plate regions crucial for bone development. This undersulfation correlated with the chondroitin synthesis rate measured via radioactive sulfate incorporation, explaining the sulfation normalization with age. Collagen orientation was reduced, and the reduction correlated with chondroitin undersulfation. Such disorientation involved the layer of collagen covering the articular surface and protecting cartilage from degradation. Malformation of this layer may contribute to the degradation progression with age and to collagen and proteoglycan depletion from the articular region, which we observed in mice already at birth. The results provide clues to in vivo sulfation, DTD treatment, and cartilage growth. PMID:22556422
Luo, Wen; Lin, Shumao; Li, Guihuan; Nie, Qinghua; Zhang, Xiquan
2016-01-01
The sex-linked dwarf (SLD) chicken is an ideal model system for understanding growth hormone (GH)-action and growth hormone receptor (GHR) function because of its recessive mutation in the GHR gene. Skeletal muscle mass is reduced in the SLD chicken with a smaller muscle fiber diameter. Our previous study has presented the mRNA and miRNA expression profiles of the SLD chicken and normal chicken between embryo day 14 and seven weeks of age. However, the molecular mechanism of GHR-deficient induced muscle mass loss is still unclear, and the key molecules and pathways underlying the GHR-deficient induced muscle mass loss also remain to be illustrated. Here, by functional network analysis of the differentially expressed miRNAs and mRNAs between the SLD and normal chickens, we revealed that let-7b, miR-128 and the MAPK pathway might play key roles in the GHR-deficient induced muscle mass loss, and that the reduced cell division and growth are potential cellular processes during the SLD chicken skeletal muscle development. Additionally, we also found some genes and miRNAs involved in chicken skeletal muscle development, through the MAPK, PI3K-Akt, Wnt and Insulin signaling pathways. This study provides new insights into the molecular mechanism underlying muscle mass loss in the SLD chickens, and some regulatory networks that are crucial for chicken skeletal muscle development. PMID:26927061
Song, Weian; Li, Hui; Wang, Huasheng; Zhang, Weidong; Zhao, Xiaogang
2004-02-20
To study the relationship between the vascular endothelial growth factor (VEGF) and the clinicopathological characteristics of the patients with pulmonary bronchoalveolar carcinoma, and to research the possible role of VEGF in the malignant growth of pulmonary bronchoalveolar carcinoma. The expression of VEGF and MVD were detected in 38 pulmonary bronchoalveolar carcinoma and 20 normal lung tissues by immunohistochemical method. The positive rate of VEGF expression (73.68%,28/38) and MVD (63.81±19.26) in pulmonary bronchoalveolar carcinoma tissues were both remarkably higher than those in normal lung tissues (0, 18.44±6.53)( P < 0.005,P < 0.001). The positive rate of VEGF expression was significantly related to the size of tumor ( P < 0.05), lymphatic metastasis ( P < 0.025) and TNM stage ( P < 0.05), and so did the MVD ( P < 0.05, P < 0.05, P < 0.05). MVD was remarkably higher in VEGF (+) carcinoma tissues than that in VEGF (-) carcinoma tissues ( P < 0.05). VEGF correlates with the clinicopathological characteristics of pulmonary bronchoalveolar carcinoma. It may play an important role in the development of pulmonary bronchoalveolar carcinoma.
Reh, Christina Southern; Geffner, Mitchell E
2010-01-01
Growth hormone (GH), also known as somatotropin, is a peptide hormone that is synthesized and secreted by the somatotrophs of the anterior pituitary gland. The main action of GH is to stimulate linear growth in children; however, it also fosters a healthy body composition by increasing muscle and reducing fat mass, maintains normal blood glucose levels, and promotes a favorable lipid profile. This article provides an overview of the normal pathophysiology of GH production and action. We discuss the history of GH therapy and the development of the current formulation of recombinant human GH given as daily subcutaneous injections. This paper reviews two of the longest standing FDA-approved indications for GH treatment, GH deficiency and Turner syndrome. We will highlight the pathogenesis of these disorders, including presentations, presumed mechanism(s) for the associated short stature, and diagnostic criteria, with a review of stimulation test benefits and pitfalls. This review also includes current recommendations for GH therapy to help maximize final height in these children, as well as data demonstrating the efficacy and safety of GH treatment in these populations. PMID:22291494
Phukoetphim, Niphaphat; Salakkam, Apilak; Laopaiboon, Pattana; Laopaiboon, Lakkana
2017-02-10
The aim of this study was to model batch ethanol production from sweet sorghum juice (SSJ), under normal gravity (NG, 160g/L of total sugar) and high gravity (HG, 240g/L of total sugar) conditions with and without nutrient supplementation (9g/L of yeast extract), by Saccharomyces cerevisiae NP 01. Growth and ethanol production increased with increasing initial sugar concentration, and the addition of yeast extract enhanced both cell growth and ethanol production. From the results, either logistic or a modified Gompertz equation could be used to describe yeast growth, depending on information required. Furthermore, the modified Gompertz model was suitable for modeling ethanol production. Both the models fitted the data very well with coefficients of determination exceeding 0.98. The results clearly showed that these models can be employed in the development of ethanol production processes using SSJ under both NG and HG conditions. The models were also shown to be applicable to other ethanol fermentation systems employing pure and mixed sugars as carbon sources. Copyright © 2016 Elsevier B.V. All rights reserved.
Khosla, S; Dean, W; Brown, D; Reik, W; Feil, R
2001-03-01
Culture of preimplantation mammalian embryos and cells can influence their subsequent growth and differentiation. Previously, we reported that culture of mouse embryonic stem cells is associated with deregulation of genomic imprinting and affects the potential for these cells to develop into normal fetuses. The purpose of our current study was to determine whether culture of preimplantation mouse embryos in a chemically defined medium (M16) with or without fetal calf serum (FCS) can affect their subsequent development and imprinted gene expression. Only one third of the blastocysts that had been cultured from two-cell embryos in M16 medium complemented with FCS developed into viable Day 14 fetuses after transfer into recipients. These M16 + FCS fetuses were reduced in weight as compared with controls and M16 fetuses and had decreased expression of the imprinted H19 and insulin-like growth factor 2 genes associated with a gain of DNA methylation at an imprinting control region upstream of H19. They also displayed increased expression of the imprinted gene Grb10. The growth factor receptor binding gene Grb7, in contrast, was strongly reduced in its expression in most of the M16 + FCS fetuses. No alterations were detected for the imprinted gene MEST: Preimplantation culture in the presence of serum can influence the regulation of multiple growth-related imprinted genes, thus leading to aberrant fetal growth and development.
Zheng, Xiaofen; De Paiva, Cintia S; Rao, Kavita; Li, De-Quan; Farley, William J; Stern, Michael; Pflugfelder, Stephen C
2010-09-01
To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye. Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay. The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P < 0.05). Among patients with DE, TGF-beta bioactivity was highest in those with Sjögren syndrome. Approximately, 79.1% of TGF-beta in DE tears and 37.6% TGF-beta in normal tears were found to be biologically active. The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where elevated levels of TGF-beta1 transcripts in the conjunctival epithelium have been previously detected.
Spake, Laure; Cardoso, Hugo F V
2018-01-01
The population on which forensic juvenile skeletal age estimation methods are applied has not been critically considered. Previous research suggests that child victims of homicide tend to be from socioeconomically disadvantaged contexts, and that these contexts impair linear growth. This study investigates whether juvenile skeletal remains examined by forensic anthropologists are short for age compared to their normal healthy peers. Cadaver lengths were obtained from records of autopsies of 1256 individuals, aged birth to eighteen years at death, conducted between 2000 and 2015 in Australia, New Zealand, and the U.S. Growth status of the forensic population, represented by homicide victims, and general population, represented by accident victims, were compared using height for age Z-scores and independent sample t-tests. Cadaver lengths of the accident victims were compared to growth references using one sample t-tests to evaluate whether accident victims reflect the general population. Homicide victims are shorter for age than accident victims in samples from the U.S., but not in Australia and New Zealand. Accident victims are more representative of the general population in Australia and New Zealand. Different results in Australia and New Zealand as opposed to the U.S. may be linked to socioeconomic inequality. These results suggest that physical anthropologists should critically select reference samples when devising forensic juvenile skeletal age estimation methods. Children examined in forensic investigations may be short for age, and thus methods developed on normal healthy children may yield inaccurate results. A healthy reference population may not necessarily constitute an appropriate growth comparison for the forensic anthropology population. Copyright © 2017 Elsevier B.V. All rights reserved.
Manganese (Mn) is ubiquitous in the environment and essential for normal growth and development, yet excessive exposure can lead to impairments in neurological function. This study modeled ambient Mn concentrations as an alternative to stationary and personal air sampling to asse...
Do vulnerable populations consume adequate amounts of dietary protein?
USDA-ARS?s Scientific Manuscript database
In the previous year there has been a renewed interest in the adequacy of protein intake to maintain optimal health and to promote normal growth and development (1, 2). In this issue of the Journal there is an excellent report on protein consumption among children aged 6–36 mo from low-income countr...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-04
... revision may be warranted, in part because in our judgment specific qualities were required to explain how... Rico. (iii) Water quality to support normal growth, reproduction, development, viability, and health... areas, rather than on any specific qualities of the physical and biological features of the habitat...
Hori, Katsuyoshi; Nishihara, Masamichi; Yokoyama, Masayuki
2010-01-01
Particles larger than a specific size have been thought to extravasate from tumor vessels but not from normal vessels. Therefore, various nanoparticles incorporating anticancer drugs have been developed to realize selective drug delivery to solid tumors. However, it is not yet clear whether nanoparticles extravasate readily from all tumor vessels including vessels of microtumors. To answer this question, we synthesized new polymeric micelles labeled with fluorescein isothiocyanate (FITC) and injected them into the tail vein of rats with implanted skinfold transparent chambers. We also analyzed, by means of time-lapse vital microscopy with image analysis, extravasation of FITC micelles from tumor vessels at different stages of growth of Yoshida ascites sarcoma LY80. Polymeric micelles readily leaked from vessels at the interface between normal and tumor tissues and those at the interface between tumor tissues and necrotic areas. The micelles showed negligible extravasation, however, from the vascular network of microtumors less than 1 mm in diameter and did not accumulate in the microtumor. Our results suggest that we must develop a novel therapeutic strategy that can deliver sufficient nanomedicine to microtumors.
NASA Technical Reports Server (NTRS)
Kern, Volker D.; Schwuchow, Jochen M.; Reed, David W.; Nadeau, Jeanette A.; Lucas, Jessica; Skripnikov, Alexander; Sack, Fred D.
2005-01-01
In addition to shoots and roots, the gravity (g)-vector orients the growth of specialized cells such as the apical cell of dark-grown moss protonemata. Each apical cell of the moss Ceratodon purpureus senses the g-vector and adjusts polar growth accordingly producing entire cultures of upright protonemata (negative gravitropism). The effect of withdrawing a constant gravity stimulus on moss growth was studied on two NASA Space Shuttle (STS) missions as well as during clinostat rotation on earth. Cultures grown in microgravity (spaceflight) on the STS-87 mission exhibited two successive phases of non-random growth and patterning, a radial outgrowth followed by the formation of net clockwise spiral growth. Also, cultures pre-aligned by unilateral light developed clockwise hooks during the subsequent dark period. The second spaceflight experiment flew on STS-107 which disintegrated during its descent on 1 February 2003. However, most of the moss experimental hardware was recovered on the ground, and most cultures, which had been chemically fixed during spaceflight, were retrieved. Almost all intact STS-107 cultures displayed strong spiral growth. Non-random culture growth including clockwise spiral growth was also observed after clinostat rotation. Together these data demonstrate the existence of default non-random growth patterns that develop at a population level in microgravity, a response that must normally be overridden and masked by a constant g-vector on earth.
Physically Based Failure Criteria for Transverse Matrix Cracking
NASA Technical Reports Server (NTRS)
Davila, Carlos G.; Camanho, Pedro P.
2003-01-01
A criterion for matrix failure of laminated composite plies in transverse tension and in-plane shear is developed by examining the mechanics of transverse matrix crack growth. Matrix cracks are assumed to initiate from manufacturing defects and can propagate within planes parallel to the fiber direction and normal to the ply mid-plane. Fracture mechanics models of cracks in unidirectional laminates, embedded plies and outer plies are developed to determine the onset and direction of propagation for unstable crack growth. The models for each ply configuration relate ply thickness and ply toughness to the corresponding in-situ ply strength. Calculated results for several materials are shown to correlate well with experimental results.
Molecular genetics of craniosynostosis
NASA Astrophysics Data System (ADS)
Caterine; Auerkari, Elza Ibrahim
2018-03-01
Tight regulation process and complex interplay occur along the osteogenic interfaces of the cranial sutures in normal growth and development of the skull. Cranial sutures serve as sites of bone growth while maintaining a state of patency to accommodate the developing brain. Cranial sutures are fibro-cellular structures that separate the rigid plates of the skull bones. Premature fusion of one or more cranial sutures leads to a condition known as craniosynostosis. Craniosynostosis is one of the most common craniofacial anomalies with a prevalence of 1 in 2,500 newborns. Several genes have been identified in the pathogenesis of craniosynostosis. Molecular signaling events and the intracellular signal transduction pathways implicated in the suture pathobiology will provide a useful approach for therapeutic targeting.
Reduction of Defects in Germanium-Silicon
NASA Technical Reports Server (NTRS)
2003-01-01
Crystals grown without contact with a container have far superior quality to otherwise similar crystals grown in direct contact with a container. In addition to float-zone processing, detached- Bridgman growth is a promising tool to improve crystal quality, without the limitations of float zoning or the defects introduced by normal Bridgman growth. Goals of this project include the development of the detached Bridgman process to be reproducible and well understood and to quantitatively compare the defect and impurity levels in crystals grown by these three methods. Germanium (Ge) and germanium-silicon (Ge-Si) alloys are being used. At MSFC, we are responsible for the detached Bridgman experiments intended to differentiate among proposed mechanisms of detachment, and to confirm or refine our understanding of detachment. Because the contact angle is critical to determining the conditions for detachment, the sessile drop method was used to measure the contact angles as a function of temperature and composition for a large number of substrates made of potential ampoule materials. Growth experiments have used pyrolytic boron nitride (pBN) and fused silica ampoules with the majority of the detached results occurring predictably in the pBN. Etch pit density (EPD) measurements of normal and detached Bridgman-grown Ge samples show a two order of magnitude improvement in the detached-grown samples. The nature and extent of detachment is determined by using profilometry in conjunction with optical and electron microscopy. The stability of detachment has been analyzed, and an empirical model for the conditions necessary to achieve sufficient stability to maintain detached growth for extended periods has been developed. We have investigated the effects on detachment of ampoule material, pressure difference above and below the melt, and Si concentration; samples that are nearly completely detached can be grown repeatedly in pBN. Current work is concentrated on developing a method to make in situ pressure measurements in the growth ampoules.
Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew
2016-11-01
The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.
Embryonic development during chronic acceleration
NASA Technical Reports Server (NTRS)
Smith, A. H.; Abbott, U. K.
1982-01-01
Experiments carried out on chicken eggs indicate that the embryo is affected during very early development, especially over the first four days, and during hatching. In the first four days, the brain develops as well as the anlage for all other organs. In addition, the heart commences to function and the extraembryonic membranes that compartmentalize the egg contents form. The latter require an appreciable extension and folding of tissue which may be disrupted by the mechanical load. Observations of embryonic abnormalities that occur during chronic acceleration suggest an inhibition of development of the axial skeleton, which is rarely seen otherwise, a general retardation of embryonic growth, and circulatory problems. The final stages of development (after 18 days) involve the uptake of fluids, the transition to aerial respiration, and the reorientation of the embryo into a normal hatching position. At 4 G mortality is very high during this period, with a majority of embryos failing to reorient into the normal hatching position.
Mammalian oocyte growth and development in vitro.
Eppig, J J; O'Brien, M; Wigglesworth, K
1996-06-01
This paper is a review of the current status of technology for mammalian oocyte growth and development in vitro. It compares and contrasts the characteristics of the various culture systems that have been devised for the culture of either isolated preantral follicles or the oocyte-granulosa cell complexes form preantral follicles. The advantages and disadvantages of these various systems are discussed. Endpoints for the evaluation of oocyte development in vitro, including oocyte maturation and embryogenesis, are described. Considerations for the improvement of the culture systems are also presented. These include discussions of the possible effects of apoptosis and inappropriate differentiation of oocyte-associated granulosa cells on oocyte development. Finally, the potential applications of the technology for oocyte growth and development in vitro are discussed. For example, studies of oocyte development in vitro could help to identify specific molecules produced during oocyte development that are essential for normal early embryogenesis and perhaps recognize defects leading to infertility or abnormalities in embryonic development. Moreover, the culture systems may provide the methods necessary to enlarge the populations of valuable agricultural, pharmaceutical product-producing, and endangered animals, and to rescue the oocytes of women about to undergo clinical procedures that place oocytes at risk.
Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency.
Mazzola, A; Meazza, C; Travaglino, P; Pagani, S; Frattini, D; Bozzola, E; Corneli, G; Aimaretti, G; Bozzola, M
2008-02-01
In this study we investigated 9 prepubertal children with blunted GH response to classic pharmacological stimuli in contrast with normal auxological evaluation. The children were followed to evaluate their growth velocity for a longer period before starting replacement GH therapy. To evaluate the pituitary reserve a supraphysiologic stimulus such as GHRH plus arginine was used. Serum GH levels were measured by a time-resolved immunofluorimetric assay before and after 1 microg/kg body weight iv injection of GHRH, while serum PRL, IGF-I, and insulin were evaluated only in basal conditions using an automatic immunometric assay. Out of 9 studied subjects, 7 underwent GHRH plus arginine administration and showed a normal GH response; the parents of the remaining 2 children refused the test. Normal serum levels of PRL, IGF-I, insulin, and a normal insulin sensitivity were observed in all children. After 1 yr, the growth rate in each patient was further improved and reached almost normal values. Our results further confirm that the decision to start replacement GH therapy should be based on both auxological parameters and laboratory findings. The GHRH plus arginine test appears to be useful to identify false GH deficiency in children showing a blunted GH response to classic stimuli in contrast with normal growth rate.
Bao, Aili; Zhao, Zhuqing; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei
2015-01-01
Glutamine synthetase 2 (GS2) is a key enzyme involved in the ammonium metabolism in plant leaves. In our previous study, we obtained GS2-cosuppressed plants, which displayed a normal growth phenotype at the seedling stage, while at the tillering stage they showed a chlorosis phenotype. In this study, to investigate the chlorosis mechanism, we systematically analyzed the plant growth, carbon-nitrogen metabolism and gene expressions between the GS2-cosuppressed rice and wild-type plants. The results revealed that the GS2-cosuppressed plants exhibited a poor plant growth phenotype and a poor nitrogen transport ability, which led to nitrogen accumulation and a decline in the carbon/nitrogen ratio in the stems. Interestingly, there was a higher concentration of soluble proteins and a lower concentration of carbohydrates in the GS2-cosuppressed plants at the seedling stage, while a contrasting result was displayed at the tillering stage. The analysis of the metabolic profile showed a significant increase of sugars and organic acids. Additionally, gene expression patterns were different in root and leaf of GS2-cosuppressed plants between the seedling and tillering stage. These results indicated the important role of a stable level of GS2 transcription during normal rice development and the importance of the carbon-nitrogen metabolic balance in rice growth. PMID:26053400
Bao, Aili; Zhao, Zhuqing; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei
2015-06-04
Glutamine synthetase 2 (GS2) is a key enzyme involved in the ammonium metabolism in plant leaves. In our previous study, we obtained GS2-cosuppressed plants, which displayed a normal growth phenotype at the seedling stage, while at the tillering stage they showed a chlorosis phenotype. In this study, to investigate the chlorosis mechanism, we systematically analyzed the plant growth, carbon-nitrogen metabolism and gene expressions between the GS2-cosuppressed rice and wild-type plants. The results revealed that the GS2-cosuppressed plants exhibited a poor plant growth phenotype and a poor nitrogen transport ability, which led to nitrogen accumulation and a decline in the carbon/nitrogen ratio in the stems. Interestingly, there was a higher concentration of soluble proteins and a lower concentration of carbohydrates in the GS2-cosuppressed plants at the seedling stage, while a contrasting result was displayed at the tillering stage. The analysis of the metabolic profile showed a significant increase of sugars and organic acids. Additionally, gene expression patterns were different in root and leaf of GS2-cosuppressed plants between the seedling and tillering stage. These results indicated the important role of a stable level of GS2 transcription during normal rice development and the importance of the carbon-nitrogen metabolic balance in rice growth.
Captopril inhibits tumour growth in a xenograft model of human renal cell carcinoma.
Hii, S. I.; Nicol, D. L.; Gotley, D. C.; Thompson, L. C.; Green, M. K.; Jonsson, J. R.
1998-01-01
The effect of captopril on tumour growth was examined in a xenograft model of human renal cell carcinoma (RCC). Inoculation of the human RCC cell line SN12K-1 (10(6) cells) under the left kidney capsule of severe combined immunodeficient (SCID) mice resulted in the growth of large tumours, with an increase in weight of the inoculated kidney of 3.69+/-1.63-fold (mean+/-s.d.) when compared with the contralateral normal kidney. In mice treated with captopril (19 mg kg(-1) day(-1) or 94 mg kg(-1) day(-1) administered in the drinking water), there was a significant dose-related reduction in tumour development; the tumour bearing kidneys weighed 1.9+/-0.42 and 1.55+/-0.42 times the normal kidneys, respectively (P< 0.05 compared with untreated animals). In vitro, captopril at clinically achievable doses (0.1-10 microM) had no significant effect on the incorporation of [3H]thymidine into SN12K-1 cells. Thus, this highly significant attenuation by captopril of in vivo tumour growth does not appear to be due to a direct effect on the proliferation of the tumour cells. Further studies are required to determine the mechanism of inhibition of tumour growth by captopril, in particular to evaluate the role of angiotensin II in this process. Images Figure 1 PMID:9528828
Milne, E; Martinez Pereira, Y; Muir, C; Scase, T; Shaw, D J; McGregor, G; Oldroyd, L; Scurrell, E; Martin, M; Devine, C; Hodgkiss-Geere, H
2018-05-01
To develop a provisional immunohistochemistry panel for distinguishing reactive pericardium, atypical mesothelial proliferation and mesothelioma in dogs. Archived pericardial biopsies were subject to haematoxylin and eosin staining, immunohistochemistry for cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Samples were scored for intensity and number of cells stained. Ten biopsies of reactive mesothelium, 17 of atypical mesothelial proliferation, 26 of mesothelioma and five of normal pericardium were identified on the basis of haematoxylin and eosin staining. Cytokeratin and vimentin were expressed in all biopsies, confirming mesothelial origin. Normal pericardial samples had the lowest scores for insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Mesothelioma and atypical proliferative samples were similar to each other, with higher scores for insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 than the reactive samples. Desmin staining was variable. Insulin-like growth factor II mRNA-binding protein 3 was the best to distinguish between disease groups. An immunohistochemistry panel of cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 could provide superior information compared with haematoxylin and eosin staining alone in the diagnosis of cases of mesothelial proliferation in canine pericardium, but further validation is warranted. © 2018 British Small Animal Veterinary Association.
Kawamura, Kazuhiro; Chen, Yuan; Shu, Yimin; Cheng, Yuan; Qiao, Jie; Behr, Barry; Pera, Renee A Reijo; Hsueh, Aaron J W
2012-01-01
Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility treatment and future derivation of patient-specific embryonic stem cells.
Moia, Stefania; Tessaris, Daniele; Einaudi, Silvia; de Sanctis, Luisa; Bona, Gianni; Bellone, Simonetta; Prodam, Flavia
2017-10-12
Mutations localized in the Growth Hormone Receptor (GHR) gene are often associated with the pathogenesis of Laron Syndrome, an autosomal recessive hereditary disorder characterized by severe growth retardation. Biochemically, patients present normal to high circulating GH levels, in presence of very low or undetectable IGF-I levels, which do not rise after rhGH treatment. We describe the case of a 3.8 years old girl with symmetrical short stature (-3.76 SDS), low IGF-1 and IGFBP-3, in presence of normal GH levels. Parents were not relatives and there was no family history of short stature. During the second day of birth, she developed severe hypoglycaemia that required glucose infusion. She presented frontal bossing and depressed nasal bridge. IGF-1 generation test showed no response, suggesting a GH resistance evidence. In the hypothesis of Laron Syndrome, we decided to perform a molecular analysis of Growth Hormone Receptor (GHR) gene. This analysis demonstrated that the patient was compound heterozygote for two missense mutations. GHR gene mutations are a well demonstrated cause of GH insensitivity. In heterozygous patients, probably the normal stature may be achieved by a compensatory mechanism of GH secretion or signalling. On the contrary, in homozygous or compound heterozygous patients these compensatory mechanisms are inadequate, and short stature may be the consequence.
Investigation of Nucleate Boiling Mechanisms Under Microgravity Conditions
NASA Technical Reports Server (NTRS)
Dhir, V. K.; Qiu, D. M.; Ramanujapu, N.; Hasan, M. M.
1999-01-01
The present work is aimed at the experimental studies and numerical modeling of the bubble growth mechanisms of a single bubble attached to a heating surface and of a bubble sliding along an inclined heated plate. Single artificial cavity of 10 microns in diameter was made on the polished Silicon wafer which was electrically heated at the back side in order to control the surface nucleation superheat. Experiments with a sliding bubble were conducted at different inclination angles of the downward facing heated surface for the purpose of studying the effect of magnitude of components of gravity acting parallel to and normal to the heat transfer surface. Information on the bubble shape and size, the bubble induced liquid velocities as well as the surface temperature were obtained using the high speed imaging and hydrogen bubble techniques. Analytical/numerical models were developed to describe the heat transfer through the micro-macro layer underneath and around a bubble formed at a nucleation site. In the micro layer model the capillary and disjoining pressures were included. Evolution of the bubble-liquid interface along with induced liquid motion was modeled. As a follow-up to the studies at normal gravity, experiments are being conducted in the KC-135 aircraft to understand the bubble growth/detachment under low gravity conditions. Experiments have been defined to be performed under long duration of microgravity conditions in the space shuttle. The experiment in the space shuttle will provide bubble growth and detachment data at microgravity and will lead to validation of the nucleate boiling heat transfer model developed from the preceding studies conducted at normal and low gravity (KC-135) conditions.
Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin; Birkebæk, Niels; Christiansen, Peter; Ellermann, Annie; Holm, Kirsten; Jeppesen, Eva Mosfeldt; Kremke, Britta; Marcinski, Pawel; Pedersen, Carsten; Saurbrey, Nina; Thisted, Ebbe; Main, Katharina M; Juul, Anders
2014-12-01
To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Green, J.E.; Maroulakou, I.G.; Anver, M.
Transgenic mice expressing the SV40 large T-antigen (T{sup AG}) under the regultory control of the hormone-responsive rat C3(1) prostatein promoter develop unusual bone and cartilage lesions, as well as ectopic bone and cartilage formation. Two lines of transgenic animals have been propagated in which the expression of the transgene in chondrocytes results in a mild to moderate generalized disorganization of cartilage growth which appears to affect multiple tissues, including the trachea, ear pinna and articular cartilage. The epiphyseal plates are also affected with normal architecture of the zones of proliferation and maturation, but marked elongation of the zone of hypertrophy.more » Immunocytochemistry demonstrates that expression of T{sup AG} is limited to the zone of hypertropny in the epiphyseal plates, suggesting that the chondrocytes become hormone-responsive at this particular stage of differentiation. Normal mineralization and trabecular formation in long bone appears to occur. Ectopic bone and cartilage formation occurs in the foot pads of the fore- and hind- feet over the course of several months. This is preceded by proliferation of sweat gland epithelial cells followed by the appearance of nodules of cartilage and bone. The nodules are closely associated with proliferating epithelium but are not contiguous with bony structures normally found in the feet. The roles of BMP`s, growth factors, oncogenes and hormones in the development of these lesions will be presented. These transgenic animals may provide new insights into hormone-responsiveness of chondrocytes, as well as factors involved in the processes of bone and cartilage differentiation and growth. These transgenic animals may serve as a useful model for human heterotopic bone formation.« less
Wiedemann-Rautenstrauch syndrome. A case report and review of the literature.
Stoll, C; Labay, F; Geisert, J; Alembik, Y
1998-01-01
In 1977 Rautenstrauch and Snigula reported on two sisters with a previously undescribed, progeria-like syndrome. Two years later Wiedemann described two unrelated males with the same condition. Since than only a few published cases appeared in the literature. We had the opportunity to study a boy affected by this extremely rare condition. This boy was born after intrauterine growth retardation. At birth two natal teeth were present. OFC was normal despite apparent macrocephaly. During infancy a progeroid appearance was noted with sparse hair, prominent scalp veins, greatly widened anterior fontanelles, malar hypoplasia, and generalized lipoatrophy. The face was triangular with a small maxilla and a protuding chin, the eyes were low-set, the eyebrows and eyelashes were scanty. At the age of 3.5 years there was striking general deficiency of subcutaneous fatty tissue apart from accumulation of adipose tissue on the buttocks and flanks, growth was retarded, mental development was at the low borderline of normal. Cholesterolemia was at the upper range of normal, there was an increase of triglycerides: 3.31 mmol/L (Normal < 1 mmol/L). Other progeroid syndromes such as Hutchinson-Guilford, Berardinelli-Seip, De Barsy, leprechaunism, Cockayne and Hallerman-Streiff could be excluded as well as the CDG syndrome. This condition is most probably inherited as an autosomal recessive trait.
Empty sella syndrome secondary to intrasellar cyst in adolescence.
Raiti, S; Albrink, M J; Maclaren, N K; Chadduck, W M; Gabriele, O F; Chou, S M
1976-09-01
A 15-year-old boy had growth failure and failure of sexual development. The probable onset was at age 10. Endocrine studies showed hypopituitarism with deficiency of growth hormone and follicle-stimulating hormone, an abnormal response to metyrapone, and deficiency of thyroid function. Luteinizing hormone level was in the low-normal range. Posterior pituitary function was normal. Roentgenogram showed a large sella with some destruction of the posterior clinoids. Transsphenoidal exploration was carried out. The sella was empty except for a whitish membrane; no pituitary tissue was seen. The sella was packed with muscle. Recovery was uneventful, and the patient was given replacement therapy. On histologic examination,the cyst wall showed low pseudostratified cuboidal epithelium and occasional squamous metaplasia. Hemosiderin-filled phagocytes and acinar structures were also seen. The diagnosis was probable rupture of an intrasellar epithelial cyst, leading to empty sella syndrome.
[Efficacy of highly active antiretroviral therapy for childhood acquired immunodeficiency syndrome].
Hao, Jin-Li; Wang, Bao-Jin; Baptiste, Jean
2010-11-01
To investigate the efficacy of highly active antiretroviral therapy (HAART) for acquired immunodeficiency syndrome (AIDS) in children. The clinical data of 38 children (2-15 years old) with AIDS from a region of Rwanda and who had received HAART were retrospectively reviewed. All of 13 children with anemia showed improved anemia symptoms after HAART. The hemoglobin contents returned to normal levels in 12 children with mild or moderate anemia. CD4 T lymphocytes increased by 24%-1 181% in 5 out of 6 cases with severe immunodeficiency after HAART. During the HAART, the weight gain averaged 2.3 kg yearly. The growth and development in 5 out of 8 children with delayed growth restored the levels of normal children of the same age after HAART. HAART can improve the health status in children with AIDS and is effective for childhood AIDS.
Lindroth, M; Mortensson, W
1986-09-01
Chest X-ray, pulmonary mechanics, clinical lung disease and growth were studied in 48 low birthweight infants surviving after ventilator treatment in the neonatal period. Bronchopulmonary dysplasia (BPD) was present in 14 infants shortly after weaning off ventilator. At 4 to 6 years of age most patients had normal chest radiographs but 13 still showed signs of pulmonary fibrosis and hyperinflation. Most patients had low dynamic compliance and high pulmonary resistance shortly after ventilator treatment. All but 8, however, had normal findings at 1 to 1 1/2 years of age. Pneumonias and bronchitis were common during the first two years but thereafter declined in frequency. Weight and length development were retarded for BPD patients during the first two years and for non-BPD patients for the first year. Both groups had a complete catch-up.
Comparison and evaluation of gene therapy and epigenetic approaches for wound healing.
Cutroneo, K R; Chiu, J F
2000-01-01
During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article.
Huang, Li-Li; Xiong, Fei; Yang, Fan
2016-10-01
To study the effect of breast milk composition on weight growth velocity of infants fed with exclusive breast milk. One hundred and thirty-eight full-term singleton infants who received regular follow-up visits and fed with exclusive breast milk and their mothers were recruited. Body height, weight and head circumference of these infants were measured at regular visits. Z scores were used to evaluate growth velocity. The subjects were classified into a failure to thrive group (ΔZ scores≤-0.67), a poor growth group (-0.67<ΔZ scores<0) and a normal control group (ΔZ scores≥0). The samples of mature breast milk were collected for composition analysis. The differences in the levels of the protein, fats, energy, carbohydrates and minerals in breast milk were compared among the three groups. ΔZ scores for weight in the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). There was no significant difference in the levels of protein, fats and energy in breast milk among the failure to thrive, poor growth and normal control groups. However, the levels of carbohydrates and minerals in both the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). Weight growth velocity of infants can be affected by the composition of breast milk to a certain degree in a short period. In order to maintain a good weight growth velocity of infants, mothers should have a balanced diet to improve the quality of breast milk.
Moro, Christian; Covino, Jessica
2018-03-01
Measuring skeletal development throughout juvenile growth can provide a greater understanding into the health, hormonal function and genetics of children. The metacarpals have been of interest for their potential to provide insights into healthy juvenile skeletal development. This study investigated the growth patterns of developing females from isolated communities who had varied diets. Anthropometrical measurements and hand-wrist X-rays were taken of 353 juvenile females from three populations: Pari Coastal Village and Bundi Highlands Village, Papua New Guinea (PNG); and Brisbane, Australia between 1968 to 1983. Radiographs were digitized, and the length and width of the second and third metacarpals compared to each subject's height and weight. As subject heights increased, metacarpal length and width increased. However, stature and second metacarpal length indicated the strongest correlation ( P <0.01), compared to third metacarpal length ( P <0.01) or width. From 11 to 13 years of age, Brisbane subjects were significantly heavier and taller in comparison to subjects from PNG, and coastal females were heavier and taller than the highland females. A prominent difference between the two PNG populations was the regional intake of protein in their diets. The second metacarpal presents particularly accurate measurements when determining the height or development of a child. Nutritional intake appears to have a major influence normal childhood growth, with a potential for protein deficiency to strongly inhibit growth. Any delayed growth is particularly evident in the child's stature, as well as in the development of the metacarpal long bones of the hand.
Nedukha, O; Kordyum, E; Ovrutska, I; Martyn, G; Shnyukova, E
2001-07-01
It is established that high plant growth and development in microgravity occurred normal. However, the change of plant growth rate is accompanied by the change of carbohydrate metabolism in photosynthesized cells (Kordyum, 1997). The decrease of starch grain size in chloroplasts and the decrease of content cellulose in cell wall were revealed (Sytnik et al., 1984; Nedukha, 1996). The change carbohydrate metabolism in photosynthesized organs could influence on the growth of underground organs and content of storage carbohydrates in these organs. Therefore, the aim of our study was to investigate the long-term clinorotation influence on the formation, structure of potato minitubers and content of starch and sugars in minitubers.
Economics of Future Growth in Photovoltaics Manufacturing
DOE Office of Scientific and Technical Information (OSTI.GOV)
Basore, Paul A.; Chung, Donald; Buonassisi, Tonio
2015-06-14
The past decade's record of growth in the photovoltaics manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life ofmore » the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.« less
Plasma-electric field controlled growth of oriented graphene for energy storage applications
NASA Astrophysics Data System (ADS)
Ghosh, Subrata; Polaki, S. R.; Kamruddin, M.; Jeong, Sang Mun; (Ken Ostrikov, Kostya
2018-04-01
It is well known that graphene grows as flat sheets aligned with the growth substrate. Oriented graphene structures typically normal to the substrate have recently attracted major attention. Most often, the normal orientation is achieved in a plasma-assisted growth and is believed to be due to the plasma-induced in-built electric field, which is usually oriented normal to the substrate. This work focuses on the effect of an in-built electric field on the growth direction, morphology, interconnectedness, structural properties and also the supercapacitor performance of various configurations of graphene structures and reveals the unique dependence of these features on the electric field orientation. It is shown that tilting of growth substrates from parallel to the normal direction with respect to the direction of in-built plasma electric field leads to the morphological transitions from horizontal graphene layers, to oriented individual graphene sheets and then interconnected 3D networks of oriented graphene sheets. The revealed transition of the growth orientation leads to a change in structural properties, wetting nature, types of defect in graphitic structures and also affects their charge storage capacity when used as supercapacitor electrodes. This simple and versatile approach opens new opportunities for the production of potentially large batches of differently oriented and structured graphene sheets in one production run.
Wang, Yan-ling; Ge, Peng-fei; Ma, Qi-yi; Cao, Yong-qin; Li, Hong-bo; Zheng, Jing; Shi, Wen-quan; Sun, Wei
2012-02-01
To investigate the relationship between iodine nutrition and growth/development in infants at the key period of brain development. All women from pregnancy to the end of lactation and the weaning infants within 3 years in the Linxia Hui Autonomous Prefecture (Linxia Prefecture) were added iodized oil in 2006 - 2010. In 2006, 2010 one town was randomly selected from each of the five directions (east, south, west, north, central) of each county in Linxia Prefecture. One village was chosen from every town and 20 infants, 20 pregnant women and 20 lactating women were randomly selected in each town. Urinary iodine (UI) of the infants, pregnant and lactating women were determined. DQ value, height and weight of part of infants were measured. According to the above sampling plan, UI of pregnant women, lactating women and infants had been monitored every year after intervention. 0-3 infants were choosing to be control before intervention. UI of 1056 and 2989 0-3 infants were investigated before and after the iodine oil intervention. After the 'iodine oil' intervention, the median UI of infants increased from 107.3 µg/L to 139.6 - 190.7 µg/L, the percentage of UI level that lower than 50 µg/L, decreased from 23.9% to 6.7% - 12.9%. DQ value increased from 92.8 to 104.3, the percentage of normal height and above increased from 65.0% to 82.1% and the percentage of the normal weight and above, increased from 59.3% to 81.4%. The outcomes of DQ value, height and weight showed statistically significant differences, compared to the pre-intervention outcomes (P < 0.05). The median UI of pregnant and lactating women increased from 89.3 µg/L to 118.2 - 187.8 µg/L and from 84.9 µg/L to 135.2 - 187.5 µg/L respectively. Infant's growth and development were retarded when iodine deficiency existed at the key period of brain development. Intake of oral iodine oil at key period of brain development could provide adequate nutrition thus improve growth and development on infants.
Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice.
Garcia, Stéphanie; Dirat, Béatrice; Tognacci, Thomas; Rochet, Nathalie; Mouska, Xavier; Bonnafous, Stéphanie; Patouraux, Stéphanie; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Gennero, Isabelle; Gouze, Elvire
2013-09-18
Achondroplasia is a rare genetic disease characterized by abnormal bone development, resulting in short stature. It is caused by a single point mutation in the gene coding for fibroblast growth factor receptor 3 (FGFR3), which leads to prolonged activation upon ligand binding. To prevent excessive intracellular signaling and rescue the symptoms of achondroplasia, we have developed a recombinant protein therapeutic approach using a soluble form of human FGFR3 (sFGFR3), which acts as a decoy receptor and prevents FGF from binding to mutant FGFR3. sFGFR3 was injected subcutaneously to newborn Fgfr3(ach/+) mice-the mouse model of achondroplasia-twice per week throughout the growth period during 3 weeks. Effective maturation of growth plate chondrocytes was restored in bones of treated mice, with a dose-dependent enhancement of skeletal growth in Fgfr3(ach/+) mice. This resulted in normal stature and a significant decrease in mortality and associated complications, without any evidence of toxicity. These results describe a new approach for restoring bone growth and suggest that sFGFR3 could be a potential therapy for children with achondroplasia and related disorders.
Microstructure and growth model for rice-hull-derived SiC whiskers
NASA Technical Reports Server (NTRS)
Nutt, Steven R.
1988-01-01
The microstructure of silicon carbide whiskers grown from rice hulls has been studied using methods of high-resolution analytical electron microscopy. Small, partially crystalline inclusions (about 10 nm) containing calcium, manganese, and oxygen are concentrated in whisker core regions, while peripheral regions are generally inclusion free. The distinct microphase distribution is evidence of a two-stage growth process in which the core region grows first, followed by normal growth toward whisker sides. Partial dislocations extend radially from the core region to the surface and tend to be paired in V-shaped configurations. Whisker surfaces exhibit microroughness due to a tendency to develop small facets on close-packed planes. The microstructural data obtained from TEM observations are used as a basis for discussion of the mechanisms involved in whisker growth, and a model of the growth process is proposed. The model includes a two-dimensional growth mechanism involving vapor, liquid, and solid phases, although it is significantly different from the classical vapor-liquid-solid (VLS) process of whisker growth.
MSX-1 gene expression and regulation in embryonic palatal tissue.
Nugent, P; Greene, R M
1998-01-01
The palatal cleft seen in Msx-1 knock-out mice suggests a role for this gene in normal palate development. The cleft is presumed secondary to tooth and jaw malformations, since in situ hybridization suggests that Msx-1 mRNA is not highly expressed in developing palatal tissue. In this study we demonstrate, by Northern blot analysis, the expression of Msx-1, but not Msx-2, in the developing palate and in primary cultures of murine embryonic palate mesenchymal cells. Furthermore, we propose a role for Msx-1 in retinoic acid-induced cleft palate, since retinoic acid inhibits Msx-1 mRNA expression in palate mesenchymal cells. We also demonstrate that transforming growth factor beta inhibits Msx-1 mRNA expression in palate mesenchymal cells, with retinoic acid and transforming growth factor beta acting synergistically when added simultaneously to these cells. These data suggest a mechanistic interaction between retinoic acid, transforming growth factor beta, and Msx-1 in the etiology of retinoic acid-induced cleft palate.
Decapentaplegic and growth control in the developing Drosophila wing.
Akiyama, Takuya; Gibson, Matthew C
2015-11-19
As a central model for morphogen action during animal development, the bone morphogenetic protein 2/4 (BMP2/4)-like ligand Decapentaplegic (Dpp) is proposed to form a long-range signalling gradient that directs both growth and pattern formation during Drosophila wing disc development. While the patterning role of Dpp secreted from a stripe of cells along the anterior-posterior compartmental boundary is well established, the mechanism by which a Dpp gradient directs uniform cell proliferation remains controversial and poorly understood. Here, to determine the precise spatiotemporal requirements for Dpp during wing disc development, we use CRISPR-Cas9-mediated genome editing to generate a flippase recognition target (FRT)-dependent conditional null allele. By genetically removing Dpp from its endogenous stripe domain, we confirm the requirement of Dpp for the activation of a downstream phospho-Mothers against dpp (p-Mad) gradient and the regulation of the patterning targets spalt (sal), optomotor blind (omb; also known as bifid) and brinker (brk). Surprisingly, however, third-instar wing blade primordia devoid of compartmental dpp expression maintain relatively normal rates of cell proliferation and exhibit only mild defects in growth. These results indicate that during the latter half of larval development, the Dpp morphogen gradient emanating from the anterior-posterior compartment boundary is not directly required for wing disc growth.
De Smet, Stefanie; Cuypers, Ann; Vangronsveld, Jaco; Remans, Tony
2015-01-01
Plant survival under abiotic stress conditions requires morphological and physiological adaptations. Adverse soil conditions directly affect root development, although the underlying mechanisms remain largely to be discovered. Plant hormones regulate normal root growth and mediate root morphological responses to abiotic stress. Hormone synthesis, signal transduction, perception and cross-talk create a complex network in which metal stress can interfere, resulting in root growth alterations. We focus on Arabidopsis thaliana, for which gene networks in root development have been intensively studied, and supply essential terminology of anatomy and growth of roots. Knowledge of gene networks, mechanisms and interactions related to the role of plant hormones is reviewed. Most knowledge has been generated for auxin, the best-studied hormone with a pronounced primary role in root development. Furthermore, cytokinins, gibberellins, abscisic acid, ethylene, jasmonic acid, strigolactones, brassinosteroids and salicylic acid are discussed. Interactions between hormones that are of potential importance for root growth are described. This creates a framework that can be used for investigating the impact of abiotic stress factors on molecular mechanisms related to plant hormones, with the limited knowledge of the effects of the metals cadmium, copper and zinc on plant hormones and root development included as case example. PMID:26287175
Loverde, Joseph R.; Pfister, Bryan J.
2015-01-01
Elongation of nerve fibers intuitively occurs throughout mammalian development, and is synchronized with expansion of the growing body. While most tissue systems enlarge through mitosis and differentiation, elongation of nerve fibers is remarkably unique. The emerging paradigm suggests that axons undergo stretch as contiguous tissues enlarge between the proximal and distal segments of spanning nerve fibers. While stretch is distinct from growth, tension is a known stimulus which regulates the growth of axons. Here, we hypothesized that the axon stretch-growth process may be a natural form of injury, whereby regenerative processes fortify elongating axons in order to prevent disconnection. Harnessing the live imaging capability of our axon stretch-growth bioreactors, we assessed neurons both during and following stretch for biomarkers associated with injury. Utilizing whole-cell patch clamp recording, we found no evidence of changes in spontaneous action potential activity or degradation of elicited action potentials during real-time axon stretch at strains of up to 18% applied over 5 min. Unlike traumatic axonal injury, functional calcium imaging of the soma revealed no shifts in free intracellular calcium during axon stretch. Finally, the cross-sectional areas of nuclei and cytoplasms were normal, with no evidence of chromatolysis following week-long stretch-growth limited to the lower of 25% strain or 3 mm total daily stretch. The neuronal growth cascade coupled to stretch was concluded to be independent of the changes in membrane potential, action potential generation, or calcium flux associated with traumatic injury. While axon stretch-growth is likely to share overlap with regenerative processes, we conclude that developmental stretch is a distinct stimulus from traumatic axon injury. PMID:26379492
Kobayashi, Shinji; Hirakawa, Takashi; Fukawa, Toshihiko; Maegawa, Jiro
2015-06-01
In bilateral cleft lip and palate (BCLP) with premaxillary protrusion, a good outcome with adequate maxillary development is difficult to achieve. The purpose of this article is to evaluate the maxillary growth after using presurgical orthopedics (PSO), gingivoperiosteoplasty (GPP), Furlow palatoplasty, and maxillary protraction appliance (MPA) for BCLP with premaxillary protrusion. Seven patients with complete BCLP with premaxillary protrusion were treated by PSO, cheiloplasty, GPP, and Furlow palatoplasty. MPA was used as part of the protocol for 6 months to 1 year for postoperative retardation of maxillary growth cases. Maxillary growth was evaluated by cephalometric analysis at 4 and 10 years of age, and bone formation at the alveolar cleft was evaluated by computed tomography (CT) imaging at 5 years of age. At 4 years of age, three of seven patients had apparent retardation of maxillary growth. The maxillary growth at 10 years of age was equivalent to the average value of normal Japanese after using MPA in three cases. At 5 years of age, only two of seven patients showed sufficient bone formation at the alveolar cleft to avoid alveolar bone grafting (ABG). Subsequently, ABG was performed in five patients. Although three of seven patients had apparent crossbite at 4 years of age, the maxillary growth of all patients at 10 years of age was approximately equivalent to the average value of normal Japanese after using MPA. A treatment protocol based on PSO, GPP, Furlow palatoplasty, and MPA may be an option, but long-term growth is unknown. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Bender, Kevin J.; Rangel, Juliana; Feldman, Daniel E.
2011-01-01
The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14 –26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8 –11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8 –9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons. PMID:14507976
Investigational agents for the treatment of growth hormone-insensitivity syndrome.
Kemp, Stephen F; Thrailkill, Kathryn M
2006-04-01
Growth hormone-insensitivity syndrome (GHIS) is usually caused by mutations in the growth hormone receptor. Recombinant IGF-I has been used to treat GHIS either alone (mecasermin) or in combination with IGF-binding protein (IGFBP)-3 (mecasermin rinfabate). IGF-I increases the growth velocity of children with IGF deficiency, which is either as a result of GHIS or an IGF-I gene deletion. Hypoglycaemia has been reported with administration of unbound IGF-I and, in addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS (who have low serum concentrations of its binding protein IGFBP-3) than when administered to normal volunteers or to patients with an IGF-I gene deletion (but normal IGFBP-3 levels). The IGF-I-IGFBP-3 combination was developed to prolong the half-life and counteract the acute adverse events (particularly hypoglycaemia) that are associated with administration of IGF-I. It seems that the IGF-I-IGFBP-3 combination has a longer half-life in patients with GHIS than unbound IGF-I, with fewer reports of adverse events (including hypoglycaemia) when administered to patients with diabetes. There are no studies comparing the efficacy of mecasermin with mecasermin rinfabate; both drugs have been shown to be effective but cannot be differentiated in terms of efficacy.
Androgens stimulate early stages of follicular growth in the primate ovary.
Vendola, K A; Zhou, J; Adesanya, O O; Weil, S J; Bondy, C A
1998-01-01
The concept that androgens are atretogenic, derived from murine ovary studies, is difficult to reconcile with the fact that hyperandrogenic women have more developing follicles than normal-cycling women. To evaluate androgen's effects on primate follicular growth and survival, normal-cycling rhesus monkeys were treated with placebo-, testosterone-(T), or dihydrotestosterone-sustained release implants, and ovaries were taken for histological analysis after 3-10 d of treatment. Growing preantral and small antral follicles up to 1 mm in diameter were significantly and progressively increased in number and thecal layer thickness in T-treated monkeys from 3-10 d. Granulosa and thecal cell proliferation, as determined by immunodetection of the Ki67 antigen, were significantly increased in these follicles. Preovulatory follicles (> 1 mm), however, were not increased in number in androgen-treated animals. Follicular atresia was not increased and there were actually significantly fewer apoptotic granulosa cells in the T-treated groups. Dihydrotestosterone treatment had identical effects, indicating that these growth-promoting actions are mediated by the androgen receptor. These findings show that, over the short term at least, androgens are not atretogenic and actually enhance follicular growth and survival in the primate. These new data provide a plausible explanation for the pathogenesis of "polycystic" ovaries in hyperandrogenism. PMID:9637695
NASA Astrophysics Data System (ADS)
Tikhomirova, Natalia; Ushakova, Sofya; Kalacheva, Galina; Tikhomirov, Alexander
2016-09-01
The study addresses the effectiveness of using ion exchange substrates (IES) to optimize mineral nutrition of plants grown in the nutrient solutions containing oxidized human wastes for application in bio-technical life support systems. The study shows that the addition of IES to the root-inhabited substrate is favorable for the growth of wheat vegetative organs but causes a decrease in the grain yield. By contrast, the addition of IES to the nutrient solution does not influence the growth of vegetative organs but favors normal development of wheat reproductive organs. Thus, to choose the proper method of adjusting the solution with IES, one should take into account specific parameters of plant growth and development and the possibility of multiple recycling of IES based on the liquid products of mineralization of human wastes.
Movement maintains forebrain neurogenesis via peripheral neural feedback in larval zebrafish
Hall, Zachary Jonas
2018-01-01
The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons. Physical cues associated with swimming (bodily movement) increase neurogenesis and these cues appear to be conveyed by dorsal root ganglia (DRG) in the zebrafish body: DRG-deficient larvae exhibit attenuated neurogenic responses to movement and targeted photoactivation of DRG in immobilized larvae expands the pallial pool of proliferative cells. Our results demonstrate the importance of movement in neurogenic brain growth and reveal a fundamental sensorimotor association that may couple early motor and brain development. PMID:29528285
QRC Evaluation of Materials and Processes.
1982-10-01
Fatigue Crack Growth Data for Normal and "Soft" Aluminum 2024 - T351 65 27...Spectrum Fatigue Crack Growth Data for Normal and "Soft" Aluminum 7075-T651 66 28 Constant Amplitude FCGR Data for Normal and "Soft" Aluminum 2024 - T351 67...in Figure 29. The same trends observed in the spectrum fatigue tests are repeated in the S constant amplitude data: for aluminum 2024 - T351 , the
Playford, R J; Hanby, A M; Gschmeissner, S; Peiffer, L P; Wright, N A; McGarrity, T
1996-01-01
BACKGROUND: While it is clear that luminal epidermal growth factor (EGF) stimulates repair of the damaged bowel, its significance in maintaining normal gut growth remains uncertain. If EGF is important in maintaining normal gut growth, the EGF receptor (EGF-R) should be present on the apical (luminal) surface in addition to the basolateral surface. AIMS/SUBJECTS/METHODS: This study examined the distribution of the EGF-R in the epithelium throughout the human gastro-intestinal tract using immunohistochemistry, electron microscopy, and western blotting of brush border preparations. RESULTS: Immunostaining of the oesophagus showed circumferential EGF-R positivity in the cells of the basal portions of the stratified squamous epithelium but surface cells were EGF-R negative. In the normal stomach, small intestine, and colon, immunostaining localised the receptor to the basolateral surface with the apical membranes being consistently negative. EGF-R positivity within the small intestine appeared to be almost entirely restricted to the proliferative (crypt) region. Western blotting demonstrated a 170 kDa protein in whole tissue homogenates but not in the brush border vesicle preparations. CONCLUSIONS: As the EGF-R is located only on the basolateral surfaces in the normal adult gastrointestinal tract, the major role of luminal EGF is probably to stimulate repair rather than to maintain normal gut growth. Images Figure 1 Figure 2 Figure 3 PMID:8977341
Kovács, Péter; Rab, Attila; Szentpéteri, Imre; Joó, József Gábor; Kornya, László
2017-04-01
Placental vascular endothelial growth factor A (VEGF-A) gene and endoglin gene are both overexpressed in placental samples obtained from pregnancies with intrauterine growth restriction compared to normal pregnancies. In the background of these changes a mechanism can be supposed, in which the increased endoglin activity in intrauterine growth restriction (IUGR) leads to impaired placental circulation through an antioangiogenetic effect. This results in the development of placental vascular dysfunction and chronic fetal hypoxia. It is chronic hypoxia that turns on VEGF-A as a compensatory mechanism to improve fetal vascular blood supply by promoting placental blood vessel formation. Although the maternal serum placental growth factor (PlGF) level is a potential predictor for both IUGR and praeeclampsia, placental PlGF gene activity may be less of an active in the regulation of placental circulation in IUGR pregnancies during the later stages of gestation. Orv. Hetil., 2017, 158(16), 612-617.
Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L
1999-05-01
Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P < 0.0001), indicating a specific impairment in gland structure. Administration of des(1-3)-IGF-I for 7 days partially reversed the deficit by increasing those parameters of prostate development (P < 0.006). That IGF-I production probably mediates an effect of GH in this process was indicated by the observations that GH antagonist transgenic mice also had significantly impaired prostate development (P < 0.0002) and that bovine GH had no independent effect on stimulating prostate development in IGF-I null animals. The data indicate that IGF-I deficiency is the proximate cause of impaired prostate development and give credence to the idea that, like testosterone, GH and IGF-I may be involved in prostate cancer growth as an extension of a normal process.
Paths to future growth in photovoltaics manufacturing
Basore, Paul A.
2016-03-01
The past decade has seen rapid growth in the photovoltaics industry, followed in the past few years by a period of much slower growth. A simple model that is consistent with this historical record can be used to predict the future evolution of the industry. Two key parameters are identified that determine the outcome. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units dollar/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service lifemore » of the assets (capacity-normalized capital demand rate, CapDR, units dollar/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a modest improvement in CapIR to ensure future growth in photovoltaics. Here, several approaches are presented that can enable the required improvement in CapIR. If, in addition, there is an accompanying improvement in CapDR, the rate of growth can be substantially accelerated.« less
Adrenomedullin promotes lung angiogenesis, alveolar development, and repair.
Vadivel, Arul; Abozaid, Sameh; van Haaften, Tim; Sawicka, Monika; Eaton, Farah; Chen, Ming; Thébaud, Bernard
2010-08-01
Bronchopulmonary dysplasia (BPD) and emphysema are significant global health problems at the extreme stages of life. Both are characterized by alveolar simplification and abnormal distal airspace enlargement due to arrested development or loss of alveoli, respectively. Both lack effective treatments. Mechanisms that inhibit distal lung growth are poorly understood. Adrenomedullin (AM), a recently discovered potent vasodilator, promotes angiogenesis and has protective effects on the cardiovascular and respiratory system. Its role in the developing lung is unknown. We hypothesized that AM promotes lung angiogenesis and alveolar development. Accordingly, we report that lung mRNA expression of AM increases during normal alveolar development. In vivo, intranasal administration of the AM antagonist, AM22-52 decreases lung capillary density (12.4 +/- 1.5 versus 18 +/- 1.5 in control animals; P < 0.05) and impairs alveolar development (mean linear intercept, 52.3 +/- 1.5 versus 43.8 +/- 1.8 [P < 0.05] and septal counts 62.0 +/- 2.7 versus 90.4 +/- 3.5 [P < 0.05]) in neonatal rats, resulting in larger and fewer alveoli, reminiscent of BPD. This was associated with decreased lung endothelial nitric oxide synthase and vascular endothelial growth factor-A mRNA expression. In experimental oxygen-induced BPD, a model of arrested lung vascular and alveolar growth, AM attenuates arrested lung angiogenesis (vessel density, 6.9 +/- 1.1 versus 16.2 +/- 1.3, P < 0.05) and alveolar development (mean linear intercept, 51.9 +/- 3.2 versus 44.4 +/- 0.7, septal counts 47.6 +/- 3.4 versus 67.7 +/- 4.0, P < 0.05), an effect in part mediated by inhibition of apoptosis. AM also prevents pulmonary hypertension in this model, as assessed by decreased right ventricular hypertrophy and pulmonary artery medial wall thickness. Our findings suggest a role for AM during normal alveolar development. AM may have therapeutic potential in diseases associated with alveolar injury.
2009-09-11
conditions in their upper part. Anaerobic soil conditions are conducive to the establishment of vegetation that is adapted for growth under oxygen...sufficient to support, and that under normal circumstances do support, a prevalence of vegetation typically adapted to life in saturated soil...species adapted to dense commercial development and heavy vehicular traffic would be expected to move back into the area after development of the
Samach, A; Klenz, J E; Kohalmi, S E; Risseeuw, E; Haughn, G W; Crosby, W L
1999-11-01
Genetic and molecular studies have suggested that the UNUSUAL FLORAL ORGANS (UFO) gene, from Arabidopsis thaliana, is expressed in all shoot apical meristems, and is involved in the regulation of a complex set of developmental events during floral development, including floral meristem and floral organ identity. Results from in situ hybridization using genes expressed early in floral development as probes indicate that UFO controls growth of young floral primordia. Transgenic constructs were used to provide evidence that UFO regulates floral organ identity by activating or maintaining transcription of the class B organ-identity gene APETALA 3, but not PISTILLATA. In an attempt to understand the biochemical mode of action of the UFO gene product, we show here that UFO is an F-box protein that interacts with Arabidopsis SKP1-like proteins, both in the yeast two-hybrid system and in vitro. In yeast and other organisms both F-box proteins and SKP1 homologues are subunits of specific ubiquitin E3 enzyme complexes that target specific proteins for degradation. The protein selected for degradation by the complex is specified by the F-box proteins. It is therefore possible that the role of UFO is to target for degradation specific proteins controlling normal growth patterns in the floral primordia, as well as proteins that negatively regulate APETALA 3 transcription.
Thyroid Hormone, Cancer, and Apoptosis.
Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J
2016-06-13
Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.
Cytomegalovirus infection of the BS-1 human stroma cell line: effect on murine hemopoiesis.
Steinberg, H N; Anderson, J; Lim, B; Chatis, P A
1993-10-01
BS-1, a stromal cell line derived from human bone marrow, can support the growth of murine erythroid (BFU-E), granulocyte-macrophage (CFU-GM), and megakaryocyte (CFU-M) progenitor cells in a short term in vitro coculture system. Exposure of BS-1 cells to cytomegalovirus (CMV) for 3 hr prior to coculture results in a marked reduction in the stroma cell's ability to support murine hemopoiesis. CMV's effect on the BS-1 cell's hematopoietic support function is dependent on the multiplicity of infection with total suppression of BFU-E observed at a 1:1 ratio of virus to bone marrow cells. A 50% loss in the ability of BS-1 cells to support BFU-E is observed at a 0.1:1 ratio. No effect of CMV is observed with further log dilutions of virus. CMV infection of BS-1 cells affects its support of erythroid progenitor cell growth to a greater extent than its influence on the development of granulocyte-macrophage colonies. Antibody to CMV or heat inactivation of the virus reverses the inhibitory affect on BS-1 cells. The results suggest that CMV can infect a cell that constitutes one of the cellular elements of the normal bone marrow microenvironment causing a decrease in the stroma's ability to support the growth and development of normal progenitor cells.
Kanna, P Rishimugesh; Shetty, Ajoy Prasad; Rajasekaran, S
2011-07-15
Prospective analysis of computed tomographic images of 376 normal pediatric cervical pedicles. To study the normal cervical pedicle morphometrics, the changes in pedicle morphology with skeletal growth, and the possibility of pedicle screw insertion. Although the usage of cervical pedicle screws in adults has become established, the feasibility of its application in children has not been studied. There are no in vivo studies that define the normal pediatric cervical pedicle morphometrics and its changes with growth and development of the child. A total of 376 normal pediatric cervical spine pedicles of 30 children (mean age = 6.7 ± 3.9 years) were analyzed for pedicle width (PW), pedicle height (PH), pedicle length (PL), pedicle axis length (PAL), transverse pedicle angle (TPA), and sagittal pedicle angle (SPA). The study population was categorized into three age groups (A: <5 years, B: 5-10 years, and C >10 years). The mean values of these parameters in the different age groups and the possibility of application cervical pedicle screws were studied. RESULTS.: The mean PW was lowest in the C3 vertebra and increased distally to be widest at C7. Sixty percent of C3 pedicles had a width less than 4 mm making screw passage risky and unsafe. With growth, the PW increased at all levels but this increase was significant only up to the age of 10 years. More than 75% of adult pedicle dimensions were achieved by 5 years of age. The mean PL at all levels remained the same with no significant increase with growth. However, the PAL showed continuous increase with growth similar to PW. The PAL also showed an increase from C3 to C7. The PH was always more than the PW at any level. Mild insignificant asymmetry was present between the right and left side pedicles in all values. With growth, there was a gradual increase in PW, PH, and PAL but was mainly before the age of 10 years. Majority of C3 pedicles were thin making screw fixation unsafe. However, at all other levels, the pedicle morphometrics per se were adequate and do not restrict safe application of 3-mm cervical pedicle screw.
Takeuchi, Akihito; Yorifuji, Takashi; Nakamura, Kazue; Tamai, Kei; Mori, Shigehiro; Nakamura, Makoto; Kageyama, Misao; Kubo, Toshihide; Ogino, Tatsuya; Kobayashi, Katsuhiro; Doi, Hiroyuki
2018-01-01
To examine the relationship between catch-up growth of full-term, small for gestational age (SGA) children and their neurobehavioral development. Data were obtained from a population-based nationwide Japanese longitudinal survey that started in 2001. Study participants were full-term children with information on height at 2 years of age (n = 32 533). Catch-up growth for SGA infants was defined as achieving a height at 2 years of age of more than -2.0 standard deviations for chronological age. Logistic regression analyses were used to estimate ORs and 95% CIs for the associations of SGA and catch-up growth status with neurobehavioral development at 2.5 and 8 years of age, adjusting for potential infant- and parent-related confounding factors. Fifteen percent of term SGA infants failed to catch up in height. At 2.5 years of age, SGA children without catch-up growth were more likely to be unable to climb stairs (OR, 10.42; 95% CI, 5.55-19.56) and unable to compose a 2-word sentence (OR, 3.58; 95% CI, 1.81-7.08) compared with children with normal growth at birth. Furthermore, SGA children without catch-up growth were at increased risk for aggressive behaviors (OR, 3.85; 95% CI, 1.19-12.47) at 8 years of age. Continuous follow-up for full-term SGA infants with failure of catch-up growth or poor postnatal growth may be beneficial for early detection and intervention for behavioral problems. Copyright © 2017 Elsevier Inc. All rights reserved.
Graff, Jeremy R.; Konicek, Bruce W.; Vincent, Thomas M.; Lynch, Rebecca L.; Monteith, David; Weir, Spring N.; Schwier, Phil; Capen, Andrew; Goode, Robin L.; Dowless, Michele S.; Chen, Yuefeng; Zhang, Hong; Sissons, Sean; Cox, Karen; McNulty, Ann M.; Parsons, Stephen H.; Wang, Tao; Sams, Lillian; Geeganage, Sandaruwan; Douglass, Larry E.; Neubauer, Blake Lee; Dean, Nicholas M.; Blanchard, Kerry; Shou, Jianyong; Stancato, Louis F.; Carter, Julia H.; Marcusson, Eric G.
2007-01-01
Expression of eukaryotic translation initiation factor 4E (eIF4E) is commonly elevated in human and experimental cancers, promoting angiogenesis and tumor growth. Elevated eIF4E levels selectively increase translation of growth factors important in malignancy (e.g., VEGF, cyclin D1) and is thereby an attractive anticancer therapeutic target. Yet to date, no eIF4E-specific therapy has been developed. Herein we report development of eIF4E-specific antisense oligonucleotides (ASOs) designed to have the necessary tissue stability and nuclease resistance required for systemic anticancer therapy. In mammalian cultured cells, these ASOs specifically targeted the eIF4E mRNA for destruction, repressing expression of eIF4E-regulated proteins (e.g., VEGF, cyclin D1, survivin, c-myc, Bcl-2), inducing apoptosis, and preventing endothelial cells from forming vessel-like structures. Most importantly, intravenous ASO administration selectively and significantly reduced eIF4E expression in human tumor xenografts, significantly suppressing tumor growth. Because these ASOs also target murine eIF4E, we assessed the impact of eIF4E reduction in normal tissues. Despite reducing eIF4E levels by 80% in mouse liver, eIF4E-specific ASO administration did not affect body weight, organ weight, or liver transaminase levels, thereby providing the first in vivo evidence that cancers may be more susceptible to eIF4E inhibition than normal tissues. These data have prompted eIF4E-specific ASO clinical trials for the treatment of human cancers. PMID:17786246
Sangtawesin, Varaporn; Singarj, Yupayao; Kanjanapattanakul, Wiboon
2011-08-01
The number of very low birth weight (VLBW) births is increasing worldwide. Despite better care in recent years, they have a high incidence of delayed growth and development. There are no previous studies regarding the growth and development of these infants at Queen Sirikit National Institute of Child Health (QSNICH). To study growth and developmental outcome of VLBW infants, aged 18-24 months who were discharged from QSNICH. VLBW infants who were discharged from QSNICH during the year 2007 were recruited in the study. Patients with chromosomal abnormalities, major congenital anomalies, definite congenital infections and positive maternal anti-HIV tests were excluded. At the corrected age of 18-24 months, the parents were called upon to bring their infants for complete physical examination and developmental evaluation on 2 occasions, two months apart. There were 111 cases of VLBW infants who were discharged from QSNICH during the year 2007. Fifty-four patients were eligible for the present study. Thirty cases (55.56%) were contacted for the first examination. During this examination, there were 3 cases (10%) with low head circumference, 1 case (3.33%) with poor weight gain, 5 cases (16.67%) with visual defect, 1 case (3.33%) with moderately severe hearing loss, 1 case (3.33%) with cerebral palsy and 7 cases (23.33%) with delayed development. Twenty-one cases could be recalled for a second evaluation. Two of the 5 cases had delayed language development. There were no cases with hydrocephalous, blindness or profound hearing loss. VLBW infants at QSNICH had much better survival during recent years. Most of these survivors had normal growth and development. Those with delayed growth and development need aggressive intervention and long-term follow-up for enhancement of quality of their lives.
Adult's Responses to the Physical Appearance of Children with Growth Disorders.
ERIC Educational Resources Information Center
Alley, Thomas R.; Hall, Debora L.
1989-01-01
Reports reactions of university students to the physical appearance of children with growth disorders of dwarfism, or sex-linked trisomy, compared to children with normal body proportions. Normal children were rated more favorably on physical attractiveness. Discussed the impact of perceived age and height-weight characteristics on…
Genes involved in immortalization of human mammary cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stampfer, Martha R.; Yaswen, Paul
2001-09-27
Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings ofmore » this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal transformation uncovered by our lab, termed conversion. Immortal cells that have not undergone conversion (e.g., cells immortalized by exogenous introduction of the immortalizing enzyme, telomerase) remain growth inhibited. (2) Finite lifespan HMEC growth arrest in response to oncogenic Raf using mediators of growth inhibition that are very different from those used in response to oncogenic Raf by rodent cells and certain other human cell types, including the connective tissue cells from the same breast tissue. While many diverse cell types appear to have in common a tumor-suppressive response to this oncogenic signal, they also have developed multiple mechanisms to elicit this response. Understanding how cancer cells acquire the crucial capacity to be immortal and to abrogate normal tumor-suppressive mechanisms may serve both to increase our understanding of breast cancer progression, and to provide new targets for therapeutic intervention. Our results indicate that normal HMEC have novel means of enforcing a Raf-induced growth arrest and that this tumor suppressive function is lost at a specific stage in malignant transformation. Further studies to elucidate the ways by which immortal, converted HMEC escape this arrest may provide a more complete model of breast carcinogenesis as well as ways to intervene in that process.« less
Casanova, J R; Nishimura, Masataka; Swann, John W
2014-04-01
Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the underlying molecular mechanisms will likely prove crucial for developing therapeutic strategies aimed at ameliorating the intellectual developmental disabilities associated with intractable childhood epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.
Development and validation of the Hogan Grief Reaction Checklist.
Hogan, N S; Greenfield, D B; Schmidt, L A
2001-01-01
The purpose of this article is to provide data on a recently developed instrument to measure the multidimensional nature of the bereavement process. In contrast to widely used grief instruments that have been developed using rational methods of instrument construction, the Hogan Grief Reaction Checklist (HGRC) was developed empirically from data collected from bereaved adults who had experienced the death of a loved one. Factor analysis of the HGRC revealed 6 factors in the normal trajectory of the grieving process: Despair, Panic Behavior, Blame and Anger, Detachment, Disorganization, and Personal Growth. Additional data are provided that support reliability and validity of the HGRC as well as its ability to discriminate variability in the grieving process as a function of cause of death and time lapsed since death. Empirical support is also provided for Personal Growth as an integral component of the bereavement process. The article concludes by considering the substantive as well as psychometric findings of this research for such issues as traumatic grief, anticipatory grief, change in the bereaved person's self-schema, and spiritual and existential growth.
ERIC Educational Resources Information Center
MELLON, JOHN C.
THIS STUDY REPORTS AN EXPERIMENT ON THE HYPOTHESIS THAT GRAMMAR-RELATED SENTENCE-COMBINING PRACTICE WILL MEANINGFULLY ENHANCE THE NORMAL GROWTH OF SYNTACTIC FLUENCY. TRADITIONAL STUDIES ON ERROR THERAPY AND SENTENCE STRUCTURE ARE REVIEWED, AND DESIGN AND RATIONALE ARE INFERRED FROM THE RESEARCH OF BATEMAN AND ZIDONIS. RULE LEARNING, PATTERN…
Using Fairy Tales to Change Perceptions of Self and Others.
ERIC Educational Resources Information Center
Gornicki, Sylvia B.
Fairy tales can be used in the classroom to promote normal growth and development as well as carry a message of hope and faith in the strength and goodness of humans. Because fairy tales are imaginative literature, readers can safely experience and work through scary situations which are analogous to situations in real life. Bibliotherapy refers…
Suggested stocking levels for forest stands in northeastern Oregon and southeastern Washington.
P.H. Cochran; J.M. Geist; D.L. Clemens; Rodrick R. Clausnitzer; David C. Powell
1993-01-01
Catastrophes and manipulation of stocking levels are important determinants of stand development and the appearance of future forest landscapes. Managers need stocking level guides, particularly for sites incapable of supporting stocking levels presented in normal yield tables. Growth basal area (GBA) has been used by some managers in attempts to assess inherent...
Rittling, S R; Wejse, P L; Yagiz, K; Warot, G A; Hui, T
2014-03-04
The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice. Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the α₉ integrin was determined. o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the α₉ integrin was detected on both tumour cells and blood vessels. Potential active peptides from the α₉ binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth. These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the α₉ integrin are likely involved.
Verwoerd-Dikkeboom, Christine M; van Heesch, Peter N A C M; Koning, Anton H J; Galjaard, Robert-Jan H; Exalto, Niek; Steegers, Eric A P
2008-11-01
To demonstrate the use of a novel three-dimensional (3D) virtual reality (VR) system in the visualization of first trimester growth and development in a case of confined placental trisomy 16 mosaicism (CPM+16). Case report. Prospective study on first trimester growth using a 3D VR system. A 34-year-old gravida 1, para 0 was seen weekly in the first trimester for 3D ultrasound examinations. Chorionic villus sampling was performed because of an enlarged nuchal translucency (NT) measurement and low pregnancy-associated plasma protein-A levels, followed by amniocentesis. Amniocentesis revealed a CPM+16. On two-dimensional (2D) and 3D ultrasound no structural anomalies were found with normal fetal Dopplers. Growth remained below the 2.3 percentile. At 37 weeks, a female child of 2010 g (<2.5 percentile) was born. After birth, growth climbed to the 50th percentile in the first 2 months. The I-Space VR system provided information about phenotypes not obtainable by standard 2D ultrasound. In this case, the delay in growth and development could be observed very early in pregnancy. Since first trimester screening programs are still improving and becoming even more important, systems such as the I-Space open a new era for in vivo studies on the physiologic and pathologic processes involved in embryogenesis.
Gasperini, Robert J; Pavez, Macarena; Thompson, Adrian C; Mitchell, Camilla B; Hardy, Holly; Young, Kaylene M; Chilton, John K; Foa, Lisa
2017-10-01
The precision with which neurons form connections is crucial for the normal development and function of the nervous system. The development of neuronal circuitry in the nervous system is accomplished by axon pathfinding: a process where growth cones guide axons through the embryonic environment to connect with their appropriate synaptic partners to form functional circuits. Despite intense efforts over many years to understand how this process is regulated, the complete repertoire of molecular mechanisms that govern the growth cone cytoskeleton and hence motility, remain unresolved. A central tenet in the axon guidance field is that calcium signals regulate growth cone behaviours such as extension, turning and pausing by regulating rearrangements of the growth cone cytoskeleton. Here, we provide evidence that not only the amplitude of a calcium signal is critical for growth cone motility but also the source of calcium mobilisation. We provide an example of this idea by demonstrating that manipulation of calcium signalling via L-type voltage gated calcium channels can perturb sensory neuron motility towards a source of netrin-1. Understanding how calcium signals can be transduced to initiate cytoskeletal changes represents a significant gap in our current knowledge of the mechanisms that govern axon guidance, and consequently the formation of functional neural circuits in the developing nervous system. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.
Cauley, K A; Hu, Y; Och, J; Yorks, P J; Fielden, S W
2018-04-01
The majority of brain growth and development occur in the first 2 years of life. This study investigated these changes by analysis of the brain radiodensity histogram of head CT scans from the clinical population, 0-2 years of age. One hundred twenty consecutive head CTs with normal findings meeting the inclusion criteria from children from birth to 2 years were retrospectively identified from 3 different CT scan platforms. Histogram analysis was performed on brain-extracted images, and histogram mean, mode, full width at half maximum, skewness, kurtosis, and SD were correlated with subject age. The effects of scan platform were investigated. Normative curves were fitted by polynomial regression analysis. Average total brain volume was 360 cm 3 at birth, 948 cm 3 at 1 year, and 1072 cm 3 at 2 years. Total brain tissue density showed an 11% increase in mean density at 1 year and 19% at 2 years. Brain radiodensity histogram skewness was positive at birth, declining logarithmically in the first 200 days of life. The histogram kurtosis also decreased in the first 200 days to approach a normal distribution. Direct segmentation of CT images showed that changes in brain radiodensity histogram skewness correlated with, and can be explained by, a relative increase in gray matter volume and an increase in gray and white matter tissue density that occurs during this period of brain maturation. Normative metrics of the brain radiodensity histogram derived from routine clinical head CT images can be used to develop a model of normal brain development. © 2018 by American Journal of Neuroradiology.
p62 as a therapeutic target for inhibition of autophagy in prostate cancer.
Wang, Lei; Kim, Donghern; Wise, James T F; Shi, Xianglin; Zhang, Zhuo; DiPaola, Robert S
2018-04-01
To test the hypothesis that p62 is an optimal target for autophagy inhibition and Verteporfin, a clinically available drug approved by FDA to treat macular degeneration that inhibits autophagy by targeting p62 protein, can be developed clinically to improve therapy for advanced prostate cancer. Forced expression of p62 in PC-3 cells and normal prostate epithelial cells, RWPE-1 and PZ-HPV7, were carried out by transfection of these cells with pcDNA3.1/p62 or p62 shRNA plasmid. Autophagosomes and autophagic flux were measured by transfection of tandem fluorescence protein mCherry-GFP-LC3 construct. Apoptosis was measured by Annexin V/PI staining. Tumorigenesis was measured by a xenograft tumor growth model. Verteporfin inhibited cell growth and colony formation in PC-3 cells. Verteporfin generated crosslinked p62 oligomers, resulting in inhibition of autophagy and constitutive activation of Nrf2 as well as its target genes, Bcl-2 and TNF-α. In normal prostate epithelial cells, forced expression of p62 caused constitutive Nrf2 activation, development of apoptosis resistance, and Verteporfin treatment exhibited inhibitory effects. Verteporfin treatment also inhibited starvation-induced autophagic flux of these cells. Verteporfin inhibited tumorigenesis of both normal prostate epithelial cells with p62 expression and prostate cancer cells and decreased p62, constitutive Nrf2, and Bcl-xL in xenograft tumor tissues, indicating that p62 can be developed as a drug target against prostate cancer. p62 has a high potential to be developed as a therapeutic target. Verteporfin represents a prototypical agent with therapeutic potential against prostate cancer through inhibition of autophagy by a novel mechanism of p62 inhibition. © 2018 Wiley Periodicals, Inc.
Corn response to climate stress detected with satellite-based NDVI time series
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Ruoyu; Cherkauer, Keith; Bowling, Laura
Corn growth conditions and yield are closely dependent on climate variability. Leaf growth, measured as the leaf area index, can be used to identify changes in crop growth in response to climate stress. This research was conducted to capture patterns of spatial and temporal corn leaf growth under climate stress for the St. Joseph River watershed, in northeastern Indiana. Leaf growth is represented by the Normalized Difference Vegetative Index (NDVI) retrieved from multiple years (2000–2010) of Landsat 5 TM images. By comparing NDVI values for individual image dates with the derived normal curve, the response of crop growth to environmentalmore » factors is quantified as NDVI residuals. Regression analysis revealed a significant relationship between yield and NDVI residual during the pre-silking period, indicating that NDVI residuals reflect crop stress in the early growing period that impacts yield. Both the mean NDVI residuals and the percentage of image pixels where corn was under stress (risky pixel rate) are significantly correlated with water stress. Dry weather is prone to hamper potential crop growth, with stress affecting most of the observed corn pixels in the area. Oversupply of rainfall at the end of the growing season was not found to have a measurable effect on crop growth, while above normal precipitation earlier in the growing season reduces the risk of yield loss at the watershed scale. Furthermore, the spatial extent of stress is much lower when precipitation is above normal than under dry conditions, masking the impact of small areas of yield loss at the watershed scale.« less
Corn response to climate stress detected with satellite-based NDVI time series
Wang, Ruoyu; Cherkauer, Keith; Bowling, Laura
2016-03-23
Corn growth conditions and yield are closely dependent on climate variability. Leaf growth, measured as the leaf area index, can be used to identify changes in crop growth in response to climate stress. This research was conducted to capture patterns of spatial and temporal corn leaf growth under climate stress for the St. Joseph River watershed, in northeastern Indiana. Leaf growth is represented by the Normalized Difference Vegetative Index (NDVI) retrieved from multiple years (2000–2010) of Landsat 5 TM images. By comparing NDVI values for individual image dates with the derived normal curve, the response of crop growth to environmentalmore » factors is quantified as NDVI residuals. Regression analysis revealed a significant relationship between yield and NDVI residual during the pre-silking period, indicating that NDVI residuals reflect crop stress in the early growing period that impacts yield. Both the mean NDVI residuals and the percentage of image pixels where corn was under stress (risky pixel rate) are significantly correlated with water stress. Dry weather is prone to hamper potential crop growth, with stress affecting most of the observed corn pixels in the area. Oversupply of rainfall at the end of the growing season was not found to have a measurable effect on crop growth, while above normal precipitation earlier in the growing season reduces the risk of yield loss at the watershed scale. Furthermore, the spatial extent of stress is much lower when precipitation is above normal than under dry conditions, masking the impact of small areas of yield loss at the watershed scale.« less
Dandache, Sophie; Wouters, Jan; Ghesquière, Pol
2014-11-01
The main focus of this article is to develop a better understanding of the developmental trajectories of literacy and phonological skills within Dutch-speaking children. Children at high and low risk for dyslexia were followed and compared at four different moments: kindergarten and first, third and sixth grades. Three groups were then compared: (1) dyslexic readers; (2) normal readers at high risk for dyslexia; and (3) normal readers at low risk for dyslexia. Children diagnosed with dyslexia scored lower than high-risk normal readers on phonological awareness (PA), rapid automatized naming (RAN), verbal short-term memory and literacy skills. Normal readers at high risk scored between both groups, confirming that dyslexia is to be considered as a continuum rather than an all-or-none condition. Growth analyses showed that the three groups evolved similarly on all measures except for phoneme deletion and literacy measures. Finally, solely PA and RAN explained a significant amount of variance in the evolution of reading skills. Copyright © 2014 John Wiley & Sons, Ltd.
Computational Identification of MicroRNAs and Their Targets from Finger Millet (Eleusine coracana).
Usha, S; Jyothi, M N; Suchithra, B; Dixit, Rekha; Rai, D V; Nagesh Babu, R
2017-03-01
MicroRNAs are endogenous small RNAs regulating intrinsic normal growth and development of plant. Discovering miRNAs, their targets and further inferring their functions had become routine process to comprehend the normal biological processes of miRNAs and their roles in plant development. In this study, we used homology-based analysis with available expressed sequence tag of finger millet (Eleusine coracana) to predict conserved miRNAs. Three potent miRNAs targeting 88 genes were identified. The newly identified miRNAs were found to be homologous with miR166 and miR1310. The targets recognized were transcription factors and enzymes, and GO analysis showed these miRNAs played varied roles in gene regulation. The identification of miRNAs and their targets is anticipated to hasten the pace of key epigenetic regulators in plant development.
GaN based nanorods for solid state lighting
NASA Astrophysics Data System (ADS)
Li, Shunfeng; Waag, Andreas
2012-04-01
In recent years, GaN nanorods are emerging as a very promising novel route toward devices for nano-optoelectronics and nano-photonics. In particular, core-shell light emitting devices are thought to be a breakthrough development in solid state lighting, nanorod based LEDs have many potential advantages as compared to their 2 D thin film counterparts. In this paper, we review the recent developments of GaN nanorod growth, characterization, and related device applications based on GaN nanorods. The initial work on GaN nanorod growth focused on catalyst-assisted and catalyst-free statistical growth. The growth condition and growth mechanisms were extensively investigated and discussed. Doping of GaN nanorods, especially p-doping, was found to significantly influence the morphology of GaN nanorods. The large surface of 3 D GaN nanorods induces new optical and electrical properties, which normally can be neglected in layered structures. Recently, more controlled selective area growth of GaN nanorods was realized using patterned substrates both by metalorganic chemical vapor deposition (MOCVD) and by molecular beam epitaxy (MBE). Advanced structures, for example, photonic crystals and DBRs are meanwhile integrated in GaN nanorod structures. Based on the work of growth and characterization of GaN nanorods, GaN nanoLEDs were reported by several groups with different growth and processing methods. Core/shell nanoLED structures were also demonstrated, which could be potentially useful for future high efficient LED structures. In this paper, we will discuss recent developments in GaN nanorod technology, focusing on the potential advantages, but also discussing problems and open questions, which may impose obstacles during the future development of a GaN nanorod based LED technology.
Testicular growth and development in puberty.
Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma
2017-06-01
To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.
Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah
2008-01-01
We report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.
Young, Blanche; Minugh-Purvis, Nancy; Shimo, Tsuyoshi; St-Jacques, Benoit; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi; Koyama, Eiki; Pacifici, Maurizio
2006-11-01
The synchondroses consist of mirror-image growth plates and are critical for cranial base elongation, but relatively little is known about their formation and regulation. Here we show that synchondrosis development is abnormal in Indian hedgehog-null mice. The Ihh(-/-) cranial bases displayed reduced growth and chondrocyte proliferation, but chondrocyte hypertrophy was widespread. Rather than forming a typical narrow zone, Ihh(-/-) hypertrophic chondrocytes occupied an elongated central portion of each growth plate and were flanked by immature collagen II-expressing chondrocytes facing perichondrial tissues. Endochondral ossification was delayed in much of the Ihh(-/-) cranial bases but, surprisingly, was unaffected most posteriorly. Searching for an explanation, we found that notochord remnants near incipient spheno-occipital synchondroses at E13.5 expressed Sonic hedgehog and local chondrocytes expressed Patched, suggesting that Shh had sustained chondrocyte maturation and occipital ossification. Equally unexpected, Ihh(-/-) growth plates stained poorly with Alcian blue and contained low aggrecan transcript levels. A comparable difference was seen in cultured wild-type versus Ihh(-/-) synchondrosis chondrocytes. Treatment with exogenous Ihh did not fully restore normal proteoglycan levels in mutant cultures, but a combination of Ihh and BMP-2 did. In summary, Ihh is required for multiple processes during synchondrosis and cranial base development, including growth plate zone organization, chondrocyte orientation, and proteoglycan production. The cranial base appears to be a skeletal structure in which growth and ossification patterns along its antero-posterior axis are orchestrated by both Ihh and Shh.
Role of mechanical factors in cortical folding development
NASA Astrophysics Data System (ADS)
Razavi, Mir Jalil; Zhang, Tuo; Li, Xiao; Liu, Tianming; Wang, Xianqiao
2015-09-01
Deciphering mysteries of the structure-function relationship in cortical folding has emerged as the cynosure of recent research on brain. Understanding the mechanism of convolution patterns can provide useful insight into the normal and pathological brain function. However, despite decades of speculation and endeavors the underlying mechanism of the brain folding process remains poorly understood. This paper focuses on the three-dimensional morphological patterns of a developing brain under different tissue specification assumptions via theoretical analyses, computational modeling, and experiment verifications. The living human brain is modeled with a soft structure having outer cortex and inner core to investigate the brain development. Analytical interpretations of differential growth of the brain model provide preliminary insight into the critical growth ratio for instability and crease formation of the developing brain followed by computational modeling as a way to offer clues for brain's postbuckling morphology. Especially, tissue geometry, growth ratio, and material properties of the cortex are explored as the most determinant parameters to control the morphogenesis of a growing brain model. As indicated in results, compressive residual stresses caused by the sufficient growth trigger instability and the brain forms highly convoluted patterns wherein its gyrification degree is specified with the cortex thickness. Morphological patterns of the developing brain predicted from the computational modeling are consistent with our neuroimaging observations, thereby clarifying, in part, the reason of some classical malformation in a developing brain.
Orientations of dendritic growth during solidification
NASA Astrophysics Data System (ADS)
Lee, Dong Nyung
2017-03-01
Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.
Barczynska, Renata; Kapusniak, Janusz; Litwin, Mieczyslaw; Slizewska, Katarzyna; Szalecki, Mieczyslaw
2016-06-01
Unarguably, diet has a significant impact on human intestinal microbiota. The role of prebiotics as substances supporting the maintenance of appropriate body weight and reducing the demand for energy via stimulation of the growth of beneficial microbiota of the gut and formation products such as short-chain fatty acids, is more and more often highlighted. The objective of this study was to evaluate whether dextrins from maize starch resistant to enzymatic digestion stimulate the growth of Bacteroidetes and Actinobacteria strains representing a majority of the population of colon microbiota in lean individuals and limit the growth of Firmicutes bacterial strains representing a majority of the population of colon microbiota in obese individuals. The study was conducted with the use of in vitro method, using isolates from faeces of children characterized by normal weight, overweight and obesity. It was demonstrated that dextrins from maize starch equally efficient stimulate the growth of the isolates derived from normal-weight, overweight and obese children, and therefore may be added to foods as a beneficial component stimulating growth of strains belonging to Actinobacteria and Bacteroidetes for both overweight, obese and normal-weight children.
Jiang, Lingyan; Luo, Xiuquan; Shi, Jingxue; Sun, Hong; Sun, Qing; Sheikh, M Saeed
2011-01-01
We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDRG1 may be linked to cell growth regulation. Yeast two-hybrid screening also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression. PMID:21193842
Sarker, Rim Sabrina Jahan; Ahsan, Nazmul; Hossain, Khaled; Ghosh, Paritosh Kumar; Ahsan, Chowdhury Rafiqul; Akhand, Anwarul Azim
2012-07-01
In this study, we evaluated the protective effects of water Hyacinth Root Powder (HRP) on arsenic-mediated toxic effects in mice. Swiss albino mice, used in this study, were divided into four different groups (for each group n=5). The control group was supplied with normal feed and water, Arsenic group (As-group) was supplied with normal feed plus arsenic (sodium arsenite)-containing water, and arsenic+hyacinth group (As+Hy group) was supplied with feed supplemented with HRP plus arsenic water. The remaining Hy-group was supplied with feed supplemented with HRP plus normal water. Oral administration of arsenic reduced the normal growth of the mice as evidenced by weight loss. Interestingly, tip of the tails of these mice developed wound that caused gradual reduction of the tail length. Supplementation of HRP in feed significantly prevented mice growth retardation and tail wounding in As+Hy group mice. However, the growth pattern in Hy-group mice was observed to be almost similar to that of the control group indicating that HRP itself has no toxic or negative effect in mice. Ingested arsenic also distorted the shape of the blood cells and elevated the serum enzymes such as lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and serum glutamic pyruvic transaminase (SGPT). Importantly, elevation of these enzymes and distortion of blood cell shape were partially reduced in mice belong to As+Hy group, indicating HRP-mediated reduction of arsenic toxicity. Therefore, the preventive effect of hyacinth root on arsenic-poisoned mice suggested the future application of hyacinth to reduce arsenic toxicity in animal and human.