Sample records for human early growth

  1. Basic fibroblast growth factor promotes the development of human ovarian early follicles during growth in vitro.

    PubMed

    Wang, Tian-ren; Yan, Li-ying; Yan, Jie; Lu, Cui-ling; Xia, Xi; Yin, Tai-lang; Zhu, Xiao-hui; Gao, Jiang-man; Ding, Ting; Hu, Wei-hong; Guo, Hong-yan; Li, Rong; Qiao, Jie

    2014-03-01

    What is the effect of basic fibroblast growth factor (bFGF) on the growth of individual early human follicles in a three-dimensional (3D) culture system in vitro? The addition of 200 ng bFGF/ml improves human early follicle growth, survival and viability during growth in vitro. It has been demonstrated that bFGF enhances primordial follicle development in human ovarian tissue culture. However, the growth and survival of individual early follicles in encapsulated 3D culture have not been reported. The maturation in vitro of human ovarian follicles was investigated. Ovarian tissue (n= 11) was obtained from 11 women during laparoscopic surgery for gynecological disease, after obtaining written informed consent. One hundred and fifty-four early follicles were isolated by enzymic digestion and mechanical disruption. They were individually encapsulated into alginate (1% w/v) and randomly assigned to be cultured with 0, 100, 200 or 300 ng bFGF/ml for 8 days. Individual follicles were cultured in minimum essential medium α (αMEM) supplemented with bFGF. Follicle survival and growth were assessed by microscopy. Follicle viability was evaluated under confocal laser scanning microscope following Calcein-AM and Ethidium homodimer-I (Ca-AM/EthD-I) staining. After 8 days in culture, all 154 follicles had increased in size. The diameter and survival rate of the follicles and the percentage with good viability were significantly higher in the group cultured with 200 ng bFGF/ml than in the group without bFGF (P < 0.05). The percentage of follicles in the pre-antral stage was significantly higher in the 200 ng bFGF/ml group than in the group without bFGF (P < 0.05), while the percentages of primordial and primary follicles were significantly lower (P < 0.05). The study focuses on the effect of bFGF on the development of individual human early follicles in 3D culture in vitro and has limited ability to reveal the specific effect of bFGF at each different stage. The findings

  2. Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors.

    PubMed

    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

  3. Regulation of early human growth: impact on long-term health.

    PubMed

    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.

  4. Metabolic effects of growth factors and polycyclic aromatic hydrocarbons on cultured human placental cells of early and late gestation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guyda, H.J.

    1991-03-01

    The metabolic effects of epidermal growth factor (EGF), insulin, insulin-like growth factor-I (IGF-I), and IGF-II were determined on human placental cells in monolayer culture obtained from early gestation (less than 20 weeks) and late gestation (38-42 weeks). Parameters studied were uptake of aminoisobutyric acid (AIB), uptake of 3-O-methylglucose and (3H)thymidine incorporation into cell protein. Since benzo(alpha)pyrene (BP) inhibits EGF binding and autophosphorylation in cultured human placental cells, particularly in early gestation, we also studied the effect of benzo(alpha)pyrene and other polycyclic aromatic hydrocarbons (PAHs) on EGF-mediated AIB uptake. The metabolic effects of EGF, insulin, and the IGFs in cultured humanmore » placental cells varied with gestational age and the growth factor studied. All three classes of growth factors stimulated AIB uptake in both early and late gestation at concentrations from 10-100 micrograms/L, well within a physiological range. However, insulin stimulation of AIB uptake was maximal at a high concentration in both early and late gestation cells, suggesting an action via type 1 IGF receptors rather than via insulin receptors. EGF stimulated 3-O-methylglucose uptake only in term placental cells. No significant stimulation of (3H)thymidine incorporation by any of the growth factors tested was seen with either early or late gestation cells. The effect of PAHs on AIB uptake by cultured placental cells was variable. BP alone stimulated AIB uptake by both very early and late gestation cells and enhanced EGF-stimulated AIB uptake. alpha-naphthoflavone alone inhibited AIB uptake at all gestational ages and inhibited EGF-stimulated AIB uptake. beta-Naphthoflavone and 3-methylcholanthrene minimally inhibited AIB uptake by early gestation cells and did not modify EGF-stimulated uptake at any gestational period.« less

  5. Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors.

    PubMed

    Kimber, S J; Sneddon, S F; Bloor, D J; El-Bareg, A M; Hawkhead, J A; Metcalfe, A D; Houghton, F D; Leese, H J; Rutherford, A; Lieberman, B A; Brison, D R

    2008-05-01

    Little is understood about the regulation of gene expression in human preimplantation embryos. We set out to examine the expression in human preimplantation embryos of a number of genes known to be critical for early development of the murine embryo. The expression profile of these genes was analysed throughout preimplantation development and in response to growth factor (GF) stimulation. Developmental expression of a number of genes was similar to that seen in murine embryos (OCT3B/4, CDX2, NANOG). However, GATA6 is expressed throughout preimplantation development in the human. Embryos were cultured in IGF-I, leukaemia inhibitory factor (LIF) or heparin-binding EGF-like growth factor (HBEGF), all of which are known to stimulate the development of human embryos. Our data show that culture in HBEGF and LIF appears to facilitate human embryo expression of a number of genes: ERBB4 (LIF) and LIFR and DSC2 (HBEGF) while in the presence of HBEGF no blastocysts expressed EOMES and when cultured with LIF only two out of nine blastocysts expressed TBN. These data improve our knowledge of the similarities between human and murine embryos and the influence of GFs on human embryo gene expression. Results from this study will improve the understanding of cell fate decisions in early human embryos, which has important implications for both IVF treatment and the derivation of human embryonic stem cells.

  6. [Early childhood growth and development].

    PubMed

    Arce, Melitón

    2015-01-01

    This article describes and discusses issues related to the process of childhood growth and development, with emphasis on the early years, a period in which this process reaches critical speed on major structures and functions of the human economy. We reaffirm that this can contribute to the social availability of a generation of increasingly better adults, which in turn will be able to contribute to building a better world and within it a society that enjoys greater prosperity. In the first chapter, we discuss the general considerations on the favorable evolution of human society based on quality of future adults, meaning the accomplishments that today’s children will gain. A second chapter mentions the basics of growth and development in the different fields and the various phenomena that occur in it. In the third we refer to lost opportunities and negative factors that can affect delaying the process and thereby result in not obtaining the expected accomplishments. In the fourth, conclusions and recommendations are presented confirming the initial conception that good early child care serves to build a better society and some recommendations are formulated to make it a good practice.

  7. Growth hormone and early treatment.

    PubMed

    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.

  8. Hormones and Human and Nonhuman Primate Growth.

    PubMed

    Bernstein, Robin Miriam

    2017-01-01

    The aim of this paper was to review information pertaining to the hormonal regulation of nonhuman primate growth, with specific focus on the growth hormone (GH)-insulin-like growth factor (IGF) axis and adrenal androgens. Hormones of the GH-IGF axis are consistently associated with measures of growth - linear, weight, or both - during the growth period; in adulthood, concentrations of IGF-I, IGF-binding protein-3, and GH-binding protein are not associated with any measures of size. Comparing patterns of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) may be especially relevant for understanding whether the childhood stage of growth and development is unique to humans and perhaps other apes. Genetic, hormonal, and morphological data on adrenarche in other nonhuman primate species suggest that this endocrine transition is delayed in humans, chimpanzees, and possibly gorillas, while present very early in postnatal life in macaques. This suggests that although perhaps permitted by an extension of the pre-adolescent growth period, childhood builds upon existing developmental substrates rather than having been inserted de novo into an ancestral growth trajectory. Hormones can provide insight regarding the evolution of the human growth trajectory. © 2017 S. Karger AG, Basel.

  9. The Not-so-Dark Ages: ecology for human growth in medieval and early twentieth century Portugal as inferred from skeletal growth profiles.

    PubMed

    Cardoso, Hugo F V; Garcia, Susana

    2009-02-01

    This study attempts to address the issue of relative living standards in Portuguese medieval and early 20th century periods. Since the growth of children provides a good measure of environmental quality for the overall population, the skeletal growth profiles of medieval Leiria and early 20th century Lisbon were compared. Results show that growth in femur length of medieval children did not differ significantly from that of early 20th century children, but after puberty medieval adolescents seem to have recovered, as they have significantly longer femora as adults. This is suggestive of greater potential for catch-up growth in medieval adolescents. We suggest that this results from distinct child labor practices, which impact differentially on the growth of Leiria and Lisbon adolescents. Work for medieval children and adolescents were related to family activities, and care and attention were provided by family members. Conversely, in early 20th century Lisbon children were more often sent to factories at around 12 years of age as an extra source of family income, where they were exploited for their labor. Since medieval and early 20th century children were stunted at an early age, greater potential for catch-up growth in medieval adolescents results from exhausting work being added to modern adolescent's burdens of disease and poor diet, when they entered the labor market. Although early 20th century Lisbon did not differ in overall unfavorable living conditions from medieval Leiria, after puberty different child labor practices may have placed modern adolescents at greater risk of undernutrition and poor growth. 2008 Wiley-Liss, Inc.

  10. Retrieving chronological age from dental remains of early fossil hominins to reconstruct human growth in the past.

    PubMed

    Dean, M Christopher

    2010-10-27

    A chronology of dental development in Pan troglodytes is arguably the best available model with which to compare and contrast reconstructed dental chronologies of the earliest fossil hominins. Establishing a time scale for growth is a requirement for being able to make further comparative observations about timing and rate during both dento-skeletal growth and brain growth. The absolute timing of anterior tooth crown and root formation appears not to reflect the period of somatic growth. In contrast, the molar dentition best reflects changes to the total growth period. Earlier initiation of molar mineralization, shorter crown formation times, less root length formed at gingival emergence into functional occlusion are cumulatively expressed as earlier ages at molar eruption. Things that are similar in modern humans and Pan, such as the total length of time taken to form individual teeth, raise expectations that these would also have been the same in fossil hominins. The best evidence there is from the youngest fossil hominin specimens suggests a close resemblance to the model for Pan but also hints that Gorilla may be a better developmental model for some. A mosaic of great ape-like features currently best describes the timing of early hominin dental development.

  11. Retrieving chronological age from dental remains of early fossil hominins to reconstruct human growth in the past

    PubMed Central

    Dean, M. Christopher

    2010-01-01

    A chronology of dental development in Pan troglodytes is arguably the best available model with which to compare and contrast reconstructed dental chronologies of the earliest fossil hominins. Establishing a time scale for growth is a requirement for being able to make further comparative observations about timing and rate during both dento-skeletal growth and brain growth. The absolute timing of anterior tooth crown and root formation appears not to reflect the period of somatic growth. In contrast, the molar dentition best reflects changes to the total growth period. Earlier initiation of molar mineralization, shorter crown formation times, less root length formed at gingival emergence into functional occlusion are cumulatively expressed as earlier ages at molar eruption. Things that are similar in modern humans and Pan, such as the total length of time taken to form individual teeth, raise expectations that these would also have been the same in fossil hominins. The best evidence there is from the youngest fossil hominin specimens suggests a close resemblance to the model for Pan but also hints that Gorilla may be a better developmental model for some. A mosaic of great ape-like features currently best describes the timing of early hominin dental development. PMID:20855313

  12. 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...

  13. An assessment of early mandibular growth.

    PubMed

    Hutchinson, E F; L'Abbé, E N; Oettlé, A C

    2012-04-10

    Quantification of skeletal data has been shown to be an effective and reliable method of demonstrating variation in human growth as well as for monitoring and interpreting growth. In South Africa as well as internationally, few researchers have assessed mandibular growth in late fetal period and early childhood and therefore standards for growth and age determination in these groups are limited. The purpose of this study was to evaluate growth in the mandible from the period of 31 gestational weeks to 36 months postnatal. A total of 74 mandibles were used. Dried mandibles were sourced from the Raymond A. Dart Collection (University of Witwatersrand), and cadaveric remains were obtained from the Universities of Pretoria and the Witwatersrand. The sample was divided into four groups; 31-40 gestational weeks (group 1), 0-11 months (group 2), 12-24 months (group 3), and 25-36 months (group 4). Twenty-one osteological landmarks were digitized using a MicroScribe G2. Ten standard measurements were created and included: the maximum length of mandible, mandibular body length and width, mandibular notch width and depth, mental foramen to inferior border of mandible, mandibular basilar widths bigonial and biantegonial, bigonial width of mental foramen and mental angle. Data were analyzed using PAST statistical software and Morphologika2 v2.5. Statistically significant differences were noted in the linear measurements for all group comparisons except between groups 3 and 4. The mandible morphologically changed from a round, smooth contour anteriorly to adopt a more sharp and narrow adult shape. A progressive increase in the depth and definition of the mandibular arch was also noted. In conclusion, the mandible initially grows to accommodate the developing tongue (up to 11 months), progressive dental eruption and mastication from 12 to 36 months. Mastication is associated with muscle mass development; this would necessitate an increase in the dimensions of the mandibular notch

  14. A case of functional growth hormone deficiency and early growth retardation in a child with IFT172 mutations.

    PubMed

    Lucas-Herald, Angela K; Kinning, Esther; Iida, Aritoshi; Wang, Zheng; Miyake, Noriko; Ikegawa, Shiro; McNeilly, Jane; Ahmed, S Faisal

    2015-04-01

    Ciliopathies are a group of rare conditions that present through a wide range of manifestations. Given the relative common occurrence of defects of the GH/IGF-I axis in children with short stature and growth retardation, the association between ciliopathies and these defects needs further attention. Our patient is a boy who was born at term and noted to have early growth retardation and weight gain within the first 18 months of life. Biochemical tests demonstrated low IGF-I but a normal peak GH on stimulation and an adequate increase in IGF-I on administration of recombinant human growth hormone (rhGH). A magnetic resonance imaging scan revealed pituitary hypoplasia and an ectopic posterior pituitary. His growth responded well to rhGH therapy. Subsequently he also developed a retinopathy of his rods and cones, metaphyseal dysplasia, and hypertension with renal failure requiring renal replacement therapy. Whole-exome sequencing demonstrated compound heterozygous mutations of IFT172, thus consistent with a ciliopathy. This is the first reported case of a child with a mutation in IFT172 who presented with growth retardation in early childhood and was initially managed as a case of functional GH deficiency that responded to rhGH therapy. This case highlights the importance of ciliary function in pituitary development and the link between early onset growth failure and ciliopathies.

  15. A Big Bang model of human colorectal tumor growth

    PubMed Central

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A.; Salomon, Matthew P.; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F.; Shibata, Darryl; Curtis, Christina

    2015-01-01

    What happens in the early, still undetectable human malignancy is unknown because direct observations are impractical. Here we present and validate a “Big Bang” model, whereby tumors grow predominantly as a single expansion producing numerous intermixed sub-clones that are not subject to stringent selection, and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors revealed the absence of selective sweeps, uniformly high intra-tumor heterogeneity (ITH), and sub-clone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations, and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear born-to-be-bad, with sub-clone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH with significant clinical implications. PMID:25665006

  16. A Big Bang model of human colorectal tumor growth.

    PubMed

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  17. Biomonitoring of human fetal exposure to environmental chemicals in early pregnancy.

    PubMed

    Cooke, Gerard M

    2014-01-01

    The first trimester of human fetal life, a period of extremely rapid development of physiological systems, represents the most rapid growth phase in human life. Interference in the establishment of organ systems may result in abnormal development that may be manifest immediately or programmed for later abnormal function. Exposure to environmental chemicals may be affecting development at these early stages, and yet there is limited knowledge of the quantities and identities of the chemicals to which the fetus is exposed during early pregnancy. Clearly, opportunities for assessing fetal chemical exposure directly are extremely limited. Hence, this review describes indirect means of assessing fetal exposure in early pregnancy to chemicals that are considered disrupters of development. Consideration is given to such matrices as maternal hair, fingernails, urine, saliva, sweat, breast milk, amniotic fluid and blood, and fetal matrices such as cord blood, cord tissue, meconium, placenta, and fetal liver. More than 150 articles that presented data from chemical analysis of human maternal and fetal tissues and fluids were reviewed. Priority was given to articles where chemical analysis was conducted in more than one matrix. Where correlations between maternal and fetal matrices were determined, these articles were included and are highlighted, as these may provide the basis for future investigations of early fetal exposure. The determination of fetal chemical exposure, at the time of rapid human growth and development, will greatly assist regulatory agencies in risk assessments and establishment of advisories for risk management concerning environmental chemicals.

  18. High early life mortality in free-ranging dogs is largely influenced by humans

    PubMed Central

    Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

    2016-01-01

    Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

  19. Early development of synchrony in cortical activations in the human.

    PubMed

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Falls, sarcopenia and growth in early life

    PubMed Central

    Sayer, Avan Aihie; Syddall, Holly E; Martin, Helen J; Dennison, Elaine M; Anderson, Frazer H; Cooper, Cyrus

    2007-01-01

    Recent studies have shown that people with poor early growth have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls but it is not known whether poor early growth is related to falls. We investigated this in the Hertfordshire Cohort Study where 2148 participants completed a falls history. Grip strength was used as a marker of sarcopenia. Birth weight, weight at one year and conditional infant growth were analysed in relation to falls history. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height and walking speed in men and women as well as to lower conditional infant growth in men (OR 1.27 [95% CI 1.04, 1.56] per SD decrease in conditional infant growth, p=0.02). This association was attenuated after adjustment for grip strength. Our findings support an association between poor early growth and falls in older men which appears to be mediated partly through sarcopenia. The lack of relationship with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important for risk of falls in later life. PMID:16905644

  1. Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

    PubMed

    Buklijas, Tatjana

    2014-09-01

    Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Effect of Early Expressed Human Milk on Insulin-Like Growth Factor 1 and Short-Term Outcomes in Preterm Infants.

    PubMed

    Serrao, Francesca; Papacci, Patrizia; Costa, Simonetta; Giannantonio, Carmen; Cota, Francesco; Vento, Giovanni; Romagnoli, Costantino

    2016-01-01

    Preterm breast milk contains high levels of bioactive components, including insulin-like growth factor 1 (IGF-1), that are reduced by Holder pasteurization. Animal studies have shown that milk-borne IGF-1 is likely absorbed intact in a bioactive form by the intestines. The aim of this study was to assess if early non-pasteurized expressed breast milk nutrition may affect IGF-1 plasma levels in premature infants. We also investigated the possible association between early expressed milk nutrition and short-term outcomes. Fifty-two preterm infants with gestational age < 31 weeks were divided into two groups according to expressed breast milk intake (< or ≥ 50 mL/Kg/day) until 32 weeks of postmenstrual age when blood sampling for IGF-1 analysis was performed. In our population, early expressed breast milk does not affect IGF-1 plasma levels (p 0.48). An association was observed between early expressed milk nutrition and a lower incidence of bronchopulmonary dysplasia, sepsis, feeding intolerance, need for parenteral nutrition and length of hospitalization. Contrary to the results in some animal studies, our results did not seem to show that early expressed breast milk can help to maintain postnatal IGF-1 near foetal levels in preterm infants. The observed protective effect of expressed breast milk on short-term outcomes can be the starting point for further study of the effects of non-pasteurized human milk in preterm infants.

  3. Germination and Early Growth of Brassica juncea in Copper Mine Tailings Amended with Technosol and Compost

    PubMed Central

    González, Luís

    2014-01-01

    Mine tailings represent a serious threat to the environment and human health; thus their restoration has become a major concern. In this study, the interactions between Brassica juncea and different mine soil treatments were evaluated in order to understand their effect on germination and early growth. Three soil treatments containing 25% and 50% of technosol and 30% of compost were prepared. Germination and early growth were assessed in soil and pore water extracts from the treatments. Unlike the untreated mine soil, the three treatments allowed germination and growth, achieving levels comparable to those of seedlings from the same species developed in normal conditions. The seedlings grown in 50% of technosol and 30% of compost exhibited greater germination percentages, higher growth, and more efficient mechanisms against oxidative stress, ascribed to the organic matter and nutrients content of these treatments. Considering the unequivocal ability of B. juncea for phytoremediation, the results suggest that technosol and compost may be an auspicious solution to allow the germination and early growth of this species in mine tailings. PMID:25386602

  4. Cow milk consumption, insulin-like growth factor-I, and human biology: a life history approach.

    PubMed

    Wiley, Andrea S

    2012-01-01

    To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences. Copyright © 2011 Wiley Periodicals, Inc.

  5. A general theory of early growth?. Comment on: "Mathematical models to characterize early epidemic growth: A review" by Gerardo Chowell et al.

    NASA Astrophysics Data System (ADS)

    House, Thomas

    2016-09-01

    Chowell et al. [1] consider the early growth behaviour of various epidemic models that range from phenomenological approaches driven by data to mechanistic descriptions of complex interactions between individuals. This is particularly timely given the recent Ebola epidemic, although non-exponential early growth may be more common (but less immediately evident) than we realise.

  6. Progressive loss of sensitivity to growth control by retinoic acid and transforming growth factor-beta at late stages of human papillomavirus type 16-initiated transformation of human keratinocytes.

    PubMed

    Creek, K E; Geslani, G; Batova, A; Pirisi, L

    1995-01-01

    Retinoids (vitamin A and its natural and synthetic derivatives) have shown potential as chemopreventive agents, and diets poor in vitamin A and/or its precursor beta-carotene have been linked to an increased risk of cancer at several sites including the cervix. Human papillomavirus (HPV) plays an important role in the etiology of cervical cancer. We have developed an in vitro model of cancer progression using human keratinocytes (HKc) immortalized by HPV16 DNA (HKc/HPV16). Although immortal, early passage HKc/HPV16, like normal HKc, require epidermal growth factor (EGF) and bovine pituitary extract (BPE) for proliferation and undergo terminal differentiation in response to serum and calcium. However, following prolonged culture, growth factor independent HKc/HPV16 lines that no longer require EGF and BPE can be selected (HKc/GFI). Further selection of HKc/GFI produces lines that are resistant to serum- and calcium- induced terminal differentiation (HKc/DR). HKc/DR, but not early passage HKc/HPV16, are susceptible to malignant conversion following transfection with viral Harvey ras or Herpes simplex virus type II DNA. We have investigated the sensitivity of low to high passage HKc/HPV16 and HKc/GFI to growth control by all-trans-retinoic acid (RA, an active metabolite of vitamin A). Early passage HKc/HPV16 are very sensitive to growth inhibition by RA, and in these cells RA decreases the expression of the HPV16 oncogenes E6 and E7. However, as the cells progress in culture they lose their sensitivity to RA. Growth inhibition by RA may be mediated through the cytokine transforming growth factor-beta (TGF-beta), a potent inhibitor of epithelial cell proliferation. RA treatment of HKc/HPV16 and HKc/GFI results in a dose-and time-dependent induction (maximal of 3-fold) in secreted levels of TGF-beta. Also, Northern blot analysis of mRNA isolated from HKc/HPV16 demonstrated that RA treatment induced TGF-beta 1 and TGF-beta 2 expression about 3- and 50-fold, respectively

  7. Normal development and growth of the human neurocranium and cranial base.

    PubMed

    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.

  8. The early spread and epidemic ignition of HIV-1 in human populations

    PubMed Central

    Faria, Nuno R.; Rambaut, Andrew; Suchard, Marc A.; Baele, Guy; Bedford, Trevor; Ward, Melissa J.; Tatem, Andrew J.; Sousa, João D.; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G.; Lemey, Philippe

    2014-01-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. PMID:25278604

  9. Human-Friendly Light-Emitting Diode Source Stimulates Broiler Growth.

    PubMed

    Pan, Jinming; Yang, Yefeng; Yang, Bo; Dai, Wenhua; Yu, Yonghua

    2015-01-01

    Previous study and our laboratory have reported that short-wavelength (blue and green) light and combination stimulate broiler growth. However, short-wavelength stimuli could have negative effects on poultry husbandry workers. The present study was conducted to evaluate the effects of human-friendly yellow LED light, which is acceptable to humans and close to green light, on broiler growth. We also aimed to investigate the potential quantitative relationship between the wavelengths of light used for artificial illumination and growth parameters in broilers. After hatching, 360 female chicks ("Meihuang" were evenly divided into six lighting treatment groups: white LED strips (400-700 nm, WL); red LED strips (620 nm, RL); yellow LED strips (580 nm, YL); green LED strips (514 nm, GL); blue LED strips (455 nm, BL); and fluorescent strips (400-700 nm, FL). From 30 to 72 days of age, broilers reared under YL and GL were heavier than broilers treated with FL (P < 0.05). Broilers reared under YL obtained the similar growth parameters with the broilers reared under GL and BL (P > 0.05). Moreover, YL significantly improved feeding efficiency when compared with GL and BL at 45 and 60 days of age (P < 0.05). In addition, we found an age-dependent effect of light spectra on broiler growth and a quantitative relationship between LED light spectra (455 to 620 nm) and the live body weights of broilers. The wavelength of light (455 to 620 nm) was found to be negatively related (R2 = 0.876) to live body weight at an early stage of development, whereas the wavelength of light (455 to 620 nm) was found to be positively correlated with live body weight (R2 = 0.925) in older chickens. Our results demonstrated that human-friendly yellow LED light (YL), which is friendly to the human, can be applied to the broilers production.

  10. Stock size affects early growth of a loblolly pine

    Treesearch

    David B. South; Al Lyons; Russ Pohl

    2015-01-01

    For decades, forest researchers in the South have known that early gains in survival and growth of loblolly pine (Pinus taeda L.) can be achieved by planting large-diameter seedlings (South 1993; Wakeley 1949). For P. radiata, increasing size of planting stock also increases early growth of both seedlings (Mason and others 1996) and cuttings (South and others 2005)....

  11. Hyaluronan up-regulates growth and invasion of trophoblasts in an autocrine manner via PI3K/AKT and MAPK/ERK1/2 pathways in early human pregnancy.

    PubMed

    Zhu, R; Huang, Y-H; Tao, Y; Wang, S-C; Sun, Ch; Piao, H-L; Wang, X-Q; Du, M-R; Li, D-J

    2013-09-01

    As one of the key molecules in the extracellular matrix in human conceptus, hyaluronan (HA) has been receiving particular attention. Here, we have investigated the expression and regulation of different molecular weight HA on the biological behaviors of primary human trophoblasts during the first trimester of pregnancy. The expression of HA and HA synthetase (HAS) by human first trimester trophoblasts was analyzed in placentae from normal pregnancy or miscarriage by immunochemistry and real-time RT-PCR, respectively. ELISA was used to measure the secretion of HA by primary trophoblasts. The effects of HA on the proliferation, apoptosis and invasiveness of trophoblasts were examined. We also investigated the signaling pathways involved in HA activation in human trophoblasts. The higher HAS2 expression and HA secretion were observed in normal villi than that of miscarriage, and the primary trophoblasts secreted HA continuously. High molecular weight HA (HMW-HA) and medium molecular weight HA (MMW-HA) promoted proliferation and invasiveness while inhibited apoptosis of trophoblasts. However, low molecular weight HA (LMW-HA) had no obvious effect on the growth or invasiveness of human trophoblasts. In addition, HMW-HA showed more efficiently than MMW-HA on the growth while MMW-HA displayed a more obvious effect on the invasiveness of trophoblasts than HMW-HA. HMW-HA activated PI3K/AKT and MAPK/ERK1/2 signaling pathways in trophoblasts. Blocking PI3K/AKT or MAPK/ERK1/2 signaling inhibited the HA-upregulated growth and invasiveness of human trophoblasts. Our results suggest that higher level and greater molecular mass of HA can promote trophoblast growth and invasion in an autocrine manner, which was beneficial to placentation and maintenance of human early pregnancy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Growth charts of human development.

    PubMed

    van Buuren, Stef

    2014-08-01

    This article reviews and compares two types of growth charts for tracking human development over age. Both charts assume the existence of a continuous latent variable, but relate to the observed data in different ways. The D-score diagram summarizes developmental indicators into a single aggregate score measuring global development. The relations between the indicators should be consistent with the Rasch model. If true, the D-score is a measure with interval scale properties, and allows for the calculation of meaningful differences both within and across age. The stage line diagram describes the natural development of ordinal indicators. The method models the transition probabilities between successive stages of the indicator as smoothly varying functions of age. The location of each stage is quantified by the mid-P-value. Both types of diagrams assist in identifying early and delayed development, as well as finding differences in tempo. The relevant techniques are illustrated to track global development during infancy and early childhood (0-2 years) and Tanner pubertal stages (8-21 years). New reference values for both applications are provided. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  13. Utilization of Microgravity Bioreactor for Differentiation and Growth of Human Vascular Endothelial Cells

    NASA Technical Reports Server (NTRS)

    Chen, Chu-Huang; Pellis, Neal R.

    1997-01-01

    The goal was to delineate mechanisms of genetic responses to angiogenic stimulation of human coronary arterial and dermal microvascular endothelial cells during exposure to microgravity. The NASA-designed rotating-wall vessel was used to create a three-dimensional culture environment with low shear-stress and microgravity simulating that in space. The primary specific aim was to determine whether simulated microgravity enhances endothelial cell growth and whether the growth enhancement is associated by augmented expression of Basic Fibroblast Growth Factor (BFGF) and c-fos, an immediate early gene and component of the transcription factor AP-1.

  14. Early maternal serum ß-human chorionic gonadotropin (ß-hCG) levels and sex-related growth difference of IVF embryos.

    PubMed

    Esh-Broder, Efrat; Oron, Galia; Son, Weon-Young; Holzer, Hananel; Tulandi, Togas

    2015-10-01

    Maternal serum ß-human chorionic gonadotropin (ß-hCG) represents the trophoblastic cell mass and is an indirect measurement of embryo development at early implantation stage. Studies in animals and human embryos detected sex-related growth differences (SRGD) in favour of male embryos during the pre-implantation period. The purpose of our study was to correlate SRGD and maternal serum ß-hCG at 16 days after embryo transfer. We retrospectively analysed all (fresh and frozen) non-donor, single embryo transfers (SET), elective and not elective, that were performed between December 2008 and December 2013. We included ß-hCG values from day 16 after oocyte collection of pregnancies resulting in live birth. Neonatal gender was retrieved from patient files. Male and female embryos were further grouped to cleavage and blastocyst stage transfers. Regression analysis for confounding variables included maternal age, maternal body mass index (BMI), use of micromanipulation (ICSI), embryo quality (grade), assisted hatching, day of transfer and fresh or frozen embryo transfer. Seven hundred eighty-six non-donor SETs resulted in live birth. After including only day 16 serum ß-hCG results, 525 SETs were analysed. Neonatal gender was available for 522 cases. Mean maternal serum ß-hCG levels were similar, 347 ± 191 IU/L in the male newborn group and 371 ± 200 IU/L in the female group. The difference between ß-hCG levels remained insignificant after adjusting for confounding variables. Early maternal ß-hCG levels after embryo transfers did not represent SRGD in our study.

  15. Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

    NASA Image and Video Library

    1995-08-08

    Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

  16. Transcriptomic profile of leg muscle during early growth in chicken

    PubMed Central

    Zhang, Genxi; Li, Tingting; Ling, Jiaojiao; Zhang, Xiangqian; Wang, Jinyu

    2017-01-01

    The early growth pattern, especially the age of peak growth, of broilers affects the time to market and slaughter weight, which in turn affect the profitability of the poultry industry. However, the underlying mechanisms regulating chicken growth and development have rarely been studied. This study aimed to identify candidate genes involved in chicken growth and investigated the potential regulatory mechanisms of early growth in chicken. RNA sequencing was applied to compare the transcriptomes of chicken muscle tissues at three developmental stages during early growth. In total, 978 differentially expressed genes (DEGs) (fold change ≥ 2; false discovery rate < 0.05) were detected by pairwise comparison. Functional analysis showed that the DEGs are mainly involved in the processes of cell growth, muscle development, and cellular activities (such as junction, migration, assembly, differentiation, and proliferation). Many of the DEGs are well known to be related to chicken growth, such as MYOD1, GH, IGF2BP2, IGFBP3, SMYD1, CEBPB, FGF2, and IGFBP5. KEGG pathway analysis identified that the DEGs were significantly enriched in five pathways (P < 0.1) related to growth and development: extracellular matrix–receptor interaction, focal adhesion, tight junction, insulin signaling pathway, and regulation of the actin cytoskeleton. A total of 42 DEGs assigned to these pathways are potential candidate genes inducing the difference in growth among the three developmental stages, such as MYH10, FGF2, FGF16, FN1, CFL2, MAPK9, IRS1, PHKA1, PHKB, and PHKG1. Thus, our study identified a series of genes and several pathways that may participate in the regulation of early growth in chicken. These results should serve as an important resource revealing the molecular basis of chicken growth and development. PMID:28291821

  17. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  18. Early growth and chronic disease: a public health overview.

    PubMed

    Law, Catherine

    2005-07-01

    Infant and childhood growth result from and reflect a range of influences in pre- and postnatal life. These include nutrition, burden of infection and the psycho-social environment. Nutrition in young children is dependent on individual level factors such as fetal experience, infant feeding and weaning practices, and on societal factors such as education of women and economic conditions. The relationship of early postnatal growth to adult disease may be indicative or causal, and may reveal both biological and sociological processes. Although non-insulin-dependent diabetes mellitus (NIDDM) and obesity are risk factors for ischaemic heart disease, the relationships of these three conditions to infant growth differ. Poor infant growth has been associated with higher levels of NIDDM and ischaemic heart disease, but lower levels of adult obesity. Most research has been of populations living in developed countries at different stages of nutritional transition. However, differences in context are not simply limited to the stage of the nutritional transition. They also need to consider the nature of that transition and its social correlates, which may result in the clustering of aetiological influences such as increased body mass and poverty. The size of effect of the relationship of infant growth to adult disease is important not only to determine its relative aetiological importance but also for its potential for public health policy. Such policy also needs to consider the relationships of infant growth to a range of outcomes, both health and human capital, which are not the subject of this workshop.

  19. Mathematical models to characterize early epidemic growth: A Review

    PubMed Central

    Chowell, Gerardo; Sattenspiel, Lisa; Bansal, Shweta; Viboud, Cécile

    2016-01-01

    There is a long tradition of using mathematical models to generate insights into the transmission dynamics of infectious diseases and assess the potential impact of different intervention strategies. The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing reliable models that capture the baseline transmission characteristics of specific pathogens and social contexts. More refined models are needed however, in particular to account for variation in the early growth dynamics of real epidemics and to gain a better understanding of the mechanisms at play. Here, we review recent progress on modeling and characterizing early epidemic growth patterns from infectious disease outbreak data, and survey the types of mathematical formulations that are most useful for capturing a diversity of early epidemic growth profiles, ranging from sub-exponential to exponential growth dynamics. Specifically, we review mathematical models that incorporate spatial details or realistic population mixing structures, including meta-population models, individual-based network models, and simple SIR-type models that incorporate the effects of reactive behavior changes or inhomogeneous mixing. In this process, we also analyze simulation data stemming from detailed large-scale agent-based models previously designed and calibrated to study how realistic social networks and disease transmission characteristics shape early epidemic growth patterns, general transmission dynamics, and control of international disease emergencies such as the 2009 A/H1N1 influenza pandemic and the 2014-15 Ebola epidemic in West Africa. PMID:27451336

  20. Mathematical models to characterize early epidemic growth: A review

    NASA Astrophysics Data System (ADS)

    Chowell, Gerardo; Sattenspiel, Lisa; Bansal, Shweta; Viboud, Cécile

    2016-09-01

    There is a long tradition of using mathematical models to generate insights into the transmission dynamics of infectious diseases and assess the potential impact of different intervention strategies. The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing reliable models that capture the baseline transmission characteristics of specific pathogens and social contexts. More refined models are needed however, in particular to account for variation in the early growth dynamics of real epidemics and to gain a better understanding of the mechanisms at play. Here, we review recent progress on modeling and characterizing early epidemic growth patterns from infectious disease outbreak data, and survey the types of mathematical formulations that are most useful for capturing a diversity of early epidemic growth profiles, ranging from sub-exponential to exponential growth dynamics. Specifically, we review mathematical models that incorporate spatial details or realistic population mixing structures, including meta-population models, individual-based network models, and simple SIR-type models that incorporate the effects of reactive behavior changes or inhomogeneous mixing. In this process, we also analyze simulation data stemming from detailed large-scale agent-based models previously designed and calibrated to study how realistic social networks and disease transmission characteristics shape early epidemic growth patterns, general transmission dynamics, and control of international disease emergencies such as the 2009 A/H1N1 influenza pandemic and the 2014-2015 Ebola epidemic in West Africa.

  1. Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells

    NASA Technical Reports Server (NTRS)

    Hughes-Fulford, M.; Chen, Y.; Tjandrawinata, R. R.

    2001-01-01

    It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

  2. Fatty acid regulates gene expression and growth of human prostate cancer PC-3 cells.

    PubMed

    Hughes-Fulford, M; Chen, Y; Tjandrawinata, R R

    2001-05-01

    It has been proposed that the omega-6 fatty acids increase the rate of tumor growth. Here we test that hypothesis in the PC-3 human prostate tumor. We found that the essential fatty acids, linoleic acid (LA) and arachidonic acid (AA), and the AA metabolite PGE(2) stimulate tumor growth while oleic acid (OA) and the omega-3 fatty acid, eicosapentaenoic acid (EPA) inhibited growth. In examining the role of AA in growth response, we extended our studies to analyze changes in early gene expression induced by AA. We demonstrate that c-fos expression is increased within minutes of addition in a dose-dependent manner. Moreover, the immediate early gene cox-2 is also increased in the presence of AA in a dose-dependent manner, while the constitutive cox-1 message was not increased. Three hours after exposure to AA, the synthesis of PGE(2) via COX-2 was also increased. Previous studies have demonstrated that AA was primarily delivered by low density lipoprotein (LDL) via its receptor (LDLr). Since it is known that hepatomas, acute myelogenous leukemia and colorectal tumors lack normal cholesterol feedback, we examined the role of the LDLr in growth regulation of the PC-3 prostate cancer cells. Analysis of ldlr mRNA expression and LDLr function demonstrated that human PC-3 prostate cancer cells lack normal feedback regulation. While exogenous LDL caused a significant stimulation of cell growth and PGE(2) synthesis, no change was seen in regulation of the LDLr by LDL. Taken together, these data show that normal cholesterol feedback of ldlr message and protein is lost in prostate cancer. These data suggest that unregulated over-expression of LDLr in tumor cells would permit increased availability of AA, which induces immediate early genes c-fos and cox-2 within minutes of uptake.

  3. [Establishment of sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo].

    PubMed

    Jiang, Hua; Feng, You-Ji; Xie, Yi; Han, Jin-Lan; Wang, Zack; Chen, Tong

    2008-10-14

    To establish a sprouting embryoid body model mimicking early embryonic vasculogenesis in human embryo. Human embryonic stem were (hESCs) were cultured on the mouse embryo fibroblasts and then were induced to differentiate to form three-dimensional EB. The hEBs were cultured in media containing various angiogenesis-related factors: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), endostatin, angiostatin, and platelet factor (PF)-4 of different concentrations for 3 days to observe the sprouting of the hEBs. 3, 3, 3', 3'-tetramethylindo-carbocyanine perchlorate labeled acetylated low density lipoprotein (Dil-AcLDL) was added onto the hEBs foe 4 h Immunofluorescence assay was used to observe if Dil-AcLDL was absorbed and if CD31 was expressed so as to determine the existence of embryonic endothelial cells in the sprouting structures. The ideal culturing condition was analyzed. The differentiated EBs formed sprouting structures in the collagen I matrix containing VEGF and FGF. The sprouts among individual EBs were able to link to each other and form vascular network-like structures. In the presence of VEGF and FGF, the sprouts branching from the EBs assimilated Dil-AcLDL, expressed CD31 and formed a 3-dimensional cylindrical organization. The concentrations of growth factors ideally stimulating sprouting growth were 100 ng/ml of VEGF and 50 ng/ml of FGF. The networks among the EBs were abolished by the angiostatin, endostatin, and PF4. The sprouting from hEBs accumulates embryonic endothelial cells and the sprouting network-like structures are indeed endothelial in nature. Inducing of sprouting EBs is an ideal model that mimics early embryonic vasculogenesis in humans.

  4. The Early Growth of the First Black Holes

    NASA Astrophysics Data System (ADS)

    Johnson, Jarrett L.; Haardt, Francesco

    2016-03-01

    With detections of quasars powered by increasingly massive black holes at increasingly early times in cosmic history over the past decade, there has been correspondingly rapid progress made on the theory of early black hole formation and growth. Here, we review the emerging picture of how the first massive black holes formed from the primordial gas and then grew to supermassive scales. We discuss the initial conditions for the formation of the progenitors of these seed black holes, the factors dictating the initial masses with which they form, and their initial stages of growth via accretion, which may occur at super-Eddington rates. Finally, we briefly discuss how these results connect to large-scale simulations of the growth of supermassive black holes in the first billion years after the Big Bang.

  5. Human-Friendly Light-Emitting Diode Source Stimulates Broiler Growth

    PubMed Central

    Yang, Bo; Dai, Wenhua; Yu, Yonghua

    2015-01-01

    Previous study and our laboratory have reported that short-wavelength (blue and green) light and combination stimulate broiler growth. However, short-wavelength stimuli could have negative effects on poultry husbandry workers. The present study was conducted to evaluate the effects of human-friendly yellow LED light, which is acceptable to humans and close to green light, on broiler growth. We also aimed to investigate the potential quantitative relationship between the wavelengths of light used for artificial illumination and growth parameters in broilers. After hatching, 360 female chicks (“Meihuang” were evenly divided into six lighting treatment groups: white LED strips (400–700 nm, WL); red LED strips (620 nm, RL); yellow LED strips (580 nm, YL); green LED strips (514 nm, GL); blue LED strips (455 nm, BL); and fluorescent strips (400–700 nm, FL). From 30 to 72 days of age, broilers reared under YL and GL were heavier than broilers treated with FL (P < 0.05). Broilers reared under YL obtained the similar growth parameters with the broilers reared under GL and BL (P > 0.05). Moreover, YL significantly improved feeding efficiency when compared with GL and BL at 45 and 60 days of age (P < 0.05). In addition, we found an age-dependent effect of light spectra on broiler growth and a quantitative relationship between LED light spectra (455 to 620 nm) and the live body weights of broilers. The wavelength of light (455 to 620 nm) was found to be negatively related (R 2 = 0.876) to live body weight at an early stage of development, whereas the wavelength of light (455 to 620 nm) was found to be positively correlated with live body weight (R 2 = 0.925) in older chickens. Our results demonstrated that human-friendly yellow LED light (YL), which is friendly to the human, can be applied to the broilers production. PMID:26270988

  6. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth hormone...

  7. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human growth hormone test system. 862.1370 Section... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test system is a device intended to measure the levels of human growth hormone in plasma. Human growth hormone...

  8. Breast Milk Lipidome Is Associated with Early Growth Trajectory in Preterm Infants

    PubMed Central

    Moyon, Thomas; Antignac, Jean-Philippe; Qannari, El Mostafa; Croyal, Mikaël; Soumah, Mohamed; David-Sochard, Agnès; Billard, Hélène; Legrand, Arnaud; Boscher, Cécile; Darmaun, Dominique; Rozé, Jean-Christophe

    2018-01-01

    Human milk is recommended for feeding preterm infants. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth-pattern of preterm infants fed their own mother’s milk. A prospective-monocentric-observational birth-cohort was established, enrolling 138 preterm infants, who received their own mother’s breast-milk throughout hospital stay. All infants were ranked according to the change in weight Z-score between birth and hospital discharge. Then, we selected infants who experienced “slower” (n = 15, −1.54 ± 0.42 Z-score) or “faster” (n = 11, −0.48 ± 0.19 Z-score) growth; as expected, although groups did not differ regarding gestational age, birth weight Z-score was lower in the “faster-growth” group (0.56 ± 0.72 vs. −1.59 ± 0.96). Liquid chromatography–mass spectrometry lipidomic signatures combined with multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between groups. Validation of the selected biomarkers was performed using multidimensional statistical, false-discovery-rate and ROC (Receiver Operating Characteristic) tools. Breast-milk associated with faster growth contained more medium-chain saturated fatty acid and sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. The ability of such biomarkers to predict early-growth was validated in presence of confounding clinical factors but remains to be ascertained in larger cohort studies. PMID:29385065

  9. Classification of human pathogen bacteria for early screening using electronic nose

    NASA Astrophysics Data System (ADS)

    Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan

    2017-10-01

    This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.

  10. Comparative proteomic analysis of Populus trichocarpa early stem from primary to secondary growth.

    PubMed

    Liu, Jinwen; Hai, Guanghui; Wang, Chong; Cao, Shenquan; Xu, Wenjing; Jia, Zhigang; Yang, Chuanping; Wang, Jack P; Dai, Shaojun; Cheng, Yuxiang

    2015-08-03

    Wood is derived from the secondary growth of tree stems. In this study, we investigated the global changes of protein abundance in Populus early stems using a proteomic approach. Morphological and histochemical analyses revealed three typical stages during Populus early stems, which were the primary growth stage, the transition stage from primary to secondary growth and the secondary growth stage. A total of 231 spots were differentially abundant during various growth stages of Populus early stems. During Populus early stem lignifications, 87 differential spots continuously increased, while 49 spots continuously decreased. These two categories encompass 58.9% of all differential spots, which suggests significant molecular changes from primary to secondary growth. Among 231 spots, 165 unique proteins were identified using LC-ESI-Q-TOF-MS, which were classified into 14 biological function groups. The proteomic characteristics indicated that carbohydrate metabolism, oxido-reduction, protein degradation and secondary cell wall metabolism were the dominantly occurring biochemical processes during Populus early stem development. This study helps in elucidating biochemical processes and identifies potential wood formation-related proteins during tree early stem development. It is a comprehensive proteomic investigation on tree early stem development that, for the first time, reveals the overall molecular networks that occur during Populus early stem lignifications. Copyright © 2015. Published by Elsevier B.V.

  11. The early growth of the first black holes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, Jarrett L.; Haardt, Francesco

    With detections of quasars powered by increasingly massive black holes at increasingly early times in cosmic history over the past decade, there has been correspondingly rapid progress made on the theory of early black hole formation and growth. Here, we review the emerging picture of how the first massive black holes formed from the primordial gas and then grew to supermassive scales. We discuss the initial conditions for the formation of the progenitors of these seed black holes, the factors dictating the initial masses with which they form, and their initial stages of growth via accretion, which may occur atmore » super-Eddington rates. Lastly, we briefly discuss how these results connect to large-scale simulations of the growth of supermassive black holes in the first billion years after the Big Bang.« less

  12. The early growth of the first black holes

    DOE PAGES

    Johnson, Jarrett L.; Haardt, Francesco

    2016-03-04

    With detections of quasars powered by increasingly massive black holes at increasingly early times in cosmic history over the past decade, there has been correspondingly rapid progress made on the theory of early black hole formation and growth. Here, we review the emerging picture of how the first massive black holes formed from the primordial gas and then grew to supermassive scales. We discuss the initial conditions for the formation of the progenitors of these seed black holes, the factors dictating the initial masses with which they form, and their initial stages of growth via accretion, which may occur atmore » super-Eddington rates. Lastly, we briefly discuss how these results connect to large-scale simulations of the growth of supermassive black holes in the first billion years after the Big Bang.« less

  13. Early stages of zeolite growth

    NASA Astrophysics Data System (ADS)

    Kumar, Sandeep

    Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

  14. Characterizing the reproduction number of epidemics with early subexponential growth dynamics

    PubMed Central

    Viboud, Cécile; Simonsen, Lone; Moghadas, Seyed M.

    2016-01-01

    Early estimates of the transmission potential of emerging and re-emerging infections are increasingly used to inform public health authorities on the level of risk posed by outbreaks. Existing methods to estimate the reproduction number generally assume exponential growth in case incidence in the first few disease generations, before susceptible depletion sets in. In reality, outbreaks can display subexponential (i.e. polynomial) growth in the first few disease generations, owing to clustering in contact patterns, spatial effects, inhomogeneous mixing, reactive behaviour changes or other mechanisms. Here, we introduce the generalized growth model to characterize the early growth profile of outbreaks and estimate the effective reproduction number, with no need for explicit assumptions about the shape of epidemic growth. We demonstrate this phenomenological approach using analytical results and simulations from mechanistic models, and provide validation against a range of empirical disease datasets. Our results suggest that subexponential growth in the early phase of an epidemic is the rule rather the exception. Mechanistic simulations show that slight modifications to the classical susceptible–infectious–removed model result in subexponential growth, and in turn a rapid decline in the reproduction number within three to five disease generations. For empirical outbreaks, the generalized-growth model consistently outperforms the exponential model for a variety of directly and indirectly transmitted diseases datasets (pandemic influenza, measles, smallpox, bubonic plague, cholera, foot-and-mouth disease, HIV/AIDS and Ebola) with model estimates supporting subexponential growth dynamics. The rapid decline in effective reproduction number predicted by analytical results and observed in real and synthetic datasets within three to five disease generations contrasts with the expectation of invariant reproduction number in epidemics obeying exponential growth. The

  15. Randomized Controlled Trial on Effect of Intermittent Early Versus Late Kangaroo Mother Care on Human Milk Feeding in Low-Birth-Weight Neonates.

    PubMed

    Jayaraman, Dhaarani; Mukhopadhyay, Kanya; Bhalla, Anil Kumar; Dhaliwal, Lakhbir Kaur

    2017-08-01

    Breastfeeding at discharge among sick low-birth-weight (LBW) infants is low despite counseling and intervention like kangaroo mother care (KMC). Research aim: The aim was to study the effects of early initiation of KMC on exclusive human milk feeding, growth, mortality, and morbidities in LBW neonates compared with late initiation of KMC during the hospital stay and postdischarge. A randomized controlled trial was conducted in level 2 and 3 areas of a tertiary care neonatal unit over 15 months. Inborn neonates weighing 1 to 1.8 kg and hemodynamically stable were randomized to receive either early KMC, initiated within the first 4 days of life, or late KMC (off respiratory support and intravenous fluids). Follow-up was until 1 month postdischarge. Outcomes were proportion of infants achieving exclusive human milk feeding and direct breastfeeding, growth, mortality and morbidities during hospital stay, and postdischarge feeding and KMC practices until 1 month. The early KMC group ( n = 80) achieved significantly higher exclusive human milk feeding (86% vs. 45%, p < .001) and direct breastfeeding (49% vs. 30%, p = .021) in hospital and almost exclusive human milk feeding (73% vs. 36%, p < .001) until 1 month postdischarge than the late KMC group ( n = 80). The incidence of apnea (11.9% vs. 20%, p = .027) and recurrent apnea requiring ventilation (8.8% vs. 15%, p = .02) were significantly reduced in the early KMC group. There was no significant difference in mortality, morbidities, and growth during the hospital stay and postdischarge. Early KMC significantly increased exclusive human milk feeding and direct breastfeeding in LBW infants.

  16. Developmental insights from early mammalian embryos and core signaling pathways that influence human pluripotent cell growth and differentiation.

    PubMed

    Chen, Kevin G; Mallon, Barbara S; Johnson, Kory R; Hamilton, Rebecca S; McKay, Ronald D G; Robey, Pamela G

    2014-05-01

    Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. Published by Elsevier B.V.

  17. NFI-Ski interactions mediate transforming growth factor beta modulation of human papillomavirus type 16 early gene expression.

    PubMed

    Baldwin, Amy; Pirisi, Lucia; Creek, Kim E

    2004-04-01

    Human papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor beta (TGF-beta). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-beta. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-beta modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-beta modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-beta-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-beta. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-beta treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-beta sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-beta to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-beta treatment, we explored the possibility that Ski may provide a link between TGF-beta signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI

  18. Measures of maturation in early fossil hominins: events at the first transition from australopiths to early Homo

    PubMed Central

    Dean, M. Christopher

    2016-01-01

    An important question in palaeoanthropology is whether, among the australopiths and the first fossil hominins attributed to early Homo, there was a shift towards a more prolonged period of growth that can be distinguished from that of the living great apes and whether between the end of weaning and the beginning of puberty there was a slow period of growth as there is in modern humans. Evidence for the pace of growth in early fossil hominins comes from preserved tooth microstructure. A record of incremental growth in enamel and dentine persists, which allows us to reconstruct tooth growth and compare key measures of dental maturation with modern humans and living great apes. Despite their diverse diets and way of life, it is currently difficult to identify any clear differences in the timing of dental development among living great apes, australopiths and the earliest hominins attributed to the genus Homo. There is, however, limited evidence that some early hominins may have attained a greater proportion of their body mass and stature relatively earlier in the growth period than is typical of modern humans today. This article is part of the themed issue ‘Major transitions in human evolution’. PMID:27298465

  19. Expression of a synthetic gene encoding human insulin-like growth factor I in cultured mouse fibroblasts

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bayne, M.L.; Cascieri, M.A.; Kelder, B.

    1987-05-01

    A synthetic gene encoding human insulin-like growth factor I (hIGF-I) was assembled and inserted into an expression vector containing the cytomegalovirus immediate early (CMV-IE) transcriptional regulatory region and portions of the bovine growth hormone gene. The recombinant plasmid encodes a 97 amino acid fusion protein containing the first 27 amino acids of the bovine growth hormone precursor and the 70 amino acids of hIGF-I. This plasmid, when transiently introduced into cultured mouse fibroblasts, directs synthesis of the fusion protein, subsequent proteolytic removal of the bovine growth hormone signal peptide, and secretion of hIGF-I into the culture medium. Conditioned medium frommore » transfected cells inhibits binding of /sup 125/I-labeled IGF-I to type I IGF receptors on human placental membranes and to acid-stable human serum carrier proteins. The recombinant hIGF-I produced is biologically active, as monitored by the stimulation of DNA synthesis in vascular smooth muscle cells.« less

  20. Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

    PubMed

    Ikeda, Naho; Shoji, Hiromichi; Suganuma, Hiroki; Ohkawa, Natsuki; Kantake, Masato; Murano, Yayoi; Sakuraya, Koji; Shimizu, Toshiaki

    2016-05-01

    Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period. © 2015 Japan Pediatric Society.

  1. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    PubMed

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-03

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations. Copyright © 2014, American Association for the Advancement of Science.

  2. Early growth, dominance acquisition and lifetime reproductive success in male and female cooperative meerkats

    PubMed Central

    English, Sinead; Huchard, Elise; Nielsen, Johanna F; Clutton-Brock, Tim H

    2013-01-01

    In polygynous species, variance in reproductive success is higher in males than females. There is consequently stronger selection for competitive traits in males and early growth can have a greater influence on later fitness in males than in females. As yet, little is known about sex differences in the effect of early growth on subsequent breeding success in species where variance in reproductive success is higher in females than males, and competitive traits are under stronger selection in females. Greater variance in reproductive success has been documented in several singular cooperative breeders. Here, we investigated consequences of early growth for later reproductive success in wild meerkats. We found that, despite the absence of dimorphism, females who exhibited faster growth until nutritional independence were more likely to become dominant, whereas early growth did not affect dominance acquisition in males. Among those individuals who attained dominance, there was no further influence of early growth on dominance tenure or lifetime reproductive success in males or females. These findings suggest that early growth effects on competitive abilities and fitness may reflect the intensity of intrasexual competition even in sexually monomorphic species. PMID:24340181

  3. Effect of human milk fortifiers on bacterial growth in human milk.

    PubMed

    Santiago, Myla S; Codipilly, Champa N; Potak, Debra C; Schanler, Richard J

    2005-10-01

    As a component in human milk fortifiers (HMF), iron may equilibrate with human milk for as long as 24 hours, bind important bacteriostatic proteins, and potentially affect the host defense properties of human milk. We compared bacterial growth in human milk prepared with each of two HMF differing in their content of iron. Samples of human milk obtained from mothers of premature infants were divided and mixed with one of two HMF and maintained at refrigerator temperature. Refrigerated milk samples were removed at 0, 24, and 72 hours for determination of total bacterial colony counts (TBCC). TBCC did not differ between groups but declined from 0 to 72 hours, p<0.001. These data suggest that differences in iron content, or other nutrients in HMF, do not affect bacterial growth in human milk. Storage of fortified human milk at refrigerator temperature for 72 hours results in decreased bacterial growth. As a component in human milk fortifiers (HMF), iron may equilibrate with human milk for as long as 24 hours, bind important bacteriostatic proteins, and potentially affect the host defense properties of human milk. We compared bacterial growth in human milk prepared with each of two HMF differing in their content of iron. Samples of human milk obtained from mothers of premature infants were divided and mixed with one of two HMF and maintained at refrigerator temperature. Refrigerated milk samples were removed at 0, 24, and 72 hours for determination of total bacterial colony counts (TBCC).

  4. Earliest evidence of modern human life history in North African early Homo sapiens.

    PubMed

    Smith, Tanya M; Tafforeau, Paul; Reid, Donald J; Grün, Rainer; Eggins, Stephen; Boutakiout, Mohamed; Hublin, Jean-Jacques

    2007-04-10

    Recent developmental studies demonstrate that early fossil hominins possessed shorter growth periods than living humans, implying disparate life histories. Analyses of incremental features in teeth provide an accurate means of assessing the age at death of developing dentitions, facilitating direct comparisons with fossil and modern humans. It is currently unknown when and where the prolonged modern human developmental condition originated. Here, an application of x-ray synchrotron microtomography reveals that an early Homo sapiens juvenile from Morocco dated at 160,000 years before present displays an equivalent degree of tooth development to modern European children at the same age. Crown formation times in the juvenile's macrodont dentition are higher than modern human mean values, whereas root development is accelerated relative to modern humans but is less than living apes and some fossil hominins. The juvenile from Jebel Irhoud is currently the oldest-known member of Homo with a developmental pattern (degree of eruption, developmental stage, and crown formation time) that is more similar to modern H. sapiens than to earlier members of Homo. This study also underscores the continuing importance of North Africa for understanding the origins of human anatomical and behavioral modernity. Corresponding biological and cultural changes may have appeared relatively late in the course of human evolution.

  5. Improvement in skin wrinkles using a preparation containing human growth factors and hyaluronic acid serum.

    PubMed

    Lee, Do Hyun; Oh, In Young; Koo, Kyo Tan; Suk, Jang Mi; Jung, Sang Wook; Park, Jin Oh; Kim, Beom Joon; Choi, Yoo Mi

    2015-02-01

    Skin aging is accompanied by wrinkle formation. At some sites, such as the periorbital skin, this is a relatively early phenomenon. We evaluated the anti-wrinkle effect of a preparation containing human growth factor and hyaluronic acid serum on periorbital wrinkles (crow's feet). In total, 23 Korean women (age range: 39-59 years), who were not pregnant, nursing, or undergoing any concurrent therapy, were enrolled in this study. All the patients completed an 8-week trial of twice-daily application of human growth factor and hyaluronic acid serum on the entire face. Efficacy was based on a global photodamage score, photographs, and image analysis using replicas and visiometer analysis every 4 weeks. The standard wrinkle and roughness parameters used in assessing skin by visiometer were calculated and statistically analyzed. Periorbital wrinkles were significantly improved after treatment, with improvements noted both by physician's assessment and visiometer analysis. Topical application of human growth factor and hyaluronic acid was beneficial in reducing periorbital wrinkles.

  6. Role of Insulin-like growth factors in initiation of follicle growth in normal and polycystic human ovaries.

    PubMed

    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.

  7. IVF culture medium affects human intrauterine growth as early as the second trimester of pregnancy.

    PubMed

    Nelissen, Ewka C M; Van Montfoort, Aafke P A; Smits, Luc J M; Menheere, Paul P C A; Evers, Johannes L H; Coonen, Edith; Derhaag, Josien G; Peeters, Louis L; Coumans, Audrey B; Dumoulin, John C M

    2013-08-01

    When does a difference in human intrauterine growth of singletons conceived after IVF and embryo culture in two different culture media appear? Differences in fetal development after culture of embryos in one of two IVF media were apparent as early as the second trimester of pregnancy. Abnormal fetal growth patterns are a major risk factor for the development of chronic diseases in adult life. Previously, we have shown that the medium used for culturing embryos during the first few days after fertilization significantly affects the birthweight of the resulting human singletons. The exact onset of this growth difference was unknown. In this retrospective cohort study, all 294 singleton live births after fresh embryo transfer in the period July 2003 to December 2006 were included. These embryos originated from IVF treatments that were part of a previously described clinical trial. Embryos were allocated to culture in either Vitrolife or Cook commercially available sequential culture media. We analysed ultrasound examinations at 8 (n = 290), 12 (n = 83) and 20 weeks' (n = 206) gestation and used first-trimester serum markers [pregnancy-associated plasma protein-A (PAPP-A) and free β-hCG]. Differences between study groups were tested by the Student's t-test, χ(2) test or Fisher's exact test, and linear multivariable regression analysis to adjust for possible confounders (for example, parity, gestational age at the time of ultrasound and fetal gender). A total of 294 singleton pregnancies (Vitrolife group nVL = 168, Cook group: nC = 126) from 294 couples were included. At 8 weeks' gestation, there was no difference between crown-rump length-based and ovum retrieval-based gestational age (ΔGA) (nVL = 163, nC = 122, adjusted mean difference, -0.04 days, P = 0.84). A total of 83 women underwent first-trimester screening at 12 weeks' gestation (nVL = 45, nC = 38). ΔGA, nuchal translucency (multiples of median, MoM) and PAPP-A (MoM) did not differ between the study

  8. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

  9. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 862.1370 Human growth hormone test system. (a) Identification. A human growth hormone test...

  10. The human early-life exposome (HELIX): project rationale and design.

    PubMed

    Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

    2014-06-01

    Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

  11. Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

    PubMed

    Mastrangelo, F; Sberna, M T; Tettamanti, L; Cantatore, G; Tagliabue, A; Gherlone, E

    2016-01-01

    Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

  12. Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1.

    PubMed Central

    Liu, C; Adamson, E; Mercola, D

    1996-01-01

    The early growth response 1 (EGR-1) gene product is a transcription factor with role in differentiation and growth. We have previously shown that expression of exogenous EGR-1 in various human tumor cells unexpectedly and markedly reduces growth and tumorigenicity and, conversely, that suppression of endogenous Egr-1 expression by antisense RNA eliminates protein expression, enhances growth, and promotes phenotypic transformation. However, the mechanism of these effects remained unknown. The promoter of human transforming growth factor beta 1 (TGF-beta 1) contains two GC-rich EGR-1 binding sites. We show that expression of EGR-1 in human HT-1080 fibrosarcoma cells uses increased secretion of biologically active TGF-beta 1 in direct proportion (rPearson = 0.96) to the amount of EGR-1 expressed and addition of recombinant human TGF-beta 1 is strongly growth-suppressive for these cells. Addition of monoclonal anti-TGF-beta 1 antibodies to EGR-1-expressing HT-1080 cells completely reverses the growth inhibitory effects of EGR-1. Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector. Expression of delta EGR-1, a mutant that cannot interact with the corepressors, nerve growth factor-activated factor binding proteins NAB1 and NAB2, due to deletion of the repressor domain, exhibited enhanced transactivation of 2- to 3.5-fold over that of wild-type EGR-1 showing that the reporter construct reflected the appropriate in vivo regulatory context. The EGR-1-stimulated transactivation was inhibited by expression of the Wilms tumor suppressor, a known specific DNA-binding competitor. These results indicate that EGR-1 suppresses growth of human HT-1080 fibrosarcoma cells by induction of TGF-beta 1. Images Fig. 1 Fig. 5 PMID:8876223

  13. Annual Growth of Contract Costs for Major Programs in Development and Early Production

    DTIC Science & Technology

    2016-03-21

    changes, we can identify some underlying drivers and rule out others. Development and Early Production Differences BBP-era drops are driven by dropping...Annual Growth of Contract Costs for Major Programs in Development and Early Production Dan Davis and Philip S...Growth of Contract Costs for Major Programs in Development and Early Production Dan Davis and Philip S. Antón March 21, 2016 SUMMARY Cost is

  14. Effects of glucocorticoid treatment given in early or late gestation on growth and development in sheep.

    PubMed

    Li, S; Sloboda, D M; Moss, T J M; Nitsos, I; Polglase, G R; Doherty, D A; Newnham, J P; Challis, J R G; Braun, T

    2013-04-01

    Antenatal corticosteroids are used to augment fetal lung maturity in human pregnancy. Dexamethasone (DEX) is also used to treat congenital adrenal hyperplasia of the fetus in early pregnancy. We previously reported effects of synthetic corticosteroids given to sheep in early or late gestation on pregnancy length and fetal cortisol levels and glucocorticoids alter plasma insulin-like growth factor (IGF) and insulin-like growth factor binding protein (IGFBP) concentrations in late pregnancy and reduce fetal weight. The effects of administering DEX in early pregnancy on fetal organ weights and betamethasone (BET) given in late gestation on weights of fetal brain regions or organ development have not been reported. We hypothesized that BET or DEX administration at either stage of pregnancy would have deleterious effects on fetal development and associated hormones. In early pregnancy, DEX was administered as four injections at 12-hourly intervals over 48 h commencing at 40-42 days of gestation (dG). There was no consistent effect on fetal weight, or individual fetal organ weights, except in females at 7 months postnatal age. When BET was administered at 104, 111 and 118 dG, the previously reported reduction in total fetal weight was associated with significant reductions in weights of fetal brain, cerebellum, heart, kidney and liver. Fetal plasma insulin, leptin and triiodothyronine were also reduced at different times in fetal and postnatal life. We conclude that at the amounts given, the sheep fetus is sensitive to maternal administration of synthetic glucocorticoid in late gestation, with effects on growth and metabolic hormones that may persist into postnatal life.

  15. Adult consequences of growth failure in early childhood123

    PubMed Central

    Hoddinott, John; Behrman, Jere R; Maluccio, John A; Melgar, Paul; Quisumbing, Agnes R; Ramirez-Zea, Manuel; Stein, Aryeh D; Yount, Kathryn M

    2013-01-01

    Background: Growth failure is associated with adverse consequences, but studies need to control adequately for confounding. Objective: We related height-for-age z scores (HAZs) and stunting at age 24 mo to adult human capital, marriage, fertility, health, and economic outcomes. Design: In 2002–2004, we collected data from 1338 Guatemalan adults (aged 25–42 y) who were studied as children in 1969–1977. We used instrumental variable regression to correct for estimation bias and adjusted for potentially confounding factors. Results: A 1-SD increase in HAZ was associated with more schooling (0.78 grades) and higher test scores for reading and nonverbal cognitive skills (0.28 and 0.25 SDs, respectively), characteristics of marriage partners (1.39 y older, 1.02 grade more schooling, and 1.01 cm taller) and, for women, a higher age at first birth (0.77 y) and fewer number of pregnancies and children (0.63 and 0.43, respectively). A 1-SD increase in HAZ was associated with increased household per capita expenditure (21%) and a lower probability of living in poverty (10 percentage points). Conversely, being stunted at 2 y was associated with less schooling, a lower test performance, a lower household per capita expenditure, and an increased probability of living in poverty. For women, stunting was associated with a lower age at first birth and higher number of pregnancies and children. There was little relation between either HAZ or stunting and adult health. Conclusion: Growth failure in early life has profound adverse consequences over the life course on human, social, and economic capital. PMID:24004889

  16. [Effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation].

    PubMed

    Cai, Yue-Ju; Song, Yan-Yan; Huang, Zhi-Jian; Li, Jian; Qi, Jun-Ye; Xiao, Xu-Wen; Wang, Lan-Xiu

    2015-09-01

    To study the effects of postnatal growth retardation on early neurodevelopment in premature infants with intrauterine growth retardation (IUGR). A retrospective analysis was performed on the clinical data of 171 premature infants who were born between May 2008 and May 2012 and were followed up until a corrected gestational age of 6 months. These infants were classified into two groups: IUGR group (n=40) and appropriate for gestational age (AGA) group (n=131). The growth retardation rates at the corrected gestational ages of 40 weeks, 3 months, and 6 months, as well as the neurodevelopmental outcome (evaluated by Gesell Developmental Scale) at corrected gestational ages of 3 and 6 months, were compared between the two groups. The growth retardation rate in the IUGR group was significantly higher than in the AGA group at the corrected gestational ages of 40 weeks, 3 months, and 6 months. All five developmental quotients evaluated by Gesell Developmental Scale (gross motor, fine motor, language, adaptability and individuality) in the IUGR group were significantly lower than in the AGA group at the corrected gestational ages of 3 months. At the corrected gestational age of 6 months, the developmental quotients of fine motor and language in the IUGR group were significantly lower than in the AGA group, however, there were no significant differences in the developmental quotients of gross motor, adaptability and individuality between the two groups. All five developmental quotients in IUGR infants with catch-up lag in weight were significantly lower than in IUGR and AGA infants who had caught up well. Growth retardation at early postnatal stages may adversely affect the early neurodevelopment in infants with IUGR.

  17. The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

    PubMed Central

    Large, Michael J.; Wetendorf, Margeaux; Lanz, Rainer B.; Hartig, Sean M.; Creighton, Chad J.; Mancini, Michael A.; Kovanci, Ertug; Lee, Kuo-Fen; Threadgill, David W.; Lydon, John P.; Jeong, Jae-Wook; DeMayo, Francesco J.

    2014-01-01

    Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets. PMID

  18. HUMAN BODY SHAPE INDEX BASED ON AN EXPERIMENTALLY DERIVED MODEL OF HUMAN GROWTH

    PubMed Central

    Lebiedowska, Maria K.; Alter, Katharine E.; Stanhope, Steven J.

    2009-01-01

    Objectives To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5–18 years; to use the derived growth models to establish a new Human Body Shape Index (HBSI) based on natural age related changes in HBS; and to compare various metrics of relative body weight (body mass index, ponderal index, HBSI) in a sample of 5–18 year old children. Study design Non-disabled Polish children (N=847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex with the allometric equation M= miHχ. HBSI and HBSI were calculated separately for girls and boys, using sex-specific values for χ and a general HBSI from combined data. The customary body mass and ponderal indices were calculated and compared to HBSI values. Results The models of growth were M=13.11H2.84 (R2=.90) and M=13.64H2.68 (R2=.91) for girls and boys respectively. HBSI values contained less inherent variability and were influenced least by growth (age and height) than customary indices. Conclusion Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of human body shape formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for the characterization of human body shape in children during the formative growth years. PMID:18154897

  19. Early growth patterns are associated with intelligence quotient scores in children born small-for-gestational age.

    PubMed

    Varella, Marcia H; Moss, William J

    2015-08-01

    To assess whether patterns of growth trajectory during infancy are associated with intelligence quotient (IQ) scores at 4 years of age in children born small-for-gestational age (SGA). Children in the Collaborative Perinatal Project born SGA were eligible for analysis. The primary outcome was the Stanford-Binet IQ score at 4 years of age. Growth patterns were defined based on changes in weight-for-age z-scores from birth to 4 months and 4 to 12 months of age and consisted of steady, early catch-up, late catch-up, constant catch-up, early catch-down, late catch-down, constant catch-down, early catch-up & late catch-down, and early catch-down & late catch-up. Multivariate linear regression was used to assess associations between patterns of growth and IQ. We evaluated patterns of growth and IQ in 5640 children. Compared with children with steady growth, IQ scores were 2.9 [standard deviation (SD)=0.54], 1.5 (SD=0.63), and 2.2 (SD=0.9) higher in children with early catch-up, early catch-up and later catch-down, and constant catch-up growth patterns, respectively, and 4.4 (SD=1.4) and 3.9 (SD=1.5) lower in children with early catch-down & late catch-up, and early catch-down growth patterns, respectively. Patterns in weight gain before 4 months of age were associated with differences in IQ scores at 4 years of age, with children with early catch-up having slightly higher IQ scores than children with steady growth and children with early catch-down having slightly lower IQ scores. These findings have implications for early infant nutrition in children born SGA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. DYZ1 copy number variation, Y chromosome polymorphism and early recurrent spontaneous abortion/early embryo growth arrest.

    PubMed

    Yan, Junhao; Fan, Lingling; Zhao, Yueran; You, Li; Wang, Laicheng; Zhao, Han; Li, Yuan; Chen, Zi-Jiang

    2011-12-01

    To find the association between recurrent spontaneous abortion (RSA)/early embryo growth arrest and Y chromosome polymorphism. Peripheral blood samples of the male patients of big Y chromosome, small Y chromosome and other male patients whose partners suffered from unexplained RSA/early embryo growth arrest were collected. PCR and real-time fluorescent quantitative PCR were used to test the deletion and the copy number variation of DYZ1 region in Y chromosome of the patients. A total of 79 big Y chromosome patients (48 of whose partners suffered from RSA or early embryo growth arrest), 7 small Y chromosome patients, 106 other male patients whose partners had suffered from unexplained RSA or early embryo growth arrest, and 100 normal male controls were enrolled. There was no fraction deletion of DYZ1 detected both in big Y patients and in normal men. Of RSA patients, 1 case showed deletion of 266bp from the gene locus 25-290bp, and 2 cases showed deletion of 773bp from 1347 to 2119bp. Of only 7 small Y chromosome patients, 2 cases showed deletion of 266bp from 25 to 290bp, and 4 cases showed deletion of 773bp from 1347 to 2119bp and 275bp from 3128 to 3420bp. The mean of DYZ1 copies was 3900 in normal control men; the mean in big Y patients was 5571, in RSA patients was 2655, and in small Y patients was 1059. All of the others were significantly different (P<0.01) compared with normal control men, which meant that DYZ1 copy number in normal control men was less than that of big Y chromosome patients, and was more than that of unexplained early RSA patients and small Y patients. The integrity and copy number variation of DYZ1 are closely related to the Y chromosome length under microscope. The cause of RSA/early embryo growth arrest in some couples may be the increase (big Y patients) or decrease of DYZ1 copy number in the husbands' Y chromosome. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Speleothem evidence for the greening of the Sahara and its implications for the early human dispersal out of sub-Saharan Africa

    NASA Astrophysics Data System (ADS)

    El-Shenawy, Mohammed I.; Kim, Sang-Tae; Schwarcz, Henry P.; Asmerom, Yemane; Polyak, Victor J.

    2018-05-01

    Although there is a consensus that there were wet periods (greening events) in the Sahara in the past, the spatial extent and the timing of these greening events are still in dispute, yet critical to our understanding of the early human dispersal out of Africa. Our U-series dates of speleothems from the Northeastern Sahara (Wadi Sannur cave, Egypt) reveal that the periods of speleothem growth were brief and restricted to the interglacial Marine Isotope Stages MIS 5.5, MIS 7.3, and the early MIS 9 with a remarkable absence of the Holocene deposition of speleothems. These growth periods of Wadi Sannur cave speleothems correspond to periods of high rainfall and spread of vegetation (green Sahara). Distinct low δ18O values of speleothems indicate a distal moisture source that we interpret to be the Atlantic Ocean. These two lines of evidence from the Wadi Sannur speleothems thus suggest that maximal northward shifts in the West African monsoon system occurred during the growth periods of the speleothems, leading to greening of the Sahara, facilitating human migration into Eurasia. The periods of speleothem growth at Wadi Sannur cave are contemporaneous with important archeological events: (1) the earliest occurrence of the Middle Stone Age assemblages and Homo sapiens in North Africa (Jebel Irhoud), suggesting wide spread of greening conditions over the East-West transect of the Sahara, (2) the sharp technological break between the Acheulo-Yabrudian and the Mousterian industries, and (3) the arrival of Homo sapiens in Levant, indicating a key role of the Sahara route in early human dispersal out of Africa.

  2. Pro-inflammatory NF-κB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epithelial cells.

    PubMed

    Choi, Hye Jin; Kim, Juil; Park, Seong-Hwan; Do, Kee Hun; Yang, Hyun; Moon, Yuseok

    2012-06-20

    The widely used food additive carrageenan (CGN) has been shown to induce intestinal inflammation, ulcerative colitis-like symptoms, or neoplasm in the gut epithelia in animal models, which are also clinical features of human inflammatory bowel disease. In this study, the effects of CGN on pro-inflammatory transcription factors NF-κB and early growth response gene 1 product (EGR-1) were evaluated in terms of human intestinal epithelial barrier integrity. Both pro-inflammatory transcription factors were elevated by CGN and only NF-κB activation was shown to be involved in the induction of pro-inflammatory cytokine interleukin-8. Moreover, the integrity of the in vitro epithelial monolayer under the CGN insult was maintained by both activated pro-inflammatory transcription factors NF-κB and EGR-1. Suppression of NF-κB or EGR-1 aggravated barrier disruption by CGN, which was associated with the reduced gene expression of tight junction component zonula occludens 1 and its irregular localization in the epithelial monolayer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  3. Studying Individual Plant AOX Gene Functionality in Early Growth Regulation: A New Approach.

    PubMed

    Arnholdt-Schmitt, Birgit; Patil, Vinod Kumar

    2017-01-01

    AOX1 and AOX2 genes are thought to play different physiological roles. Whereas AOX1 is typically expected to associate to stress and growth responses, AOX2 was more often found to be linked to development and housekeeping functions. However, this view is questioned by several adverse observations. For example, co-regulated expression for DcAOX1 and DcAOX2a genes was recently reported during growth induction in carrot (Daucus carota L.). Early expression peaks for both genes during the lag phase of growth coincided with a critical time point for biomass prediction, a result achieved by applying calorespirometry. The effect of both AOX family member genes cannot easily be separated. However, separate functional analysis is required in order to identify important gene-specific polymorphisms or patterns of polymorphisms for functional marker development and its use in breeding. Specifically, a methodology is missing that enables studying functional effects of individual genes or polymorphisms/polymorphic patterns on early growth regulation.This protocol aims to provide the means for identifying plant alternative oxidase (AOX) gene variants as functional markers for early growth regulation. Prerequisite for applying this protocol is available Schizosaccharomyces pombe strains that were transformed with individual AOX genes following published protocols from Anthony Moore's group (Albury et al., J Biol Chem 271:17062-17066, 1996; Affourtit et al., J Biol Chem 274:6212-6218, 1999). The novelty of the present protocol comes by modifying yeast cell densities in a way that allows studying critical qualitative and quantitative effects of AOX gene variants (isoenzymes or polymorphic genes) during the early phase of growth. Calorimetry is used as a novel tool to confirm differences obtained by optical density measurements in early growth regulation by metabolic phenotyping (released heat rates). This protocol enables discriminating between AOX genes that inhibit growth and

  4. Human body shape index based on an experimentally derived model of human growth.

    PubMed

    Lebiedowska, Maria K; Alter, Katharine E; Stanhope, Steven J

    2008-01-01

    To test the assumption of geometrically similar growth by developing experimentally derived models of human body growth during the age interval of 5 to 18 years; to use these derived growth models to establish a new human body shape index (HBSI) based on natural age-related changes in human body shape (HBS); and to compare various metrics of relative body weight (body mass index [BMI], ponderal index [PI], and HBSI) in a sample of 5- to 18-year-old children. Nondisabled Polish children (n = 847) participated in this descriptive study. To model growth, the best fit between body height (H) and body mass (M) was calculated for each sex using the allometric equation M = m(i) H(chi). HBSI was calculated separately for girls and boys, using sex-specific values for chi and a general HBSI from combined data. The customary BMI and PI were calculated and compared with HBSI values. The models of growth were M = 13.11H(2.84) (R2 = 0.90) for girls and M = 13.64H(2.68) (R2 = 0.91) for boys. HBSI values contained less inherent variability and were less influenced by growth (age and height) compared with BMI and PI. Age-related growth during childhood is sex-specific and not geometrically similar. Therefore, indices of HBS formulated from experimentally derived models of human growth are superior to customary geometric similarity-based indices for characterizing HBS in children during the formative growth years.

  5. Early treatment with metformin induces resistance against tumor growth in adult rats

    PubMed Central

    Trombini, Amanda B; Franco, Claudinéia CS; Miranda, Rosiane A; de Oliveira, Júlio C; Barella, Luiz F; Prates, Kelly V; de Souza, Aline A; Pavanello, Audrei; Malta, Ananda; Almeida, Douglas L; Tófolo, Laize P; Rigo, Kesia P; Ribeiro, Tatiane AS; Fabricio, Gabriel S; de Sant’Anna, Juliane R; Castro-Prado, Marialba AA; de Souza, Helenir Medri; de Morais, Hely; Mathias, Paulo CF

    2015-01-01

    It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer. PMID:26024008

  6. Human Milk Oligosaccharides Promote the Growth of Staphylococci

    PubMed Central

    Hunt, K. M.; Preuss, J.; Nissan, C.; Davlin, C. A.; Williams, J. E.; Shafii, B.; Richardson, A. D.; McGuire, M. K.; Bode, L.

    2012-01-01

    Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (n = 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of Staphylococcus and total HMO content (r = 0.66). In a follow-up study, we conducted a series of in vitro growth curve experiments utilizing Staphylococcus aureus or Staphylococcus epidermidis and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of Staphylococcus species in the lactating mammary gland. PMID:22562995

  7. Schooling and wage income losses due to early-childhood growth faltering in developing countries: national, regional, and global estimates.

    PubMed

    Fink, Günther; Peet, Evan; Danaei, Goodarz; Andrews, Kathryn; McCoy, Dana Charles; Sudfeld, Christopher R; Smith Fawzi, Mary C; Ezzati, Majid; Fawzi, Wafaie W

    2016-07-01

    The growth of >300 million children <5 y old was mildly, moderately, or severely stunted worldwide in 2010. However, national estimates of the human capital and financial losses due to growth faltering in early childhood are not available. We quantified the economic cost of growth faltering in developing countries. We combined the most recent country-level estimates of linear growth delays from the Nutrition Impact Model Study with estimates of returns to education in developing countries to estimate the impact of early-life growth faltering on educational attainment and future incomes. Primary outcomes were total years of educational attainment lost as well as the net present value of future wage earnings lost per child and birth cohort due to growth faltering in 137 developing countries. Bootstrapped standard errors were computed to account for uncertainty in modeling inputs. Our estimates suggest that early-life growth faltering in developing countries caused a total loss of 69.4 million y of educational attainment (95% CI: 41.7 million, 92.6 million y) per birth cohort. Educational attainment losses were largest in South Asia (27.6 million y; 95% CI: 20.0 million, 35.8 million y) as well as in Eastern (10.3 million y; 95% CI: 7.2 million, 12.9 million y) and Western sub-Saharan Africa (8.8 million y; 95% CI: 6.4 million, 11.5 million y). Globally, growth faltering in developing countries caused a total economic cost of $176.8 billion (95% CI: $100.9 billion, $262.6 billion)/birth cohort at nominal exchange rates, and $616.5 billion (95% CI: $365.3 billion, $898.9 billion) at purchasing power parity-adjusted exchange rates. At the regional level, economic costs were largest in South Asia ($46.6 billion; 95% CI: $33.3 billion, $61.1 billion), followed by Latin America ($44.7 billion; 95% CI: $19.2 billion, $74.6 billion) and sub-Saharan Africa ($34.2 billion; 95% CI: $24.4 billion, $45.3 billion). Our results indicate that the annual cost of early

  8. Hematopoietic growth factors and human acute leukemia.

    PubMed

    Löwenberg, B; Touw, I

    1988-10-22

    The study of myelopoietic maturation arrest in acute myeloblastic leukemia (AML) has been eased by availability of the human recombinant hemopoietic growth factors, macrophage colony stimulating factor (M-CSF), granulocyte-(G-CSF), granulocyte-macrophage-(GM-CSF) and multilineage stimulating factor (IL-3). Nonphysiological expansion of the leukemic population is not due to escape from control by these factors. Proliferation in vitro of AML cells is dependent on the presence of one or several factors in most cases. The pattern of factor-dependency does not correlate with morphological criteria in individual cases, and may thus offer a new tool for classification of AML. Overproduction of undifferentiated cells is not due to abnormal expression of receptors for the stimulating factors acting at an immature level. Rather, autocrine secretion of early acting lymphokines maintains proliferation of the leukemic clone. When looking at causes of leukemic dysregulation, yet undefined inhibitors of differentiation probably are of equal importance as dysequilibrated stimulation by lymphokines.

  9. Quinones are growth factors for the human gut microbiota.

    PubMed

    Fenn, Kathrin; Strandwitz, Philip; Stewart, Eric J; Dimise, Eric; Rubin, Sarah; Gurubacharya, Shreya; Clardy, Jon; Lewis, Kim

    2017-12-20

    The human gut microbiome has been linked to numerous components of health and disease. However, approximately 25% of the bacterial species in the gut remain uncultured, which limits our ability to properly understand, and exploit, the human microbiome. Previously, we found that growing environmental bacteria in situ in a diffusion chamber enables growth of uncultured species, suggesting the existence of growth factors in the natural environment not found in traditional cultivation media. One source of growth factors proved to be neighboring bacteria, and by using co-culture, we isolated previously uncultured organisms from the marine environment and identified siderophores as a major class of bacterial growth factors. Here, we employ similar co-culture techniques to grow bacteria from the human gut microbiome and identify novel growth factors. By testing dependence of slow-growing colonies on faster-growing neighboring bacteria in a co-culture assay, eight taxonomically diverse pairs of bacteria were identified, in which an "induced" isolate formed a gradient of growth around a cultivatable "helper." This set included two novel species Faecalibacterium sp. KLE1255-belonging to the anti-inflammatory Faecalibacterium genus-and Sutterella sp. KLE1607. While multiple helper strains were identified, Escherichia coli was also capable of promoting growth of all induced isolates. Screening a knockout library of E. coli showed that a menaquinone biosynthesis pathway was required for growth induction of Faecalibacterium sp. KLE1255 and other induced isolates. Purified menaquinones induced growth of 7/8 of the isolated strains, quinone specificity profiles for individual bacteria were identified, and genome analysis suggests an incomplete menaquinone biosynthetic capability yet the presence of anaerobic terminal reductases in the induced strains, indicating an ability to respire anaerobically. Our data show that menaquinones are a major class of growth factors for bacteria

  10. Differential growth and development of the upper and lower human thorax.

    PubMed

    Bastir, Markus; García Martínez, Daniel; Recheis, Wolfgang; Barash, Alon; Coquerelle, Michael; Rios, Luis; Peña-Melián, Angel; García Río, Francisco; O'Higgins, Paul

    2013-01-01

    The difficulties in quantifying the 3D form and spatial relationships of the skeletal components of the ribcage present a barrier to studies of the growth of the thoracic skeleton. Thus, most studies to date have relied on traditional measurements such as distances and indices from single or few ribs. It is currently known that adult-like thoracic shape is achieved early, by the end of the second postnatal year, with the circular cross-section of the newborn thorax transforming into the ovoid shape of adults; and that the ribs become inclined such that their anterior borders come to lie inferior to their posterior. Here we present a study that revisits growth changes using geometric morphometrics applied to extensive landmark data taken from the ribcage. We digitized 402 (semi) landmarks on 3D reconstructions to assess growth changes in 27 computed tomography-scanned modern humans representing newborns to adults of both sexes. Our analyses show a curved ontogenetic trajectory, resulting from different ontogenetic growth allometries of upper and lower thoracic units. Adult thoracic morphology is achieved later than predicted, by diverse modifications in different anatomical regions during different ontogenetic stages. Besides a marked increase in antero-posterior dimensions, there is an increase in medio-lateral dimensions of the upper thorax, relative to the lower thorax. This transforms the pyramidal infant thorax into the barrel-shaped one of adults. Rib descent is produced by complex changes in 3D curvature. Developmental differences between upper and lower thoracic regions relate to differential timings and rates of maturation of the respiratory and digestive systems, the spine and the locomotor system. Our findings are relevant to understanding how changes in the relative rates of growth of these systems and structures impacted on the development and evolution of modern human body shape.

  11. Differential Growth and Development of the Upper and Lower Human Thorax

    PubMed Central

    Bastir, Markus; García Martínez, Daniel; Recheis, Wolfgang; Barash, Alon; Coquerelle, Michael; Rios, Luis; Peña-Melián, Ángel; García Río, Francisco; O’Higgins, Paul

    2013-01-01

    The difficulties in quantifying the 3D form and spatial relationships of the skeletal components of the ribcage present a barrier to studies of the growth of the thoracic skeleton. Thus, most studies to date have relied on traditional measurements such as distances and indices from single or few ribs. It is currently known that adult-like thoracic shape is achieved early, by the end of the second postnatal year, with the circular cross-section of the newborn thorax transforming into the ovoid shape of adults; and that the ribs become inclined such that their anterior borders come to lie inferior to their posterior. Here we present a study that revisits growth changes using geometric morphometrics applied to extensive landmark data taken from the ribcage. We digitized 402 (semi) landmarks on 3D reconstructions to assess growth changes in 27 computed tomography-scanned modern humans representing newborns to adults of both sexes. Our analyses show a curved ontogenetic trajectory, resulting from different ontogenetic growth allometries of upper and lower thoracic units. Adult thoracic morphology is achieved later than predicted, by diverse modifications in different anatomical regions during different ontogenetic stages. Besides a marked increase in antero-posterior dimensions, there is an increase in medio-lateral dimensions of the upper thorax, relative to the lower thorax. This transforms the pyramidal infant thorax into the barrel-shaped one of adults. Rib descent is produced by complex changes in 3D curvature. Developmental differences between upper and lower thoracic regions relate to differential timings and rates of maturation of the respiratory and digestive systems, the spine and the locomotor system. Our findings are relevant to understanding how changes in the relative rates of growth of these systems and structures impacted on the development and evolution of modern human body shape. PMID:24073239

  12. Genetic and Environmental Influences on the Growth of Early Reading Skills

    ERIC Educational Resources Information Center

    Petrill, Stephen A.; Hart, Sara A.; Harlaar, Nicole; Logan, Jessica; Justice, Laura M.; Schatschneider, Christopher; Thompson, Lee; DeThorne, Laura S.; Deater-Deckard, Kirby; Cutting, Laurie

    2010-01-01

    Background: Studies have suggested genetic and environmental influences on overall level of early reading whereas the larger reading literature has shown environmental influences on the rate of growth of early reading skills. This study is the first to examine the genetic and environmental influences on both initial level of performance and rate…

  13. Population Dynamics of Early Human Migration in Britain

    PubMed Central

    Vahia, Mayank N.; Ladiwala, Uma; Mahathe, Pavan; Mathur, Deepak

    2016-01-01

    Background Early human migration is largely determined by geography and human needs. These are both deterministic parameters when small populations move into unoccupied areas where conflicts and large group dynamics are not important. The early period of human migration into the British Isles provides such a laboratory which, because of its relative geographical isolation, may allow some insights into the complex dynamics of early human migration and interaction. Method and Results We developed a simulation code based on human affinity to habitable land, as defined by availability of water sources, altitude, and flatness of land, in choosing the path of migration. Movement of people on the British island over the prehistoric period from their initial entry points was simulated on the basis of data from the megalithic period. Topographical and hydro-shed data from satellite databases was used to define habitability, based on distance from water bodies, flatness of the terrain, and altitude above sea level. We simulated population movement based on assumptions of affinity for more habitable places, with the rate of movement tempered by existing populations. We compared results of our computer simulations with genetic data and show that our simulation can predict fairly accurately the points of contacts between different migratory paths. Such comparison also provides more detailed information about the path of peoples’ movement over ~2000 years before the present era. Conclusions We demonstrate an accurate method to simulate prehistoric movements of people based upon current topographical satellite data. Our findings are validated by recently-available genetic data. Our method may prove useful in determining early human population dynamics even when no genetic information is available. PMID:27148959

  14. Fibroblast growth factor signaling is required for early somatic gonad development in zebrafish.

    PubMed

    Leerberg, Dena M; Sano, Kaori; Draper, Bruce W

    2017-09-01

    The vertebrate ovary and testis develop from a sexually indifferent gonad. During early development of the organism, primordial germ cells (the gamete lineage) and somatic gonad cells coalesce and begin to undergo growth and morphogenesis to form this bipotential gonad. Although this aspect of development is requisite for a fertile adult, little is known about the genetic regulation of early gonadogenesis in any vertebrate. Here, we provide evidence that fibroblast growth factor (Fgf) signaling is required for the early growth phase of a vertebrate bipotential gonad. Based on mutational analysis in zebrafish, we show that the Fgf ligand 24 (Fgf24) is required for proliferation, differentiation, and morphogenesis of the early somatic gonad, and as a result, most fgf24 mutants are sterile as adults. Additionally, we describe the ultrastructural elements of the early zebrafish gonad and show that distinct somatic cell populations can be identified soon after the gonad forms. Specifically, we show that fgf24 is expressed in an epithelial population of early somatic gonad cells that surrounds an inner population of mesenchymal somatic gonad cells that are in direct contact with the germ cells, and that fgf24 is required for stratification of the somatic tissue. Furthermore, based on gene expression analysis, we find that differentiation of the inner mesenchymal somatic gonad cells into functional cell types in the larval and early juvenile-stage gonad is dependent on Fgf24 signaling. Finally, we argue that the role of Fgf24 in zebrafish is functionally analogous to the role of tetrapod FGF9 in early gonad development.

  15. Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum-free cultures of human hepatocytes.

    PubMed

    Runge, D M; Runge, D; Dorko, K; Pisarov, L A; Leckel, K; Kostrubsky, V E; Thomas, D; Strom, S C; Michalopoulos, G K

    1999-02-01

    Serum-free primary cultures of hepatocytes are a useful tool to study factors triggering hepatocyte proliferation and regeneration. We have developed a chemically defined serum-free system that allows human hepatocyte proliferation in the presence of epidermal growth factor and hepatocyte growth factor. DNA synthesis and accumulation were determined by [3H]thymidine incorporation and fluorometry, respectively. Western blot analyses and co-immunoprecipitations were used to investigate the association of proteins involved in epidermal growth factor and hepatocyte growth factor activation and signaling: epidermal growth factor receptor, hepatocyte growth factor receptor (MET), urokinase-type plasminogen activator and its receptor, and a member of the signal transducer and activator of transcription family, STAT-3. Primary human hepatocytes proliferated under serum-free conditions in a chemically defined medium for up to 12 days. Epidermal growth factor-receptor and MET were present and functional, decreasing over time. MET, urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor co-precipitated to varying degrees during the culture period. STAT-3 co-precipitated with epidermal growth factor-receptor and MET to varying degrees. Proliferation of human hepatocytes can improve by modification of a chemically defined medium originally used for rat hepatocyte cultures. In these long-term cultures of human hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate growth and differentiation by interacting with their receptors and initiating downstream signaling. This involves complex formation of the receptors with other plasma membrane components for MET (urokinase-type plasminogen activator in context of its receptor) and activation of STAT-3 for both receptors.

  16. Human Capital Composition and Economic Growth

    ERIC Educational Resources Information Center

    Tsai, Chun-Li; Hung, Ming-Cheng; Harriott, Kevin

    2010-01-01

    The objective of this paper is to analyze the effect of various compositions of human capital on economic growth. We construct alternative measures of human capital composition using five fields of study. In each instance, the measure represents the number of graduates in the respective field as a percentage of all graduates. The measures are as…

  17. Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure

    PubMed Central

    Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

    2015-01-01

    Objectives In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. Methods This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. Results Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. Conclusion This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula. PMID:26622960

  18. Effectiveness of Recombinant Human Growth Hormone for Pharyngocutaneous Fistula Closure.

    PubMed

    Kucuk, Nurten; Sari, Murat; Midi, Ahmet; Yumusakhuylu, Ali Cemal; Findik, Ozan; Binnetoglu, Adem

    2015-12-01

    In laryngeal cancer, which comprises 25% of head and neck cancer, chemotherapy has come into prominence with the increase in organ-protective treatments. With such treatment, salvage surgery has increased following recurrence; the incidence of pharyngocutaneous fistula has also increased in both respiratory and digestive system surgery. We investigated the effects of recombinant human growth hormone on pharyngocutaneous fistula closure in Sprague-Dawley rats, based on an increase in amino acid uptake and protein synthesis for wound healing, an increase in mitogenesis, and enhancement of collagen formation by recombinant human growth hormone. This study was experimental animal study. Forty Sprague-Dawley rats were separated into two groups, and pharyngoesophagotomy was performed. The pharyngoesophagotomy was sutured with vicryl in both groups. Rats in group 1 (control group) received no treatment, while those in group 2 were administered a subcutaneous injection of recombinant human growth hormone daily. On day 14, the pharynx, larynx, and upper oesophagus were excised and examined microscopically. Pharyngocutaneous fistula exhibited better closure macroscopically in the recombinant human growth hormone group. There was a significant difference in collagen formation and epithelisation in the recombinant human growth hormone group compared to the control group. This study is believed to be the first in which the effect of recombinant human growth hormone on pharyngocutaneous fistula closure was evaluated, and the findings suggest the potential of use of growth hormone for treatment of pharyngocutaneous fistula.

  19. Human Life History Evolution Explains Dissociation between the Timing of Tooth Eruption and Peak Rates of Root Growth

    PubMed Central

    Dean, M. Christopher; Cole, Tim J.

    2013-01-01

    We explored the relationship between growth in tooth root length and the modern human extended period of childhood. Tooth roots provide support to counter chewing forces and so it is advantageous to grow roots quickly to allow teeth to erupt into function as early as possible. Growth in tooth root length occurs with a characteristic spurt or peak in rate sometime between tooth crown completion and root apex closure. Here we show that in Pan troglodytes the peak in root growth rate coincides with the period of time teeth are erupting into function. However, the timing of peak root velocity in modern humans occurs earlier than expected and coincides better with estimates for tooth eruption times in Homo erectus. With more time to grow longer roots prior to eruption and smaller teeth that now require less support at the time they come into function, the root growth spurt no longer confers any advantage in modern humans. We suggest that a prolonged life history schedule eventually neutralised this adaptation some time after the appearance of Homo erectus. The root spurt persists in modern humans as an intrinsic marker event that shows selection operated, not primarily on tooth tissue growth, but on the process of tooth eruption. This demonstrates the overarching influence of life history evolution on several aspects of dental development. These new insights into tooth root growth now provide an additional line of enquiry that may contribute to future studies of more recent life history and dietary adaptations within the genus Homo. PMID:23342167

  20. Human myostatin negatively regulates human myoblast growth and differentiation

    PubMed Central

    McFarlane, Craig; Hui, Gu Zi; Amanda, Wong Zhi Wei; Lau, Hiu Yeung; Lokireddy, Sudarsanareddy; XiaoJia, Ge; Mouly, Vincent; Butler-Browne, Gillian; Gluckman, Peter D.; Sharma, Mridula

    2011-01-01

    Myostatin, a member of the transforming growth factor-β superfamily, has been implicated in the potent negative regulation of myogenesis in murine models. However, little is known about the mechanism(s) through which human myostatin negatively regulates human skeletal muscle growth. Using human primary myoblasts and recombinant human myostatin protein, we show here that myostatin blocks human myoblast proliferation by regulating cell cycle progression through targeted upregulation of p21. We further show that myostatin regulates myogenic differentiation through the inhibition of key myogenic regulatory factors including MyoD, via canonical Smad signaling. In addition, we have for the first time demonstrated the capability of myostatin to regulate the Notch signaling pathway during inhibition of human myoblast differentiation. Treatment with myostatin results in the upregulation of Hes1, Hes5, and Hey1 expression during differentiation; moreover, when we interfere with Notch signaling, through treatment with the γ-secretase inhibitor L-685,458, we find enhanced myotube formation despite the presence of excess myostatin. Therefore, blockade of the Notch pathway relieves myostatin repression of differentiation, and myostatin upregulates Notch downstream target genes. Immunoprecipitation studies demonstrate that myostatin treatment of myoblasts results in enhanced association of Notch1-intracellular domain with Smad3, providing an additional mechanism through which myostatin targets and represses the activity of the myogenic regulatory factor MyoD. On the basis of these results, we suggest that myostatin function and mechanism of action are very well conserved between species, and that myostatin regulation of postnatal myogenesis involves interactions with numerous downstream signaling mediators, including the Notch pathway. PMID:21508334

  1. Human myostatin negatively regulates human myoblast growth and differentiation.

    PubMed

    McFarlane, Craig; Hui, Gu Zi; Amanda, Wong Zhi Wei; Lau, Hiu Yeung; Lokireddy, Sudarsanareddy; Xiaojia, Ge; Mouly, Vincent; Butler-Browne, Gillian; Gluckman, Peter D; Sharma, Mridula; Kambadur, Ravi

    2011-07-01

    Myostatin, a member of the transforming growth factor-β superfamily, has been implicated in the potent negative regulation of myogenesis in murine models. However, little is known about the mechanism(s) through which human myostatin negatively regulates human skeletal muscle growth. Using human primary myoblasts and recombinant human myostatin protein, we show here that myostatin blocks human myoblast proliferation by regulating cell cycle progression through targeted upregulation of p21. We further show that myostatin regulates myogenic differentiation through the inhibition of key myogenic regulatory factors including MyoD, via canonical Smad signaling. In addition, we have for the first time demonstrated the capability of myostatin to regulate the Notch signaling pathway during inhibition of human myoblast differentiation. Treatment with myostatin results in the upregulation of Hes1, Hes5, and Hey1 expression during differentiation; moreover, when we interfere with Notch signaling, through treatment with the γ-secretase inhibitor L-685,458, we find enhanced myotube formation despite the presence of excess myostatin. Therefore, blockade of the Notch pathway relieves myostatin repression of differentiation, and myostatin upregulates Notch downstream target genes. Immunoprecipitation studies demonstrate that myostatin treatment of myoblasts results in enhanced association of Notch1-intracellular domain with Smad3, providing an additional mechanism through which myostatin targets and represses the activity of the myogenic regulatory factor MyoD. On the basis of these results, we suggest that myostatin function and mechanism of action are very well conserved between species, and that myostatin regulation of postnatal myogenesis involves interactions with numerous downstream signaling mediators, including the Notch pathway.

  2. Association Between Early Life Growth and Blood Pressure Trajectories in Black South African Children.

    PubMed

    Kagura, Juliana; Adair, Linda S; Munthali, Richard J; Pettifor, John M; Norris, Shane A

    2016-11-01

    Early growth is associated with blood pressure measured on one occasion, but whether early life growth patterns are associated with longitudinal blood pressure trajectories is under-researched. Therefore, we sought to examine the association between early growth and blood pressure trajectories from childhood to adulthood. Blood pressure was measured on 7 occasions between ages 5 and 18 years in the Birth to Twenty cohort study, and conditional variables for growth in infancy and mid-childhood were computed from anthropometric measures (n=1937, 52% girls). We used a group-based trajectory modeling approach to identify distinct height-adjusted blood pressure trajectories and then tested their association with growth between birth and mid-childhood adjusting for several covariates. Three trajectory groups were identified for systolic and diastolic blood pressure: lower, middle, and upper in boys and girls, separately. In boys, predictors of the middle or upper systolic blood pressure trajectories versus the lower trajectory were in birth weight (odds ratio 0.75 [95% confidence interval 0.58-0.96] per SD) and relative weight gain in infancy (4.11 [1.25-13.51] per SD). In girls, greater relative weight gain and linear growth in both infancy and mid-childhood were consistently associated with an almost 2-fold higher likelihood of being in the upper versus lower systolic blood pressure trajectory. The associations for the diastolic blood pressure trajectories were inconsistent. These findings emphasize the importance of identifying children at risk of progression to high blood pressure. Accelerated growth in infancy and mid-childhood may be a key target for early life intervention in prevention of elevated blood pressure progression. © 2016 American Heart Association, Inc.

  3. Early Learning and Educational Technology Policy Brief

    ERIC Educational Resources Information Center

    Lee, Joan

    2016-01-01

    Recognizing the growth of technology use in early learning settings, the U.S. Department of Education and U.S. Department of Health and Human Services collaborated in the development of the "Early Learning and Educational Technology Policy Brief" to promote developmentally appropriate use of technology in homes and early learning…

  4. Analysis of early thrombus dynamics in a humanized mouse laser injury model.

    PubMed

    Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

    2014-01-01

    Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

  5. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE PAGES

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz; ...

    2017-03-22

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  6. Somatic mutations reveal asymmetric cellular dynamics in the early human embryo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ju, Young Seok; Martincorena, Inigo; Gerstung, Moritz

    Somatic cells acquire mutations throughout the course of an individual’s life. Mutations occurring early in embryogenesis are often present in a substantial proportion of, but not all, cells in postnatal humans and thus have particular characteristics and effects. Depending on their location in the genome and the proportion of cells they are present in, these mosaic mutations can cause a wide range of genetic disease syndromes and predispose carriers to cancer. They have a high chance of being transmitted to offspring as de novo germline mutations and, in principle, can provide insights into early human embryonic cell lineages and theirmore » contributions to adult tissues. Although it is known that gross chromosomal abnormalities are remarkably common in early human embryos, our understanding of early embryonic somatic mutations is very limited. Here we use whole-genome sequences of normal blood from 241 adults to identify 163 early embryonic mutations. We estimate that approximately three base substitution mutations occur per cell per cell-doubling event in early human embryogenesis and these are mainly attributable to two known mutational signatures. We used the mutations to reconstruct developmental lineages of adult cells and demonstrate that the two daughter cells of many early embryonic cell-doubling events contribute asymmetrically to adult blood at an approximately 2:1 ratio. As a result, this study therefore provides insights into the mutation rates, mutational processes and developmental outcomes of cell dynamics that operate during early human embryogenesis.« less

  7. Early Acceleration of Mathematics Students and its Effect on Growth in Self-esteem: A Longitudinal Study

    NASA Astrophysics Data System (ADS)

    Ma, Xin

    2002-11-01

    The Longitudinal Study of American Youth (LSAY) database was employed to examine the educational practice of early acceleration of students of mathematics on the development of their self-esteem across the entire secondary grade levels. Students were classified into three different academic categories (gifted, honors, and regular). Results indicated that, in terms of the development of their self-esteem, gifted students benefited from early acceleration, honors students neither benefited nor were harmed by early acceleration, and regular students were harmed by early acceleration. Early acceleration in mathematics promoted significant growth in self-esteem among gifted male students and among gifted, honors, and regular minority students. When students were accelerated, schools showed similar average growth in self-esteem among gifted students and regular students and a large effect of general support for mathematics on the average growth in self-esteem among honors students.

  8. Population growth, human development, and deforestation in biodiversity hotspots.

    PubMed

    Jha, S; Bawa, K S

    2006-06-01

    Human population and development activities affect the rate of deforestation in biodiversity hotspots. We quantified the effect of human population growth and development on rates of deforestation and analyzed the relationship between these causal factors in the 1980s and 1990s. We compared the averages of population growth, human development index (HDI, which measures income, health, and education), and deforestation rate and computed correlations among these variables for countries that contain biodiversity hotspots. When population growth was high and HDI was low there was a high rate of deforestation, but when HDI was high, rate of deforestation was low, despite high population growth. The correlation among variables was significant for the 1990s but not for the 1980s. The relationship between population growth and HDI had a regional pattern that reflected the historical process of development. Based on the changes in HDI and deforestation rate over time, we identified two drivers of deforestation: policy choice and human-development constraints. Policy choices that disregard conservation may cause the loss of forests even in countries that are relatively developed. Lack of development in other countries, on the other hand, may increase the pressure on forests to meet the basic needs of the human population. Deforestation resulting from policy choices may be easier to fix than deforestation arising from human development constraints. To prevent deforestation in the countries that have such constraints, transfer of material and intellectual resources from developed countries may be needed. Popular interest in sustainable development in developed countries can facilitate the transfer of these resources.

  9. Growth of alveoli during postnatal development in humans based on stereological estimation.

    PubMed

    Herring, Matt J; Putney, Lei F; Wyatt, Gregory; Finkbeiner, Walter E; Hyde, Dallas M

    2014-08-15

    Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats. Copyright © 2014 the American Physiological Society.

  10. Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells

    PubMed Central

    Vlismas, Antonis; Bletsa, Ritsa; Mavrogianni, Despina; Mamali, Georgina; Pergamali, Maria; Dinopoulou, Vasiliki; Partsinevelos, George; Drakakis, Peter; Loutradis, Dimitris

    2016-01-01

    Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1, -2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that

  11. Early variability in the conceptualisation of "sustainable development and human factors".

    PubMed

    Thatcher, Andrew

    2012-01-01

    The sub-discipline of "sustainable development and human factors" is relatively new, first being used in 2006 with a Technical Committee of the IEA being established only in 2009 and a similar special interest group on "green ergonomics" at the Institute of Ergonomics and Human Factors being established in 2010. In general though, the definitions and practice of "sustainable development" is highly contentious and ambiguous across a range of disciplines. This paper examines the diversity of definitions and approaches to sustainable development and human factors in the early papers in this sub-discipline. An examination of 45 chapters and papers (from 2008 to 2011) reveals a surprising consistency in the definitions used for sustainable development but also a large proportion of the papers where no definitions are given at all. The majority of papers were, however, biased towards an economic capital and social capital emphasis, which is to be expected of work traditionally in the ergonomics paradigm. Further, most papers were theoretical in nature demonstrating a great opportunity for empirical work. The variability in definitions is discussed in relation to the future challenges facing the growth of this emergent sub-discipline and opportunities for further theoretical and empirical work.

  12. Telomere dynamics in wild brown trout: effects of compensatory growth and early growth investment.

    PubMed

    Näslund, Joacim; Pauliny, Angela; Blomqvist, Donald; Johnsson, Jörgen I

    2015-04-01

    After a period of food deprivation, animals often respond with a period of faster than normal growth. Such responses have been suggested to result in decreased chromosomal maintenance, which in turn may affect the future fitness of an individual. Here, we present a field experiment in which a food deprivation period of 24 days was enforced on fish from a natural population of juvenile brown trout (Salmo trutta) at the start of the high-growth season in spring. The growth of the food-deprived fish and a non-deprived control group was then monitored in the wild during 1 year. Fin tissue samples were taken at the start of the experiment and 1 year after food deprivation to monitor the telomere dynamics, using reduced telomere length as an indicator of maintenance cost. The food-deprived fish showed partial compensatory growth in both mass and length relative to the control group. However, we found no treatment effects on telomere dynamics, suggesting that growth-compensating brown trout juveniles are able to maintain their telomeres during their second year in the stream. However, body size at the start of the experiment, reflecting growth rate during their first year of life, was negatively correlated with change in telomere length over the following year. This result raises the possibility that rapid growth early in life induces delayed costs in cellular maintenance.

  13. Beyond birth-weight: early growth and adolescent blood pressure in a Peruvian population.

    PubMed

    Sterling, Robie; Checkley, William; Gilman, Robert H; Cabrera, Lilia; Sterling, Charles R; Bern, Caryn; Miranda, J Jaime

    2014-01-01

    Background. Longitudinal investigations into the origins of adult essential hypertension have found elevated blood pressure in children to accurately track into adulthood, however the direct causes of essential hypertension in adolescence and adulthood remains unclear. Methods. We revisited 152 Peruvian adolescents from a birth cohort tracked from 0 to 30 months of age, and evaluated growth via monthly anthropometric measurements between 1995 and 1998, and obtained anthropometric and blood pressure measurements 11-14 years later. We used multivariable regression models to study the effects of infantile and childhood growth trends on blood pressure and central obesity in early adolescence. Results. In regression models adjusted for interim changes in weight and height, each 0.1 SD increase in weight for length from 0 to 5 months of age, and 1 SD increase from 6 to 30 months of age, was associated with decreased adolescent systolic blood pressure by 1.3 mm Hg (95% CI -2.4 to -0.1) and 2.5 mm Hg (95% CI -4.9 to 0.0), and decreased waist circumference by 0.6 (95% CI -1.1 to 0.0) and 1.2 cm (95% CI -2.3 to -0.1), respectively. Growth in infancy and early childhood was not significantly associated with adolescent waist-to-hip ratio. Conclusions. Rapid compensatory growth in early life has been posited to increase the risk of long-term cardiovascular morbidities such that nutritional interventions may do more harm than good. However, we found increased weight growth during infancy and early childhood to be associated with decreased systolic blood pressure and central adiposity in adolescence.

  14. Growth curve analyses of the relationship between early maternal age and children's mathematics and reading performance.

    PubMed

    Torres, D Diego

    2015-03-01

    Regarding the methods used to examine the early maternal age-child academic outcomes relationship, the extant literature has tended to examine change using statistical analyses that fail to appreciate that individuals vary in their rates of growth. Of the one study I have been able to find that employs a true growth model to estimate this relationship, the authors only controlled for characteristics of the maternal household after family formation; confounding background factors of mothers that might select them into early childbearing, a possible source of bias, were ignored. The authors' findings nonetheless suggested an inverse relationship between early maternal age, i.e., a first birth between the ages of 13 and 17, and Canadian adolescents' mean math performance at age 10. Early maternal age was not related to the linear slope of age. To elucidate whether the early maternal age-child academic outcomes association, treated in a growth context, is consistent with this finding, the present study built on it using US data and explored children's mathematics and reading trajectories from age 5 on. Its unique contribution is that it further explicitly controlled for maternal background factors and employed a three-level growth model with repeated measures of children nested within their mothers. Though the strength of the relationship varied between mean initial academic performance and mean academic growth, results confirmed that early maternal age was negatively related to children's mathematics and reading achievement, net of post-teen first birth child-specific and maternal household factors. Once maternal background factors were included, there was no statistically significant relationship between early maternal age and either children's mean initial mathematics and reading scores or their mean mathematics and reading growth. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ayyagari, R.R.; Khan-Dawood, F.S.

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2more » hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol /sup 125/I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function.« less

  16. Predictors of Longitudinal Growth in Inhibitory Control in Early Childhood

    PubMed Central

    Moilanen, Kristin L.; Shaw, Daniel S.; Dishion, Thomas J.; Gardner, Frances; Wilson, Melvin

    2009-01-01

    In the current study, we examined latent growth in 731 young children’s inhibitory control from ages 2 to 4, and whether demographic characteristics or parenting behaviors were related to initial levels and growth in inhibitory control. As part of an ongoing longitudinal evaluation of the Family Check-Up (FCU), children’s inhibitory control was assessed yearly at ages 2, 3, and 4. Inhibitory control was initially low and increased linearly to age 4. High levels of harsh parenting and male gender were associated with low initial status in inhibitory control. High levels of supportive parenting were associated with faster growth. Extreme family poverty and African American ethnicity were also associated with slower growth. The results highlight parenting as a target for early interventions in contexts of high socioeconomic risk. PMID:20376201

  17. Late effects of early growth hormone treatment in Down syndrome.

    PubMed

    Myrelid, Å; Bergman, S; Elfvik Strömberg, M; Jonsson, B; Nyberg, F; Gustafsson, J; Annerén, G

    2010-05-01

    Down syndrome (DS) is associated with short stature and psychomotor delay. We have previously shown that growth hormone (GH) treatment during infancy and childhood normalizes growth velocity and improves fine motor skill performance in DS. The aim of this study was to investigate late effects of early GH treatment on growth and psychomotor development in the DS subjects from the previous trial. Twelve of 15 adolescents with DS (3 F) from the GH group and 10 of 15 controls (5 F) participated in this follow-up study. Fifteen other subjects with DS (6 F) were included as controls in anthropometric analyses. Cognitive function was assessed with the Leiter International Performance Scale-Revised (Leiter-R) and selected subtests of the Wechsler Intelligence Scale for Children, Third edition (WISC-III). The Bruininks-Oseretsky Test of Motor Proficiency, Second edition (BOT-2), was used to assess general motor ability. Although early GH treatment had no effect on final height, the treated subjects had a greater head circumference standard deviation score (SDS) than the controls (-1.6 SDS vs. -2.2 SDS). The adolescents previously treated with GH had scores above those of the controls in all subtests of Leiter-R and WISC-III, but no difference in Brief IQ-score was seen between the groups. The age-adjusted motor performance of all subjects was below -2 SD, but the GH-treated subjects performed better than the controls in all but one subtest. The combined finding of a greater head circumference SDS and better psychomotor performance indicates that DS subjects may benefit from early GH treatment.

  18. The Growth of Human Hair.

    ERIC Educational Resources Information Center

    Jones, Helen J.

    1984-01-01

    Suggests a simple technique for collecting and observing human hair roots to compare structure, function, and variation. Students extract their own hair samples and view them using a 40-power microscope objective. Differences between active/inactive phases of hair growth are readily observed. (The activity can be adapted for younger students.) (DH)

  19. The early Upper Paleolithic human skeleton from the Abrigo do Lagar Velho (Portugal) and modern human emergence in Iberia

    PubMed Central

    Duarte, Cidália; Maurício, João; Pettitt, Paul B.; Souto, Pedro; Trinkaus, Erik; van der Plicht, Hans; Zilhão, João

    1999-01-01

    The discovery of an early Upper Paleolithic human burial at the Abrigo do Lagar Velho, Portugal, has provided evidence of early modern humans from southern Iberia. The remains, the largely complete skeleton of a ≈4-year-old child buried with pierced shell and red ochre, is dated to ca. 24,500 years B.P. The cranium, mandible, dentition, and postcrania present a mosaic of European early modern human and Neandertal features. The temporal bone has an intermediate-sized juxtamastoid eminence. The mandibular mentum osseum and the dental size and proportions, supported by mandibular ramal features, radial tuberosity orientation, and diaphyseal curvature, as well as the pubic proportions align the skeleton with early modern humans. Body proportions, reflected in femorotibial lengths and diaphyseal robusticity plus tibial condylar displacement, as well as mandibular symphyseal retreat and thoracohumeral muscle insertions, align the skeleton with the Neandertals. This morphological mosaic indicates admixture between regional Neandertals and early modern humans dispersing into southern Iberia. It establishes the complexities of the Late Pleistocene emergence of modern humans and refutes strict replacement models of modern human origins. PMID:10377462

  20. Human neuroblastoma growth inhibitory factor (h-NGIF), derived from human astrocytoma conditioned medium, has neurotrophic properties.

    PubMed

    Eksioglu, Y Z; Iida, J; Asai, K; Ueki, T; Nakanishi, K; Isobe, I; Yamagata, K; Kato, T

    1994-05-02

    Investigations on the general characteristics of human astrocytoma cell line NAC-1 revealed neuroblastoma growth inhibitory activity in conditioned medium. Neuroblastoma growth inhibitory factor (NGIF) was partially purified by Econo Q, Econo CM, and Superose 12 column chromatography. The protein is weakly basic with an estimated M(r) of 120,000, possibly having an M(r) 60,000 dimeric structure. NGIF inhibits the growth of human neuroblastoma cell lines but has no effect on morphology nor does it produce any change in the growth of human glioblastoma cell lines. Interestingly, NGIF appears to promote survival and neurite outgrowth of embryonal rat cortical neurons. These neurotrophic properties suggest a role for NGIF in the development of the nervous system.

  1. Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns

    PubMed Central

    Lewis, Maria E.; Belland, Robert J.; AbdelRahman, Yasser M.; Beatty, Wandy L.; Aiyar, Ashok A.; Zea, Arnold H.; Greene, Sheila J.; Marrero, Luis; Buckner, Lyndsey R.; Tate, David J.; McGowin, Chris L.; Kozlowski, Pamela A.; O'Brien, Michelle; Lillis, Rebecca A.; Martin, David H.; Quayle, Alison J.

    2014-01-01

    In vitro models of Chlamydia trachomatis growth have long been studied to predict growth in vivo. Alternative or persistent growth modes in vitro have been shown to occur under the influence of numerous stressors but have not been studied in vivo. Here, we report the development of methods for sampling human infections from the endocervix in a manner that permits a multifaceted analysis of the bacteria, host and the endocervical environment. Our approach permits evaluating total bacterial load, transcriptional patterns, morphology by immunofluorescence and electron microscopy, and levels of cytokines and nutrients in the infection microenvironment. By applying this approach to two pilot patients with disparate infections, we have determined that their contrasting growth patterns correlate with strikingly distinct transcriptional biomarkers, and are associated with differences in local levels of IFNγ. Our multifaceted approach will be useful to dissect infections in the human host and be useful in identifying patients at risk for chronic disease. Importantly, the molecular and morphological analyses described here indicate that persistent growth forms can be isolated from the human endocervix when the infection microenvironment resembles the in vitro model of IFNγ-induced persistence. PMID:24959423

  2. ITE inhibits growth of human pulmonary artery endothelial cells.

    PubMed

    Pang, Ling-Pin; Li, Yan; Zou, Qing-Yun; Zhou, Chi; Lei, Wei; Zheng, Jing; Huang, Shi-An

    2017-10-01

    Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.

  3. Comparison of Swirl Sign and Black Hole Sign in Predicting Early Hematoma Growth in Patients with Spontaneous Intracerebral Hemorrhage.

    PubMed

    Xiong, Xin; Li, Qi; Yang, Wen-Song; Wei, Xiao; Hu, Xi; Wang, Xing-Chen; Zhu, Dan; Li, Rui; Cao, Du; Xie, Peng

    2018-01-29

    BACKGROUND Early hematoma growth is associated with poor outcome in patients with spontaneous intracerebral hemorrhage (ICH). The swirl sign (SS) and the black hole sign (BHS) are imaging markers in ICH patients. The aim of this study was to compare the predictive value of these 2 signs for early hematoma growth. MATERIAL AND METHODS ICH patients were screened for the appearance of the 2 signs within 6 h after onset of symptoms. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 2 signs in predicting early hematoma growth were assessed. The accuracy of the 2 signs in predicting early hematoma growth was analyzed by receiver-operator analysis. RESULTS A total of 200 patients were enrolled in this study. BHS was found in 30 (15%) patients, and SS was found in 70 (35%) patients. Of the 71 patients with early hematoma growth, BHS was found on initial computed tomography scans in 24 (33.8%) and SS in 33 (46.5%). The sensitivity, specificity, PPV, and NPV of BHS for predicting early hematoma growth were 33.8%, 95.3%, 80.0%, and 72.0%, respectively. The sensitivity, specificity, PPV, and NPV of SS were 46.5%, 71.3%, 47.0%, and 71.0%, respectively. The area under the curve was 0.646 for BHS and 0.589 for SS (P=0.08). Multivariate logistic regression showed that presence of BHS is an independent predictor of early hematoma growth. CONCLUSIONS The Black hole sign seems to be good predictor for hematoma growth. The presence of swirl sign on admission CT does not independently predict hematoma growth in patients with ICH.

  4. Germination and early seedling growth of Pinus densata Mast. provenances

    Treesearch

    Yulan Xu; Nianhui Cai; Bin He; Ruili Zhang; Wei Zhao; Jianfeng Mao; Anan Duan; Yue Li; Keith Woeste

    2016-01-01

    We studied seed germination and early seedling growth of Pinus densata to explore the range of variability within the species and to inform afforestation practices. Phenotypes were evaluated at a forest tree nursery under conditions that support Pinus yunnanensis, one of the presumed parental species of P. densata...

  5. Root-zone temperature and water availability affect early root growth of planted longleaf pine

    Treesearch

    M.A. Sword

    1995-01-01

    Longleaf pine seedlings from three seed sources were exposed to three root-zone temperatures and three levels of water availability for 28 days. Root growth declined as temperature and water availability decreased. Root growth differed by seed source. Results suggest that subtle changes in the regeneration environment may influence early root growth of longleaf pine...

  6. The Growth of Early Galaxies and Reionization of Hydrogen

    NASA Astrophysics Data System (ADS)

    Chary, Ranga Ram

    2012-07-01

    The reionization of the intergalactic medium about a billion years after the Big Bang was an important event which occurred due to the release of ionizing photons from the growth of stellar mass and black holes in the early Universe. By leveraging the benefits of field galaxy surveys, I will present some recent breakthroughs in our understanding of how the earliest galaxies in the Universe evolved. I will present evidence that unlike in the local Universe where galaxy growth occurs through intermittent cannibalism, star-formation in the distant Universe is a more continuous if violent process with an overabundance of massive stars. Implications for the reionization history of the Universe will also be discussed.

  7. STATISTICAL GROWTH MODELING OF LONGITUDINAL DT-MRI FOR REGIONAL CHARACTERIZATION OF EARLY BRAIN DEVELOPMENT.

    PubMed

    Sadeghi, Neda; Prastawa, Marcel; Fletcher, P Thomas; Gilmore, John H; Lin, Weili; Gerig, Guido

    2012-01-01

    A population growth model that represents the growth trajectories of individual subjects is critical to study and understand neurodevelopment. This paper presents a framework for jointly estimating and modeling individual and population growth trajectories, and determining significant regional differences in growth pattern characteristics applied to longitudinal neuroimaging data. We use non-linear mixed effect modeling where temporal change is modeled by the Gompertz function. The Gompertz function uses intuitive parameters related to delay, rate of change, and expected asymptotic value; all descriptive measures which can answer clinical questions related to growth. Our proposed framework combines nonlinear modeling of individual trajectories, population analysis, and testing for regional differences. We apply this framework to the study of early maturation in white matter regions as measured with diffusion tensor imaging (DTI). Regional differences between anatomical regions of interest that are known to mature differently are analyzed and quantified. Experiments with image data from a large ongoing clinical study show that our framework provides descriptive, quantitative information on growth trajectories that can be directly interpreted by clinicians. To our knowledge, this is the first longitudinal analysis of growth functions to explain the trajectory of early brain maturation as it is represented in DTI.

  8. Cutting Diameter Influences Early Survival and Growth of Several Populus Clones

    Treesearch

    Donald Dickmann; Howard Phipps; Daniel Netzer

    1980-01-01

    The effects of cutting diameter on early survival and growth of several Populus clones were studied in field tests in Wisconsin and Michigan. Generally, large diameter cuttings survived and grew better than small diameter cuttings. Response differences among clones were evident.

  9. Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat

    PubMed Central

    Furukawa, Katsuro; Matsumoto, Keitaro; Nagayasu, Takeshi; Yamamoto-Fukuda, Tomomi; Tobinaga, Shuichi; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Nanashima, Atsushi; Obatake, Masayuki; Koji, Takehiko

    2013-01-01

    Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth. PMID:24610965

  10. Intratracheal Administration of Recombinant Human Keratinocyte Growth Factor Promotes Alveolar Epithelial Cell Proliferation during Compensatory Lung Growth in Rat.

    PubMed

    Furukawa, Katsuro; Matsumoto, Keitaro; Nagayasu, Takeshi; Yamamoto-Fukuda, Tomomi; Tobinaga, Shuichi; Abo, Takafumi; Yamasaki, Naoya; Tsuchiya, Tomoshi; Miyazaki, Takuro; Kamohara, Ryotaro; Nanashima, Atsushi; Obatake, Masayuki; Koji, Takehiko

    2013-12-28

    Keratinocyte growth factor (KGF) is considered to be one of the most important mitogens for lung epithelial cells. The objectives of this study were to confirm the effectiveness of intratracheal injection of recombinant human KGF (rhKGF) during compensatory lung growth and to optimize the instillation protocol. Here, trilobectomy in adult rat was performed, followed by intratracheal rhKGF instillation with low (0.4 mg/kg) and high (4 mg/kg) doses at various time-points. The proliferation of alveolar cells was assessed by the immunostaining for proliferating cell nuclear antigen (PCNA) in the residual lung. We also investigated other immunohistochemical parameters such as KGF, KGF receptor and surfactant protein A as well as terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Consequently, intratracheal single injection of rhKGF in high dose group significantly increased PCNA labeling index (LI) of alveolar cells in the remaining lung. Surprisingly, there was no difference in PCNA LI between low and high doses of rhKGF with daily injection, and PCNA LI reached a plateau level with 2 days-consecutive administration (about 60%). Our results indicate that even at low dose, daily intratracheal injection is effective to maintain high proliferative states during the early phase of compensatory lung growth.

  11. The influence of IVF/ICSI treatment on human embryonic growth trajectories.

    PubMed

    Eindhoven, S C; van Uitert, E M; Laven, J S E; Willemsen, S P; Koning, A H J; Eilers, P H C; Exalto, N; Steegers, E A P; Steegers-Theunissen, R P M

    2014-12-01

    groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively). Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies. The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories. This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre. No competing interests are declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Growth responses in a mutant dwarf rat to human growth hormone and recombinant human insulin-like growth factor I.

    PubMed

    Skottner, A; Clark, R G; Fryklund, L; Robinson, I C

    1989-05-01

    A new mutant GH-deficient dwarf rat has been used to study the effects of iv infusions of human GH (hGH) and recombinant human insulin-like growth factor I (hIGF-I). This animal has only about 5% of normal pituitary GH content, low circulating GH levels, and no regular GH surges. The defect seems to be specific for GH. Infusions of hIGF-I at 180 micrograms/day for 9 days elevated serum IGF-I concentrations significantly over those in the saline-infused controls (713 +/- 20 ng/ml vs. 395 +/- 31 ng/ml); hGH infusions did not raise IGF-I levels significantly (435 +/- 20 ng/ml). Gel filtration of serum samples showed that the high-dose hIGF-I infusions increased free IGF concentrations, without apparently altering the pattern of IGF-I binding whereas hGH infusions increased the amount of high mol wt IGF-I binding protein. Neither IGF-I nor hGH infusions affected the small amounts of rat GH present in the dwarf rat pituitary glands. Continuous iv infusions of hGH (200 mU/day for 9 days) stimulated body wt gain (2.1 +/- 0.2 g/day) and bone growth (96 +/- 9 microns/day) significantly compared to saline-infused dwarf rats (1.2 +/- 0.3 g/day and 43 +/- 3 microns/day). Infusions of hIGF-I at 180 micrograms/day produced a body wt gain (2.1 +/- 0.5 g/day) similar to that seen in the hGH-infused group but a significantly smaller stimulation of bone growth (63 +/- 3 microns/day). Infusion of a 5-fold lower dose of hIGF-I (36 micrograms/day for 9 days) had no effect on body wt or bone growth. Food intake was unaffected by either hGH or hIGF-I infusions. The pattern of tissue growth was affected differentially by hGH and IGF-I infusions that produced the same overall body wt gain. hGH induced a relatively proportional growth in most of the organs studied, whereas hIGF-I infusion at 180 micrograms/day stimulated a disproportionately greater growth of the kidney, adrenals, and spleen. In some of the animals, tissues were extracted for RIA of IGF-I; the amounts of IGF-I in the liver

  13. Human milk adiponectin is associated with infant growth in two independent cohorts.

    PubMed

    Woo, Jessica G; Guerrero, M Lourdes; Altaye, Mekibib; Ruiz-Palacios, Guillermo M; Martin, Lisa J; Dubert-Ferrandon, Alix; Newburg, David S; Morrow, Ardythe L

    2009-06-01

    Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form. This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother-infant pairs from Cincinnati, OH and 277 mother-infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot. In the population studies, initial milk adiponectin was 24.0 +/- 8.6 microg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (-0.20 +/- 0.04, p < 0.0001) and weight-for-length Z-score (-0.29 +/- 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form. Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.

  14. The Relationship between Early Growth and Survival of Hatchling Saltwater Crocodiles (Crocodylus porosus) in Captivity

    PubMed Central

    Brien, Matthew L.; Webb, Grahame J.; McGuinness, Keith; Christian, Keith A.

    2014-01-01

    Hatchling fitness in crocodilians is affected by “runtism” or failure to thrive syndrome (FTT) in captivity. In this study, 300 hatchling C. porosus, artificially incubated at 32°C for most of their embryonic development, were raised in semi-controlled conditions, with growth criteria derived for the early detection of FTT (within 24 days). Body mass, four days after hatching (BM4d), was correlated with egg size and was highly clutch specific, while snout-vent length (SVL4d) was much more variable within and between clutches. For the majority of hatchlings growth trajectories within the first 24 days continued to 90 days and could be used to predict FTT affliction up to 300 days, highlighting the importance of early growth. Growth and survival of hatchling C. porosus in captivity was not influenced by initial size (BM4d), with a slight tendency for smaller hatchlings to grow faster in the immediate post-hatching period. Strong clutch effects (12 clutches) on affliction with FTT were apparent, but could not be explained by measured clutch variables or other factors. Among individuals not afflicted by FTT (N = 245), mean growth was highly clutch specific, and the variation could be explained by an interaction between clutch and season. FTT affliction was 2.5 times higher among clutches (N = 7) that hatched later in the year when mean minimum air temperatures were lower, compared with those clutches (N = 5) that hatched early in the year. The results of this study highlight the importance of early growth in hatchling C. porosus, which has implications for the captive management of this species. PMID:24960026

  15. The public health challenge of early growth failure in India.

    PubMed

    Young, M F; Martorell, R

    2013-05-01

    Recent recognition of the early onset and high prevalence of wasting (30%) and stunting (20%) among infants 0-5 months in India draws attention to the need to understand the causes and develop prevention strategies. Such growth failure has dire consequences in the short (increased mortality) and long-term (loss of human capital and increased risk of chronic diseases). Food interventions before 6 months will increase morbidity/mortality through contamination in settings of poor sanitation and hygiene. Waiting to improve nutrition only after the initiation of complementary feeding at 6 months is a missed opportunity and may permanently alter life trajectory and potential. This underscores the importance of maternal nutrition. Iron and folic acid and protein energy supplementation during pregnancy are interventions that can improve maternal nutrition and birth outcomes. Maternal supplementation during lactation should be considered as a means to improve maternal and child outcomes, although the evidence needs strengthening. Support and counseling are also required to improve maternal diets and promote exclusive breastfeeding. Programs focused on improving maternal nutrition across the continuum of preconception, pregnancy and lactation are likely to have the greatest impact as mothers are central gatekeepers to the health and future of their children.

  16. Early Literacy Individual Growth and Development Indicators (EL-IGDIs): Growth Trajectories Using a Large, Internet-Based Sample

    ERIC Educational Resources Information Center

    Roseth, Cary J.; Missall, Kristen N.; McConnell, Scott R.

    2012-01-01

    Early literacy individual growth and development indicators (EL-IGDIs) assess preschoolers' expressive vocabulary development and phonological awareness. This study investigated longitudinal change in EL-IGDIs using a large (N=7355), internet-based sample of 36- to 60-month-old United States preschoolers without identified risks for later…

  17. Sympathetic activation during early pregnancy in humans

    PubMed Central

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  18. Ammonia Volatilization from Urea-Application Influenced Germination and Early Seedling Growth of Dry Direct-Seeded Rice

    PubMed Central

    Qi, Xiaoli; Wu, Wei; Shah, Farooq; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Liu, Hongyan; Nie, Lixiao

    2012-01-01

    Poor seed germination and early seedling growth associated with urea-induced soil ammonia volatilization are major constraints in the adoption of dry direct-seeded rice. To directly examine soil ammonia volatilization and its damage to seed germination and early seedling growth of dry direct-seeded rice when urea is applied at seeding, two Petri-dish incubation experiments and a field experiment were conducted. Ammonia volatilization due to urea application significantly reduced seed germination and early seedling growth of dry direct-seedling rice. NBPT significantly reduced ammonia volatilization following urea application. The application of ammonium sulfate, instead of urea at seeding, may mitigate poor crop establishment of dry direct-seeded rice. Root growth of dry direct-seeded rice was more seriously inhibited by soil ammonia volatilization than that of shoot. Results suggest that roots are more sensitive to soil ammonia toxicity than shoots in dry direct-seeded rice system when N is applied as urea at seeding. PMID:22454611

  19. Elongator promotes germination and early post-germination growth.

    PubMed

    Woloszynska, Magdalena; Gagliardi, Olimpia; Vandenbussche, Filip; Van Lijsebettens, Mieke

    2018-01-02

    The Elongator complex interacts with RNA polymerase II and via histone acetylation and DNA demethylation facilitates epigenetically the transcription of genes involved in diverse processes in plants, including growth, development, and immune response. Recently, we have shown that the Elongator complex promotes hypocotyl elongation and photomorphogenesis in Arabidopsis thaliana by regulating the photomorphogenesis and growth-related gene network that converges on genes implicated in cell wall biogenesis and hormone signaling. Here, we report that germination in the elo mutant was delayed by 6 h in the dark when compared to the wild type in a time lapse and germination assay. A number of germination-correlated genes were down-regulated in the elo transcriptome, suggesting a transcriptional regulation by Elongator. We also show that the hypocotyl elongation defect observed in the elo mutants in darkness originates very early in the post-germination development and is independent from the germination delay.

  20. Lost human capital from early-onset chronic depression.

    PubMed

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  1. A comparison of fatigue crack growth in human enamel and hydroxyapatite.

    PubMed

    Bajaj, Devendra; Nazari, Ahmad; Eidelman, Naomi; Arola, Dwayne D

    2008-12-01

    Cracks and craze lines are often observed in the enamel of human teeth, but they rarely cause tooth fracture. The present study evaluates fatigue crack growth in human enamel, and compares that to the fatigue response of sintered hydroxyapatite (HAp) with similar crystallinity, chemistry and density. Miniature inset compact tension (CT) specimens were prepared that embodied a small piece of enamel (N=8) or HAp (N=6). The specimens were subjected to mode I cyclic loads and the steady state crack growth responses were modeled using the Paris Law. Results showed that the fatigue crack growth exponent (m) for enamel (m=7.7+/-1.0) was similar to that for HAp (m=7.9+/-1.4), whereas the crack growth coefficient (C) for enamel (C=8.7 E-04 (mm/cycle)x(MPa m(0.5))(-m)) was significantly lower (p<0.0001) than that for HAp (C=2.0 E+00 (mm/cycle)x(MPa m(0.5))(-m)). Micrographs of the fracture surfaces showed that crack growth in the enamel occurred primarily along the prism boundaries. In regions of decussation, the microstructure promoted microcracking, crack bridging, crack deflection and crack bifurcation. Working in concert, these mechanisms increased the crack growth resistance and resulted in a sensitivity to crack growth (m) similar to bone and lower than that of human dentin. These mechanisms of toughening were not observed in the crack growth response of the sintered HAp. While enamel is the most highly mineralized tissue of the human body, the microstructural arrangement of the prisms promotes exceptional resistance to crack growth.

  2. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1979-01-01

    Efforts were directed towards maintenance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro. The production of human growth hormone (hGH) by this means would be of benefit for the treatment of certain human hypopituitary diseases such as dwarfism. One of the primary approaches was the testing of agents which may logically be expected to increase hGH release. The progress towards this goal is summarized. Results from preliminary experiments dealing with electrophoresis of pituitary cell for the purpose of somatotroph separation are described.

  3. Developmental plasticity of growth and digestive efficiency in dependence of early-life food availability

    PubMed Central

    Kotrschal, Alexander; Szidat, Sönke; Taborsky, Barbara

    2014-01-01

    Nutrition is a potent mediator of developmental plasticity. If food is scarce, developing organisms may invest into growth to outgrow size-dependent mortality (short-term benefit) and/or into an efficient digestion system (long-term benefit). We investigated this potential trade-off, by determining the influence of food availability on juvenile body and organ growth, and on adult digestive efficiency in the cichlid fish Simochromis pleurospilus. We reared two groups of fish at constant high or low food rations, and we switched four other groups between these two rations at an early and late juvenile period. We measured juvenile growth and organ sizes at different developmental stages and determined adult digestive efficiency. Fish kept at constant, high rations grew considerably faster than low-food fish. Nevertheless, S. pleurospilus partly buffered the negative effects of low food availability by developing heavier digestive organs, and they were therefore more efficient in digesting their food as adults. Results of fish exposed to a ration switch during either the early or late juvenile period suggest (i) that the ability to show compensatory growth after early exposure to low food availability persists during the juvenile period, (ii) that digestive efficiency is influenced by varying juvenile food availability during the late juvenile phase and (iii) that the efficiency of the adult digestive system is correlated with the growth rate during a narrow time window of juvenile period. PMID:25866430

  4. 7-Phloroeckol promotes hair growth on human follicles in vitro.

    PubMed

    Bak, Soon-Sun; Sung, Young Kwan; Kim, Se-Kwon

    2014-08-01

    7-Phloroeckol, phloroglucinol derivative isolated from marine brown algae, has anti-oxidative, anti-inflammatory responses and MMP inhibitory activities. In this study, we evaluated the hair growth-promoting effects of 7-phloroeckol in human hair follicles. To investigate cell viability of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells in the presence or absence of 7-phloroeckol treatment, MTT assay was employed. Moreover, gene expression and protein concentration of insulin-like growth factor (IGF)-1 was measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. 7-Phloroeckol induced an increase in proliferation of DPCs and ORS cells. In addition, hair shaft growth was measured using the hair-follicle organ culture system. 7-Phloroeckol resulted in elongation of the hair shaft in cultured human hair follicles. 7-Phloroeckol induced an IGF-1 mRNA expression and protein concentration in DPCs and conditioned media, respectively. These results suggest that 7-phloroeckol promotes hair growth through stimulation of DPCs and ORS cells.

  5. Size- and time-dependent growth properties of human induced pluripotent stem cells in the culture of single aggregate.

    PubMed

    Nath, Suman C; Horie, Masanobu; Nagamori, Eiji; Kino-Oka, Masahiro

    2017-10-01

    Aggregate culture of human induced pluripotent stem cells (hiPSCs) is a promising method to obtain high number of cells for cell therapy applications. This study quantitatively evaluated the effects of initial cell number and culture time on the growth of hiPSCs in the culture of single aggregate. Small size aggregates ((1.1 ± 0.4) × 10 1 -(2.8 ± 0.5) × 10 1 cells/aggregate) showed a lower growth rate in comparison to medium size aggregates ((8.8 ± 0.8) × 10 1 -(6.8 ± 1.1) × 10 2 cells/aggregate) during early-stage of culture (24-72 h). However, when small size aggregates were cultured in conditioned medium, their growth rate increased significantly. On the other hand, large size aggregates ((1.1 ± 0.2) × 10 3 -(3.5 ± 1.1) × 10 3 cells/aggregate) showed a lower growth rate and lower expression level of proliferation marker (ki-67) in the center region of aggregate in comparison to medium size aggregate during early-stage of culture. Medium size aggregates showed the highest growth rate during early-stage of culture. Furthermore, hiPSCs proliferation was dependent on culture time because the growth rate decreased significantly during late-stage of culture (72-120 h) at which point collagen type I accumulated on the periphery of aggregate, suggesting blockage of diffusive transport of nutrients, oxygen and metabolites into and out of the aggregates. Consideration of initial cell number and culture time are important to maintain balance between autocrine factors secretion and extracellular matrix accumulation on the aggregate periphery to achieve optimal growth of hiPSCs in the culture of single aggregate. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Role of Insulinlike Growth Factor 1 in Fetal Development and in the Early Postnatal Life of Premature Infants

    PubMed Central

    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

  7. Perturbations in growth trajectory due to early diet affect age-related deterioration in performance.

    PubMed

    Lee, Who-Seung; Monaghan, Pat; Metcalfe, Neil B

    2016-04-01

    Fluctuations in early developmental conditions can cause changes in growth trajectories that subsequently affect the adult phenotype. Here, we investigated whether compensatory growth has long-term consequences for patterns of senescence.Using three-spined sticklebacks ( Gasterosteus aculeatus ), we show that a brief period of dietary manipulation in early life affected skeletal growth rate not only during the manipulation itself, but also during a subsequent compensatory phase when fish caught up in size with controls.However, this growth acceleration influenced swimming endurance and its decline over the course of the breeding season, with a faster decline in fish that had undergone faster growth compensation.Similarly, accelerated growth led to a more pronounced reduction in the breeding period (as indicated by the duration of sexual ornamentation) over the following two breeding seasons, suggesting faster reproductive senescence. Parallel experiments showed a heightened effect of accelerated growth on these age-related declines in performance if the fish were under greater time stress to complete their compensation prior to the breeding season.Compensatory growth led to a reduction in median life span of 12% compared to steadily growing controls. While life span was independent of the eventual adult size attained, it was negatively correlated with the age-related decline in swimming endurance and sexual ornamentation.These results, complementary to those found when growth trajectories were altered by temperature rather than dietary manipulations, show that the costs of accelerated growth can last well beyond the time over which growth rates differ and are affected by the time available until an approaching life-history event such as reproduction.

  8. Growth trajectories of the human embryonic head and periconceptional maternal conditions.

    PubMed

    Koning, I V; Baken, L; Groenenberg, I A L; Husen, S C; Dudink, J; Willemsen, S P; Gijtenbeek, M; Koning, A H J; Reiss, I K M; Steegers, E A P; Steegers-Theunissen, R P M

    2016-05-01

    studied in the general population. Assessment of growth trajectories of the embryonic head may be of benefit in future early antenatal care. This study was funded by the Department of Obstetrics and Gynaecology, Erasmus MC University Medical Centre and Sophia Foundation for Medical Research, Rotterdam, The Netherlands (SSWO grant number 644). No competing interests are declared. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Purification and cultivation of human pituitary growth hormone secreting cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1978-01-01

    The maintainance of actively secreting human pituitary growth hormone cells (somatotrophs) in vitro was studied. The primary approach was the testing of agents which may be expected to increase the release of the human growth hormone (hGH). A procedure for tissue procurement is described along with the methodologies used to dissociate human pituitary tissue (obtained either at autopsy or surgery) into single cell suspensions. The validity of the Biogel cell column perfusion system for studying the dynamics of GH release was developed and documented using a rat pituitary cell system.

  10. Do infants fed directly from the breast have improved appetite regulation and slower growth during early childhood compared with infants fed from a bottle?

    PubMed Central

    2011-01-01

    Background Behavioral mechanisms that contribute to the association between breastfeeding and reduced obesity risk are poorly understood. The purpose of this study was to evaluate the hypothesis that feeding human milk from the breast (direct breastfeeding) has a more optimal association with subsequent child appetite regulation behaviors and growth, when compared to bottle-feeding. Methods Children (n = 109) aged 3- to 6- years were retrospectively classified as directly breastfed (fed exclusively at the breast), bottle-fed human milk, or bottle-fed formula in the first three months of life. Young children's appetite regulation was examined by measuring three constructs (satiety response, food responsiveness, enjoyment of food) associated with obesity risk, using the Child Eating Behavior Questionnaire. Multinomial logistic regression analyses were used to test whether children bottle-fed either human milk or formula had reduced odds of high satiety and increased odds of high food responsiveness and high enjoyment of food compared to children fed directly from the breast. Current child weight status and growth trends from 6-36 months were also examined for their relation to direct breastfeeding and appetite regulation behaviors in early childhood. Results Children fed human milk in a bottle were 67% less likely to have high satiety responsiveness compared to directly breastfed children, after controlling for child age, child weight status, maternal race/ethnicity, and maternal education. There was no association of bottle-feeding (either human milk or formula) with young children's food responsiveness and enjoyment of food. There was neither an association of direct breastfeeding with current child weight status, nor was there a clear difference between directly breastfed and bottle-fed children in growth trajectories from 6- to 36-months. More rapid infant changes in weight-for-age score were associated with lower satiety responsiveness, higher food

  11. Growth is similar in premature infants fed human milk fortified with a human milk or bovine milk-based fortifier

    USDA-ARS?s Scientific Manuscript database

    Preterm infants require fortification of human milk (HM) to provide adequate nutrients for growth. A human milk fortifier (HMF) made from donor human milk has recently been introduced. However, limited data are available comparing the growth outcomes of this product with current fortifiers. We evalu...

  12. Alternative Student Growth Measures for Teacher Evaluation: Implementation Experiences of Early-Adopting Districts. REL 2015-093

    ERIC Educational Resources Information Center

    McCullough, Moira; English, Brittany; Angus, Megan Hague; Gill, Brian

    2015-01-01

    Alternative student growth measures for teacher evaluation: Implementation experiences of early-adopting districts: State requirements to include student achievement growth in teacher evaluations are prompting the development of alternative ways to measure growth in grades and subjects not covered by state assessments. These alternative growth…

  13. Associations of Linear Growth and Relative Weight Gain in Early Life with Human Capital at 30 Years of Age.

    PubMed

    Horta, Bernardo Lessa; Victora, Cesar G; de Mola, Christian Loret; Quevedo, Luciana; Pinheiro, Ricardo Tavares; Gigante, Denise P; Motta, Janaina Vieira Dos Santos; Barros, Fernando C

    2017-03-01

    To assess the associations of birthweight, nutritional status and growth in childhood with IQ, years of schooling, and monthly income at 30 years of age. In 1982, the 5 maternity hospitals in Pelotas, Brazil, were visited daily and 5914 live births were identified. At 30 years of age, 3701 subjects were interviewed. IQ, years of schooling, and income were measured. On average, their IQ was 98 points, they had 11.4 years of schooling, and the mean income was 1593 reais. After controlling for several confounders, birthweight and attained weight and length/height for age at 2 and 4 years of age were associated positively with IQ, years of years of schooling, and income, except for the association between length at 2 years of age and income. Conditional growth analyses were used to disentangle linear growth from relative weight gain. Conditional length at 2 years of age ≥1 SD score above the expected value, compared with ≥1 SD below the expected, was associated with an increase in IQ (4.28 points; 95% CI, 2.66-5.90), years of schooling (1.58 years; 95% CI, 1.08-2.08), and monthly income (303 Brazilian reais; 95% CI, 44-563). Relative weight gain, above what would be expected from linear growth, was not associated with the outcomes. In a middle-income setting, promotion of linear growth in the first 1000 days of life is likely to increase adult IQ, years of schooling, and income. Weight gain in excess of what is expected from linear growth does not seem to improve human capital. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Origins and early development of human body knowledge.

    PubMed

    Slaughter, Virginia; Heron, Michelle

    2004-01-01

    As a knowable object, the human body is highly complex. Evidence from several converging lines of research, including psychological studies, neuroimaging and clinical neuropsychology, indicates that human body knowledge is widely distributed in the adult brain, and is instantiated in at least three partially independent levels of representation. Sensorimotor body knowledge is responsible for on-line control and movement of one's own body and may also contribute to the perception of others' moving bodies; visuo-spatial body knowledge specifies detailed structural descriptions of the spatial attributes of the human body; and lexical-semantic body knowledge contains language-based knowledge about the human body. In the first chapter of this Monograph, we outline the evidence for these three hypothesized levels of human body knowledge, then review relevant literature on infants' and young children's human body knowledge in terms of the three-level framework. In Chapters II and III, we report two complimentary series of studies that specifically investigate the emergence of visuo-spatial body knowledge in infancy. Our technique is to compare infants'responses to typical and scrambled human bodies, in order to evaluate when and how infants acquire knowledge about the canonical spatial layout of the human body. Data from a series of visual habituation studies indicate that infants first discriminate scrambled from typical human body picture sat 15 to 18 months of age. Data from object examination studies similarly indicate that infants are sensitive to violations of three-dimensional human body stimuli starting at 15-18 months of age. The overall pattern of data supports several conclusions about the early development of human body knowledge: (a) detailed visuo-spatial knowledge about the human body is first evident in the second year of life, (b) visuo-spatial knowledge of human faces and human bodies are at least partially independent in infancy and (c) infants' initial

  15. A Comparison of Fatigue Crack Growth in Human Enamel and Hydroxyapatite

    PubMed Central

    Bajaj, Devendra; Nazari, Ahmad; Eidelman, Naomi; Arola, Dwayne

    2008-01-01

    Cracks and craze lines are often observed in the enamel of human teeth, but they rarely cause tooth fracture. The present study evaluates fatigue crack growth in human enamel, and compares that to the fatigue response of sintered hydroxyapatite (HAp) with similar crystallinity, chemistry and density. Miniature inset compact tension (CT) specimens were prepared that embodied a small piece of enamel (N=8) or HAp (N=6). The specimens were subjected to mode I cyclic loads and the steady state crack growth responses were modeled using the Paris Law. Results showed that the fatigue crack growth exponent (m) for enamel (m = 7.7±1.0) was similar to that for HAp (m = 7.9±1.4), whereas the crack growth coefficient (C) for enamel (C=8.7E-04 (mm/cycle)·(MPa·m0.5)-m) was significantly lower (p<0.0001) than that for HAp (C = 2.0E+00 (mm/cycle)·(MPa·m0.5)-m). Micrographs of the fracture surfaces showed that crack growth in the enamel occurred primarily along the prism boundaries. In regions of decussation, the microstructure promoted microcracking, crack bridging, crack deflection and crack bifurcation. Working in concert, these mechanisms increased the crack growth resistance and resulted in a sensitivity to crack growth (m) similar to bone and lower than that of human dentin. These mechanisms of toughening were not observed in the crack growth response of the sintered HAp. While enamel is the most highly mineralized tissue of the human body, the microstructural arrangement of the prisms promotes exceptional resistance to crack growth. PMID:18804277

  16. Physical growth and cognitive skills in early-life: evidence from a nationally representative US birth cohort.

    PubMed

    Murasko, Jason E

    2013-11-01

    This paper establishes associations between length/height and cognitive skills in infancy, toddlerhood, and school-entry. The data come from the Early Childhood Longitudinal Study--Birth Cohort (ECLS-B), a representative longitudinal sample of US children born in 2001. A positive association between length/height and cognition is found as early as 9 months and continues through school-entry. These associations are robust to controls for birthweight and economic status. Early growth is also shown to be a stronger predictor of reading and math skills in kindergarten than attained height. Girls exhibit stronger evidence of this latter result than boys. These findings have implications for the interpretation of early life as a critical period for the growth-cognition relationship. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells

    NASA Astrophysics Data System (ADS)

    Morgan, Jeffrey R.; Barrandon, Yann; Green, Howard; Mulligan, Richard C.

    1987-09-01

    Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.

  18. Complications of growth-sparing surgery in early onset scoliosis.

    PubMed

    Akbarnia, Behrooz A; Emans, John B

    2010-12-01

    Review of available literature, authors' opinion. To describe complications associated with growth-sparing surgical treatment of early onset scoliosis (EOS). EOS has many potential etiologies and is often associated with thoracic insufficiency syndrome. The growth of the spine, thorax, and lungs are interrelated, and severe EOS typically involves disturbance of the normal development of all 3. Severe EOS may be treated during growth with surgical techniques, intended to preserve growth while controlling deformity, the most common of which are spinal "growing rods" (GR) or "vertical expandable prosthetic titanium rib" (VEPTR). Although presently popular, there is minimal long-term data on the outcome of growth-sparing surgical techniques on EOS. Review. Potential adverse outcomes of GR or VEPTR treatment of EOS include failure to prevent progressive deformity or thoracic insufficiency syndrome, an unacceptably short or stiff spine or deformed thorax, increased family burden of care, and potentially negative psychological consequences from repeated surgical interventions. Neither technique reliably controls all deformity over the entirety of growth period. Infections are common to both GR and VEPTR. Rod breakage and spontaneous premature spinal fusion beneath rods are troublesome complications in GR, whereas drift of rib attachments and chest wall scarring are anticipated complications in VEPTR treatment. Indications for GR and VEPTR overlap, but thoracogenic scoliosis and severe upper thoracic kyphosis are best treated by VEPTR and GR, respectively. Surgeons planning treatment of EOS should anticipate the many complications common to growth-sparing surgery, share their knowledge with families, and use complications as one factor in the complex decision as to when and whether to initiate the repetitive surgeries associated with GR or VEPTR in the treatment of severe EOS.

  19. Human serum provided additional values in growth factors supplemented medium for human chondrocytes monolayer expansion and engineered cartilage construction.

    PubMed

    Chua, K H; Aminuddin, B S; Fuzina, N H; Ruszymah, B H I

    2004-05-01

    We have previously formulated an optimized human chondrocytes growth medium based on 2% fetal bovine serum supplementation. For clinical usage, the animal serum must be replaced by patient own serum. We investigated the effects of human serum concentration for human nasal septum chondrocytes monolayer culture and cartilage reconstruction. Human serum demonstrated a dose dependent manner in promoting chondrocytes growth and cartilage engineering.

  20. Early Childhood Memory and Attention as Predictors of Academic Growth Trajectories

    ERIC Educational Resources Information Center

    Stipek, Deborah; Valentino, Rachel A.

    2015-01-01

    Longitudinal data from the children of the National Longitudinal Survey of Youth (NLSY) were used to assess how well measures of short-term and working memory and attention in early childhood predicted longitudinal growth trajectories in mathematics and reading comprehension. Analyses also examined whether changes in memory and attention were more…

  1. MicroRNA-93 inhibits tumor growth and early relapse of human colorectal cancer by affecting genes involved in the cell cycle.

    PubMed

    Yang, I-Ping; Tsai, Hsiang-Lin; Hou, Ming-Feng; Chen, Ku-Chung; Tsai, Pei-Chien; Huang, Szu-Wei; Chou, Wen-Wen; Wang, Jaw-Yuan; Juo, Suh-Hang Hank

    2012-08-01

    Colorectal cancer (CRC) is associated with high recurrence and mortality. Because deregulation of microRNAs is associated with CRC development and recurrence, the expression levels of microRNAs can be a simple and reliable biomarker to detect postoperative early relapse, thereby helping physicians to treat high-risk patients more efficiently. We used microRNA arrays and observed that microRNA-93 had substantially different expression levels in early (recurrence within 12 months after surgery) and non-early relapse CRC patients. The replication study, which included 35 early relapse and 42 non-early relapse subjects, further confirmed overexpression of microRNA-93 in non-early relapse samples. The in vitro and in vivo effects of microRNA-93 were investigated by examining cell proliferation, migration and invasion, as well as cell cycles, target-gene expression and xenograft in null mice. Cellular studies showed that the overexpression of microRNA-93 inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that microRNA-93 caused an accumulation of the G2 population. However, microRNA-93 could not induce cell apoptosis or necrosis. Functional studies showed that microRNA-93 could suppress CCNB1 protein expression leading to cell cycle arrest in the G2 phase. Moreover, microRNA-93 repressed expression of ERBB2, p21 and VEGF, all of which are involved in cell proliferation. MicroRNA-93 also suppressed tumor growth in null mice. This study showed that microRNA-93 can inhibit tumorigenesis and reduce the recurrence of CRC; these findings may have potential clinical applications for predicting the recurrence of CRC.

  2. The biorhythm of human skeletal growth.

    PubMed

    Mahoney, Patrick; Miszkiewicz, Justyna J; Chapple, Simon; Le Luyer, Mona; Schlecht, Stephen H; Stewart, Tahlia J; Griffiths, Richard A; Deter, Chris; Guatelli-Steinberg, Debbie

    2018-01-01

    Evidence of a periodic biorhythm is retained in tooth enamel in the form of Retzius lines. The periodicity of Retzius lines (RP) correlates with body mass and the scheduling of life history events when compared between some mammalian species. The correlation has led to the development of the inter-specific Havers-Halberg oscillation (HHO) hypothesis, which holds great potential for studying aspects of a fossil species biology from teeth. Yet, our understanding of if, or how, the HHO relates to human skeletal growth is limited. The goal here is to explore associations between the biorhythm and two hard tissues that form at different times during human ontogeny, within the context of the HHO. First, we investigate the relationship of RP to permanent molar enamel thickness and the underlying daily rate that ameloblasts secrete enamel during childhood. Following this, we develop preliminary research conducted on small samples of adult human bone by testing associations between RP, adult femoral length (as a proxy for attained adult stature) and cortical osteocyte lacunae density (as a proxy for the rate of osteocyte proliferation). Results reveal RP is positively correlated with enamel thickness, negatively correlated with femoral length, but weakly associated with the rate of enamel secretion and osteocyte proliferation. These new data imply that a slower biorhythm predicts thicker enamel for children but shorter stature for adults. Our results develop the intra-specific HHO hypothesis suggesting that there is a common underlying systemic biorhythm that has a role in the final products of human enamel and bone growth. © 2017 Anatomical Society.

  3. Short Stature, Accelerated Bone Maturation, and Early Growth Cessation Due to Heterozygous Aggrecan Mutations

    PubMed Central

    Nilsson, Ola; Guo, Michael H.; Dunbar, Nancy; Popovic, Jadranka; Flynn, Daniel; Jacobsen, Christina; Lui, Julian C.; Hirschhorn, Joel N.; Baron, Jeffrey

    2014-01-01

    Context: Many children with idiopathic short stature have a delayed bone age. Idiopathic short stature with advanced bone age is far less common. Objective: The aim was to identify underlying genetic causes of short stature with advanced bone age. Setting and Design: We used whole-exome sequencing to study three families with autosomal-dominant short stature, advanced bone age, and premature growth cessation. Results: Affected individuals presented with short stature [adult heights −2.3 to −4.2 standard deviation scores (SDS)] with histories of early growth cessation or childhood short stature (height SDS −1.9 to −3.5 SDS), advancement of bone age, and normal endocrine evaluations. Whole-exome sequencing identified novel heterozygous variants in ACAN, which encodes aggrecan, a proteoglycan in the extracellular matrix of growth plate and other cartilaginous tissues. The variants were present in all affected, but in no unaffected, family members. In Family 1, a novel frameshift mutation in exon 3 (c.272delA) was identified, which is predicted to cause early truncation of the aggrecan protein. In Family 2, a base-pair substitution was found in a highly conserved location within a splice donor site (c.2026+1G>A), which is also likely to alter the amino acid sequence of a large portion of the protein. In Family 3, a missense variant (c.7064T>C) in exon 14 affects a highly conserved residue (L2355P) and is strongly predicted to perturb protein function. Conclusions: Our study demonstrates that heterozygous mutations in ACAN can cause a mild skeletal dysplasia, which presents clinically as short stature with advanced bone age. The accelerating effect on skeletal maturation has not previously been noted in the few prior reports of human ACAN mutations. Our findings thus expand the spectrum of ACAN defects and provide a new molecular genetic etiology for the unusual child who presents with short stature and accelerated skeletal maturation. PMID:24762113

  4. Genetic control of postnatal human brain growth

    PubMed Central

    van Dyck, Laura I.; Morrow, Eric M.

    2017-01-01

    Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

  5. Early Life Growth Predictors of Childhood Adiposity Trajectories and Future Risk for Obesity: Birth to Twenty Cohort.

    PubMed

    Munthali, Richard J; Kagura, Juliana; Lombard, Zané; Norris, Shane A

    2017-10-01

    There is growing evidence of variations in adiposity trajectories among individuals, but the influence of early life growth patterns on these trajectories is underresearched in low- and middle-income countries. Therefore, our aim was to examine the association between early life conditional weight gain and childhood adiposity trajectories. We previously identified distinct adiposity trajectories (four for girls and three for boys) in black South African children (boys = 877; girls = 947). The association between the trajectories and early life growth patterns, and future obesity risk was assessed by multivariate linear and multinomial logistic and logistic regressions. Conditional weight gain independent of height was computed for infancy (0-2 years) and early childhood (2-4 years). Conditional weight gain before 5 years of age was significantly associated with early onset of obesity or overweight (excess weight) BMI trajectories in both boys and girls. In girls, greater conditional weight gain in infancy was associated with increased relative risk of being in the early-onset obese to morbid obese trajectory, with relative risk ratios of 2.03 (95% confidence interval: 1.17-3.52) compared to belonging to a BMI trajectory in the normal range. Boys and girls in the early-onset obesity or overweight BMI trajectories were more likely to be overweight or obese in early adulthood. Excessive weight gain in infancy and early childhood, independent of linear growth, predicts childhood and adolescent BMI trajectories toward obesity. These results underscore the importance of early life factors in the development of obesity and other NCDs in later life.

  6. The autism associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain

    PubMed Central

    Peng, Yun; Lu, Zhongming; Li, Guohui; Piechowicz, Mariel; Anderson, Miranda; Uddin, Yasin; Wu, Jie; Qiu, Shenfeng

    2015-01-01

    The human MET gene imparts a replicated risk for autism spectrum disorder (ASD), and is implicated in the structural and functional integrity of brain. MET encodes a receptor tyrosine kinase, MET, which plays a pleiotropic role in embryogenesis and modifies a large number of neurodevelopmental events. Very little is known, however, on how MET signaling engages distinct cellular events to collectively affect brain development in ASD-relevant disease domains. Here, we show that MET protein expression is dynamically regulated and compartmentalized in developing neurons. MET is heavily expressed in neuronal growth cones at early developmental stages and its activation engages small GTPase Cdc42 to promote neuronal growth, dendritic arborization, and spine formation. Genetic ablation of MET signaling in mouse dorsal pallium leads to altered neuronal morphology indicative of early functional maturation. In contrast, prolonged activation of MET represses the formation and functional maturation of glutamatergic synapses. Moreover, manipulating MET signaling levels in vivo in the developing prefrontal projection neurons disrupts the local circuit connectivity made onto these neurons. Therefore, normal time-delimited MET signaling is critical in regulating the timing of neuronal growth, glutamatergic synapse maturation and cortical circuit function. Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD. PMID:26728565

  7. Assessment of Growth Factors Secreted by Human Breastmilk Mesenchymal Stem Cells.

    PubMed

    Kaingade, Pankaj Mahipatrao; Somasundaram, Indumathi; Nikam, Amar Babaso; Sarang, Shabari Amit; Patel, Jagdish Shantilal

    2016-01-01

    Human breastmilk is a dynamic, multifaceted biological fluid containing nutrients, bioactive substances, and growth factors. It is effective in supporting growth and development of an infant. As breastmilk has been found to possess mesenchymal stem cells, the importance of the components of breastmilk and their physiological roles is increasing day by day. The present study was intended to identify the secretions of growth factors, mainly vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), from human breastmilk mesenchymal stem cells under basal conditions of in vitro cell culture using synthetic media and human cord serum. The growth factors were analyzed with the enzyme-linked immunosorbent assay technique. The cultured mesenchymal stem cells of breastmilk without serum revealed significant differences in secretions of the VEGF and HGF growth factors (8.55 ± 2.26402 pg/mL and 230.8 ± 45.9861 pg/mL, respectively) compared with mesenchymal stem cells of breastmilk with serum (21.31 ± 4.69 pg/mL and 2,404.42 ± 481.593 pg/mL, respectively). Results obtained from our study demonstrate that both VEGF and HGF are secreted in vitro by human breastmilk mesenchymal stem cells. The roles of VEGF and HGF in surfactant secretion, pulmonary maturation, and neonatal maturity have been well established. Thus, we emphasize that breastmilk-derived MSCs could be a potent therapeutic source in treating neonatal diseases. Besides, due to its immense potency, the study also emphasizes the importance of breastfeeding, which is promoted by organizations like the World Heatlh Organization and UNICEF.

  8. New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth.

    PubMed

    Sebastián-Pérez, Víctor; Manoli, Maria-Tsampika; Pérez, Daniel I; Gil, Carmen; Mellado, Emilia; Martínez, Ana; Espeso, Eduardo A; Campillo, Nuria E

    2016-06-30

    Invasive aspergillosis (IA) is one of the most severe forms of fungi infection. IA disease is mainly due to Aspergillus fumigatus, an air-borne opportunistic pathogen. Mortality rate caused by IA is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment options, thus new and efficient drugs are necessary. The aim of this work is, using Aspergillus nidulans as non-pathogen model, to develop efficient drugs to treat IA. The recent discovered role of glycogen synthase kinase-3 homologue, GskA, in A. fumigatus human infection and our previous experience on human GSK-3 inhibitors focus our attention on this kinase as a target for the development of antifungal drugs. With the aim to identify effective inhibitors of colonial growth of A. fumigatus we use A. nidulans as an accurate model for in vivo and in silico studies. Several well-known human GSK-3β inhibitors were tested for inhibition of A. nidulans colony growth. Computational tools as docking studies and binding site prediction was used to explain the different biological profile of the tested inhibitors. Three of the five tested hGSK3β inhibitors are able to reduce completely the colonial growth by covalent bind to the enzyme. Therefore these compounds may be useful in different applications to eradicate IA. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  9. Hepatitis B virus X protein shifts human hepatic transforming growth factor (TGF)-beta signaling from tumor suppression to oncogenesis in early chronic hepatitis B.

    PubMed

    Murata, Miki; Matsuzaki, Koichi; Yoshida, Katsunori; Sekimoto, Go; Tahashi, Yoshiya; Mori, Shigeo; Uemura, Yoshiko; Sakaida, Noriko; Fujisawa, Junichi; Seki, Toshihito; Kobayashi, Kazuki; Yokote, Koutaro; Koike, Kazuhiko; Okazaki, Kazuichi

    2009-04-01

    Hepatitis B virus X (HBx) protein is suspected to participate in oncogenesis during chronic hepatitis B progression. Transforming growth factor beta (TGF-beta) signaling involves both tumor suppression and oncogenesis. TGF-beta activates TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Reversible shifting of Smad3-mediated signaling between tumor suppression and oncogenesis in HBx-expressing hepatocytes indicated that TbetaRI-dependent pSmad3C transmitted a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promoted cell growth. We used immunostaining, immunoblotting, and in vitro kinase assay to compare pSmad3L- and pSmad3C-mediated signaling in biopsy specimens representing chronic hepatitis, cirrhosis, or hepatocellular carcinoma (HCC) from 90 patients chronically infected with hepatitis B virus (HBV) with signaling in liver specimens from HBx transgenic mice. In proportion to plasma HBV DNA levels, early chronic hepatitis B specimens showed prominence of pSmad3L in hepatocytic nuclei. HBx-activated JNK/pSmad3L/c-Myc oncogenic pathway was enhanced, while the TbetaRI/pSmad3C/p21(WAF1) tumor-suppressive pathway was impaired as human and mouse HBx-associated hepatocarcinogenesis progressed. Of 28 patients with chronic hepatitis B who showed strong oncogenic pSmad3L signaling, six developed HCC within 12 years; only one of 32 patients showing little pSmad3L developed HCC. In contrast, seven of 30 patients with little Smad3C phosphorylation developed HCC, while no patient who retained hepatocytic tumor-suppressive pSmad3C developed HCC within 12 years. HBx shifts hepatocytic TGF-beta signaling from the tumor-suppressive pSmad3C pathway to the oncogenic pSmad3L pathway in early carcinogenic process. Hepatocytic pSmad3L and pSmad3C assessment in HBV-infected liver specimens should prove

  10. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

    PubMed

    Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

    2015-01-01

    Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

  11. 6-Gingerol inhibits hair shaft growth in cultured human hair follicles and modulates hair growth in mice.

    PubMed

    Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

    2013-01-01

    Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal.

  12. 6-Gingerol Inhibits Hair Shaft Growth in Cultured Human Hair Follicles and Modulates Hair Growth in Mice

    PubMed Central

    Miao, Yong; Sun, Yabin; Wang, Wenjun; Du, Benjun; Xiao, Shun-e; Hu, Yijue; Hu, Zhiqi

    2013-01-01

    Ginger (Zingiber officinale) has been traditionally used to check hair loss and stimulate hair growth in East Asia. Several companies produce shampoo containing an extract of ginger claimed to have anti-hair loss and hair growth promotion properties. However, there is no scientific evidence to back up these claims. This study was undertaken to measure 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo, and to investigate its effect on human dermal papilla cells (DPCs) in vivo and in vitro. 6-Gingerol suppressed hair growth in hair follicles in culture and the proliferation of cultured DPCs. The growth inhibition of DPCs by 6-gingerol in vitro may reflect a decrease in the Bcl-2/Bax ratio. Similar results were obtained in vivo. The results of this study showed that 6-gingerol does not have the ability to promote hair growth, on the contrary, can suppress human hair growth via its inhibitory and pro-apoptotic effects on DPCs in vitro, and can cause prolongation of telogen phase in vivo. Thus, 6-gingerol rather than being a hair growth stimulating drug, it is a potential hair growth suppressive drug; i.e. for hair removal. PMID:23437345

  13. Human growth hormone induced cholestatic hepatitis in a growth hormone deficient patient with short stature.

    PubMed

    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.

  14. Dietary protein intake and quality in early life: impact on growth and obesity.

    PubMed

    Lind, Mads V; Larnkjær, Anni; Mølgaard, Christian; Michaelsen, Kim F

    2017-01-01

    Obesity is an increasing problem and high-protein intake early in life seems to increase later risk of obesity. This review summarizes recent publications in the area including observational and intervention studies and publications on underlying mechanisms. Recent observational and randomized controlled trials confirmed that high-protein intake in early life seems to increase early weight gain and the risk of later overweight and obesity. Recent studies have looked at the effect of different sources of protein, and especially high-animal protein intake seems to have an effect on obesity. Specific amino acids, such as leucine, have also been implicated in increasing later obesity risk maybe via specific actions on insulin-like growth factor I. Furthermore, additional underlying mechanisms including epigenetics have been linked to long-term obesogenic programming. Finally, infants with catch-up growth or specific genotypes might be particularly vulnerable to high-protein intake. Recent studies confirm the associations between high-protein intake during the first 2 years and later obesity. Furthermore, knowledge of the mechanisms involved and the role of different dietary protein sources and amino acids has increased, but intervention studies are needed to confirm the mechanisms. Avoiding high-protein intake in early life holds promise as a preventive strategy for childhood obesity.

  15. High nutrient-use efficiency during early seedling growth in diverse Grevillea species (Proteaceae)

    PubMed Central

    He, Tianhua; Fowler, William M.; Causley, Casey L.

    2015-01-01

    Several hypotheses have been proposed to explain the rich floristic diversity in regions characterised by nutrient-impoverished soils; however, none of these hypotheses have been able to explain the rapid diversification over a relatively short evolutionary time period of Grevillea, an Australian plant genus with 452 recognised species/subspecies and only 11 million years of evolutionary history. Here, we hypothesise that the apparent evolutionary success of Grevillea might have been triggered by the highly efficient use of key nutrients. The nutrient content in the seeds and nutrient-use efficiency during early seedling growth of 12 species of Grevillea were compared with those of 24 species of Hakea, a closely related genus. Compared with Hakea, the Grevillea species achieved similar growth rates (root and shoot length) during the early stages of seedling growth but contained only approximately half of the seed nutrient content. We conclude that the high nutrient-use efficiency observed in Grevillea might have provided a selective advantage in nutrient-poor ecosystems during evolution and that this property likely contributed to the evolutionary success in Grevillea. PMID:26607493

  16. Early vs. asymptotic growth responses of herbaceous plants to elevated CO[sub 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Thomas, S.C.; Jasienski, M.; Bazzaz, F.A.

    1999-07-01

    Although many studies have examined the effects of elevated carbon dioxide on plant growth,'' the dynamics of growth involve at least two parameters, namely, an early rate of exponential size increase and an asymptotic size reached late in plant ontogeny. The common practice of quantifying CO[sub 2] responses as a single response ratio thus obscures two qualitatively distinct kinds of effects. The present experiment examines effects of elevated CO[sub 2] on both early and asymptotic growth parameters in eight C[sub 3] herbaceous plant species (Abutilon theophrasti, Cassia obtusifolia, Plantago major, Rumex crispus, Taraxacum officinale, Dactylis glomerata, Lolium multiflorum, and Panicummore » dichotomoflorum). Plants were grown for 118--172 d in a factorial design of CO[sub 2] (350 and 700 [micro]L/L) and plant density (individually grown vs. high-density monocultures) under edaphic conditions approximating those of coastal areas in Massachusetts. For Abutilon theophrasti, intraspecific patterns of plant response were also assessed using eight genotypes randomly sampled from a natural population and propagated as inbred lines.« less

  17. 21 CFR 862.1370 - Human growth hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human growth hormone test system. 862.1370 Section 862.1370 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test...

  18. Rate of Language Growth in Children with Hearing Loss in an Auditory-Verbal Early Intervention Program

    ERIC Educational Resources Information Center

    Jackson, Carla Wood; Schatschneider, Christopher

    2013-01-01

    This longitudinal study explored the rate of language growth of children in an early intervention program providing auditory-verbal therapy. A retrospective investigation, the study applied a linear growth model to estimate a mean growth curve and the extent of individual variation in language performance on the Preschool Language Scale, 4th ed.…

  19. HIV-1 Tat-mediated induction of Platelet-derived Growth Factor in Astrocytes: Role of Early Growth Response Gene 1

    PubMed Central

    Bethel-Brown, Crystal; Yao, Honghong; Callen, Shannon; Lee, Young Han; Dash, Prasanta K; Kumar, Anil; Buch, Shilpa

    2011-01-01

    HIV-associated neurological disorders (HAND) are estimated to affect almost 60% of HIV infected individuals. HIV-encephalitis (HIVE), the pathological correlate of the most severe form of HAND is often characterized by glial activation, cytokine/chemokine dysregulation, and neuronal damage and loss. However, the severity of HIVE correlates better with glial activation rather than viral load. Using the macaque model, it has been demonstrated that simian immunodeficiency virus encephalitis (SIVE) correlates with increased expression of the mitogen platelet-derived growth factor-B (PDGF-B) chain in the brain. The present study was aimed at exploring the role of PDGF-B chain in HIV-associated activation and proliferation of astrocytes. Specifically, the data herein demonstrate that exposure of rat and human astrocytes to the HIV-1 protein, Tat resulted in the induction of PDGF at both the mRNA and protein levels. Furthermore, PDGF-BB induction was regulated by activation of ERK1/2 and JNK signaling pathways and the downstream transcription factor, early growth response 1(Egr-1). Chromatin immunoprecipitation (ChIP) assays demonstrated binding of Egr-1 to the PDGF-B promoter. Exposure of astrocytes to PDGF-BB, in turn, led to both increased proliferation and release of pro-inflammatory cytokines MCP-1 and IL-1β. Since astrogliosis is linked to disease severity, understanding its regulation by PDGF-BB could aid in the development of therapeutic intervention strategies for HAND. PMID:21368226

  20. Nerve Growth Factor: Early Studies And Recent Clinical Trials.

    PubMed

    Rocco, Maria Luisa; Soligo, Marzia; Manni, Luigi; Aloe, Luigi

    2018-04-11

    Since its discovery, nerve growth factor (NGF) has long occupied a critical role in developmental and adult neurobiology for its many important regulatory functions on the survival, growth and differentiation of nerve cells in the peripheral and central nervous system. NGF is the first discovered member of a family of neurotrophic factors, collectively indicated as neurotrophins, (which include brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin 4/5). NGF was discovered for its action on the survival and differentiation of selected populations of peripheral neurons. Since then, an enormous number of basic and human studies were undertaken to explore the role of purified NGF to prevent the death of NGF-receptive cells. These studies revealed that NGF possesses important therapeutic properties, after topical administration, on human cutaneous pressure ulcer, corneal ulcers, glaucoma, retinal maculopathy, Retinitis Pigmentosa and in pediatric optic gliomas and brain traumas. The aim of this review is to present our previous, recent and ongoing clinical studies on the therapeutic properties of NGF. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Valproic acid promotes human hair growth in in vitro culture model.

    PubMed

    Jo, Seong Jin; Choi, Soon-Jin; Yoon, Sun-Young; Lee, Ji Yeon; Park, Won-Seok; Park, Phil-June; Kim, Kyu Han; Eun, Hee Chul; Kwon, Ohsang

    2013-10-01

    β-Catenin, the transducer of Wnt signaling, is critical for the development and growth of hair follicles. In the absence of Wnt signals, cytoplasmic β-catenin is phosphorylated by glycogen synthase kinase (GSK)-3 and then degraded. Therefore, inhibition of GSK-3 may enhance hair growth via β-catenin stabilization. Valproic acid is an anticonvulsant and a mood-stabilizing drug that has been used for decades. Recently, valproic acid was reported to inhibit GSK-3β in neuronal cells, but its effect on human hair follicles remains unknown. To determine the effect of VPA on human hair growth. We investigated the effect of VPA on cultured human dermal papilla cells and outer root sheath cells and on an in vitro culture of human hair follicles, which were obtained from scalp skin samples of healthy volunteers. Anagen induction by valproic acid was evaluated using C57BL/6 mice model. Valproic acid not only enhanced the viability of human dermal papilla cells and outer root sheath cells but also promoted elongation of the hair shaft and reduced catagen transition of human hair follicles in organ culture model. Valproic acid treatment of human dermal papilla cells led to increased β-catenin levels and nuclear accumulation and inhibition of GSK-3β by phosphorylation. In addition, valproic acid treatment accelerated the induction of anagen hair in 7-week-old female C57BL/6 mice. Valproic acid enhanced human hair growth by increasing β-catenin and therefore may serve as an alternative therapeutic option for alopecia. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Explosive genetic evidence for explosive human population growth

    PubMed Central

    Gao, Feng; Keinan, Alon

    2016-01-01

    The advent of next-generation sequencing technology has allowed the collection of vast amounts of genetic variation data. A recurring discovery from studying larger and larger samples of individuals had been the extreme, previously unexpected, excess of very rare genetic variants, which has been shown to be mostly due to the recent explosive growth of human populations. Here, we review recent literature that inferred recent changes in population size in different human populations and with different methodologies, with many pointing to recent explosive growth, especially in European populations for which more data has been available. We also review the state-of-the-art methods and software for the inference of historical population size changes that lead to these discoveries. Finally, we discuss the implications of recent population growth on personalized genomics, on purifying selection in the non-equilibrium state it entails and, as a consequence, on the genetic architecture underlying complex disease and the performance of mapping methods in discovering rare variants that contribute to complex disease risk. PMID:27710906

  3. [Use of recombinant Human Growth Hormone (rHGH)].

    PubMed

    Calzada-León, Raúl

    2017-01-01

    Recombinant human growth hormone, synthesized in E.coli or mammalian cells cultures, is since 1985, a useful therapeutic resource to increase growth velocity and final height. In this paper are discussed the four phases (aims, security and efficacy, utility and efficiency) indispensables to define the start of treatment, as well as the absolute, relative and metabolic indications and the transitory and permanent conditions that contraindicate its use. It is commented the way to optimize the results (simple but indispensables indications for the physician, the patients and their family). Finally it is analyzed the results of treatment in patients with growth hormone deficiency, Turner syndrome, chronic renal failure, Prader-Willi syndrome, Noonan syndrome, SHOX deficiency, intrauterine growth retardation and idiopathic short stature.

  4. Early Growth Response-1 Induces and Enhances Vascular Endothelial Growth Factor-A Expression in Lung Cancer Cells

    PubMed Central

    Shimoyamada, Hiroaki; Yazawa, Takuya; Sato, Hanako; Okudela, Koji; Ishii, Jun; Sakaeda, Masashi; Kashiwagi, Korehito; Suzuki, Takehisa; Mitsui, Hideaki; Woo, Tetsukan; Tajiri, Michihiko; Ohmori, Takahiro; Ogura, Takashi; Masuda, Munetaka; Oshiro, Hisashi; Kitamura, Hitoshi

    2010-01-01

    Vascular endothelial growth factor-A (VEGF-A) is crucial for angiogenesis, vascular permeability, and metastasis during tumor development. We demonstrate here that early growth response-1 (EGR-1), which is induced by the extracellular signal–regulated kinase (ERK) pathway activation, activates VEGF-A in lung cancer cells. Increased EGR-1 expression was found in adenocarcinoma cells carrying mutant K-RAS or EGFR genes. Hypoxic culture, siRNA experiment, luciferase assays, chromatin immunoprecipitation, electrophoretic mobility shift assays, and quantitative RT-PCR using EGR-1–inducible lung cancer cells demonstrated that EGR-1 binds to the proximal region of the VEGF-A promoter, activates VEGF-A expression, and enhances hypoxia inducible factor 1α (HIF-1α)-mediated VEGF-A expression. The EGR-1 modulator, NAB-2, was rapidly induced by increased levels of EGR-1. Pathology samples of human lung adenocarcinomas revealed correlations between EGR-1/HIF-1α and VEGF-A expressions and relative elevation of EGR-1 and VEGF-A expression in mutant K-RAS- or EGFR-carrying adenocarcinomas. Both EGR-1 and VEGF-A expression increased as tumors dedifferentiated, whereas HIF-1α expression did not. Although weak correlation was found between EGR-1 and NAB-2 expressions on the whole, NAB-2 expression decreased as tumors dedifferentiated, and inhibition of DNA methyltransferase/histone deacetylase increased NAB-2 expression in lung cancer cells despite no epigenetic alteration in the NAB-2 promoter. These findings suggest that EGR-1 plays important roles on VEGF-A expression in lung cancer cells, and epigenetic silencing of transactivator(s) associated with NAB-2 expression might also contribute to upregulate VEGF-A expression. PMID:20489156

  5. The Uniform Pattern of Growth and Skeletal Maturation during the Human Adolescent Growth Spurt.

    PubMed

    Sanders, James O; Qiu, Xing; Lu, Xiang; Duren, Dana L; Liu, Raymond W; Dang, Debbie; Menendez, Mariano E; Hans, Sarah D; Weber, David R; Cooperman, Daniel R

    2017-12-01

    Humans are one of the few species undergoing an adolescent growth spurt. Because children enter the spurt at different ages making age a poor maturity measure, longitudinal studies are necessary to identify the growth patterns and identify commonalities in adolescent growth. The standard maturity determinant, peak height velocity (PHV) timing, is difficult to estimate in individuals due to diurnal, postural, and measurement variation. Using prospective longitudinal populations of healthy children from two North American populations, we compared the timing of the adolescent growth spurt's peak height velocity to normalized heights and hand skeletal maturity radiographs. We found that in healthy children, the adolescent growth spurt is standardized at 90% of final height with similar patterns for children of both sexes beginning at the initiation of the growth spurt. Once children enter the growth spurt, their growth pattern is consistent between children with peak growth at 90% of final height and skeletal maturity closely reflecting growth remaining. This ability to use 90% of final height as easily identified important maturity standard with its close relationship to skeletal maturity represents a significant advance allowing accurate prediction of future growth for individual children and accurate maturity comparisons for future studies of children's growth.

  6. Fracture processes and mechanisms of crack growth resistance in human enamel

    NASA Astrophysics Data System (ADS)

    Bajaj, Devendra; Park, Saejin; Quinn, George D.; Arola, Dwayne

    2010-07-01

    Human enamel has a complex micro-structure that varies with distance from the tooth’s outer surface. But contributions from the microstructure to the fracture toughness and the mechanisms of crack growth resistance have not been explored in detail. In this investigation the apparent fracture toughness of human enamel and the mechanisms of crack growth resistance were evaluated using the indentation fracture approach and an incremental crack growth technique. Indentation cracks were introduced on polished surfaces of enamel at selected distances from the occlusal surface. In addition, an incremental crack growth approach using compact tension specimens was used to quantify the crack growth resistance as a Junction of distance from the occlusal surface. There were significant differences in the apparent toughness estimated using the two approaches, which was attributed to the active crack length and corresponding scale of the toughening mechanisms.

  7. Ancient gene flow from early modern humans into Eastern Neanderthals.

    PubMed

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-02-25

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and early modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously thought.

  8. Efficient isolation of human metapneumovirus using MNT-1, a human malignant melanoma cell line with early and distinct cytopathic effects.

    PubMed

    Sato, Ko; Watanabe, Oshi; Ohmiya, Suguru; Chiba, Fumiko; Suzuki, Akira; Okamoto, Michiko; Younghuang, Jiang; Hata, Akihiro; Nonaka, Hiroyuki; Kitaoka, Setsuko; Nagai, Yukio; Kawamura, Kazuhisa; Hayashi, Masahiro; Kumaki, Satoru; Suzuki, Tamio; Kawakami, Kazuyoshi; Nishimura, Hidekazu

    2017-11-01

    Isolation of human metapneumovirus (HMPV) from clinical specimens is currently inefficient because of the lack of a cell culture system in which a distinct cytopathic effect (CPE) occurs. The cell lines LLC-MK2, Vero and Vero E6 are used for isolation of HMPV; however, the CPE in these cell lines is subtle and usually requires a long observation period and sometimes blind passages. Thus, a cell line in which an early and distinct CPE occurs following HMPV inoculation is highly desired by clinical virology laboratories. In this study, it was demonstrated that, in the human malignant melanoma cell line MNT-1, obvious syncytium formation occurs shortly after inoculation with HMPV-positive clinical specimens. In addition, the growth and efficiency of isolation of HMPV were greater using MNT-1 than using any other conventional cell line. Addition of this cell line to our routine viral isolation system for clinical specimens markedly enhanced isolation frequency, allowing isolation-based surveillance. MNT-1 has the potential to facilitate clinical and epidemiological studies of HMPV. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

  9. Assessing the Effects of Soil Humic and Fulvic Acids on Germination and Early Growth of Native and Introduced Grass Varieties

    DTIC Science & Technology

    2007-01-15

    period (8 months) research plans are the following: (a) Germination and early growth experiments of the three remaining combinations by two of the...remainder of the contract period (8 months) research plans are the following: (a) Germination and early growth experiments of the three remaining... GROWTH OF NATIVE AND INTRODUCED GRASS VARIETIES NAME OF PRINCIPAL INVESTIGATOR: SENESI NICOLA-PROFESSOR NAME OF CONTRACTOR: UNIVERSITA’ DI BARI

  10. A Longitudinal Assessment of Early Acceleration of Students in Mathematics on Growth in Mathematics Achievement

    ERIC Educational Resources Information Center

    Ma, X.

    2005-01-01

    Early acceleration of students in mathematics (in the form of early access to formal abstract algebra) has been a controversial educational issue. The current study examined the rate of growth in mathematics achievement of accelerated gifted, honors, and regular students across the entire secondary years (Grades 7-12), in comparison to their…

  11. Angiogenin Expression during Early Human Placental Development; Association with Blood Vessel Formation

    PubMed Central

    Pavlov, Nadine; Guibourdenche, Jean; Degrelle, Séverine A.; Evain-Brion, Danièle

    2014-01-01

    The placenta is a transient organ essential for fetal development. During human placental development, chorionic villi grow in coordination with a large capillary network resulting from both vasculogenesis and angiogenesis. Angiogenin is one of the most potent inducers of neovascularisation in experimental models in vivo. We and others have previously mapped angiogenin expression in the human term placenta. Here, we explored angiogenin involvement in early human placental development. We studied, angiogenin expression by in situ hybridisation and/or by RT-PCR in tissues and primary cultured trophoblastic cells and angiogenin cellular distribution by coimmunolabelling with cell markers: CD31 (PECAM-1), vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGF-R2), Tie-2, von Willebrand factor, CD34, erythropoeitin receptor (Epo-R), alpha-smooth muscle actin, CD45, cytokeratin 7, and Ki-67. Extravillous and villous cytotrophoblasts, isolated and differentiated in vitro, expressed and secreted angiogenin. Angiogenin was detected in villous trophoblastic layers, and structured and nascent fetal vessels. In decidua, it was expressed by glandular epithelial cells, vascular cells and macrophages. The observed pattern of angiogenin expression is compatible with a role in blood vessel formation and in cross-talk between trophoblasts and endothelial cells. In view of angiogenin properties, we suggest that angiogenin may participate in placental vasculogenesis and organogenesis. PMID:25093183

  12. Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.

    PubMed

    Kido, Tatsuo; Sun, Zhaoyu; Lau, Yun-Fai Chris

    2017-06-23

    Sexual dimorphisms are prevalent in development, physiology and diseases in humans. Currently, the contributions of the genes on the male-specific region of the Y chromosome (MSY) in these processes are uncertain. Using a transgene activation system, the human sex-determining gene hSRY is activated in the single-cell embryos of the mouse. Pups with hSRY activated (hSRY ON ) are born of similar sizes as those of non-activated controls. However, they retard significantly in postnatal growth and development and all die of multi-organ failure before two weeks of age. Pathological and molecular analyses indicate that hSRY ON pups lack innate suckling activities, and develop fatty liver disease, arrested alveologenesis in the lung, impaired neurogenesis in the brain and occasional myocardial fibrosis and minimized thymus development. Transcriptome analysis shows that, in addition to those unique to the respective organs, various cell growth and survival pathways and functions are differentially affected in the transgenic mice. These observations suggest that ectopic activation of a Y-located SRY gene could exert male-specific effects in development and physiology of multiple organs, thereby contributing to sexual dimorphisms in normal biological functions and disease processes in affected individuals.

  13. Growth recovery and faltering through early adolescence in low- and middle-income countries: Determinants and implications for cognitive development.

    PubMed

    Georgiadis, Andreas; Benny, Liza; Duc, Le Thuc; Galab, Sheikh; Reddy, Prudhvikar; Woldehanna, Tassew

    2017-04-01

    Child chronic undernutrition, as measured by stunting, is prevalent in low- and middle-income countries and is among the major threats to child development. While stunting and its implications for cognitive development have been considered irreversible beyond early childhood there is a lack of consensus in the literature on this, as there is some evidence of recovery from stunting and that this recovery may be associated with improvements in cognition. Less is known however, about the drivers of growth recovery and the aspects of recovery linked to cognitive development. In this paper we investigate the factors associated with growth recovery and faltering through age 12 years and the implications of the incidence, timing, and persistence of post-infancy recovery from stunting for cognitive development using longitudinal data from Ethiopia, India, Peru, and Vietnam. We find that the factors most systematically associated with accelerated growth both before and after early childhood and across countries include mother's height, household living standards and shocks, community wages, food prices, and garbage collection. Our results suggest that post-infancy recovery from stunting is more likely to be systematically associated with higher achievement scores across countries when it is persistent and that associations between growth trajectories and cognitive achievement in middle childhood do not persist through early adolescence across countries. Overall, our findings indicate that growth after early childhood is responsive to changes in the household and community environments and that growth promotion after early childhood may yield improvements in child cognitive development. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Purification and Refolding of Overexpressed Human Basic Fibroblast Growth Factor in Escherichia coli

    PubMed Central

    Alibolandi, Mona; Mirzahoseini, Hasan

    2011-01-01

    This work describes the integration of expanded bed adsorption (EBA) and adsorptive protein refolding operations used to recover purified and biologically active human basic fibroblast growth factor from inclusion bodies expressed in E. coli. Insoluble overexpressed human basic fibroblast growth factor has been purified on CM Hyper Z matrix by expanded bed adsorption after isolation and solubilization in 8 M urea. The adsorption was made in expanded bed without clarification steps such as centrifugation. Column refolding was done by elimination of urea and elution with NaCl. The human basic fibroblast growth factor was obtained as a highly purified soluble monomer form with similar behavior in circular dichroism and fluorescence spectroscopy as native protein. A total of 92.52% of the available human basic fibroblast growth factor was recovered as biologically active and purified protein using the mentioned purification and refolding process. This resulted in the first procedure describing high-throughput purification and refolding of human basic fibroblast growth factor in one step and is likely to have the greatest benefit for proteins that tend to aggregate when refolded by dilution. PMID:21837279

  15. Grass control improves early growth of black walnut more than either deep ripping or irrigation

    Treesearch

    J.W. Van Sambeek; F.D. McBride

    1991-01-01

    Chemical control of a tall fescue sod (Festuca arundinacea Schreb.) using glyphosate and simazine improved early tree growth of black walnut (Juglans nigra L.) more than either deep ripping or irrigation on an upland old field site in southern Illinois. Growth of trees with irrigation and grass control was less than with grass...

  16. Early cretaceous topographic growth of the Lhasaplano, Tibetan plateau: Constraints from the Damxung conglomerate

    NASA Astrophysics Data System (ADS)

    Wang, Jian-Gang; Hu, Xiumian; Garzanti, Eduardo; Ji, Wei-Qiang; Liu, Zhi-Chao; Liu, Xiao-Chi; Wu, Fu-Yuan

    2017-07-01

    Constraining the timing of early topographic growth on the Tibetan plateau is critical for any models of India-Asia collision, Himalayan orogeny and subsequent plateau development in the Cenozoic. Stratigraphic, sedimentological and provenance analysis of the Lower Cretaceous red-beds of the Damxung Conglomerate provide new key information to reconstruct the paleogeography and the tectonic evolution of the Lhasa terrane at the time. The over 700-m-thick Damxung Conglomerate documents distal alluvial fan to braidplain sedimentation passing upward to proximal alluvial fan sedimentation. Deposition began near sea level, as documented by limestone beds occurring at the base of the unit. Zircon U-Pb dating of interbedded tuff layers constrain deposition age at ca. 111 Ma. Abundance of volcanic clasts, Cretaceous U-Pb ages and Hf isotopes of detrital zircons yielding mainly negative ɛHf(t) values together with paleocurrent data indicate an active volcanic source located in the North Lhasa subterrane. Pre-Mesozoic-aged zircon, recycled quartz and (meta) sedimentary rock fragments increase up-section, indicating progressive erosional exhumation of the Paleozoic sedimentary/metasedimentary basement. The Damxung Conglomerate thus records a significant uplift and unroofing stage in the source region, implying initial topographic growth on the Lhasa terrane at early Albian time. Early Cretaceous topographic growth on the Lhasa terrane is supported by the stratigraphic record in the Linzhou basin, the Xigaze forearc basin and the southern Nima basin. In contrast, marine strata in the central-western Lhasa terrane lasted until the early Cenomanian (ca. 96 Ma), indicating diachronous marine regression on the Lhasa terrane from east to west.

  17. Mass and size growth of early-type galaxies by dry mergers in cluster environments

    NASA Astrophysics Data System (ADS)

    Oogi, Taira; Habe, Asao; Ishiyama, Tomoaki

    2016-02-01

    We perform dry merger simulations to investigate the role of dry mergers in the size growth of early-type galaxies in high-density environments. We replace the virialized dark matter haloes obtained by a large cosmological N-body simulation with N-body galaxy models consisting of two components, a stellar bulge and a dark matter halo, which have higher mass resolution than the cosmological simulation. We then resimulate nine cluster-forming regions, whose masses range from 1 × 1014 to 5 × 1014 M⊙. Masses and sizes of stellar bulges are also assumed to satisfy the stellar mass-size relation of high-z compact massive early-type galaxies. We find that dry major mergers considerably contribute to the mass and size growth of central massive galaxies. One or two dry major mergers double the average stellar mass and quadruple the average size between z = 2 and 0. These growths favourably agree with observations. Moreover, the density distributions of our simulated central massive galaxies grow from the inside-out, which is consistent with recent observations. The mass-size evolution is approximated as R∝ M_{{ast }}^{α }, with α ˜ 2.24. Most of our simulated galaxies are efficiently grown by dry mergers, and their stellar mass-size relations match the ones observed in the local Universe. Our results show that the central galaxies in the cluster haloes are potential descendants of high-z (z ˜ 2-3) compact massive early-type galaxies. This conclusion is consistent with previous numerical studies which investigate the formation and evolution of compact massive early-type galaxies.

  18. Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm.

    PubMed

    Chen, B; Teng, Jiawen; Liu, Hongwei; Pan, X; Zhou, Y; Huang, Shu; Lai, Mowen; Bian, Guohui; Mao, Bin; Sun, Wencui; Zhou, Qiongxiu; Yang, Shengyong; Nakahata, Tatsutoshi; Ma, Feng

    2017-08-01

    RUNX1 is absolutely required for definitive hematopoiesis, but the function of RUNX1b/c, two isoforms of human RUNX1, is unclear. We established inducible RUNX1b/c-overexpressing human embryonic stem cell (hESC) lines, in which RUNX1b/c overexpression prevented the emergence of CD34+ cells from early stage, thereby drastically reducing the production of hematopoietic stem/progenitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 cell co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor (TGF)-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models. © The Author (2017). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  19. Early Arabidopsis root hair growth stimulation by pathogenic strains of Pseudomonas syringae.

    PubMed

    Pecenková, Tamara; Janda, Martin; Ortmannová, Jitka; Hajná, Vladimíra; Stehlíková, Zuzana; Žárský, Viktor

    2017-09-01

    Selected beneficial Pseudomonas spp. strains have the ability to influence root architecture in Arabidopsis thaliana by inhibiting primary root elongation and promoting lateral root and root hair formation. A crucial role for auxin in this long-term (1week), long-distance plant-microbe interaction has been demonstrated. Arabidopsis seedlings were cultivated in vitro on vertical plates and inoculated with pathogenic strains Pseudomonas syringae pv. maculicola (Psm) and P. syringae pv. tomato DC3000 (Pst), as well as Agrobacterium tumefaciens (Atu) and Escherichia coli (Eco). Root hair lengths were measured after 24 and 48h of direct exposure to each bacterial strain. Several Arabidopsis mutants with impaired responses to pathogens, impaired ethylene perception and defects in the exocyst vesicle tethering complex that is involved in secretion were also analysed. Arabidopsis seedling roots infected with Psm or Pst responded similarly to when infected with plant growth-promoting rhizobacteria; root hair growth was stimulated and primary root growth was inhibited. Other plant- and soil-adapted bacteria induced similar root hair responses. The most compromised root hair growth stimulation response was found for the knockout mutants exo70A1 and ein2. The single immune pathways dependent on salicylic acid, jasmonic acid and PAD4 are not directly involved in root hair growth stimulation; however, in the mutual cross-talk with ethylene, they indirectly modify the extent of the stimulation of root hair growth. The Flg22 peptide does not initiate root hair stimulation as intact bacteria do, but pretreatment with Flg22 prior to Psm inoculation abolished root hair growth stimulation in an FLS2 receptor kinase-dependent manner. These early response phenomena are not associated with changes in auxin levels, as monitored with the pDR5::GUS auxin reporter. Early stimulation of root hair growth is an effect of an unidentified component of living plant pathogenic bacteria. The root

  20. Blend Sign on Computed Tomography: Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage.

    PubMed

    Li, Qi; Zhang, Gang; Huang, Yuan-Jun; Dong, Mei-Xue; Lv, Fa-Jin; Wei, Xiao; Chen, Jian-Jun; Zhang, Li-Juan; Qin, Xin-Yue; Xie, Peng

    2015-08-01

    Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (κ=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth. © 2015 American Heart Association, Inc.

  1. Early release improves long-term growth and development of direct-seeded nuttall oak saplings

    Treesearch

    James S. Meadows; Robert L. Johnson; Roger M. Krinard

    2015-01-01

    Early growth of bottomland oaks is typically slow, and many oaks eventually become overtopped by trees of other species. Removal of these larger competitors in a young stand might improve growth of the oaks and lead to more free-to-grow oaks as the stand matures. Release treatments were applied in 1980 to an 11-year-old, direct-seeded Nuttall oak (Quercus texana Buckl...

  2. Growth in early life and the development of obesity by age 9 years: are there critical periods and a role for an early life stressor?

    PubMed

    Giles, L C; Whitrow, M J; Rumbold, A R; Davies, C E; de Stavola, B; Pitcher, J B; Davies, M J; Moore, V M

    2013-04-01

    Rapid growth, possibly occurring in critical periods in early life, may be important for the development of obesity. It is unknown whether this is influenced by postnatal exposures such as age-relevant sources of stress. Frequent house moves may be one such stressor. We aimed to examine if there is a period of growth in early life critical for the development of child obesity by age 9 years and assess the role of house moves in modifying any relationships between early life growth and obesity at age 9 years. Prospective Australian birth cohort study. In all, 392 children with serial body size measurements from birth to age 9 years. Standardized body mass index (z-BMI) was available for six time points (spanning birth to 3½ years), and the total number of house moves between birth and 3½ years. The outcomes considered were z-BMI and % body fat (%BF) at age 9 years. Linear regression models were used to estimate the effects of serial measurements of z-BMI and number of house moves on the outcomes. Life-course plots showed that z-BMI at 3½ years was a statistically significant predictor of z-BMI at 9 years (β=0.80; standard error (s.e.), 0.04), whereas z-BMI at 9 months (β=-1.13; s.e., 0.40) and 3½ years (β=4.82; s.e., 0.42) were significant predictors of %BF at age 9 years. There were statistically significant interactions between the number of house moves and change in z-BMI between 9 and 12 months, such that ≥ 3 house moves in early life amplified the detrimental effects of earlier rapid growth on both body size and composition at age 9 years. In the absence of evidence for a single critical period, efforts to prevent overweight and obesity are required throughout childhood. In addition, modifiable postnatal stressors may exacerbate effects of early growth on obesity in later childhood.

  3. Dietary nucleotides and early growth in formula-fed infants: a randomized controlled trial.

    PubMed

    Singhal, Atul; Kennedy, Kathy; Lanigan, J; Clough, Helen; Jenkins, Wendy; Elias-Jones, Alun; Stephenson, Terrence; Dudek, Peter; Lucas, Alan

    2010-10-01

    Dietary nucleotides are nonprotein nitrogenous compounds that are found in high concentrations in breast milk and are thought to be conditionally essential nutrients in infancy. A high nucleotide intake has been suggested to explain some of the benefits of breastfeeding compared with formula feeding and to promote infant growth. However, relatively few large-scale randomized trials have tested this hypothesis in healthy infants. We tested the hypothesis that nucleotide supplementation of formula benefits early infant growth. Occipitofrontal head circumference, weight, and length were assessed in infants who were randomly assigned to groups fed nucleotide-supplemented (31 mg/L; n=100) or control formula without nucleotide supplementation (n=100) from birth to the age of 20 weeks, and in infants who were breastfed (reference group; n=101). Infants fed with nucleotide-supplemented formula had greater occipitofrontal head circumference at ages 8, 16, and 20 weeks than infants fed control formula (mean difference in z scores at 8 weeks: 0.4 [95% confidence interval: 0.1-0.7]; P=.006) even after adjustment for potential confounding factors (P=.002). Weight at 8 weeks and the increase in both occipitofrontal head circumference and weight from birth to 8 weeks were also greater in infants fed nucleotide-supplemented formula than in those fed control formula. Our data support the hypothesis that nucleotide supplementation leads to increased weight gain and head growth in formula-fed infants. Therefore, nucleotides could be conditionally essential for optimal infant growth in some formula-fed populations. Additional research is needed to test the hypothesis that the benefits of nucleotide supplementation for early head growth, a critical period for brain growth, have advantages for long-term cognitive development.

  4. Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE™.

    PubMed

    Choi, Seunghye; Lee, Miri; Lee, Su-Hyon; Jung, Haeng-Sun; Kim, Seol-Yeong; Chung, Tae-Young; Choe, Tae-boo; Chun, Young-Jin; Lim, Kyung-Min

    2015-09-01

    Evaluation of the eye irritation is essential in the development of new cosmetic products. Draize rabbit eye irritation test has been widely used in which chemicals are directly applied to rabbit eye, and the symptoms and signs of eyes are scored. However, due to the invasive procedure, it causes substantial pain and discomfort to animals. Recently, we reported in vitro eye irritation test method using a 3D human corneal epithelial model (MCTT HCE™) which is reconstructed from remaining human tissues after a corneal transplantation. This model exhibited an excellent predictive capacity for 25 reference chemicals (sensitivity 100%, specificity 77% and accuracy 88% vs. GHS). To improve the test performance, we explored new biomarkers for the eye irritation through transcriptomic approach. Three surfactants were selected as model eye irritants that include sodium lauryl sulfate, benzalkonium chloride and triton X-100. After test chemicals were treated, we investigated differentially expressed genes through a whole-gene microarray (Affymetrix GeneChip(®) Human Gene 2.0 ST Array, 48,000 probes). As a result, we identified that mRNAs of cornifelin (CNFN), a constituent of the insoluble cornified cell envelope of stratified squamous epithelia, and early growth response-1 (EGR1), a nuclear transcriptional regulator, were significantly up-regulated by all three irritants. Up-regulation of CNFN and EGR1 was further confirmed by Q-RT-PCR, and immunohistochemistry revealed increased level of CNFN in irritant-treated tissues, supporting the relevance of CNFN and EGR1 as new biomarkers for eye irritation.

  5. Does Human Capital Contribute to Economic Growth in Mauritius?

    ERIC Educational Resources Information Center

    Neeliah, Harris; Seetanah, Boopen

    2016-01-01

    Purpose: Real gross domestic product (GDP) growth for Mauritius has averaged more than 5 per cent since 1970 and GDP per capita has increased more than tenfold between 1970 and 2012, from less than $500 to more than $9,000. It has often been reported that human capital, along with other growth enablers, has played an important role in this…

  6. Human population and atmospheric carbon dioxide growth dynamics: Diagnostics for the future

    NASA Astrophysics Data System (ADS)

    Hüsler, A. D.; Sornette, D.

    2014-10-01

    We analyze the growth rates of human population and of atmospheric carbon dioxide by comparing the relative merits of two benchmark models, the exponential law and the finite-time-singular (FTS) power law. The later results from positive feedbacks, either direct or mediated by other dynamical variables, as shown in our presentation of a simple endogenous macroeconomic dynamical growth model describing the growth dynamics of coupled processes involving human population (labor in economic terms), capital and technology (proxies by CO2 emissions). Human population in the context of our energy intensive economies constitutes arguably the most important underlying driving variable of the content of carbon dioxide in the atmosphere. Using some of the best databases available, we perform empirical analyses confirming that the human population on Earth has been growing super-exponentially until the mid-1960s, followed by a decelerated sub-exponential growth, with a tendency to plateau at just an exponential growth in the last decade with an average growth rate of 1.0% per year. In contrast, we find that the content of carbon dioxide in the atmosphere has continued to accelerate super-exponentially until 1990, with a transition to a progressive deceleration since then, with an average growth rate of approximately 2% per year in the last decade. To go back to CO2 atmosphere contents equal to or smaller than the level of 1990 as has been the broadly advertised goals of international treaties since 1990 requires herculean changes: from a dynamical point of view, the approximately exponential growth must not only turn to negative acceleration but also negative velocity to reverse the trend.

  7. Differences between WHO AND CDC early growth measurements in the assessment of Cystic Fibrosis clinical outcomes.

    PubMed

    Usatin, Danielle; Yen, Elizabeth H; McDonald, Catherine; Asfour, Fadi; Pohl, John; Robson, Jacob

    2017-07-01

    Early childhood growth status has been used to predict long-term clinical outcomes in Cystic Fibrosis (CF) patients. Adulthood CF outcomes based on early weight-for-length (WFL) measurements, using either World Health Organization (WHO) or Centers for Disease Control (CDC) scales, have not been compared. Cystic Fibrosis Foundation registry patients were studied (n=3014). Participants were categorized at age two years as WFL <50th percentile on both WHO and CDC scales, ≥50th percentile on WHO but not CDC, or ≥50th percentile on both. Pulmonary function and overall survival were assessed at age 18years. Stepwise gains in pulmonary function and lung transplant-free survival were noted across the three increasing WFL categories. Children with CF who achieve higher WFL at age two years have improved pulmonary and survival outcomes into adulthood. CF providers should continue to utilize current early growth recommendations, with goal WFL ≥50th percentile on CDC growth charts before age two. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  8. Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging.

    PubMed

    Ha, Jang-Ho; Kim, Ha-Neul; Moon, Ki-Beom; Jeon, Jae-Heung; Jung, Dai-Hyun; Kim, Su-Jung; Mason, Hugh S; Shin, Seo-Yeon; Kim, Hyun-Soon; Park, Kyung-Mok

    2017-07-01

    Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana . Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana . The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana . The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana -derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli -derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana- derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana -derived recombinant human acidic fibroblast growth factor

  9. Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth

    PubMed Central

    Higgins, Claire A.; Chen, James C.; Cerise, Jane E.; Jahoda, Colin A. B.; Christiano, Angela M.

    2013-01-01

    De novo organ regeneration has been observed in several lower organisms, as well as rodents; however, demonstrating these regenerative properties in human cells and tissues has been challenging. In the hair follicle, rodent hair follicle-derived dermal cells can interact with local epithelia and induce de novo hair follicles in a variety of hairless recipient skin sites. However, multiple attempts to recapitulate this process in humans using human dermal papilla cells in human skin have failed, suggesting that human dermal papilla cells lose key inductive properties upon culture. Here, we performed global gene expression analysis of human dermal papilla cells in culture and discovered very rapid and profound molecular signature changes linking their transition from a 3D to a 2D environment with early loss of their hair-inducing capacity. We demonstrate that the intact dermal papilla transcriptional signature can be partially restored by growth of papilla cells in 3D spheroid cultures. This signature change translates to a partial restoration of inductive capability, and we show that human dermal papilla cells, when grown as spheroids, are capable of inducing de novo hair follicles in human skin. PMID:24145441

  10. Examining the Predictive Relations between Two Aspects of Self-Regulation and Growth in Preschool Children’s Early Literacy Skills

    PubMed Central

    Lonigan, Christopher J.; Allan, Darcey M.; Phillips, Beth M.

    2016-01-01

    There is strong evidence that self-regulatory processes are linked to early academic skills both concurrently and longitudinally. The majority of extant longitudinal studies, however, have been conducted using autoregressive techniques that may not accurately model change across time. The purpose of this study was to examine the unique associations between two components of self-regulation, attention and executive functioning (EF), and growth in early literacy skills over the preschool year using latent-growth-curve analysis. The sample included 1,082 preschool children (M-age = 55.0 months, SD = 3.73). Children completed measures of vocabulary, syntax, phonological awareness, print knowledge, cognitive ability, and self-regulation, and children’s classroom teachers completed a behavior rating measure. To examine the independent relations of the self-regulatory skills and cognitive ability with children’s initial early literacy skills and growth across the preschool year, growth models in which the intercept and slope were simultaneously regressed on each of the predictor variables were examined. Because of the significant relation between intercept and slope for most outcomes, slope was regressed on intercept in the models to allow a determination of direct and indirect effects of the predictors on growth in children’s language and literacy skills across the preschool year. In general, both teacher-rated inattention and directly measured EF were uniquely associated with initial skills level; however, only teacher-rated inattention uniquely predicted growth in early literacy skills. These findings suggest that teacher-ratings of inattention may measure an aspect of self-regulation that is particularly associated with the acquisition of academic skills in early childhood. PMID:27854463

  11. Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis

    PubMed Central

    Munblit, Daniel; Treneva, Marina; Peroni, Diego G.; Colicino, Silvia; Chow, Li Yan; Dissanayeke, Shobana; Pampura, Alexander; Boner, Attilio L.; Geddes, Donna T.; Boyle, Robert J.; Warner, John O.

    2017-01-01

    The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04–0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor β (TGFβ) 2 OR 1.04 (95% CI 1.01–1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01–0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04–0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFβ2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term health outcomes in the

  12. Immune Components in Human Milk Are Associated with Early Infant Immunological Health Outcomes: A Prospective Three-Country Analysis.

    PubMed

    Munblit, Daniel; Treneva, Marina; Peroni, Diego G; Colicino, Silvia; Chow, Li Yan; Dissanayeke, Shobana; Pampura, Alexander; Boner, Attilio L; Geddes, Donna T; Boyle, Robert J; Warner, John O

    2017-05-24

    The role of breastfeeding in improving allergy outcomes in early childhood is still unclear. Evidence suggests that immune mediators in human milk (HM) play a critical role in infant immune maturation as well as protection against atopy/allergy development. We investigated relationships between levels of immune mediators in colostrum and mature milk and infant outcomes in the first year of life. In a large prospective study of 398 pregnant/lactating women in the United Kingdom, Russia and Italy, colostrum and mature human milk (HM) samples were analysed for immune active molecules. Statistical analyses used models adjusting for the site of collection, colostrum collection time, parity and maternal atopic status. Preliminary univariate analysis showed detectable interleukin (IL) 2 and IL13 in HM to be associated with less eczema. This finding was further confirmed in multivariate analysis, with detectable HM IL13 showing protective effect OR 0.18 (95% CI 0.04-0.92). In contrast, a higher risk of eczema was associated with higher HM concentrations of transforming growth factor β (TGFβ) 2 OR 1.04 (95% CI 1.01-1.06) per ng/mL. Parental-reported food allergy was reported less often when IL13 was detectable in colostrum OR 0.10 (95% CI 0.01-0.83). HM hepatocyte growth factor (HGF) was protective for common cold incidence at 12 months OR 0.19 (95% CI 0.04-0.92) per ng/mL. Data from this study suggests that differences in the individual immune composition of HM may have an influence on early life infant health outcomes. Increased TGFβ2 levels in HM are associated with a higher incidence of reported eczema, with detectable IL13 in colostrum showing protective effects for food allergy and sensitization. HGF shows some protective effect on common cold incidence at one year of age. Future studies should be focused on maternal genotype, human milk microbiome and diet influence on human milk immune composition and both short- and long-term health outcomes in the infant.

  13. Early Programming by Protein Intake: The Effect of Protein on Adiposity Development and the Growth and Functionality of Vital Organs

    PubMed Central

    Luque, Veronica; Closa-Monasterolo, Ricardo; Escribano, Joaquín; Ferré, Natalia

    2015-01-01

    This article reviews the role of protein intake on metabolic programming early in life. The observations that breastfeeding in infancy reduces the risk of being overweight and obese later in life and the differences in the protein content between formula milk and human milk have generated the early protein hypothesis. The present review focuses on a mechanistic approach to programmed adiposity and the growth and development of other organs by protein intake in infancy, which may be mediated by branched-chain amino acids, insulin, and insulin-like growth factor 1 via the mammalian target of rapamycin. Observational studies and clinical trials have shown that lowering the protein content in infant and follow-on formulas may reduce the risk of becoming obese later in life. The recent body of evidence is currently being translated into new policies. Therefore, the evolution of European regulatory laws and recommendations by expert panels on the protein content of infant and follow-on formulas are also reviewed. Research gaps, such as the critical window for programming adiposity by protein intake, testing formulas with modified amino acids, and the long-term consequences of differences in protein intake on organ functionality among well-nourished infants, have been identified. PMID:27013888

  14. Impacts of Parasites in Early Life: Contrasting Effects on Juvenile Growth for Different Family Members

    PubMed Central

    Reed, Thomas E.; Daunt, Francis; Kiploks, Adam J.; Burthe, Sarah J.; Granroth-Wilding, Hanna M. V.; Takahashi, Emi A.; Newell, Mark; Wanless, Sarah; Cunningham, Emma J. A.

    2012-01-01

    Parasitism experienced early in ontogeny can have a major impact on host growth, development and future fitness, but whether siblings are affected equally by parasitism is poorly understood. In birds, hatching asynchrony induced by hormonal or behavioural mechanisms largely under parental control might predispose young to respond to infection in different ways. Here we show that parasites can have different consequences for offspring depending on their position in the family hierarchy. We experimentally treated European Shag (Phalacrocorax aristoteli) nestlings with the broad-spectrum anti-parasite drug ivermectin and compared their growth rates with nestlings from control broods. Average growth rates measured over the period of linear growth (10 days to 30 days of age) and survival did not differ for nestlings from treated and control broods. However, when considering individuals within broods, parasite treatment reversed the patterns of growth for individual family members: last-hatched nestlings grew significantly slower than their siblings in control nests but grew faster in treated nests. This was at the expense of their earlier-hatched brood-mates, who showed an overall growth rate reduction relative to last-hatched nestlings in treated nests. These results highlight the importance of exploring individual variation in the costs of infection and suggest that parasites could be a key factor modulating within-family dynamics, sibling competition and developmental trajectories from an early age. PMID:22384190

  15. Growth from birth to early adolescence in offspring prenatally exposed to cigarettes and marijuana.

    PubMed

    Fried, P A; Watkinson, B; Gray, R

    1999-01-01

    Weight, height, and head circumference were examined in children from birth to early adolescence for whom prenatal exposure to marijuana and cigarettes had been ascertained. The subjects were from a low-risk, predominantly middle-class sample participating in an ongoing longitudinal study. The negative association between growth measures at birth and prenatal cigarette exposure was overcome, sooner in males than females, within the first few years, and by the age of six, the children of heavy smokers were heavier than control subjects. Pre and postnatal environmental tobacco smoke did not have a negative effect upon the growth parameters; however, the choice of bottle-feeding or shorter duration of breast-feeding by women who smoked during pregnancy appeared to play an important positive role in the catch-up observed among the infants of smokers. Prenatal exposure to marijuana was not significantly related to any growth measures at birth, although a smaller head circumference observed at all ages reached statistical significance among the early adolescents born to the heavy marijuana users.

  16. Human growth and body weight dynamics: an integrative systems model.

    PubMed

    Rahmandad, Hazhir

    2014-01-01

    Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%-24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations.

  17. Human Growth and Body Weight Dynamics: An Integrative Systems Model

    PubMed Central

    Rahmandad, Hazhir

    2014-01-01

    Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%–24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations. PMID:25479101

  18. Young Children's Enactments of Human Rights in Early Childhood Education

    ERIC Educational Resources Information Center

    Quennerstedt, Ann

    2016-01-01

    This paper explores ways in which human rights become part of and affect young children's everyday practices in early childhood education and, more particularly, how very young children enact human rights in the preschool setting. The study is conducted in a Swedish preschool through observations of the everyday practices of a group of children…

  19. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells.

    PubMed

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-10-12

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24-36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection.

  20. Zika virus infection dysregulates human neural stem cell growth and inhibits differentiation into neuroprogenitor cells

    PubMed Central

    Devhare, Pradip; Meyer, Keith; Steele, Robert; Ray, Ratna B; Ray, Ranjit

    2017-01-01

    The current outbreak of Zika virus-associated diseases in South America and its threat to spread to other parts of the world has emerged as a global health emergency. A strong link between Zika virus and microcephaly exists, and the potential mechanisms associated with microcephaly are under intense investigation. In this study, we evaluated the effect of Zika virus infection of Asian and African lineages (PRVABC59 and MR766) in human neural stem cells (hNSCs). These two Zika virus strains displayed distinct infection pattern and growth rates in hNSCs. Zika virus MR766 strain increased serine 139 phosphorylation of histone H2AX (γH2AX), a known early cellular response proteins to DNA damage. On the other hand, PRVABC59 strain upregulated serine 15 phosphorylation of p53, p21 and PUMA expression. MR766-infected cells displayed poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavage. Interestingly, infection of hNSCs by both strains of Zika virus for 24 h, followed by incubation in astrocyte differentiation medium, induced rounding and cell death. However, astrocytes generated from hNSCs by incubation in differentiation medium when infected with Zika virus displayed minimal cytopathic effect at an early time point. Infected hNSCs incubated in astrocyte differentiating medium displayed PARP cleavage within 24–36 h. Together, these results showed that two distinct strains of Zika virus potentiate hNSC growth inhibition by different mechanisms, but both viruses strongly induce death in early differentiating neuroprogenitor cells even at a very low multiplicity of infection. Our observations demonstrate further mechanistic insights for impaired neuronal homeostasis during active Zika virus infection. PMID:29022904

  1. Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development.

    PubMed

    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.

  2. EGFR ligands drive multipotential stromal cells to produce multiple growth factors and cytokines via early growth response-1.

    PubMed

    Kerpedjieva, Svetoslava S; Kim, Duk Soo; Barbeau, Dominique J; Tamama, Kenichi

    2012-09-01

    Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)-EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase-extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands.

  3. Placental pathology in early intrauterine growth restriction associated with maternal hypertension.

    PubMed

    Veerbeek, J H W; Nikkels, P G J; Torrance, H L; Gravesteijn, J; Post Uiterweer, E D; Derks, J B; Koenen, S V; Visser, G H A; Van Rijn, B B; Franx, A

    2014-09-01

    To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities. Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria. Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05). Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis.

    PubMed

    Wang, Haihe; Chen, Guofu; Wang, Hongzhi; Liu, Chunbo

    2013-01-01

    RBP-J-interacting and tubulin-associated (RITA) is a novel RBP-J-interacting protein that downregulates Notch-mediated transcription. The current study focuses on the antitumor effect of RITA in human hepatocellular carcinoma (HCC) and aims to explore its molecular mechanism. Thirty paired HCC and adjacent non-tumoral liver samples were analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RITA overexpression was induced by transfection of a pcDNA3.1-Flag-RITA plasmid into HepG2 cells. RITA knockdown was achieved by siRNA transfection. mRNA and protein expression of target genes were quantified by qRT-PCR and Western blotting, respectively. Cell proliferation and apoptosis were measured using MTT assay and flow cytometry. Our results demonstrate that adjacent nontumoral liver samples exhibited increased RITA expression compared to HCC tissues (p < 0.05); RITA levels were associated with tumor differentiation status. Overexpression of RITA suppressed cell proliferation and promoted early apoptosis, while its silencing promoted cell growth dramatically (p < 0.05). RITA overexpression upregulated p53 and reduced cyclin E levels, whereas silencing of RITA had the opposite effect on p53 and cyclin E expression. Our in vitro results represent the first evidence that RITA might suppress tumor growth and induce apoptosis in HCCs, and may be a potent antitumoral agent for HCC treatment that deserves further exploration.

  5. Precision-cut rat, mouse, and human intestinal slices as novel models for the early-onset of intestinal fibrosis.

    PubMed

    Pham, Bao Tung; van Haaften, Wouter Tobias; Oosterhuis, Dorenda; Nieken, Judith; de Graaf, Inge Anne Maria; Olinga, Peter

    2015-04-01

    Intestinal fibrosis (IF) is a major complication of inflammatory bowel disease. IF research is limited by the lack of relevant in vitro and in vivo models. We evaluated precision-cut intestinal slices (PCIS) prepared from human, rat, and mouse intestine as ex vivo models mimicking the early-onset of (human) IF. Precision-cut intestinal slices prepared from human (h), rat (r), and mouse (m) jejunum, were incubated up to 72 h, the viability of PCIS was assessed by ATP content and morphology, and the gene expression of several fibrosis markers was determined. The viability of rPCIS decreased after 24 h of incubation, whereas mPCIS and hPCIS were viable up to 72 h of culturing. Furthermore, during this period, gene expression of heat shock protein 47 and plasminogen activator inhibitor 1 increased in all PCIS in addition to augmented expression of synaptophysin in hPCIS, fibronectin (Fn2) and TGF-β1 in rPCIS, and Fn2 and connective tissue growth factor (Ctgf) in mPCIS. Addition of TGF-β1 to rPCIS or mPCIS induced the gene expression of the fibrosis markers Pro-collagen1a1, Fn2, and Ctgf in both species. However, none of the fibrosis markers was further elevated in hPCIS. We successfully developed a novel ex vivo model that can mimic the early-onset of fibrosis in the intestine using human, rat, and mouse PCIS. Furthermore, in rat and mouse PCIS, TGF-β1 was able to even further increase the gene expression of fibrosis markers. This indicates that PCIS can be used as a model for the early-onset of IF. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Water, plants, and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa—Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water–lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C4-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm·y−1 and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change. PMID:23267102

  7. Water, plants, and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    Water and its influence on plants likely exerted strong adaptive pressures in human evolution. Understanding relationships among water, plants, and early humans is limited both by incomplete terrestrial records of environmental change and by indirect proxy data for water availability. Here we present a continuous record of stable hydrogen-isotope compositions (expressed as δD values) for lipid biomarkers preserved in lake sediments from an early Pleistocene archaeological site in eastern Africa--Olduvai Gorge. We convert sedimentary leaf- and algal-lipid δD values into estimates for ancient source-water δD values by accounting for biochemical, physiological, and environmental influences on isotopic fractionation via published water-lipid enrichment factors for living plants, algae, and recent sediments. Reconstructed precipitation and lake-water δD values, respectively, are consistent with modern isotopic hydrology and reveal that dramatic fluctuations in water availability accompanied ecosystem changes. Drier conditions, indicated by less negative δD values, occur in association with stable carbon-isotopic evidence for open, C(4)-dominated grassland ecosystems. Wetter conditions, indicated by lower δD values, are associated with expanded woody cover across the ancient landscape. Estimates for ancient precipitation amounts, based on reconstructed precipitation δD values, range between approximately 250 and 700 mm · y(-1) and are consistent with modern precipitation data for eastern Africa. We conclude that freshwater availability exerted a substantial influence on eastern African ecosystems and, by extension, was central to early human proliferation during periods of rapid climate change.

  8. Early stress and human behavioral development: emerging evolutionary perspectives.

    PubMed

    Del Giudice, M

    2014-08-01

    Stress experienced early in life exerts a powerful, lasting influence on development. Converging empirical findings show that stressful experiences become deeply embedded in the child's neurobiology, with an astonishing range of long-term effects on cognition, emotion, and behavior. In contrast with the prevailing view that such effects are the maladaptive outcomes of 'toxic' stress, adaptive models regard them as manifestations of evolved developmental plasticity. In this paper, I offer a brief introduction to adaptive models of early stress and human behavioral development, with emphasis on recent theoretical contributions and emerging concepts in the field. I begin by contrasting dysregulation models of early stress with their adaptive counterparts; I then introduce life history theory as a unifying framework, and review recent work on predictive adaptive responses (PARs) in human life history development. In particular, I discuss the distinction between forecasting the future state of the environment (external prediction) and forecasting the future state of the organism (internal prediction). Next, I present the adaptive calibration model, an integrative model of individual differences in stress responsivity based on life history concepts. I conclude by examining how maternal-fetal conflict may shape the physiology of prenatal stress and its adaptive and maladaptive effects on postnatal development. In total, I aim to show how theoretical work from evolutionary biology is reshaping the way we think about the role of stress in human development, and provide researchers with an up-to-date conceptual map of this fascinating and rapidly evolving field.

  9. Testicular growth and development in puberty.

    PubMed

    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.

  10. Redistribution spurs growth by using a portfolio effect on risky human capital.

    PubMed

    Lorenz, Jan; Paetzel, Fabian; Schweitzer, Frank

    2013-01-01

    We demonstrate by mathematical analysis and systematic computer simulations that redistribution can lead to sustainable growth in a society. In accordance with economic models of risky human capital, we assume that dynamics of human capital is modeled as a multiplicative stochastic process which, in the long run, leads to the destruction of individual human capital. When agents are linked by fully redistributive taxation the situation might turn to individual growth in the long run. We consider that a government collects a proportion of income and reduces it by a fraction as costs for administration (efficiency losses). The remaining public good is equally redistributed to all agents. Sustainable growth is induced by redistribution despite the losses from the random growth process and despite administrative costs. Growth results from a portfolio effect. The findings are verified for three different tax schemes: proportional tax, taking proportionally more from the rich, and proportionally more from the poor. We discuss which of these tax schemes performs better with respect to maximize growth under a fixed rate of administrative costs, and the governmental income. This leads us to general conclusions about governmental decisions, the relation to public good games with free riding, and the function of taxation in a risk-taking society.

  11. Redistribution Spurs Growth by Using a Portfolio Effect on Risky Human Capital

    PubMed Central

    Lorenz, Jan; Paetzel, Fabian; Schweitzer, Frank

    2013-01-01

    We demonstrate by mathematical analysis and systematic computer simulations that redistribution can lead to sustainable growth in a society. In accordance with economic models of risky human capital, we assume that dynamics of human capital is modeled as a multiplicative stochastic process which, in the long run, leads to the destruction of individual human capital. When agents are linked by fully redistributive taxation the situation might turn to individual growth in the long run. We consider that a government collects a proportion of income and reduces it by a fraction as costs for administration (efficiency losses). The remaining public good is equally redistributed to all agents. Sustainable growth is induced by redistribution despite the losses from the random growth process and despite administrative costs. Growth results from a portfolio effect. The findings are verified for three different tax schemes: proportional tax, taking proportionally more from the rich, and proportionally more from the poor. We discuss which of these tax schemes performs better with respect to maximize growth under a fixed rate of administrative costs, and the governmental income. This leads us to general conclusions about governmental decisions, the relation to public good games with free riding, and the function of taxation in a risk-taking society. PMID:23390505

  12. Early brush control promotes growth of ponderosa pine planted on bulldozed site

    Treesearch

    Jay R. Bentley; Stanley B. Carpenter; David A. Blakeman

    1971-01-01

    Test plots in a brushfield near Mount Shasta, California, were cleared by bulldozing in 1961, and planted with ponderosa pine seedlings in 1962. Brush regrowth was subjected to varying levels of control by spraying with herbicides. In the first 5 years, brush control definitely promoted the growth of pine seedlings. And this early control also promises to reduce the...

  13. Germination and early growth of coastal tree species on organic seed beds.

    Treesearch

    Don Minore

    1972-01-01

    Germination and early growth on rotten wood and duff under several shade levels were observed for Douglas-fir, Sitka spruce, western hemlock, western redcedar, lodgepole pine, Pacific silver fir, and red alder. Nutrients were more abundant in duff than in rotten wood. Seedlings usually were larger and more abundant on duff-covered rotten logs than on duff-covered...

  14. Post-mitotic human dermal fibroblasts efficiently support the growth of human follicular keratinocytes.

    PubMed

    Limat, A; Hunziker, T; Boillat, C; Bayreuther, K; Noser, F

    1989-05-01

    For growth at low seeding densities, keratinocytes isolated from human tissues like epidermis or hair follicles are dependent on mesenchyme-derived feeder cells such as the 3T3-cell employed so far. As an alternative method, the present study describes the use of post-mitotic human dermal fibroblasts sublethally irradiated or mitomycin C-treated. Special emphasis was put on efficient growth of primary keratinocyte cultures plated at very low seeding densities. Thus, outer root sheath cells isolated from two anagen human hair follicles and plated in a 35-mm culture dish (3 - 6 X 10(2) attached cells) grew to confluence within 3 weeks (6 - 8 X 10(5) cells). Similar results were obtained for interfollicular keratinocytes. A crucial point for the function of these fibroblast feeder cells is plating at appropriate densities, considering their tremendous increase in cell size at the post-mitotic state. Plating densities of 4 - 5 X 10(3/cm2 allow full spreading of the feeder cells and do not impede the settling and expansion of the keratinocytes. Major advantages of this system include easier handling and better reproducibility than using 3T3-cells. Moreover, homologous fibroblast feeders mimic more closely the physiologic situation and therefore might provide a valuable tool for studying interactions between human mesenchymal and epithelial cells. Finally, potential hazards of using transformed feeder cells from a different species in keratinocyte cultures raised for wound covering in humans could be thus avoided.

  15. How long bones grow children: Mechanistic paths to variation in human height growth.

    PubMed

    Lampl, Michelle; Schoen, Meriah

    2017-03-01

    Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth. There are critical junctures within the chondrocytic differentiation cascade at which environmental influences are integrated and have the ability to influence progression to the hypertrophic chondrocyte phase, the primary driver of long bone elongation. Phenotypic differences in height growth patterns reflect variability in amplitude and frequency of discretely timed hypertrophic cellular expansion events, the cellular basis of saltation and stasis growth biology. Final height is a summary of the dynamic processes carried out by the growth plate cellular machinery. As these cell-level mechanisms unfold in an individual, time-specific manner, there are many critical points at which a genetic growth program can be enhanced or perturbed. Recognizing both the complexity and fluidity of this adaptive system questions the likelihood of a single, optimal growth pattern and instead identifies a larger bandwidth of saltatory frequencies for "normal" growth. Further inquiry into mechanistic sources of variability acting at critical organizational points of chondrogenesis can provide new opportunities for growth interventions. © 2017 Wiley Periodicals, Inc.

  16. Early Life Factors and Inter-Country Heterogeneity in BMI Growth Trajectories of European Children: The IDEFICS Study

    PubMed Central

    Börnhorst, Claudia; Siani, Alfonso; Russo, Paola; Kourides, Yannis; Sion, Isabelle; Molnár, Denés; Moreno, Luis A.; Rodríguez, Gerardo; Ben-Shlomo, Yoav; Howe, Laura; Lissner, Lauren; Mehlig, Kirsten; Regber, Susann; Bammann, Karin; Foraita, Ronja

    2016-01-01

    Background Starting from birth, this explorative study aimed to investigate between-country differences in body mass index (BMI) trajectories and whether early life factors explain these differences. Methods The sample included 7,644 children from seven European countries (Belgium, Cyprus, Germany, Hungary, Italy, Spain, Sweden) participating in the multi-centre IDEFICS study. Information on early life factors and in total 53,409 repeated measurements of height and weight from 0 to <12 years of age were collected during the baseline (2007/2008) and follow-up examination (2009/2010) supplemented by records of routine child health visits. Country-specific BMI growth curves were estimated using fractional polynomial mixed effects models. Several covariates focussing on early life factors were added to the models to investigate their role in the between-countries differences. Results Large between-country differences were observed with Italian children showing significantly higher mean BMI values at all ages ≥ 3 years compared to the other countries. For instance, at age 11 years mean BMI values in Italian boys and girls were 22.3 [21.9;22.8; 99% confidence interval] and 22.0 [21.5;22.4], respectively, compared to a range of 18.4 [18.1;18.8] to 20.3 [19.8;20.7] in boys and 18.2 [17.8;18.6] to 20.3 [19.8;20.7] in girls in the other countries. After adjustment for early life factors, differences between country-specific BMI curves became smaller. Maternal BMI was the factor being most strongly associated with BMI growth (p<0.01 in all countries) with associations increasing during childhood. Gestational weight gain (GWG) was weakly associated with BMI at birth in all countries. In some countries, positive associations between BMI growth and children not being breastfed, mothers’ smoking during pregnancy and low educational level of parents were found. Conclusion Early life factors seem to explain only some of the inter-country variation in growth. Maternal BMI showed

  17. Worldwide variability in growth and its association with health: Incorporating body composition, developmental plasticity, and intergenerational effects.

    PubMed

    Wells, Jonathan C K

    2017-03-01

    In their seminal book "Worldwide variation in human growth," published in 1976, Eveleth and Tanner highlighted substantial variability within and between populations in the magnitude and schedule of human growth. In the four decades since then, research has clarified why growth variability is so closely associated with human health. First, growth patterns are strongly associated with body composition, both in the short- and long-term. Poor growth in early life constrains the acquisition of lean tissue, while compensatory "catch-up" growth may elevate body fatness. Second, these data are examples of the fundamental link between growth and developmental plasticity. Growth is highly sensitive to ecological stresses and stimuli during early "critical windows," but loses much of this sensitivity as it undergoes canalization during early childhood. Crucially, the primary source of stimuli during early "critical windows" is not the external environment itself, but rather maternal phenotype, which transduces the impact of ecological conditions. Maternal phenotype, representing many dimensions of "capital," thus generates a powerful impact on the developmental trajectory of the offspring. There is increasing evidence that low levels of maternal capital impact the offspring's size at birth, schedule of maturation, and body composition and physiological function in adulthood. While evidence has accrued of substantial heritability in adult height, it is clear that the pathway through which it is attained has major implications for metabolic phenotype. Integrating these perspectives is important for understanding how developmental plasticity may on the one hand contribute to adaptation, while on the other shape susceptibility to non-communicable disease. © 2017 Wiley Periodicals, Inc.

  18. Early Life Growth Predicts Pubertal Development in South African Adolescents.

    PubMed

    Lundeen, Elizabeth A; Norris, Shane A; Martorell, Reynaldo; Suchdev, Parminder S; Mehta, Neil K; Richter, Linda M; Stein, Aryeh D

    2016-03-01

    Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty, it is important to understand the childhood predictors of pubertal timing and tempo. We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa. We analyzed prospectively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto, South Africa. Height-for-age z scores (HAZs) and body mass index-for-age z scores (BMIZs) were calculated based on height (centimeters) and body mass index (kilograms per meter squared) at ages 5 y and 8 y. The development of genitals, breasts, and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale (SMS). We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age. We used multinomial logistic regression to estimate associations of HAZ and BMIZ at ages 5 and 8 y with pubertal development. We identified 3 classes for pubic hair development (for both girls and boys) and 4 classes for breast (for girls) and genital (for boys) development. In girls, both HAZ and BMIZ at age 5 y were positively associated with pubic hair development [relative risk ratio (RRR): 1.57, P < 0.001 and RRR: 1.51, P < 0.01, respectively], as was BMI at age 8 y (RRR: 2.06, P = 0.03); similar findings were observed for breast development. In boys, HAZ and BMIZ at age 5 y were positively associated with pubic hair development (RRR: 1.78, P < 0.001 and RRR: 1.43, P < 0.01, respectively); HAZ at age 5 y was associated with development of genitals (RRR: 2.19, P < 0.01). In boys and girls, both height and body mass index in early childhood predicted the trajectory of pubertal development. This may provide a tool to identify children at risk of early pubertal onset.

  19. Physiological and morphological changes during early and later stages of fruit growth in Capsicum annuum.

    PubMed

    Tiwari, Aparna; Vivian-Smith, Adam; Ljung, Karin; Offringa, Remko; Heuvelink, Ep

    2013-03-01

    Fruit-set involves a series of physiological and morphological changes that are well described for tomato and Arabidopsis, but largely unknown for sweet pepper (Capsicum annuum). The aim of this paper is to investigate whether mechanisms of fruit-set observed in Arabidopsis and tomato are also applicable to C. annuum. To do this, we accurately timed the physiological and morphological changes in a post-pollinated and un-pollinated ovary. A vascular connection between ovule and replum was observed in fertilized ovaries that undergo fruit development, and this connection was absent in unfertilized ovaries that abort. This indicates that vascular connection between ovule and replum is an early indicator for successful fruit development after pollination and fertilization. Evaluation of histological changes in the carpel of a fertilized and unfertilized ovary indicated that increase in cell number and cell diameter both contribute to early fruit growth. Cell division contributes more during early fruit growth while cell expansion contributes more at later stages of fruit growth in C. annuum. The simultaneous occurrence of a peak in auxin concentration and a strong increase in cell diameter in the carpel of seeded fruits suggest that indole-3-acetic acid stimulates a major increase in cell diameter at later stages of fruit growth. The series of physiological and morphological events observed during fruit-set in C. annuum are similar to what has been reported for tomato and Arabidopsis. This indicates that tomato and Arabidopsis are suitable model plants to understand details of fruit-set mechanisms in C. annuum. Copyright © Physiologia Plantarum 2012.

  20. Cell phone radiations affect early growth of Vigna radiata (mung bean) through biochemical alterations.

    PubMed

    Sharma, Ved Parkash; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2010-01-01

    The indiscriminate use of wireless technologies, particularly of cell phones, has increased the health risks among living organisms including plants. We investigated the impact of cell phone electromagentic field (EMF) radiations (power density, 8.55 microW cm(-2)) on germination, early growth, proteins and carbohydrate contents, and activities of some enzymes in Vigna radiata. Cell phone EMF radiations significantly reduced the seedling length and dry weight of V radiata after exposure for 0.5, 1, 2, and 4 h. Furthermore, the contents of proteins and carbohydrates were reduced in EMF-exposed plants. However, the activities of proteases, alpha-amylases, beta-amylases, polyphenol oxidases, and peroxidases were enhanced in EMF-exposed radicles indicating their role in providing protection against EMF-induced stress. The study concludes that cell phone EMFs impair early growth of V radiata seedlings by inducing biochemical changes.

  1. The Groove of Growth: How Early Gains in Math Ability Influence Adolescent Achievement

    ERIC Educational Resources Information Center

    Watts, Tyler W.; Duncan, Greg J.; Siegler, Robert S.; Davis-Kean, Pamela E.

    2014-01-01

    A number of studies, both small scale and of nationally-representative student samples, have reported substantial associations between school entry math ability and later elementary school achievement. However, questions remain regarding the persistence of the association between early growth in math ability and later math achievement due to the…

  2. Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

    PubMed

    Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

    2016-02-01

    Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor

  3. Environmental noise and human prenatal growth

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schell, L.M.

    1981-09-01

    To determine whether chronic exposure to relatively loud noise has demonstrable biological effects in humans, a study was conducted on the effect of mother's exposure to airport noise while pregnant, and of social and biological characteristics of the family upon birthweight and gestation length. The sample of births was drawn from a community located adjacent to an international airport in the U.S., where noise levels had been measured previously. Mother's noise exposure was based upon noise levels near her residence in the community while she was pregnant. Data from 115 births were used, these being from mothers whose noise exposuremore » history was most complete throughout the pregnancy. Using multivariate analysis to correct for family characteristics, the partial correlation coefficient for noise exposure and gestation length was negative, large, and significant in girls (r . -0.49, p less than 0.001). In boys the partial correlation coefficient was also negative but was smaller and did not quite reach statistical significance. Partial correlations with birthweight were smaller in both boys and girls and not significant. These results agree best with previous studies that suggest that noise may reduce prenatal growth. The size of the observed effects may be related to a conservative research design biased towards underestimation, as well as to the real effects of noise upon human prenatal growth.« less

  4. EGFR Ligands Drive Multipotential Stromal Cells to Produce Multiple Growth Factors and Cytokines via Early Growth Response-1

    PubMed Central

    Kerpedjieva, Svetoslava S.; Kim, Duk Soo; Barbeau, Dominique J.

    2012-01-01

    Cell therapy with adult bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) presents a promising approach to promote wound healing and tissue regeneration. The strong paracrine capability of various growth factors and cytokines is a key mechanism of MSC-mediated wound healing and tissue regeneration, and the goal of this study is to understand the underlying mechanism that supports the strong paracrine machineries in MSCs. Microarray database analyses revealed that early growth response-1 (EGR1) is highly expressed in MSCs. Our previous studies showed that epidermal growth factor (EGF) treatment induces growth factor production in MSCs in vitro. Since EGF strongly upregulates EGR1, we hypothesized that EGF receptor (EGFR)–EGR1 signaling plays a pivotal role in MSC paracrine activity. EGF treatment upregulated the gene expression of growth factors and cytokines, including EGFR ligands in a protein kinase C (PKC)- and/or mitogen-activated protein kinase–extracellular-signal-regulated kinase-dependent manner, and it was reversed by shRNA against EGR1. PKC activator phorbol 12-myristate 13-acetate enhanced EGFR tyrosyl phosphorylation and upregulated the gene expression of growth factors and cytokines in a heparin-binding EGF-like growth factor (HBEGF) inhibitor CRM197 sensitive manner, indicating an involvement of autocrined HBEGF in the downstream of PKC signaling. Moreover, stimulation with growth factors and cytokines induced the expression of EGFR ligands, presumably via EGR1 upregulation. These data indicate EGR1 as a convergence point of multiple signaling pathways, which in turn augments the production of multiple growth factors and cytokines by enhancing the autocrine signaling with EGFR ligands. PMID:22316125

  5. Early modern human diversity suggests subdivided population structure and a complex out-of-Africa scenario

    PubMed Central

    Gunz, Philipp; Bookstein, Fred L.; Mitteroecker, Philipp; Stadlmayr, Andrea; Seidler, Horst; Weber, Gerhard W.

    2009-01-01

    The interpretation of genetic evidence regarding modern human origins depends, among other things, on assessments of the structure and the variation of ancient populations. Because we lack genetic data from the time when the first anatomically modern humans appeared, between 200,000 and 60,000 years ago, instead we exploit the phenotype of neurocranial geometry to compare the variation in early modern human fossils with that in other groups of fossil Homo and recent modern humans. Variation is assessed as the mean-squared Procrustes distance from the group average shape in a representation based on several hundred neurocranial landmarks and semilandmarks. We find that the early modern group has more shape variation than any other group in our sample, which covers 1.8 million years, and that they are morphologically similar to recent modern humans of diverse geographically dispersed populations but not to archaic groups. Of the currently competing models of modern human origins, some are inconsistent with these findings. Rather than a single out-of-Africa dispersal scenario, we suggest that early modern humans were already divided into different populations in Pleistocene Africa, after which there followed a complex migration pattern. Our conclusions bear implications for the inference of ancient human demography from genetic models and emphasize the importance of focusing research on those early modern humans, in particular, in Africa. PMID:19307568

  6. The neuropeptide galanin is a novel inhibitor of human hair growth.

    PubMed

    Holub, B S; Kloepper, J E; Tóth, B I; Bíro, T; Kofler, B; Paus, R

    2012-07-01

    Galanin is a trophic factor of the central and peripheral nervous system that shows widespread distribution in human skin. However, the exact localization and the role of galanin in the hair follicle (HF) remain to be clarified. To characterize galanin expression in human scalp HFs and to examine the effects of galanin on normal human scalp HF growth in organ culture. Immunohistochemistry was performed on cryosections of human female scalp skin. Anagen HFs were microdissected and cultured up to 9 days and treated with 100 nmol L(-1) galanin. Staining for Ki-67, TUNEL and Masson-Fontana were used to analyse proliferation, apoptosis and hair cycle staging of the HFs. Functional effects of galanin were tested in serum-free HF organ culture. Galanin-like immunoreactivity was detected in the outer root sheath (ORS) and inner root sheath. Additionally, galanin mRNA was detected in ORS keratinocytes and all HF samples tested. Galanin receptor transcripts (GalR2, GalR3) were also detected in selected samples. Galanin reduced proliferation of hair matrix keratinocytes in situ compared with vehicle-treated controls, shortened the hair growth phase (anagen) in vitro and reduced hair shaft elongation. This was accompanied by the premature development of a catagen-like morphology of galanin-treated HFs. We present the first evidence that human HFs are both a source and a functionally relevant target of galanin. Due to its hair growth-inhibitory properties in vitro, galanin application deserves further exploration as a potential new treatment strategy for unwanted hair growth (hirsutism, hypertrichosis). © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

  7. Parental anthropometrics, early growth and the risk of overweight in pre-school children: the Generation R Study.

    PubMed

    Durmuş, B; Arends, L R; Ay, L; Hokken-Koelega, A C; Raat, H; Hofman, A; Steegers, E A P; Jaddoe, V W V

    2013-10-01

    There are limited data regarding the associations of both maternal and paternal anthropometrics with longitudinally measured post-natal growth measures in early childhood. To assess the associations of maternal and paternal anthropometrics with growth characteristics and the risk of overweight in pre-school children. Population-based prospective cohort study from early foetal life onwards in the Netherlands. Maternal pre-pregnancy anthropometrics and gestational weight gain, and paternal anthropometrics were related to foetal and post-natal growth measures and the risk of overweight until the age of 4 years. Analyses were based on 5674 mothers, fathers and their children. Both pre-pregnancy maternal and paternal height, weight and body mass index were associated with corresponding foetal and post-natal anthropometric measures. Maternal body mass index had a significantly stronger effect on childhood body mass index than paternal body mass index. As compared to children from parents with normal body mass index, children from two obese parents had an increased risk of overweight at the age of 4 years (odds ratio 6.52 (95% confidence interval 3.44, 12.38). Maternal gestational weight gain was only among mothers with normal body mass index associated with body mass index and the risk of overweight in the children. Maternal and paternal anthropometrics affect early growth in pre-school children differently. Gestational weight gain in mothers without overweight and obesity is related to the risk of overweight in early childhood. © 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity.

  8. HRAS: a webserver for early warning of human health risk brought by aflatoxin.

    PubMed

    Hu, Ruifeng; Zeng, Xu; Gao, Weiwei; Wang, Qian; Liu, Zhihua

    2013-02-01

    Most people are aware that outdoor air pollution can damage their health, but many do not know that indoor air pollution can also exhibit significant negative health effects. Fungi parasitizing in air conditioning and ventilation systems can be one of indoor air pollution sources. Aflatoxin produced by Aspergillus flavus (A. flavus) became a central focus of indoor air pollution, especially in farmer markets. Therefore we developed an early warning system, Health Risk Assessment System, to estimate the growth rate of A. flavus, predict the amount of aflatoxin and provide early warning information. Firstly, the growth of A. flavus and the production of aflatoxin under different conditions were widely obtained through a comprehensive literature review. Secondly, three mathematical models were established to predict the A. flavus colony growth rate, lag phase duration and aflatoxin content, as functions of temperature and water activity based on present studies. Finally, all the results were evaluated by the user-supplied data using PHP programming language. We utilized the web page to show the results and display warning information. The JpGraph library was used to create a dynamic line chart, refreshing the warning information dynamically in real-time. The HARS provides accurate information for early warning purposes to let us take timely steps to protect ourselves.

  9. Seagrass ( Posidonia oceanica) vertical growth as an early indicator of fish farm-derived stress

    NASA Astrophysics Data System (ADS)

    Marbà, Núria; Santiago, Rocío; Díaz-Almela, Elena; Álvarez, Elvira; Duarte, Carlos M.

    2006-04-01

    The usefulness of vertical rhizome growth as an early indicator of fish farm impacts to Posidonia oceanica meadows was tested by comparing annual estimates of vertical rhizome growth, quantified retrospectively, at distances ranging between 5 and 1200 m from fish cages at four Mediterranean locations (Cyprus, Greece, Italy and Spain). The studied fish farms had been operating since, at least, 1997, producing between 150 and 1150 tons yr -1 of sea bream ( Sparus aurata) and sea bass ( Dicentrachus labrax), and, at Italy, also sharpsnout sea bream ( Diplodus puntazzo). The reconstructed vertical rhizome growth spanned from 19 to 25 years of growth, depending on sites, and the average vertical rhizome growth before the onset of fish farm operations ranged between 4.48 and 8.79 mm yr -1. The vertical rhizome growth after the onset of farming activities declined significantly ( t-test, P < 0.05) from the control station (at >800 m from the farm; vertical growth rate averaged 6.79, 5.52, 3.89 and 3.70 mm yr -1 at Cyprus, Greece, Italy and Spain control stations, respectively) to the impacted one (at 5-300 m from the farm; vertical growth rate was 4.82, 3.52, 2.77 and 1.92 mm yr -1 at Cyprus, Greece, Italy and Spain impacted stations, respectively) at each farm. Moreover, vertical growth significantly ( t-test, P < 0.05) declined by about twofold following the onset of fish farm operations for the extant meadow nearest to the cages, as well as those supporting intermediate impacts at distances 35-400 m from the cages. Vertical rhizome growth was not significantly affected after the onset of fish farm operations for the meadows located more than 800 m from the farm, except in those from the Italian site, the largest farm. Examination of the time course of vertical growth for individual rhizomes in the areas of the meadow nearest to the farms, except for those at Cyprus, showed that the decline in vertical growth was initiated within the year of the onset of farming

  10. Human growth is associated with distinct patterns of gene expression in evolutionarily conserved networks

    PubMed Central

    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

  11. Red ginseng extract promotes the hair growth in cultured human hair follicles.

    PubMed

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Won, Chong Hyun; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-03-01

    Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans.

  12. Red Ginseng Extract Promotes the Hair Growth in Cultured Human Hair Follicles

    PubMed Central

    Park, Gyeong-Hun; Park, Ki-young; Cho, Hong-il; Lee, Sang-Min; Han, Ji Su; Chang, Sung Eun; Lee, Mi Woo; Choi, Jee Ho; Moon, Kee Chan; Shin, Hyoseung; Kang, Yong Jung; Lee, Dong Hun

    2015-01-01

    Abstract Ginseng has been shown to promote hair growth in several recent studies. However, its effects on human hair follicles and its mechanisms of action have not been sufficiently elucidated. This study aimed to investigate the hair growth-promoting effects of red ginseng extract (RGE) and its ginsenosides. The proliferative activities of cultured human hair follicles treated with RGE and ginsenoside-Rb1 were assessed using Ki-67 immunostaining. Their effects on isolated human dermal papilla cells (hDPCs) were evaluated using cytotoxicity assays, immunoblot analysis of signaling proteins, and the determination of associated growth factors. We examined the ability of RGE and ginsenosides to protect hair matrix keratinocyte proliferation against dihydrotestosterone (DHT)-induced suppression and their effects on the expression of androgen receptor. The in vivo hair growth-promoting effect of RGE was also investigated in C57BL/6 mice. Both RGE and ginsenoside-Rb1 enhanced the proliferation of hair matrix keratinocytes. hDPCs treated with RGE or ginsenoside-Rb1 exhibited substantial cell proliferation and the associated phosphorylation of ERK and AKT. Moreover, RGE, ginsenoside-Rb1, and ginsenoside-Rg3 abrogated the DHT-induced suppression of hair matrix keratinocyte proliferation and the DHT-induced upregulation of the mRNA expression of androgen receptor in hDPCs. Murine experiments revealed that the subcutaneous injection of 3% RGE resulted in more rapid hair growth than the negative control. In conclusion, RGE and its ginsenosides may enhance hDPC proliferation, activate ERK and AKT signaling pathways in hDPCs, upregulate hair matrix keratinocyte proliferation, and inhibit the DHT-induced androgen receptor transcription. These results suggest that red ginseng may promote hair growth in humans. PMID:25396716

  13. Effects of high versus standard early protein intake on growth of extremely low birth weight infants.

    PubMed

    Maggio, Luca; Cota, Francesco; Gallini, Francesca; Lauriola, Valeria; Zecca, Chiara; Romagnoli, Costantino

    2007-01-01

    Early provision of protein has been shown to limit catabolism and could improve growth. Our objective was to determine whether early aggressive protein intake improved growth outcomes of extremely low birth weight (ELBW) infants. ELBW infants were included in the study if they had no major congenital anomalies or renal failure and were still hospitalized at 36 weeks postmenstrual age. In 25 infants (HP) the early protein intake was planned to be 20% greater than in 31 historical controls (SP). The 2 groups were similar in the baseline characteristics. The mean protein intake during the first 14 days of life was significantly greater in the HP group (3.1 +/- 0.2 vs 2.5 +/- 0.2 g/kg/d; P<0.0001). HP group showed lower postnatal weight loss (-3.1%; 95% confidence interval [CI] -5.9, -0.2) and earlier regain of birth weight (-4.1 days; 95% CI -6.6, -1.7). Mean blood urea nitrogen and bicarbonate levels were similar; mean serum glucose level was lower in the HP group (-21,7 mg/dL; 95% CI -41.9,-1.5). HP infants had a reduced fall in weight z score (-0.57; 95% CI -1.01, -0.12) and in length z score (-0.51; 95% CI -0.97, -0.05) from birth to discharge. Early high protein intake was associated with improved weight and length growth outcomes at discharge. These findings highlight the benefits of aggressive protein intake immediately after birth.

  14. A virally inactivated functional growth factor preparation from human platelet concentrates.

    PubMed

    Su, C-Y; Kuo, Y P; Lin, Y C; Huang, C-T; Tseng, Y H; Burnouf, T

    2009-08-01

    Human platelet growth factors (HPGF) are essential for tissue regeneration and may replace fetal bovine serum (FBS) in cell therapy. No method for the manufacture of standardized virally inactivated HPGF has been developed yet. Platelet concentrates (PC) were subjected to solvent/detergent (S/D) treatment (1% TnBP/1% Triton X-45), oil extraction, hydrophobic interaction chromatography and sterile filtration. Platelet-derived growth factor (PDGF)-AB, -BB and -AA, transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1) and vascular endothelium growth factor (VEGF) were measured by ELISA. Composition in proteins and lipids was determined, protein profiles were obtained by SDS-PAGE, and TnBP and Triton X-45 were assessed by gas chromatography and high-performance liquid chromatography, respectively. Cell growth promoting activity of HPGF was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay using human embryonic kidney (HEK293A) fibroblast and Statens Seruminstitute rabbit corneal (SIRC) epithelial cell lines. The GF preparation contained a mean of 16.66, 2.04, 1.53, 72.19, 0.33, 48.59 and 0.44 ng/ml of PDGF-AB, -BB, -AA, TGF-beta1, EGF, IGF-1 and VEGF, respectively. The protein profile was typical of platelet releasates and had less than 2 p.p.m. of residual S/D agents. MTS assay of HEK293A and SIRC cultures showed that the GF preparation at 10% and 0.1% (v/v), respectively, could successfully replace 10% FBS for cell proliferation. Cell-stimulating activity of HPGF on HEK293A was over twice that of PC releasates. STANDARDIZED and functional virally inactivated HPGF can be prepared from human PC for possible applications in cell therapy and regenerative medicine.

  15. Functional and Radiographic Outcomes Following Growth-Sparing Management of Early-Onset Scoliosis.

    PubMed

    Johnston, Charles E; Tran, Dong-Phuong; McClung, Anna

    2017-06-21

    In this study, we sought to evaluate radiographic, functional, and quality-of-life outcomes of patients who have completed growth-sparing management of early-onset scoliosis. This prospective study involved patients with early-onset scoliosis who underwent growth-sparing treatment and either "final" fusion or observation for ≥2 years since the last lengthening procedure. Demographics, radiographic parameters, pulmonary function test (PFT) values, and scores of patient-reported assessments (Early-Onset Scoliosis Questionnaire [EOSQ] and Scoliosis Research Society [SRS]-30) were obtained. At the most recent follow-up, patients performed 2 additional functional outcome tests: step-activity monitoring and a treadmill exercise-tolerance test. Twelve patients were evaluated as "graduates" of growth-sparing management of early-onset scoliosis (mean of 37 months since the most recent surgery). The major scoliosis curve measurement averaged 88° before treatment and 47° at the most recent follow-up. T1-S1 height increased from a mean of 22.3 cm to 34.7 cm and T1-T12 height, from 13.3 to 22.3 cm. At the most recent follow-up, the mean forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) as a percentage of the predicted volume were 52.1% and 55.3%, respectively, and were essentially unchanged from the earliest PFT that patients could perform (FEV1 = 53.8% of predicted and FVC = 53.5% of predicted). There was no difference between graduates and controls with respect to activity time or total steps in step-activity monitoring, and in the exercise-tolerance test, graduates walked at the same speed but at a higher heart rate and at a significantly higher (p <0.001) VO2 cost (rate of oxygen consumed per distance traveled). The EOSQ mean score was 102.2 of a possible 120 points, and the SRS mean score was 4.1 of a possible 5 points. A realistic long-term goal for the management of early-onset scoliosis appears to be spine elongation and maintenance of

  16. Ghrelin and the growth hormone secretagogue receptor in growth and development.

    PubMed

    Chanoine, J-P; De Waele, K; Walia, P

    2009-04-01

    The pancreas is a major source of ghrelin in the perinatal period, whereas gastric production progressively increases after birth. Loss of function of the genes for ghrelin or for the constitutively activated growth hormone secretagogue receptor (GHSR) does not affect birth weight and early postnatal growth. However, ghrl(-/-) or ghsr(-/-) mice fed a high fat diet starting soon after weaning are resistant to diet-induced obesity, suggesting that ghrelin affects the maturation of the metabolic axes involved in energy balance. In addition, animal and human studies suggest that GHSR plays a physiological role in linear growth. In mice, absence of the GHSR gene is associated with lower insulin-like growth factor 1 concentrations and lower body mass in adult animals, independently of food intake. In humans, a mutation of the GHSR gene that impairs the constitutive activity of the receptor was found in two families with short stature. Administration of acylated ghrelin to rat pups directly does not affect weight gain. In contrast, administration of ghrelin to pregnant or lactating rats results in greater fetal weight and postnatal weight gain, respectively, suggesting that maternal ghrelin may stimulate perinatal growth. These data point toward a physiological role for ghrelin and GHSR in growth and/or in the maturation of hormonal systems involved in the regulation of energy balance.

  17. Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

    PubMed

    Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

    2018-02-01

    The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

  18. Function of FEZF1 during early neural differentiation of human embryonic stem cells.

    PubMed

    Liu, Xin; Su, Pei; Lu, Lisha; Feng, Zicen; Wang, Hongtao; Zhou, Jiaxi

    2018-01-01

    The understanding of the mechanism underlying human neural development has been hampered due to lack of a cellular system and complicated ethical issues. Human embryonic stem cells (hESCs) provide an invaluable model for dissecting human development because of unlimited self-renewal and the capacity to differentiate into nearly all cell types in the human body. In this study, using a chemical defined neural induction protocol and molecular profiling, we identified Fez family zinc finger 1 (FEZF1) as a potential regulator of early human neural development. FEZF1 is rapidly up-regulated during neural differentiation in hESCs and expressed before PAX6, a well-established marker of early human neural induction. We generated FEZF1-knockout H1 hESC lines using CRISPR-CAS9 technology and found that depletion of FEZF1 abrogates neural differentiation of hESCs. Moreover, loss of FEZF1 impairs the pluripotency exit of hESCs during neural specification, which partially explains the neural induction defect caused by FEZF1 deletion. However, enforced expression of FEZF1 itself fails to drive neural differentiation in hESCs, suggesting that FEZF1 is necessary but not sufficient for neural differentiation from hESCs. Taken together, our findings identify one of the earliest regulators expressed upon neural induction and provide insight into early neural development in human.

  19. Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

    PubMed

    Groban, L; Lin, M; Kassik, K A; Ingram, R L; Sonntag, W E

    2011-04-01

    The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium

  20. Human Disturbance Influences Reproductive Success and Growth Rate in California Sea Lions (Zalophus californianus)

    PubMed Central

    French, Susannah S.; González-Suárez, Manuela; Young, Julie K.; Durham, Susan; Gerber, Leah R.

    2011-01-01

    The environment is currently undergoing changes at both global (e.g., climate change) and local (e.g., tourism, pollution, habitat modification) scales that have the capacity to affect the viability of animal and plant populations. Many of these changes, such as human disturbance, have an anthropogenic origin and therefore may be mitigated by management action. To do so requires an understanding of the impact of human activities and changing environmental conditions on population dynamics. We investigated the influence of human activity on important life history parameters (reproductive rate, and body condition, and growth rate of neonate pups) for California sea lions (Zalophus californianus) in the Gulf of California, Mexico. Increased human presence was associated with lower reproductive rates, which translated into reduced long-term population growth rates and suggested that human activities are a disturbance that could lead to population declines. We also observed higher body growth rates in pups with increased exposure to humans. Increased growth rates in pups may reflect a density dependent response to declining reproductive rates (e.g., decreased competition for resources). Our results highlight the potentially complex changes in life history parameters that may result from human disturbance, and their implication for population dynamics. We recommend careful monitoring of human activities in the Gulf of California and emphasize the importance of management strategies that explicitly consider the potential impact of human activities such as ecotourism on vertebrate populations. PMID:21436887

  1. Too much of a good thing? Economic growth and human rights, 1960 to 2010.

    PubMed

    Cole, Wade M

    2017-09-01

    Despite widespread belief in the benefits of economic growth, some scholars emphasize the potentially negative consequences of growth-and especially rapid growth-for social and political outcomes. Using data for 149 countries between 1960 and 2010, I analyze the effect of economic growth on fundamental human rights conditions. Dynamic random-effects and two-way fixed-effects estimators, both with and without instrumental variables, yield several conclusions. First, economic growth is causally prior to rights conditions. Second, economic growth has a modest positive effect on human rights, albeit with diminishing returns at high growth rates. Third, low-income countries account for much of this relationship: growth improves rights conditions for most low-income countries, but extremely rapid growth is inimical. Growth has little effect among middle-income countries, while for high-income countries the relationship is positive but not robust. I bring these findings to bear on long-standing debates between proponents and critics of modernization theory. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Being Human: A Handbook in Human Growth and Development for the Developmentally Disabled.

    ERIC Educational Resources Information Center

    Fletcher, Donna; Ogle, Peggy

    The handbook is intended to provide practitioners with information on establishing and organizing a Human Growth and Development program in agencies and facilities which provide training to developmentally disabled persons. The handbook discusses the legal foundation (Florida law) for establishing the program as well as specific methods for…

  3. Oral iron acutely elevates bacterial growth in human serum.

    PubMed

    Cross, James H; Bradbury, Richard S; Fulford, Anthony J; Jallow, Amadou T; Wegmüller, Rita; Prentice, Andrew M; Cerami, Carla

    2015-11-23

    Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses.

  4. Impact of childhood asthma on growth trajectories in early adolescence: Findings from the Childhood Asthma Prevention Study (CAPS).

    PubMed

    Movin, Maria; Garden, Frances L; Protudjer, Jennifer L P; Ullemar, Vilhelmina; Svensdotter, Frida; Andersson, David; Kruse, Andreas; Cowell, Chris T; Toelle, Brett G; Marks, Guy B; Almqvist, Catarina

    2017-04-01

    Understanding the associations between childhood asthma and growth in early adolescence by accounting for the heterogeneity of growth during puberty has been largely unexplored. The objective was to identify sex-specific classes of growth trajectories during early adolescence, using a method which takes the heterogeneity of growth into account and to evaluate the association between childhood asthma and different classes of growth trajectories in adolescence. Our longitudinal study included participants with a family history of asthma born during 1997-1999 in Sydney, Australia. Hence, all participants were at high risk for asthma. Asthma status was ascertained at 8 years of age using data from questionnaires and lung function tests. Growth trajectories between 11 and 14 years of age were classified using a latent basis growth mixture model. Multinomial regression analyses were used to evaluate the association between asthma and the categorized classes of growth trajectories. In total, 316 participants (51.6% boys), representing 51.3% of the entire cohort, were included. Sex-specific classes of growth trajectories were defined. Among boys, asthma was not associated with the classes of growth trajectories. Girls with asthma were more likely than girls without asthma to belong to a class with later growth (OR: 3.79, 95% CI: 1.33, 10.84). Excluding participants using inhaled corticosteroids or adjusting for confounders did not significantly change the results for either sex. We identified sex-specific heterogeneous classes of growth using growth mixture modelling. Associations between childhood asthma and different classes of growth trajectories were found for girls only. © 2016 Asian Pacific Society of Respirology.

  5. A Critical Point of Male Gonad Development: Neuroendocrine Correlates of Accelerated Testicular Growth in Rats during Early Life

    PubMed Central

    Dygalo, Nikolay N.; Shemenkova, Tatjana V.; Kalinina, Tatjana S.; Shishkina, Galina T.

    2014-01-01

    Testis growth during early life is important for future male fertility and shows acceleration during the first months of life in humans. This acceleration coincides with the peak in gonadotropic hormones in the blood, while the role of hypothalamic factors remains vague. Using neonatal rats to assess this issue, we found that day 9 of life is likely critical for testis development in rats. Before this day, testicular growth was proportional to body weight gain, but after that the testes showed accelerated growth. Hypothalamic kisspeptin and its receptor mRNA levels begin to elevate 2 days later, at day 11. A significant increase in the mRNA levels for gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus between days 5 and 7 was followed by a 3-fold decrease in GnRH mRNA levels in this brain region during the next 2 days. Starting from day 9, hypothalamic GnRH mRNA levels increased significantly and positively correlated with accelerated testicular growth. Triptorelin, an agonist of GnRH, at a dose that had no effect on testicular growth during “proportional” period, increased testis weights during the period of accelerated growth. The insensitivity of testicular growth to GnRH during “proportional” period was supported by inability of a 2.5-fold siRNA knockdown of GnRH expression in the hypothalamus of the 7-day-old animals to produce any effect on their testis weights. GnRH receptor blockade with cetrorelix was also without effect on testis weights during “proportional” period but the same doses of this GnRH antagonist significantly inhibited “accelerated” testicular growth. GnRH receptor mRNA levels in the pituitary as well as plasma LH concentrations were higher during “accelerated” period of testicular growth than during “proportional” period. In general, our data defined two distinct periods in rat testicular development that are primarily characterized by different responses to GnRH signaling. PMID:24695464

  6. Parental care mitigates carry-over effects of poor early conditions on offspring growth

    USGS Publications Warehouse

    Auer, Sonya K.; Martin, Thomas E.

    2017-01-01

    Poor developmental conditions can have long-lasting negative effects on offspring phenotypes, but impacts often differ among species. Contrasting responses may reflect disparities in experimental protocols among single-species studies or inherent differences among species in their sensitivity to early conditions and/or ability to mitigate negative impacts. We used a common experimental protocol to assess and compare the role of parental care in mitigating effects of poor early conditions on offspring among 4 sympatric bird species in the wild. We experimentally induced low incubation temperatures and examined effects on embryonic developmental rates, hatching success, nestling growth rates, and parental responses. We examined the generality of these effects across 4 species that differ in their phylogenetic history, breeding ecology, and life histories. We found that cooling led to delayed hatching in all species, but carry-over effects on offspring differed among species. Parents of some but not all species increased their offspring provisioning rates in response to experimental cooling with critical benefits for offspring growth rates. Our study shows for the first time that species exhibit clear differences in the degree to which they are affected by poor early conditions. Observed differences among species demonstrate that parental care is a critical mechanism for mitigating potential negative effects on offspring and suggest that parental responses may be constrained to varying degrees by ecology and life histories.

  7. Lysophosphatidic Acid Acyltransferase β (LPAATβ) Promotes the Tumor Growth of Human Osteosarcoma

    PubMed Central

    Rastegar, Farbod; Gao, Jian-Li; Shenaq, Deana; Luo, Qing; Shi, Qiong; Kim, Stephanie H.; Jiang, Wei; Wagner, Eric R.; Huang, Enyi; Gao, Yanhong; Shen, Jikun; Yang, Ke; He, Bai-Cheng; Chen, Liang; Zuo, Guo-Wei; Luo, Jinyong; Luo, Xiaoji; Bi, Yang; Liu, Xing; Li, Mi; Hu, Ning; Wang, Linyuan; Luther, Gaurav; Luu, Hue H.; Haydon, Rex C.; He, Tong-Chuan

    2010-01-01

    Background Osteosarcoma is the most common primary malignancy of bone with poorly characterized molecular pathways important in its pathogenesis. Increasing evidence indicates that elevated lipid biosynthesis is a characteristic feature of cancer. We sought to investigate the role of lysophosphatidic acid acyltransferase β (LPAATβ, aka, AGPAT2) in regulating the proliferation and growth of human osteosarcoma cells. LPAATβ can generate phosphatidic acid, which plays a key role in lipid biosynthesis as well as in cell proliferation and survival. Although elevated expression of LPAATβ has been reported in several types of human tumors, the role of LPAATβ in osteosarcoma progression has yet to be elucidated. Methodology/Principal Findings Endogenous expression of LPAATβ in osteosarcoma cell lines is analyzed by using semi-quantitative PCR and immunohistochemical staining. Adenovirus-mediated overexpression of LPAATβ and silencing LPAATβ expression is employed to determine the effect of LPAATβ on osteosarcoma cell proliferation and migration in vitro and osteosarcoma tumor growth in vivo. We have found that expression of LPAATβ is readily detected in 8 of the 10 analyzed human osteosarcoma lines. Exogenous expression of LPAATβ promotes osteosarcoma cell proliferation and migration, while silencing LPAATβ expression inhibits these cellular characteristics. We further demonstrate that exogenous expression of LPAATβ effectively promotes tumor growth, while knockdown of LPAATβ expression inhibits tumor growth in an orthotopic xenograft model of human osteosarcoma. Conclusions/Significance Our results strongly suggest that LPAATβ expression may be associated with the aggressive phenotypes of human osteosarcoma and that LPAATβ may play an important role in regulating osteosarcoma cell proliferation and tumor growth. Thus, targeting LPAATβ may be exploited as a novel therapeutic strategy for the clinical management of osteosarcoma. This is especially

  8. Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

    PubMed

    Giudice, L C; Irwin, J C

    1999-01-01

    The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

  9. Contraction and stress-dependent growth shape the forebrain of the early chicken embryo.

    PubMed

    Garcia, Kara E; Okamoto, Ruth J; Bayly, Philip V; Taber, Larry A

    2017-01-01

    During early vertebrate development, local constrictions, or sulci, form to divide the forebrain into the diencephalon, telencephalon, and optic vesicles. These partitions are maintained and exaggerated as the brain tube inflates, grows, and bends. Combining quantitative experiments on chick embryos with computational modeling, we investigated the biophysical mechanisms that drive these changes in brain shape. Chemical perturbations of contractility indicated that actomyosin contraction plays a major role in the creation of initial constrictions (Hamburger-Hamilton stages HH11-12), and fluorescent staining revealed that F-actin is circumferentially aligned at all constrictions. A finite element model based on these findings shows that the observed shape changes are consistent with circumferential contraction in these regions. To explain why sulci continue to deepen as the forebrain expands (HH12-20), we speculate that growth depends on wall stress. This idea was examined by including stress-dependent growth in a model with cerebrospinal fluid pressure and bending (cephalic flexure). The results given by the model agree with observed morphological changes that occur in the brain tube under normal and reduced eCSF pressure, quantitative measurements of relative sulcal depth versus time, and previously published patterns of cell proliferation. Taken together, our results support a biphasic mechanism for forebrain morphogenesis consisting of differential contractility (early) and stress-dependent growth (late). Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Primary cortical folding in the human newborn: an early marker of later functional development.

    PubMed

    Dubois, J; Benders, M; Borradori-Tolsa, C; Cachia, A; Lazeyras, F; Ha-Vinh Leuchter, R; Sizonenko, S V; Warfield, S K; Mangin, J F; Hüppi, P S

    2008-08-01

    In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).

  11. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

    PubMed Central

    Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

    2016-01-01

    Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

  12. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

    PubMed

    Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

    2017-10-26

    To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

  13. Implications of pleiotrophin in human PC3 prostate cancer cell growth in vivo.

    PubMed

    Tsirmoula, Sotiria; Dimas, Kostas; Hatziapostolou, Maria; Lamprou, Margarita; Ravazoula, Panagiota; Papadimitriou, Evangelia

    2012-10-01

    Pleiotrophin (PTN) is a heparin-binding growth factor with diverse functions related to tumor growth, angiogenesis, and metastasis. Pleiotrophin seems to have a significant role in prostate cancer cell growth and to mediate the stimulatory actions of other factors that affect prostate cancer cell functions. However, all studies carried out up to date are in vitro, using different types of human prostate cancer cell lines. The aim of the present work was to study the role of endogenous PTN in human prostate cancer growth in vivo. For this purpose, human prostate cancer PC3 cells were stably transfected with a plasmid vector, bearing the antisense PTN sequence, in order to inhibit PTN expression (AS-PC3). Migration, apoptosis, and adhesion on osteoblastic cells were measured in vitro. In vivo, PC3 cells were s.c. injected into male NOD/SCID mice, and tumor growth, survival rates, angiogenesis, apoptosis, and the number of metastasis were estimated. Pleiotrophin depletion resulted in a decreased migration capability of AS-PC3 cells compared with the corresponding mock-transfected or the non-transfected PC3 cells, as well as increased apoptosis and decreased adhesiveness to osteoblastic cells in vitro. In prostate cancer NOD/SCID mouse xenografts, PTN depletion significantly suppressed tumor growth and angiogenesis and induced apoptosis of cancer cells. In addition, PTN depletion decreased the number of metastases, providing a survival benefit for the animals bearing AS-PC3 xenografts. Our data suggest that PTN is implicated in human prostate cancer growth in vivo and could be considered a potential target for the development of new therapeutic approaches for prostate cancer. © 2012 Japanese Cancer Association.

  14. Establishment of human hair follicle mesenchymal stem cells with overexpressed human hepatocyte growth factor.

    PubMed

    Zhou, Dan; Cheng, Hongjing; Liu, Jinyu; Zhang, Lei

    2017-06-01

    Chronic liver disease has become a major health problem that causes serious damage to human health. Since the existing treatment effect was not ideal, we need to seek new treatment methods. We utilized the gene recombination technology to obtain the human hair mesenchymal stem cells which overexpression of human hepatocyte growth factor (hHGF). Furthermore, we verified the property of transfected cells through detecting surface marker by flow cytometry. We show here establishment of the hHGF-overexpressing lentivirus vector, and successfully transfection to human hair follicle mesenchymal stem cells. The verified experiments could demonstrate the human hair follicle mesenchymal stem cells which have been transfected still have the properties of stem cells. We successfully constructed human hair follicle mesenchymal stem cells which overexpression hHGF, and maintain the same properties compared with pro-transfected cells.

  15. Early human symbolic behavior in the Late Pleistocene of Wallacea

    PubMed Central

    Brumm, Adam; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D.; Aubert, Maxime; Zhao, Jian-xin; Huntley, Jillian; Li, Bo; Roberts, Richard G.; Saptomo, E. Wahyu; Perston, Yinika; Grün, Rainer

    2017-01-01

    Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000–22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene “symbolic” artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia. PMID:28373568

  16. Early human symbolic behavior in the Late Pleistocene of Wallacea.

    PubMed

    Brumm, Adam; Langley, Michelle C; Moore, Mark W; Hakim, Budianto; Ramli, Muhammad; Sumantri, Iwan; Burhan, Basran; Saiful, Andi Muhammad; Siagian, Linda; Suryatman; Sardi, Ratno; Jusdi, Andi; Abdullah; Mubarak, Andi Pampang; Hasliana; Hasrianti; Oktaviana, Adhi Agus; Adhityatama, Shinatria; van den Bergh, Gerrit D; Aubert, Maxime; Zhao, Jian-Xin; Huntley, Jillian; Li, Bo; Roberts, Richard G; Saptomo, E Wahyu; Perston, Yinika; Grün, Rainer

    2017-04-18

    Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000-22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene "symbolic" artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia.

  17. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    PubMed Central

    Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

    2011-01-01

    Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

  18. The Early Effects of Rapid Androgen Deprivation on Human Prostate Cancer.

    PubMed

    Shaw, Greg L; Whitaker, Hayley; Corcoran, Marie; Dunning, Mark J; Luxton, Hayley; Kay, Jonathan; Massie, Charlie E; Miller, Jodi L; Lamb, Alastair D; Ross-Adams, Helen; Russell, Roslin; Nelson, Adam W; Eldridge, Matthew D; Lynch, Andrew G; Ramos-Montoya, Antonio; Mills, Ian G; Taylor, Angela E; Arlt, Wiebke; Shah, Nimish; Warren, Anne Y; Neal, David E

    2016-08-01

    The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate the human transcriptome is of paramount importance. The early effects of castration on human PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour with matched, controlled, untreated PCa tissue. All patients had levels of serum androgen, with reduced levels of intraprostatic androgen at prostatectomy. We observed differential expression of known androgen-regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5). We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of α-methylacyl-CoA racemase expression and three other genes (FAM129A, RAB27A, and KIAA0101) was confirmed. Upregulation of oestrogen receptor 1 (ESR1) expression was observed in malignant epithelia and was associated with differential expression of ESR1-regulated genes and correlated with proliferation (Ki-67 expression). This first-in-man study defines the rapid gene expression changes taking place in prostate cancer (PCa) following castration. Expression levels of the genes that the androgen receptor regulates are predictive of treatment outcome. Upregulation of oestrogen receptor 1 is a mechanism by which PCa cells may survive despite castration. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  19. Early kit mortality and growth in farmed mink are affected by litter size rather than nest climate.

    PubMed

    Schou, T M; Malmkvist, J

    2017-09-01

    We investigated the effects of nest box climate on early mink kit mortality and growth. We hypothesised that litters in warm nest boxes experience less hypothermia-induced mortality and higher growth rates during the 1st week of life. This study included data from 749, 1-year-old breeding dams with access to nesting materials. Kits were weighed on days 1 and 7, dead kits were collected daily from birth until day 7 after birth, and nest climate was measured continuously from days 1 to 6. We tested the influences of the following daily temperature (T) and humidity (H) parameters on the number of live-born kit deaths and kit growth: T mean, T min, T max, T var (fluctuation) and H mean. The nest microclimate experienced by the kits was buffered against the ambient climate, with higher temperatures and reduced climate fluctuation. Most (77.0%) live-born kit deaths in the 1st week occurred on days 0 and 1. Seven of 15 climate parameters on days 1 to 3 had significant effects on live-born kit mortality. However, conflicting effects among days, marginal effects and late effects indicated that climate was not the primary cause of kit mortality. Five of 30 climate parameters had significant effects on kit growth. Few and conflicting effects indicated that the climate effect on growth was negligible. One exception was that large nest temperature fluctuations on day 1 were associated with reduced deaths of live-born kit (P<0.001) and increased kit growth (P=0.003). Litter size affected kit vitality; larger total litter size at birth was associated with greater risks of kit death (P<0.001) and reduced growth (P<0.001). The number of living kits in litters had the opposite effect, as kits in large liveborn litters had a reduced risk of death (P<0.001) and those with large mean litter size on days 1 to 7 had increased growth (P=0.026). Nest box temperature had little effect on early kit survival and growth, which could be due to dams' additional maternal behaviour. Therefore, we

  20. Ecosystem variability and early human habitats in eastern Africa.

    PubMed

    Magill, Clayton R; Ashley, Gail M; Freeman, Katherine H

    2013-01-22

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma--the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ(13)C values) of lipid biomarkers from ancient plants. Within this framework, δ(13)C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C(4) grasslands abruptly transitioned to closed C(3) forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth's orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution.

  1. Ecosystem variability and early human habitats in eastern Africa

    PubMed Central

    Magill, Clayton R.; Ashley, Gail M.; Freeman, Katherine H.

    2013-01-01

    The role of savannas during the course of early human evolution has been debated for nearly a century, in part because of difficulties in characterizing local ecosystems from fossil and sediment records. Here, we present high-resolution lipid biomarker and isotopic signatures for organic matter preserved in lake sediments at Olduvai Gorge during a key juncture in human evolution about 2.0 Ma—the emergence and dispersal of Homo erectus (sensu lato). Using published data for modern plants and soils, we construct a framework for ecological interpretations of stable carbon-isotope compositions (expressed as δ13C values) of lipid biomarkers from ancient plants. Within this framework, δ13C values for sedimentary leaf lipids and total organic carbon from Olduvai Gorge indicate recurrent ecosystem variations, where open C4 grasslands abruptly transitioned to closed C3 forests within several hundreds to thousands of years. Carbon-isotopic signatures correlate most strongly with Earth’s orbital geometry (precession), and tropical sea-surface temperatures are significant secondary predictors in partial regression analyses. The scale and pace of repeated ecosystem variations at Olduvai Gorge contrast with long-held views of directional or stepwise aridification and grassland expansion in eastern Africa during the early Pleistocene and provide a local perspective on environmental hypotheses of human evolution. PMID:23267092

  2. Epidermal growth factor-like growth factors prevent apoptosis of alcohol-exposed human placental cytotrophoblast cells.

    PubMed

    Wolff, Garen S; Chiang, Po Jen; Smith, Susan M; Romero, Roberto; Armant, D Randall

    2007-07-01

    Maternal alcohol abuse during pregnancy can produce an array of birth defects comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is intrauterine growth retardation, which is associated with elevated apoptosis of placental cytotrophoblast cells. Using a human first trimester cytotrophoblast cell line, we examined the relationship between exposure to ethanol and cytotrophoblast survival, as well as the ameliorating effects of epidermal growth factor (EGF)-like growth factors produced by human cytotrophoblast cells. After exposure to 0-100 mM ethanol, cell death was quantified by the TUNEL method, and expression of the nuclear proliferation marker, Ki67, was measured by immunohistochemistry. The mode of cell death was determined by assessing annexin V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol significantly reduced proliferation and increased cell death approximately 2.5-fold through the apoptotic pathway within 1-2 h of exposure to 50 mM alcohol. Exposure to 25-50 mM ethanol significantly increased transforming growth factor alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting activity required ligation of either of its cognate receptors, HER1 or HER4. These findings reveal the potential for ethanol to rapidly induce cytotrophoblast apoptosis. However, survival factor induction could provide cytotrophoblasts with an endogenous cytoprotective mechanism.

  3. Altered growth pattern, not altered growth per se, is the hallmark of early lesions preceding cancer development.

    PubMed

    Doratiotto, S; Marongiu, F; Faedda, S; Pani, P; Laconi, E

    2009-01-01

    Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.

  4. Human milk feeding supports adequate growth in infants

    USDA-ARS?s Scientific Manuscript database

    Despite current nutritional strategies, premature infants remain at high risk for extrauterine growth restriction. The use of an exclusive human milk-based diet is associated with decreased incidence of necrotizing enterocolitis (NEC), but concerns exist about infants achieving adequate growth. The ...

  5. Short-term effects of recombinant human growth hormone and feeding on gluconeogenesis in humans

    USDA-ARS?s Scientific Manuscript database

    After a short-term fast, lactating women have increased rates of glucose production but not gluconeogenesis (GNG) despite relative hypoinsulinemia. We explored the effects of non-insulin-dependent increase in glucose utilization and recombinant human growth hormone (rhGH) on glucose production, glyc...

  6. Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth.

    PubMed

    Suzuki, Kohta; Sato, Miri; Zheng, Wei; Shinohara, Ryoji; Yokomichi, Hiroshi; Yamagata, Zentaro

    2014-01-01

    Maternal smoking during pregnancy is a major cause of intrauterine growth restriction and childhood obesity, but only a few studies have examined the association of smoking cessation before and during pregnancy with fetal and childhood growth. We examined this association in a prospective cohort study in Japan. Our study included children born between 1991 and 2006 and their mothers. Using a questionnaire, maternal smoking status was recorded at pregnancy. The anthropometric data of the children were collected during a medical check-up at age 3 years. Multiple linear and logistic regression models were used for data analysis stratified by sex. In total, 2663 mothers reported their smoking status during early pregnancy, and data were collected from 2230 (83.7%) children at age 3 years. Maternal smoking during pregnancy was associated with a significant reduction in birth weight (approximately 120-150 g). Body mass index at age 3 years was significantly higher among boys born to smoking mothers than among boys born to nonsmoking mothers. Maternal smoking during pregnancy was associated with overweight at age 3 years among boys (adjusted odds ratio, 2.4; 95% CI, 1.03-5.4). However, among women who stopped smoking in early pregnancy, there was no increase in the risks of a small for gestational age birth or childhood overweight at age 3 years. Children born to mothers who stopped smoking before or during early pregnancy had appropriate fetal and childhood growth.

  7. Human Growth: Guide to a Healthier You. A Middle School Science Curriculum. Instructor's Manual.

    ERIC Educational Resources Information Center

    Huba, Jeanne C.; Crow, Tracy L.

    This instructor's manual contains information and activities related to human growth processes. The curriculum focuses on choices students can make for a healthy lifestyle and is based on the most up-to-date research about human growth and development. Students generate and test their hypotheses throughout each of five modules which include…

  8. The additive effects of minoxidil and retinol on human hair growth in vitro.

    PubMed

    Yoo, Hyeon Gyeong; Chang, In-Young; Pyo, Hyun Keol; Kang, Yong Jung; Lee, Seung Ho; Kwon, Oh Sang; Cho, Kwang Hyun; Eun, Hee Chul; Kim, Kyu Han

    2007-01-01

    Minoxidil enhances hair growth by prolonging the anagen phase and induces new hair growth in androgenetic alopecia (AGA), whereas retinol significantly improves scalp skin condition and promotes hair growth. We investigated the combined effects of minoxidil and retinol on human hair growth in vitro and on cultured human dermal papilla cells (DPCs) and epidermal keratinocytes (HaCaT). The combination of minoxidil and retinol additively promoted hair growth in hair follicle organ cultures. In addition, minoxidil plus retinol more effectively elevated phosphorylated Erk, phosphorylated Akt levels, and the Bcl-2/Bax ratio than minoxidil alone in DPCs and HaCaT. We found that the significant hair shaft elongation demonstrated after minoxidil plus retinol treatment would depend on the dual kinetics associated with the activations of Erk- and Akt-dependent pathways and the prevention of apoptosis by increasing the Bcl-2/Bax ratio.

  9. Phenotypic conversion of human mammary carcinoma cells by autocrine human growth hormone

    PubMed Central

    Mukhina, Svetlana; Mertani, Hichem C.; Guo, Ke; Lee, Kok-Onn; Gluckman, Peter D.; Lobie, Peter E.

    2004-01-01

    We report here that autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell, including expression of fibronectin and vimentin. Autocrine production of hGH resulted in reduced plakoglobin expression and relocalization of E-cadherin to the cytoplasm, leading to dissolution of cell-cell contacts and decreased cell height. These phenotypic changes were accompanied by an increase in cell motility, elevated activity of specific matrix metalloproteinases, and an acquired ability to invade a reconstituted basement membrane. Forced expression of plakoglobin significantly decreased mammary carcinoma cell migration and invasion stimulated by autocrine hGH. In vivo, autocrine hGH stimulated local invasion of mammary carcinoma cells concomitant with a prominent stromal reaction in comparison with well delineated and capsulated growth of mammary carcinoma cells lacking autocrine production of hGH. Thus, autocrine production of hGH by mammary carcinoma cells is sufficient for generation of an invasive phenotype. Therapeutic targeting of autocrine hGH may provide a mechanistic approach to prevent metastatic extension of human mammary carcinoma. PMID:15353581

  10. Attachment and growth of human keratinocytes in a serum-free environment.

    PubMed

    Gilchrest, B A; Calhoun, J K; Maciag, T

    1982-08-01

    Using a serum-free system, we have investigated the influence of human fibronectin (HFN) and selected growth factors (GF) on the attachment and growth of normal human keratinocytes in vitro. Single-cell suspensions of keratinocytes from near-confluent primary plates, plated on 5-10 microgram/cm2 HFN, showed approximately 30-40% attachment after 2-24 hours of incubation at 37 degrees C, compared with 4-6% attachment on uncoated platic plates. Percentage of attached cells was independent of seed density, tissue donor age, in vitro culture age, or medium composition, while subsequent cellular proliferation was strongly dependent on these factors. Keratinocytes grown on an adequate HFN matrix in a previously described hormone-supplemented medium (Maciag et al., 1981a) achieved four to eight population doubling over 7-12 days at densities greater than or equal to 104 cell/cm2. Removal of most GF individually from the medium had little or no effect on growth, while removal of epidermal growth factor (EGF) alone reduced growth by 30-35% and removal of bovine brain extract (BE) alone reduced growth by approximately 90%. Conversely, EGF alone in basal medium supported approximately 10% control growth, BE alone supported 30-40% control growth, and the combination of EGF and BE approximately 70%. In addition to its major effect on proliferation in this system, BE was necessary to preserve normal keratinocyte morphology and protein production. These findings expand earlier observations that HFN facilitates keratinocyte attachment in vitro and that a brain-derived extract can exert a major positive influence on cultured keratinocytes.

  11. Treatment of dwarfism with recombinant human insulin-like growth factor-1.

    PubMed

    Ranke, Michael B; Wölfle, Joachim; Schnabel, Dirk; Bettendorf, Markus

    2009-10-01

    The growth hormone-IGF (insulin-like growth factor) system plays a central role in hormonal growth regulation. Recombinant human (rh) growth hormone (GH) has been available since the late 1980s for replacement therapy in GH-deficient patients and for the stimulation of growth in patients with short stature of various causes. Growth promotion by GH occurs in part indirectly through the induction of IGF-1 synthesis. In primary disturbances of IGF-1 production, short stature can only be treated with recombinant human IGF-1 (rhIGF-1). rhIGF-1 was recently approved for this indication but can also be used to treat other conditions. Selective review of the literature on IGF-1 therapy, based on a PubMed search. In children with severe primary IGF-1 deficiency (a rare condition whose prevalence is less than 1:10,000), the prognosis for final height is very poor (ca. 130 cm), and IGF-1 therapy is the appropriate form of pathophysiologically based treatment. There is no alternative treatment at present. The subcutaneous administration of IGF-1 twice daily in doses of 80 to 120 microg/kg accelerates growth and increases final height by 12 to 15 cm, according to current data. There is, however, a risk of hypoglycemia, as IGF-1 has an insulin-like effect. As treatment with IGF-1 is complex, this new medication should only be prescribed, for the time being, by experienced pediatric endocrinologists and diabetologists.

  12. Early maternal depressive symptoms and child growth trajectories: a longitudinal analysis of a nationally representative US birth cohort

    PubMed Central

    2014-01-01

    Background Maternal depressive symptoms are negatively associated with early child growth in developing countries; however, few studies have examined this relation in developed countries or used a longitudinal design with data past the second year of the child’s life. We investigated if and when early maternal depressive symptoms affect average growth in young children up to age 6 in a nationally representative sample of US children. Methods Using data from 6,550 singleton births from the Early Childhood Longitudinal Study -- Birth Cohort (ECLS-B), we fit growth trajectory models with random effects to examine the relation between maternal depressive symptoms at 9 months based on the twelve-item version of the Center for Epidemiologic Studies Depression Scale (CES-D) and child height and body mass index (BMI) to age 6 years. Results Mothers with moderate/severe depressive symptoms at 9 months postpartum had children with shorter stature at this same point in time [average 0.26 cm shorter; 95% CI: 5 cm, 48 cm] than mothers without depressive symptoms; children whose mothers reported postpartum depressive symptoms remained significantly shorter throughout the child’s first 6 years. Conclusions Results suggest that the first year postpartum is a critical window for addressing maternal depressive symptoms in order to optimize child growth. Future studies should investigate the role of caregiving and feeding practices as potential mechanisms linking maternal depressive symptoms and child growth trajectories. PMID:25047367

  13. Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells.

    PubMed

    Vander Griend, Donald J; D'Antonio, Jason; Gurel, Bora; Antony, Lizamma; Demarzo, Angelo M; Isaacs, John T

    2010-01-01

    The lethality of prostate cancer is due to the continuous growth of cancer initiating cells (CICs) which are often stimulated by androgen receptor (AR) signaling. However, the underlying molecular mechanism(s) for such AR-mediated growth stimulation are not fully understood. Such mechanisms may involve cancer cell-dependent induction of tumor stromal cells to produce paracrine growth factors or could involve cancer cell autonomous autocrine and/or intracellular AR signaling pathways. We utilized clinical samples, animal models and a series of AR-positive human prostate cancer cell lines to evaluate AR-mediated growth stimulation of prostate CICs. The present studies document that stromal AR expression is not required for prostate cancer growth, since tumor stroma surrounding AR-positive human prostate cancer metastases (N = 127) are characteristically AR-negative. This lack of a requirement for AR expression in tumor stromal cells is also documented by the fact that human AR-positive prostate cancer cells grow equally well when xenografted in wild-type versus AR-null nude mice. AR-dependent growth stimulation was documented to involve secretion, extracellular binding, and signaling by autocrine growth factors. Orthotopic xenograft animal studies documented that the cellautonomous autocrine growth factors which stimulate prostate CIC growth are not the andromedins secreted by normal prostate stromal cells. Such cell autonomous and extracellular autocrine signaling is necessary but not sufficient for the optimal growth of prostate CICs based upon the response to anti-androgen plus/or minus preconditioned media. AR-induced growth stimulation of human prostate CICs requires AR-dependent intracellular pathways. The identification of such AR-dependent intracellular pathways offers new leads for the development of effective therapies for prostate cancer. (c) 2009 Wiley-Liss, Inc.

  14. Cadmium contamination of early human milk.

    PubMed

    Sikorski, R; Paszkowski, T; Radomański, T; Szkoda, J

    1989-01-01

    The concentration of cadmium was measured by flame atomic absorption spectrometry in colostrum samples obtained from 110 women on the 4th postpartum day. Detectable amounts of cadmium were found in 95% of the examined samples and the geometric mean of the determined values was 0.002 mg/kg. In 3 cases (2.7%, the examined neonates received via mother's milk an amount of cadmium exceeding the maximum daily intake level for this metal. Maternal age, parity and place of residence did not affect the determined cadmium levels of milk. Cadmium content in the early human milk of current smokers did not differ significantly from that of nonsmoking mothers.

  15. Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study

    PubMed Central

    Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

    2015-01-01

    Objective To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Study design Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Results Mean length-for-age z score was −0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m2; 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (−41.5 g per twofold increase in ferritin; 95% CI −78 to −5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of −0.06 per 20 nmol/L; 95% CI −0.11 to −0.01) was observed. Conclusions Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. PMID:25246090

  16. SKI knockdown inhibits human melanoma tumor growth in vivo.

    PubMed

    Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

    2009-12-01

    The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors.

  17. Preventing growth in amphetamine use: long-term effects of the Midwestern Prevention Project (MPP) from early adolescence to early adulthood.

    PubMed

    Riggs, Nathaniel R; Chou, Chih-Ping; Pentz, Mary Ann

    2009-10-01

    The aim of the current study was to examine the long-term effect of an early adolescent substance abuse prevention program on trajectories and initiation of amphetamine use into early adulthood. Eight middle schools were assigned randomly to a program or control condition. The randomized controlled trial followed participants through 15 waves of data, from ages 11-28 years. This longitudinal study design includes four separate periods of development from early adolescence to early adulthood. The intervention took place in middle schools. A total of 1002 adolescents from one large mid-western US city were the participants in the study. The intervention was a multi-component community-based program delivered in early adolescence with a primary emphasis on tobacco, alcohol and marijuana use. At each wave of data collection participants completed a self-report survey that included questions about life-time amphetamine use. Compared to a control group, participants in the Midwestern Prevention Project (MPP) intervention condition had reduced growth (slope) in amphetamine use in emerging adulthood, a lower amphetamine use intercept at the commencement of the early adulthood and delayed amphetamine use initiation. The pattern of results suggests that the program worked first to prevent amphetamine use, and then to maintain the preventive effect into adulthood. Study findings suggest that early adolescent substance use prevention programs that focus initially on the 'gateway' drugs have utility for long-term prevention of amphetamine use. © 2009 The Authors. Journal compilation © 2009 Society for the Study of Addiction.

  18. Computational modeling of hypertensive growth in the human carotid artery

    NASA Astrophysics Data System (ADS)

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-06-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.

  19. Insulin-like growth factor-I and growth differentiation factor-5 promote the formation of tissue-engineered human nasal septal cartilage.

    PubMed

    Alexander, Thomas H; Sage, August B; Chen, Albert C; Schumacher, Barbara L; Shelton, Elliot; Masuda, Koichi; Sah, Robert L; Watson, Deborah

    2010-10-01

    Tissue engineering of human nasal septal chondrocytes offers the potential to create large quantities of autologous material for use in reconstructive surgery of the head and neck. Culture with recombinant human growth factors may improve the biochemical and biomechanical properties of engineered tissue. The objectives of this study were to (1) perform a high-throughput screen to assess multiple combinations of growth factors and (2) perform more detailed testing of candidates identified in part I. In part I, human nasal septal chondrocytes from three donors were expanded in monolayer with pooled human serum (HS). Cells were then embedded in alginate beads for 2 weeks of culture in medium supplemented with 2% or 10% HS and 1 of 90 different growth factor combinations. Combinations of insulin-like growth factor-I (IGF-1), bone morphogenetic protein (BMP)-2, BMP-7, BMP-13, growth differentiation factor-5 (GDF-5), transforming growth factor β (TGFβ)-2, insulin, and dexamethasone were evaluated. Glycosaminoglycan (GAG) accumulation was measured. A combination of IGF-1 and GDF-5 was selected for further testing based on the results of part I. Chondrocytes from four donors underwent expansion followed by three-dimensional alginate culture for 2 weeks in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5. Chondrocytes and their associated matrix were then recovered and cultured for 4 weeks in 12 mm transwells in medium supplemented with 2% or 10% HS with or without IGF-1 and GDF-5 (the same medium used for alginate culture). Biochemical and biomechanical properties of the neocartilage were measured. In part I, GAG accumulation was highest for growth factor combinations including both IGF-1 and GDF-5. In part II, the addition of IGF-1 and GDF-5 to 2% HS resulted in a 12-fold increase in construct thickness compared with 2% HS alone (p < 0.0001). GAG and type II collagen accumulation was significantly higher with IGF-1 and GDF-5. Confined compression

  20. Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

    PubMed

    Delisle, Richard G

    2012-06-01

    The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Contrasting shrub species respond to early summer temperatures leading to correspondence of shrub growth patterns

    NASA Astrophysics Data System (ADS)

    Weijers, Stef; Pape, Roland; Löffler, Jörg; Myers-Smith, Isla H.

    2018-03-01

    The Arctic-alpine biome is warming rapidly, resulting in a gradual replacement of low statured species by taller woody species in many tundra ecosystems. In northwest North America, the remotely sensed normalized difference vegetation index (NDVI), suggests an increase in productivity of the Arctic and alpine tundra and a decrease in productivity of boreal forests. However, the responses of contrasting shrub species growing at the same sites to climate drivers remain largely unexplored. Here, we test growth, climate, and NDVI relationships of two contrasting species: the expanding tall deciduous shrub Salix pulchra and the circumarctic evergreen dwarf shrub Cassiope tetragona from an alpine tundra site in the Pika valley in the Kluane Region, southwest Yukon Territories, Canada. We found that annual growth variability of both species at this site is strongly driven by early summer temperatures, despite their contrasting traits and habitats. Shrub growth chronologies for both species were correlated with the regional climate signal and showed spatial correspondence with interannual variation in NDVI in surrounding alpine and Arctic regions. Our results suggest that early summer warming represents a common driver of vegetation change for contrasting shrub species growing in different habitats in the same alpine environments.

  2. Placenta growth factor not vascular endothelial growth factor A or C can predict the early recurrence after radical resection of hepatocellular carcinoma.

    PubMed

    Ho, Ming-Chih; Chen, Chiung-Nien; Lee, Hsinyu; Hsieh, Fon-Jou; Shun, Chia-Tung; Chang, Chi-Lun; Lai, Yeun-Tyng; Lee, Po-Huang

    2007-06-08

    The purpose of this study was to evaluate the relationship between the expression of PlGF in tumor tissue and clinical outcomes in HCC patients. Tumor PlGF and vascular endothelial growth factor (VEGF)-A and VEGF-C mRNA were analyzed. Results demonstrated that patients with PlGF expression levels higher than median tended to have early recurrence compared to patients with PlGF expression lower than median (P=.031). In patients with AJCC stage II-III disease, this difference was even more significant (P=.002). In contrast, VEGF-A and VEGF-C could not predict early recurrence-free survival. Since PlGF expression correlated with early recurrence of HCC, PlGF may be an important prognostic indicator in HCC.

  3. Is preterm birth a human-specific syndrome?

    PubMed Central

    Phillips, Julie Baker; Abbot, Patrick; Rokas, Antonis

    2015-01-01

    Human preterm birth (PTB), a multifactorial syndrome affecting offspring born before 37 completed weeks of gestation, is the leading cause of newborn death worldwide. Remarkably, the degree to which early parturition contributes to mortality in other placental mammals remains unclear. To gain insights on whether PTB is a human-specific syndrome, we examined within- and between-species variation in gestation length across placental mammals and the impact of early parturition on offspring fitness. Within species, gestation length is normally distributed, and all species appear to occasionally give birth before the ‘optimal’ time. Furthermore, human gestation length, like that of many mammalian species, scales proportionally to body mass, suggesting that this trait, like many others, is constrained by body size. Premature humans suffer from numerous cognitive impairments, but little is known of cognitive impairments in other placental mammals. Human gestation differs in the timing of the ‘brain growth spurt’, where unlike many mammals, including closely related primates, the trajectory of human brain growth directly overlaps with the parturition time window. Thus, although all mammals experience early parturition, the fitness costs imposed by the cognitive impairments may be unique to our species. Describing PTB broadly in mammals opens avenues for comparative studies on the physiological and genetic regulators of birth timing as well as the development of new mammalian models of the disease. PMID:26077822

  4. The growth of human fibroblasts and A431 epidermoid carcinoma cells on gamma-irradiated human amnion collagen substrata.

    PubMed

    Liu, B; Harrell, R; Lamb, D J; Dresden, M H; Spira, M

    1989-10-15

    Human fibroblasts and A431 human epidermoid carcinoma cells were cultured on gamma-irradiated human amnion collagen as well as on plastic dishes and non-irradiated collagen coated dishes. The morphology, attachment, growth and short-term cytotoxicity of these culture conditions have been determined. Both irradiated and non-irradiated amnion collagen enhanced the attachment and proliferation of fibroblasts as compared to the plastic dishes. No differences in these properties were observed for A431 cells cultured on irradiated collagen when compared with culture on non-irradiated collagen substrates. Cytotoxicity assays showed that irradiated and non-irradiated collagens were not cytotoxic for either fibroblasts or A431 cells. The results demonstrated that amnion collagen irradiated at doses of 0.25-2.0 Mrads is optimal for cell growth.

  5. Heparin-binding growth factor isolated from human prostatic extracts.

    PubMed

    Mydlo, J H; Bulbul, M A; Richon, V M; Heston, W D; Fair, W R

    1988-01-01

    Prostatic tissue extracts from patients with benign prostatic hyperplasia (BPH) and prostatic carcinoma were fractionated using heparin-Sepharose chromatography. The mitogenic activity of eluted fractions on quiescent subconfluent Swiss Albino 3T3 fibroblasts was tested employing a tritiated-thymidine-incorporation assay. Two peaks of activity were consistently noted--one in the void volume and a second fraction which eluted with 1.3-1.6 M NaCl and contained the majority of the mitogenic activity. Both non-heparin- and heparin-binding fractions increased tritiated incorporation into a mouse osteoblast cell line (MC3T3), while only the heparin-binding fractions stimulated a human umbilical vein endothelial cell line (HUV). No increased uptake of thymidine was seen using a human prostatic carcinoma cell line (PC-3). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of lyophilized active fractions showed a persistent band at 17,500 daltons. The purified protein demonstrated angiogenic properties using the chick embryo chorioallantoic membrane (CAM) assay. Western blot analysis using antibodies specific to basic fibroblast growth factor (bFGF) or acidic FGF (aFGF) demonstrated that the former, but not the latter, bound to prostatic growth factor (PrGF), and inhibited its mitogenic activity as well. It appears that PrGF shares homology with basic fibroblast growth factors.

  6. Effects of clustered transmission on epidemic growth Comment on "Mathematical models to characterize early epidemic growth: A review" by Gerardo Chowell et al.

    NASA Astrophysics Data System (ADS)

    Merler, Stefano

    2016-09-01

    Characterizing the early growth profile of an epidemic outbreak is key for predicting the likely trajectory of the number of cases and for designing adequate control measures. Epidemic profiles characterized by exponential growth have been widely observed in the past and a grounding theoretical framework for the analysis of infectious disease dynamics was provided by the pioneering work of Kermack and McKendrick [1]. In particular, exponential growth stems from the assumption that pathogens spread in homogeneous mixing populations; that is, individuals of the population mix uniformly and randomly with each other. However, this assumption was readily recognized as highly questionable [2], and sub-exponential profiles of epidemic growth have been observed in a number of epidemic outbreaks, including HIV/AIDS, foot-and-mouth disease, measles and, more recently, Ebola [3,4].

  7. Early Modern Humans and Morphological Variation in Southeast Asia: Fossil Evidence from Tam Pa Ling, Laos

    PubMed Central

    Demeter, Fabrice; Shackelford, Laura; Westaway, Kira; Duringer, Philippe; Bacon, Anne-Marie; Ponche, Jean-Luc; Wu, Xiujie; Sayavongkhamdy, Thongsa; Zhao, Jian-Xin; Barnes, Lani; Boyon, Marc; Sichanthongtip, Phonephanh; Sénégas, Frank; Karpoff, Anne-Marie; Patole-Edoumba, Elise; Coppens, Yves; Braga, José

    2015-01-01

    Little is known about the timing of modern human emergence and occupation in Eastern Eurasia. However a rapid migration out of Africa into Southeast Asia by at least 60 ka is supported by archaeological, paleogenetic and paleoanthropological data. Recent discoveries in Laos, a modern human cranium (TPL1) from Tam Pa Ling‘s cave, provided the first evidence for the presence of early modern humans in mainland Southeast Asia by 63-46 ka. In the current study, a complete human mandible representing a second individual, TPL 2, is described using discrete traits and geometric morphometrics with an emphasis on determining its population affinity. The TPL2 mandible has a chin and other discrete traits consistent with early modern humans, but it retains a robust lateral corpus and internal corporal morphology typical of archaic humans across the Old World. The mosaic morphology of TPL2 and the fully modern human morphology of TPL1 suggest that a large range of morphological variation was present in early modern human populations residing in the eastern Eurasia by MIS 3. PMID:25849125

  8. Maize early endosperm growth and development: from fertilization through cell type differentiation.

    PubMed

    Leroux, Brian M; Goodyke, Austin J; Schumacher, Katelyn I; Abbott, Chelsi P; Clore, Amy M; Yadegari, Ramin; Larkins, Brian A; Dannenhoffer, Joanne M

    2014-08-01

    • Given the worldwide economic importance of maize endosperm, it is surprising that its development is not the most comprehensively studied of the cereals. We present detailed morphometric and cytological descriptions of endosperm development in the maize inbred line B73, for which the genome has been sequenced, and compare its growth with four diverse Nested Association Mapping (NAM) founder lines.• The first 12 d of B73 endosperm development were described using semithin sections of plastic-embedded kernels and confocal microscopy. Longitudinal sections were used to compare endosperm length, thickness, and area.• Morphometric comparison between Arizona- and Michigan-grown B73 showed a common pattern. Early endosperm development was divided into four stages: coenocytic, cellularization through alveolation, cellularization through partitioning, and differentiation. We observed tightly synchronous nuclear divisions in the coenocyte, elucidated that the onset of cellularization was coincident with endosperm size, and identified a previously undefined cell type (basal intermediate zone, BIZ). NAM founders with small mature kernels had larger endosperms (0-6 d after pollination) than lines with large mature kernels.• Our B73-specific model of early endosperm growth links developmental events to relative endosperm size, while accounting for diverse growing conditions. Maize endosperm cellularizes through alveolation, then random partitioning of the central vacuole. This unique cellularization feature of maize contrasts with the smaller endosperms of Arabidopsis, barley, and rice that strictly cellularize through repeated alveolation. NAM analysis revealed differences in endosperm size during early development, which potentially relates to differences in timing of cellularization across diverse lines of maize. © 2014 Botanical Society of America, Inc.

  9. Growth, Development, and Behavior in Early Childhood Following Prenatal Cocaine Exposure

    PubMed Central

    Frank, Deborah A.; Augustyn, Marilyn; Knight, Wanda Grant; Pell, Tripler; Zuckerman, Barry

    2008-01-01

    Context Despite recent studies that failed to show catastrophic effects of prenatal cocaine exposure, popular attitudes and public policies still reflect the belief that cocaine is a uniquely dangerous teratogen. Objective To critically review outcomes in early childhood after prenatal cocaine exposure in 5 domains: physical growth; cognition; language skills; motor skills; and behavior, attention, affect, and neurophysiology. Data Sources Search of MEDLINE and Psychological Abstracts from 1984 to October 2000. Study Selection Studies selected for detailed review (1) were published in a peerreviewed English-language journal; (2) included a comparison group; (3) recruited samples prospectively in the perinatal period; (4) used masked assessment; and (5) did not include a substantial proportion of subjects exposed in utero to opiates, amphetamines, phencyclidine, or maternal human immunodeficiency virus infection. Data Extraction Thirty-six of 74 articles met criteria and were reviewed by 3 authors. Disagreements were resolved by consensus. Data Synthesis After controlling for confounders, there was no consistent negative association between prenatal cocaine exposure and physical growth, developmental test scores, or receptive or expressive language. Less optimal motor scores have been found up to age 7 months but not thereafter, and may reflect heavy tobacco exposure. No independent cocaine effects have been shown on standardized parent and teacher reports of child behavior scored by accepted criteria. Experimental paradigms and novel statistical manipulations of standard instruments suggest an association between prenatal cocaine exposure and decreased attentiveness and emotional expressivity, as well as differences on neurophysiologic and attentional/affective findings. Conclusions Among children aged 6 years or younger, there is no convincing evidence that prenatal cocaine exposure is associated with developmental toxic effects that are different in severity

  10. Placental 11 β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) expression very early during human pregnancy.

    PubMed

    Salvante, K G; Milano, K; Kliman, H J; Nepomnaschy, P A

    2017-04-01

    Maternal physiologic stress during gestation has been reported to be associated with negative developmental outcomes, including intra-uterine growth restriction and reduced birth weight, which can impact postnatal development, behavior and health. The human fetus is partially protected from elevated cortisol exposure by placental 11 β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which oxidizes bioactive cortisol into bio-inactive cortisone. Importantly, despite the critical protective role hypothesized for 11β-HSD2, the onset of its placental expression has yet to be clearly established. To this aim, we present immunocytochemical analysis of placentas collected 3-6 weeks post-conception. 11β-HSD2 was present as early as 3 weeks post-conception in syncytiotrophoblasts, where most maternal-fetal exchange occurs, and in columnar epithelial cells encircling uterine endometrial glands, which provide early histiopathic nutrition to the embryo. 11β-HSD2 expression in these critical maternal-fetal exchange areas is consistent with its hypothesized protective role. Future studies should investigate the mechanisms that may modulate embryonic glucocorticoid exposure earlier, immediately post-conception.

  11. Late Pleistocene climate drivers of early human migration.

    PubMed

    Timmermann, Axel; Friedrich, Tobias

    2016-10-06

    On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50-120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect.

  12. Late Pleistocene climate drivers of early human migration

    NASA Astrophysics Data System (ADS)

    Timmermann, Axel; Friedrich, Tobias

    2016-10-01

    On the basis of fossil and archaeological data it has been hypothesized that the exodus of Homo sapiens out of Africa and into Eurasia between ~50-120 thousand years ago occurred in several orbitally paced migration episodes. Crossing vegetated pluvial corridors from northeastern Africa into the Arabian Peninsula and the Levant and expanding further into Eurasia, Australia and the Americas, early H. sapiens experienced massive time-varying climate and sea level conditions on a variety of timescales. Hitherto it has remained difficult to quantify the effect of glacial- and millennial-scale climate variability on early human dispersal and evolution. Here we present results from a numerical human dispersal model, which is forced by spatiotemporal estimates of climate and sea level changes over the past 125 thousand years. The model simulates the overall dispersal of H. sapiens in close agreement with archaeological and fossil data and features prominent glacial migration waves across the Arabian Peninsula and the Levant region around 106-94, 89-73, 59-47 and 45-29 thousand years ago. The findings document that orbital-scale global climate swings played a key role in shaping Late Pleistocene global population distributions, whereas millennial-scale abrupt climate changes, associated with Dansgaard-Oeschger events, had a more limited regional effect.

  13. Impact of Early Versus Late Diuretic Exposure on Metabolic Bone Disease and Growth in Premature Neonates.

    PubMed

    Orth, Lucas E; O'Mara, Keliana L

    2018-01-01

    This study aimed to determine whether there are differences in the incidence of metabolic bone disease (MBD) between preterm neonates first exposed to diuretics prior to 2 weeks of life versus those exposed after 2 weeks. This study was a retrospective analysis of premature neonates born at a tertiary care center between 2011 and 2015 who received either furosemide or chlorothiazide. The primary outcome was incidence of MBD. Secondary outcomes included growth, electrolyte disturbances, oxygen requirement, and length of stay. A total of 147 patients were included. Early initiation (n = 90) and late initiation (n = 57) arms were balanced with respect to birth weight and gestational age. There was no difference in incidence of MBD in the early group (76%) versus the late group (65%; p = 0.164). Stratification by cumulative dose showed incidence of 85% in patients receiving ≥8 mg/kg of furosemide, compared with 68% and 64% of those in the <4 mg/kg and 4 to 7.9 mg/kg strata, respectively (p = 0.06). The early group experienced greater reductions in length-for-age growth during diuretic therapy (-70% versus -40%; p = 0.009). Electrolyte abnormalities were more prevalent in the early group. Although there was no difference in duration of mechanical ventilation, duration of supplemental oxygen requirement was reduced in the late group (75 versus 89 days; p = 0.003). Timing of diuretic initiation did not affect incidence of MBD. Increased cumulative furosemide exposure may be associated with higher incidence. Patients first exposed to diuretics within 2 weeks of life are at higher risk for electrolyte abnormalities and reduced growth velocity.

  14. Being Human: A Resource Guide in Human Growth and Development for the Developmentally Disabled.

    ERIC Educational Resources Information Center

    Ogle, Peggy

    The resource guide is intended to help practitioners develop curricula in human growth and development for developmentally disabled students. A matrix guide is presented for evaluating clients in three domains (social identity, health and hygiene, and physiological identity). Behavioral indicators are then noted which relate to adaptive behaviors…

  15. The Genetic and Environmental Etiologies of Individual Differences in Early Reading Growth in Australia, the United States, and Scandinavia

    PubMed Central

    Christopher, Micaela E.; Hulslander, Jacqueline; Byrne, Brian; Samuelsson, Stefan; Keenan, Janice M.; Pennington, Bruce; DeFries, John C.; Wadsworth, Sally J.; Willcutt, Erik; Olson, Richard K.

    2013-01-01

    This first cross-country twin study of individual differences in reading growth from post-kindergarten to post-2nd grade analyzed data from 487 twin pairs from the United States, 267 pairs from Australia, and 280 pairs from Scandinavia. Data from two reading measures were fit to biometric latent growth models. Individual differences for the reading measures at post-kindergarten in the U.S. and Australia were due primarily to genetic influences, and to both genetic and shared environmental influences in Scandinavia. In contrast, individual differences in growth generally had large genetic influences in all countries. These results suggest that genetic influences are largely responsible for individual differences in early reading development. In addition, the timing of the start of formal literacy instruction may affect the etiology of individual differences in early reading development, but have only limited influence on the etiology of individual differences in growth. PMID:23665180

  16. P-cadherin regulates human hair growth and cycling via canonical Wnt signaling and transforming growth factor-β2.

    PubMed

    Samuelov, Liat; Sprecher, Eli; Tsuruta, Daisuke; Bíró, Tamás; Kloepper, Jennifer E; Paus, Ralf

    2012-10-01

    P-cadherin is a key component of epithelial adherens junctions, and it is prominently expressed in the hair follicle (HF) matrix. Loss-of-function mutations in CDH3, which encodes P-cadherin, result in hypotrichosis with juvenile macular dystrophy (HJMD), an autosomal recessive disorder featuring sparse and short hair. Here, we attempted to recapitulate some aspects of HJMD in vitro by transfecting normal, organ-cultured human scalp HFs with lipofectamine and CDH3-specific or scrambled control siRNAs. As in HJMD patients, P-cadherin silencing inhibited hair shaft growth, prematurely induced HF regression (catagen), and inhibited hair matrix keratinocyte proliferation. In situ, membrane β-catenin expression and transcription of the β-catenin target gene, axin2, were significantly reduced, whereas glycogen synthase kinase 3 β (GSK3β) and phospho-β-catenin immunoreactivity were increased. These effects were partially reversed by inhibiting GSK3β. P-cadherin silencing reduced the expression of the anagen-promoting growth factor, IGF-1, whereas that of transforming growth factor β 2 (TGFβ2; catagen promoter) was enhanced. Neutralizing TGFβ antagonized the catagen-promoting effects of P-cadherin silencing. In summary, we introduce human HFs as an attractive preclinical model for studying the functions of P-cadherin in human epithelial biology and pathology. This model demonstrates that cadherins can be successfully knocked down in an intact human organ in vitro, and shows that P-cadherin is needed for anagen maintenance by regulating canonical Wnt signaling and suppressing TGFβ2.

  17. The Use of Multinutrient Human Milk Fortifiers in Preterm Infants: A Systematic Review of Unanswered Questions.

    PubMed

    Mimouni, Francis B; Nathan, Natalie; Ziegler, Ekhard E; Lubetzky, Ronit; Mandel, Dror

    2017-03-01

    There is evidence that multinutrient fortification of human milk increases in-hospital growth of preterm infants, but fortification has not been shown to improve long-term growth and neurodevelopmental outcome. We aimed to ascertain whether randomized controlled trials have determined the effect of early versus late introduction of fortifiers on growth and/or other outcomes, and have compared the efficacy/adverse effects of human milk-based versus cow milk-based fortifiers. We conclude that there is little evidence that early introduction of human milk fortification affects important outcomes, and limited evidence that a bovine fortifier places the infant at a higher risk of NEC. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Early androgen exposure and human gender development.

    PubMed

    Hines, Melissa; Constantinescu, Mihaela; Spencer, Debra

    2015-01-01

    During early development, testosterone plays an important role in sexual differentiation of the mammalian brain and has enduring influences on behavior. Testosterone exerts these influences at times when the testes are active, as evidenced by higher concentrations of testosterone in developing male than in developing female animals. This article critically reviews the available evidence regarding influences of testosterone on human gender-related development. In humans, testosterone is elevated in males from about weeks 8 to 24 of gestation and then again during early postnatal development. Individuals exposed to atypical concentrations of testosterone or other androgenic hormones prenatally, for example, because of genetic conditions or because their mothers were prescribed hormones during pregnancy, have been consistently found to show increased male-typical juvenile play behavior, alterations in sexual orientation and gender identity (the sense of self as male or female), and increased tendencies to engage in physically aggressive behavior. Studies of other behavioral outcomes following dramatic androgen abnormality prenatally are either too small in their numbers or too inconsistent in their results, to provide similarly conclusive evidence. Studies relating normal variability in testosterone prenatally to subsequent gender-related behavior have produced largely inconsistent results or have yet to be independently replicated. For studies of prenatal exposures in typically developing individuals, testosterone has been measured in single samples of maternal blood or amniotic fluid. These techniques may not be sufficiently powerful to consistently detect influences of testosterone on behavior, particularly in the relatively small samples that have generally been studied. The postnatal surge in testosterone in male infants, sometimes called mini-puberty, may provide a more accessible opportunity for measuring early androgen exposure during typical development. This

  19. Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

    PubMed

    Hara, Y; Ogata, Y; Shirouzu, K

    2000-12-01

    We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

  20. Intrauterine growth-restricted Yucatan miniature pigs experience early catch-up growth, leading to greater adiposity and impaired lipid metabolism as young adults.

    PubMed

    Myrie, Semone B; McKnight, Leslie L; King, J Christopher; McGuire, John J; Van Vliet, Bruce N; Cheema, Sukhinder K; Bertolo, Robert F

    2017-12-01

    Early nutrition has critical influences on cardiovascular disease risk in adulthood. The study objectives were to evaluate the impact of low birth weight on fasting and postprandial lipid metabolism and endothelium function in Yucatan miniature pigs. Intrauterine growth-restricted (IUGR) piglets (n = 6; 3 days old, 0.73 ± 0.04 kg) were paired with normal-weight (NW) same-sex littermates (n = 6; 1.11 ± 0.05 kg) and fed milk replacer ad libitum for 4 weeks. Thereafter, all pigs were fed a standard diet ad libitum for 5 h/day with growth, intakes, and blood samples collected for 8 months. At 9 months old, pigs were surgically fitted with venous catheters and an oral fat tolerance test was performed. At 10 months old, pigs were killed and endothelium-dependent and -independent vasodilations of isolated coronary arteries were measured using wire-myographs. IUGR pigs demonstrated catch-up growth (P < 0.05) in body weight and abdominal circumference prior to sexual maturity (<7 months old) and had more (P < 0.05) subcutaneous fat at 10 months old compared with NW pigs. IUGR pigs had consistently higher fasting plasma triglyceride concentrations from 5 to 10 months old and higher liver triglyceride and total cholesterol concentrations at 10 months old (P < 0.05). The fat tolerance test revealed delayed postprandial triglyceride clearance in IUGR pigs, but no differences in plaque formation or vascular reactivity. To conclude, IUGR and early postnatal catch-up growth are associated with increased overall body fat deposition and altered triglyceride metabolism in adult Yucatan miniature swine.

  1. Childhood growth predicts higher bone mass and greater bone area in early old age: findings among a subgroup of women from the Helsinki Birth Cohort Study.

    PubMed

    Mikkola, T M; von Bonsdorff, M B; Osmond, C; Salonen, M K; Kajantie, E; Cooper, C; Välimäki, M J; Eriksson, J G

    2017-09-01

    We examined the associations between childhood growth and bone properties among women at early old age. Early growth in height predicted greater bone area and higher bone mineral mass. However, information on growth did not improve prediction of bone properties beyond that predicted by body size at early old age. We examined the associations between body size at birth and childhood growth with bone area, bone mineral content (BMC), and areal bone mineral density (aBMD) in early old age. A subgroup of women (n = 178, mean 60.4 years) from the Helsinki Birth Cohort Study, born 1934-1944, participated in dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and hip. Height and weight at 0, 2, 7, and 11 years, obtained from health care records, were reconstructed into conditional variables representing growth velocity independent of earlier growth. Weight was adjusted for corresponding height. Linear regression models were adjusted for multiple confounders. Birth length and growth in height before 7 years of age were positively associated with femoral neck area (p < 0.05) and growth in height at all age periods studied with spine bone area (p < 0.01). Growth in height before the age of 7 years was associated with BMC in the femoral neck (p < 0.01) and birth length and growth in height before the age of 7 years were associated with BMC in the spine (p < 0.05). After entering adult height into the models, nearly all associations disappeared. Weight gain during childhood was not associated with bone area or BMC, and aBMD was not associated with early growth. Optimal growth in height in girls is important for obtaining larger skeleton and consequently higher bone mass. However, when predicting bone mineral mass among elderly women, information on early growth does not improve prediction beyond that predicted by current height and weight.

  2. An In vitro Model for Bacterial Growth on Human Stratum Corneum.

    PubMed

    van der Krieken, Danique A; Ederveen, Thomas H A; van Hijum, Sacha A F T; Jansen, Patrick A M; Melchers, Willem J G; Scheepers, Paul T J; Schalkwijk, Joost; Zeeuwen, Patrick L J M

    2016-11-02

    The diversity and dynamics of the skin microbiome in health and disease have been studied recently, but adequate model systems to study skin microbiotas in vitro are largely lacking. We developed an in vitro system that mimics human stratum corneum, using human callus as substrate and nutrient source for bacterial growth. The growth of several commensal and pathogenic bacterial strains was measured for up to one week by counting colony-forming units or by quantitative PCR with strain-specific primers. Human skin pathogens were found to survive amidst a minimal microbiome consisting of 2 major skin commensals: Staphylococcus epidermidis and Propionibacterium acnes. In addition, complete microbiomes, taken from the backs of healthy volunteers, were inoculated and maintained using this system. This model may enable the modulation of skin microbiomes in vitro and allow testing of pathogens, biological agents and antibiotics in a medium-throughput format.

  3. Light at night activates IGF-1R/PDK1 signaling and accelerates tumor growth in human breast cancer xenografts.

    PubMed

    Wu, Jinghai; Dauchy, Robert T; Tirrell, Paul C; Wu, Steven S; Lynch, Darin T; Jitawatanarat, Potjana; Burrington, Christine M; Dauchy, Erin M; Blask, David E; Greene, Michael W

    2011-04-01

    Regulation of diurnal and circadian rhythms and cell proliferation are coupled in all mammals, including humans. However, the molecular mechanisms by which diurnal and circadian rhythms regulate cell proliferation are relatively poorly understood. In this study, we report that tumor growth in nude rats bearing human steroid receptor-negative MCF-7 breast tumors can be significantly accelerated by exposing the rats to light at night (LAN). Under normal conditions of an alternating light/dark cycle, proliferating cell nuclear antigen (PCNA) levels in tumors were maximal in the early light phase but remained at very low levels throughout the daily 24-hour cycle period monitored. Surprisingly, PCNA was expressed in tumors continually at a high level throughout the entire 24-hour period in LAN-exposed nude rats. Daily fluctuations of Akt and mitogen activated protein kinase activation in tumors were also disrupted by LAN. These fluctuations did not track with PCNA changes, but we found that activation of the Akt stimulatory kinase phosphoinositide-dependent protein kinase 1 (PDK1) directly correlated with PCNA levels. Expression of insulin-like growth factor 1 receptor (IGF-1R), an upstream signaling molecule for PDK1, also correlated with fluctuations of PDK1/PCNA in the LAN group. In addition, circulating IGF-1 concentrations were elevated in LAN-exposed tumor-bearing nude rats. Finally, RNAi-mediated knockdown of PDK1 led to a reduction in PCNA expression and cell proliferation in vitro and tumor growth in vivo, indicating that PDK1 regulates breast cancer growth in a manner correlated with PCNA expression. Taken together, our findings demonstrate that LAN exposure can accelerate tumor growth in vivo, in part through continuous activation of IGF-1R/PDK1 signaling.

  4. A Rat Model for Human Ductal Carcinoma In Situ

    DTIC Science & Technology

    2006-09-01

    complexes in early stages of mouse mammary preneoplasia. Cell Growth Differ 12:285-95. 14. Gudmundur Thordarson , Adrian V. Lee, Meghan McCarty...S.M., Thordarson , G., Collins, G., Talamantes, F., and Nandi, S. (1995) In vivo growth stimulation of collagen gel embedded normal human and mouse

  5. Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

    EPA Science Inventory

    The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

  6. Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.

    PubMed

    Song, Jian; Wang, Xiaobo; Zhu, Jiaxue; Liu, Jun

    2016-01-01

    Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known. We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models. Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin. These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

  7. Inhibition of canonical WNT signaling attenuates human leiomyoma cell growth

    PubMed Central

    Ono, Masanori; Yin, Ping; Navarro, Antonia; Moravek, Molly B.; Coon, John S.; Druschitz, Stacy A.; Gottardi, Cara J.; Bulun, Serdar E.

    2014-01-01

    Objective Dysregulation of WNT signaling plays a central role in tumor cell growth and progression. Our goal was to assess the effect of three WNT/β-catenin pathway inhibitors, Inhibitor of β-Catenin And TCF4 (ICAT), niclosamide, and XAV939 on the proliferation of primary cultures of human uterine leiomyoma cells. Design Prospective study of human leiomyoma cells obtained from myomectomy or hysterectomy. Setting University research laboratory. Patient(s) Women (n=38) aged 27–53 years undergoing surgery. Intervention(s) Adenoviral ICAT overexpression or treatment with varying concentrations of niclosamide or XAV939. Main Outcome Measure(s) Cell proliferation, cell death, WNT/β-catenin target gene expression or reporter gene regulation, β-catenin levels and cellular localization. Result(s) ICAT, niclosamide, or XAV939 inhibit WNT/β-catenin pathway activation and exert anti-proliferative effects in primary cultures of human leiomyoma cells. Conclusion(s) Three WNT/β-catenin pathway inhibitors specifically block human leiomyoma growth and proliferation, suggesting that the canonical WNT pathway may be a potential therapeutic target for the treatment of uterine leiomyoma. Our findings provide rationale for further preclinical and clinical evaluation of ICAT, niclosamide, and XAV939 as candidate anti-tumor agents for uterine leiomyoma. PMID:24534281

  8. Early-season avian deaths from West Nile virus as warnings of human infection

    USGS Publications Warehouse

    Guptill, S.C.; Julian, K.G.; Campbell, G.L.; Price, S.D.; Marfin, A.A.

    2003-01-01

    An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds.

  9. Improving Growth for Infants ≤1250 Grams Receiving an Exclusive Human Milk Diet.

    PubMed

    Huston, Robert K; Markell, Andrea M; McCulley, Elizabeth A; Gardiner, Stuart K; Sweeney, Sean L

    2018-02-16

    An exclusive human milk diet (EHM) fortified with human milk-based fortifier decreases necrotizing enterocolitis (NEC) compared to maternal milk supplemented with preterm formula and bovine fortifier (PTF). Growth has been less with EHM and also maternal milk supplemented with donor human milk and bovine fortifier (HMBF). The objective was to evaluate the effect of a standardized feeding protocol on the growth of infants ≤1250 g birth weight supported with EHM and HMBF. The effect on the incidence of NEC was also evaluated. A retrospective study of growth before and after implementation of a feeding protocol for infants who received either EHM or HMBF. Primary outcomes were weight, length, and head circumference gain velocities from birth to discharge. The incidence of NEC was also recorded. Analysis of covariance for 379 total infants showed that earlier day of life for fortification to 24 Kcal/oz was associated with increased weight gain (p = 0.0166) and length gain (p = 0.0064). Implementation of the feeding protocol was associated with increased head circumference gain (p = 0.006). EHM was associated with decreased incidence of NEC (p = 0.0302). Implementation of a standardized feeding protocol including earlier fortification of maternal milk was associated with improved growth for infants receiving human milk feedings. EHM significantly decreased NEC. Earlier fortification had no effect on NEC. © 2018 American Society for Parenteral and Enteral Nutrition.

  10. Predictors of early growth in academic achievement: the head-toes-knees-shoulders task

    PubMed Central

    McClelland, Megan M.; Cameron, Claire E.; Duncan, Robert; Bowles, Ryan P.; Acock, Alan C.; Miao, Alicia; Pratt, Megan E.

    2014-01-01

    Children's behavioral self-regulation and executive function (EF; including attentional or cognitive flexibility, working memory, and inhibitory control) are strong predictors of academic achievement. The present study examined the psychometric properties of a measure of behavioral self-regulation called the Head-Toes-Knees-Shoulders (HTKS) by assessing construct validity, including relations to EF measures, and predictive validity to academic achievement growth between prekindergarten and kindergarten. In the fall and spring of prekindergarten and kindergarten, 208 children (51% enrolled in Head Start) were assessed on the HTKS, measures of cognitive flexibility, working memory (WM), and inhibitory control, and measures of emergent literacy, mathematics, and vocabulary. For construct validity, the HTKS was significantly related to cognitive flexibility, working memory, and inhibitory control in prekindergarten and kindergarten. For predictive validity in prekindergarten, a random effects model indicated that the HTKS significantly predicted growth in mathematics, whereas a cognitive flexibility task significantly predicted growth in mathematics and vocabulary. In kindergarten, the HTKS was the only measure to significantly predict growth in all academic outcomes. An alternative conservative analytical approach, a fixed effects analysis (FEA) model, also indicated that growth in both the HTKS and measures of EF significantly predicted growth in mathematics over four time points between prekindergarten and kindergarten. Results demonstrate that the HTKS involves cognitive flexibility, working memory, and inhibitory control, and is substantively implicated in early achievement, with the strongest relations found for growth in achievement during kindergarten and associations with emergent mathematics. PMID:25071619

  11. Comparison of two models of intrauterine growth restriction for early catch-up growth and later development of glucose intolerance and obesity in rats.

    PubMed

    Shahkhalili, Yasaman; Moulin, Julie; Zbinden, Irene; Aprikian, Olivier; Macé, Katherine

    2010-01-01

    Two models of intrauterine growth restriction, maternal food restriction (FR), and dexamethasone (DEX) exposure were compared for early postnatal catch-up growth and later development of glucose intolerance and obesity in Sprague-Dawley rats. Mated dams were randomly divided into three groups at 10 days gestational age. Group FR was food restricted (50% of nongestating rats) during the last 11 days of gestation; Group DEX received DEX injections during the last week of gestation, and Group CON, the control group, had no intervention. Birth weight, catch-up growth, body weight, and food intake were measured in male offspring for 22 wk. Body composition, blood glucose, and plasma insulin in response to a glucose load were assessed at 8, 16, and 22 wk. Pups from both FR and DEX dams had similarly lower birth weights than CON (22% and 25%, P < 0.0001), but catch-up growth, which occurred during the suckling period, was much more rapid in FR than DEX offspring (6 vs. 25 days, 95% CI). Postweaning, there were no significant differences between groups in food intake, body weight, body fat, and plasma insulin, but baseline plasma glucose at 22 wk and 2-h glucose area-under-the-curve at 8 and 22 wk were greater only in FR vs. CON offspring (P < 0.05), thereby contrasting with the lack of significant differences between DEX and CON. These results suggest that prenatal food restriction is a more sensitive model than DEX exposure for studies aimed at investigating the link between low birth weight, early postnatal catch-up growth, and later development of glucose intolerance.

  12. Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells

    PubMed Central

    Veeramani, S; Yuan, T-C; Lin, F-F; Lin, M-F

    2009-01-01

    p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5α-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect the transcriptional activity of androgen receptor (AR) as observed by its inability to block DHT-induced prostate-specific antigen expression, an AR-dependent correlate of prostate cancer progression. Elevated expression of p66Shc by cDNA transfection increases the basal cell proliferation and, thus, reduces additional DHT-induced cell proliferation. Furthermore, DHT increases the translocation of p66Shc into mitochondria and its interaction with cytochrome c. Conversely, both redox-negative p66Shc mutant (W134F), which is deficient in cytochrome c interaction, and p66Shc small interfering RNA decrease DHT-induced cell proliferation. These results collectively reveal a novel role for p66Shc–ROS pathway in androgen-induced prostate cancer cell proliferation and, thus, may play a role in early prostate carcinogenesis. PMID:18504439

  13. Monitoring of human populations for early markers of cadmium toxicity: A review

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fowler, Bruce A.

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure.more » Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system

  14. Monitoring of human populations for early markers of cadmium toxicity: a review.

    PubMed

    Fowler, Bruce A

    2009-08-01

    Exposure of human populations to cadmium (Cd) from air, food and water may produce effects in organs such as the kidneys, liver, lungs, cardiovascular, immune and reproductive systems. Since Cd has been identified as a human carcinogen, biomarkers for early detection of susceptibility to cancer are of an importance to public health. The ability to document Cd exposure and uptake of this element through biological monitoring is a first step towards understanding its health effects. Interpretation and application of biological monitoring data for predicting human health outcomes require correlation with biological measures of organ system responses to the documented exposure. Essential to this understanding is the detection and linkage of early biological responses toxic effects in target cell populations. Fortunately, advances in cell biology have resulted in the development of pre-clinical biological markers (biomarkers) that demonstrate measurable and characteristic molecular changes in organ systems following chemical exposures that occur prior to the onset of overt clinical disease or development of cancer. Technical advances have rendered a number of these biomarkers practical for monitoring Cd-exposed human populations. Biomarkers will be increasingly important in relation to monitoring effects from the exposure to new Cd-based high technology materials. For example, cadmium-selenium (CdSe), nano-materials made from combinations of these elements have greatly altered cellular uptake characteristics due to particle size. These differences may greatly alter effects at the target cell level and hence risks for organ toxicities from such exposures. The value of validated biomarkers for early detection of systemic Cd-induced effects in humans cannot be underestimated due to the rapid expansion of nano-material technologies. This review will attempt to briefly summarize the applications, to date, of biomarker endpoints for assessing target organ system effects in

  15. TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.

    PubMed

    Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad

    2017-11-01

    Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.

  16. Influence of prenatal and postnatal growth on intellectual functioning in school-aged children.

    PubMed

    Pongcharoen, Tippawan; Ramakrishnan, Usha; DiGirolamo, Ann M; Winichagoon, Pattanee; Flores, Rafael; Singkhornard, Jintana; Martorell, Reynaldo

    2012-05-01

    To assess the relative influence of size at birth, infant growth, and late postnatal growth on intellectual functioning at 9 years of age. A follow-up, cross-sectional study. Three districts in Khon Kaen province, northeast Thailand. A total of 560 children, or 92% of former participants of a trial of iron and/or zinc supplementation during infancy. Prenatal (size at birth), early infancy (birth to 4 months), late infancy (4 months to 1 year), and late postnatal (1 to 9 years) growth. Multiple-stage least squares analyses were used to generate uncorrelated residuals of postnatal growth. Intellectual functioning was measured at 9 years using the Wechsler Intelligence Scale for Children and the Raven's Colored Progressive Matrices (Pearson). Analyses included adjustment for maternal, household, and school characteristics. Significant relationships were found between growth and IQ (Wechsler Intelligence Scale for children, third edition, Thai version), but only up to 1 year of age; overall, growth was not related to the Raven's Colored Progressive Matrices. The strongest and most consistent relationships were with length (birth, early infancy, and late infancy); for weight, only early infancy gain was consistently related to IQ. Head circumference at birth was not collected routinely; head circumference at 4 months (but not head circumference growth thereafter) was related to IQ. Late postnatal growth was not associated with any outcome. Physical growth in early infancy (and, to a lesser extent, physical growth in late infancy and at birth) is associated with IQ at 9 years of age. Early infancy may be a critical window for human development.

  17. Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

    PubMed

    Mulder, Gemma M; Nijboer, Willemijn N; Seelen, Marc A; Sandovici, Maria; Bos, Eelke M; Melenhorst, Wynand B W H; Trzpis, Monika; Kloosterhuis, Niels J; Visser, Lydia; Henning, Rob H; Leuvenink, Henri G D; Ploeg, Rutger J; Sunnarborg, Susan W; van Goor, Harry

    2010-06-01

    The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

  18. Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Sunagawa, Mayumi; Mangala, Lingegowda; Zhang, Ye; Kahdim, Munira; Wilson, Bobby; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

  19. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru

    PubMed Central

    Kuzminsky, Susan; Rohland, Nadin; Santos, Fabrício R.; Kaulicke, Peter; Valverde, Guido; Richards, Stephen M.; Nordenfelt, Susanne; Seidenberg, Verena; Mallick, Swapan; Cooper, Alan; Reich, David; Haak, Wolfgang

    2015-01-01

    The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960’s provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960’s. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations. PMID:26061688

  20. Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.

    PubMed

    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.

  1. Early competitive effects on growth of loblolly pine grown in co-culture with switchgrass

    Treesearch

    Kurt J. Krapfl; Scott D. Roberts; Randall J. Rosseau; Jeff A. Hatten

    2015-01-01

    This study: (1) examined competitive interactions between switchgrass and loblolly pine grown in co-culture, and (2) assessed early growth rates of loblolly pine as affected by differing switchgrass competition treatments. Co-cultures were established and monitored on two Upper Coastal Plain sites for 2 years. The Pontotoc site has a history of agricultural use with...

  2. Four queries concerning the metaphysics of early human embryogenesis.

    PubMed

    Howsepian, A A

    2008-04-01

    In this essay, I attempt to provide answers to the following four queries concerning the metaphysics of early human embryogenesis. (1) Following its first cellular fission, is it coherent to claim that one and only one of two "blastomeric" twins of a human zygote is identical with that zygote? (2) Following the fusion of two human pre-embryos, is it coherent to claim that one and only one pre-fusion pre-embryo is identical with that postfusion pre-embryo? (3) Does a live human being come into existence only when its brain comes into existence? (4) At implantation, does a pre-embryo become a mere part of its mother? I argue that either if things have quidditative properties or if criterialism is false, then queries (1) and (2) can be answered in the affirmative; that in light of recent developments in theories of human death and in light of a more "functional" theory of brains, query (3) can be answered in the negative; and that plausible mereological principles require a negative answer to query (4).

  3. Human implantation: the last barrier in assisted reproduction technologies?

    PubMed

    Edwards, Robert G

    2006-12-01

    Implantation processes are highly complex involving the actions of numerous hormones, immunoglobulins, cytokines and other factors in the endometrium. They are also essential matters for the success of assisted reproduction. The nature of early embryonic development is of equal significance. It involves ovarian follicle growth, ovulation, fertilization and preimplantation growth. These processes are affected by imbalanced chromosomal constitutions or slow developmental periods. Post-implantation death is also a significant factor in cases of placental insufficiency or recurrent abortion. Clearly, many of these matters can significantly affect birth rates. This review is concerned primarily with the oocyte, the early embryo and its chromosomal anomalies, and the nature of factors involved in implantation. These are clearly among the most important features in determining successful embryonic and fetal growth. Successive sections cover the endocrine stimulation of follicle growth in mice and humans, growth of human embryos in vitro, their apposition and attachment to the uterus, factors involved in embryo attachment to uterine epithelium and later stages of implantation, and understanding the gene control of polarities and other aspects of preimplantation embryo differentiation. New aspects of knowledge include the use of human oocyte maturation in vitro as an approach to simpler forms of IVF, and new concepts in developmental genetics.

  4. [Anti-sense miRNA-21 oligonucleotide inhibits Tb 3.1 human tongue squamous cell carcinoma growth in vitro].

    PubMed

    Tao, Ying-jie; Ren, Yu; Dong, Jia-bin; Zhang, Lun; Cheng, Jun-ping; Zhou, Xuan

    2011-02-01

    To investigate the effect of micro RNA-21 (miRNA-21) knocking on the Tb3.1 human tongue squamous cell carcinoma growth. Anti-sense miRNA-21 oligonucleotide was delivered with oligofectamine to suppress Tb 3.1 tongue cancer cell growth in vitro. Real-time polymerase chain reaction (PCR) was conducted to detect the miRNA-21 expression after transfection. Methyl thiazolyl tetrazolium (MTT) assay was used to determine Tb 3.1 cell survival rate. Apoptosis were examined by flow-cytometry. Matrigel matrix and transwell assay were used to determine Tb 3.1 cell colony formation and migration ability. Antigen KI-67 (Ki67), B cell lymphoma (Bcl-2), phosphatase and tensin homolog (PTEN), matrirx metalloproteinase 2 (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) protein expression in Tb 3.1 cell were measured by Western blotting. miRNA-21 expression was decreased in miRNA-21 antisense oligonucleotide (ASODN) group. The survival rate of Tb 3.1 cells with AS-miRNA-21 transfection was significantly suppressed (F = 27.02, P = 0.00) and early phase apoptosis (F = 26.641, P = 0.001) induced in Tb 3.1 cell. Ki67, Bcl-2, MMP-2 and MMP-9 protein were down regulated while PTEN and TIMP-1 protein expression was increased. Blocking miRNA-21 expression in Tb3.1 cell could suppress cancer cell growth in vitro and miRNA-21 can serve as a novel target candidate for human tongue cancer gene therapy.

  5. Comparative study of MSX-2, DLX-5, and DLX-7 gene expression during early human tooth development.

    PubMed

    Davideau, J L; Demri, P; Hotton, D; Gu, T T; MacDougall, M; Sharpe, P; Forest, N; Berdal, A

    1999-12-01

    Msx and Dlx family transcription factors are key elements of craniofacial development and act in specific combinations with growth factors to control the position and shape of various skeletal structures in mice. In humans, the mutations of MSX and DLX genes are associated with specific syndromes, such as tooth agenesis, craniosynostosis, and tricho-dento-osseous syndrome. To establish some relationships between those reported human syndromes, previous experimental data in mice, and the expression patterns of MSX and DLX homeogenes in the human dentition, we investigated MSX-2, DLX-5, and DLX-7 expression patterns and compared them in orofacial tissues of 7.5- to 9-wk-old human embryos by using in situ hybridization. Our data showed that MSX-2 was strongly expressed in the progenitor cells of human orofacial skeletal structures, including mandible and maxilla bones, Meckel's cartilage, and tooth germs, as shown for DLX-5. DLX-7 expression was restricted to the vestibular lamina and, later on, to the vestibular part of dental epithelium. The comparison of MSX-2, DLX-5, and DLX-7 expression patterns during the early stages of development of different human tooth types showed the existence of spatially ordered sequences of homeogene expression along the vestibular/lingual axis of dental epithelium. The expression of MSX-2 in enamel knot, as well as the coincident expression of MSX-2, DLX-5, and DLX-7 in a restricted vestibular area of dental epithelium, suggests the existence of various organizing centers involved in the control of human tooth morphogenesis.

  6. Early Complementopathy after Multiple Injuries in Humans

    PubMed Central

    Burk, Anne-Maud; Martin, Myriam; Flierl, Michael A.; Rittirsch, Daniel; Helm, Matthias; Lampl, Lorenz; Bruckner, Uwe; Stahl, Gregory L.; Blom, Anna M.; Perl, Mario; Gebhard, Florian; Huber-Lang, Markus

    2012-01-01

    After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In the present study we hypothesized that multiple trauma results in immediate activation, consumption and dysfunction of the complement cascade and that the resulting severe “complementopathy” may be associated with morbidity and mortality. Therefore a prospective multicenter study with 25 healthy volunteers and 40 polytrauma patients (mean injury severity score [ISS] = 30.3 ± 2.9) was performed. After polytrauma serum was collected as early as possible at the scene, upon admission to the emergency room and 4, 12, 24, 120 and 240 hours post trauma and analysed for the complement profile. Complement hemolytic activity (CH-50) was massively reduced within the first 24 h after injury, recovered only 5 days after trauma and discriminated between lethal and non-lethal 28-day outcome. Serum levels of the complement activation products C3a and C5a were significantly elevated throughout the entire observation period and correlated with the severity of traumatic brain injury and survival. The soluble terminal complement complex SC5b-9 and mannose-binding lectin (MBL) showed a biphasic response after trauma. Key fluid phase inhibitors of complement, such as C4b-binding protein (C4BP) and factor I, were significantly diminished early after trauma. The present data indicate an almost synchronically rapid activation and dysfunction of complement suggesting a trauma-induced “complementopathy” early after injury. These events may participate to the impairment of the innate immune response observed after severe trauma. PMID:22258234

  7. Lipoxins Regulate the Early Growth Response-1 Network and Reverse Diabetic Kidney Disease.

    PubMed

    Brennan, Eoin P; Mohan, Muthukumar; McClelland, Aaron; Tikellis, Christos; Ziemann, Mark; Kaspi, Antony; Gray, Stephen P; Pickering, Raelene; Tan, Sih Min; Ali-Shah, Syed Tasadaque; Guiry, Patrick J; El-Osta, Assam; Jandeleit-Dahm, Karin; Cooper, Mark E; Godson, Catherine; Kantharidis, Phillip

    2018-05-01

    Background The failure of spontaneous resolution underlies chronic inflammatory conditions, including microvascular complications of diabetes such as diabetic kidney disease. The identification of endogenously generated molecules that promote the physiologic resolution of inflammation suggests that these bioactions may have therapeutic potential in the context of chronic inflammation. Lipoxins (LXs) are lipid mediators that promote the resolution of inflammation. Methods We investigated the potential of LXA 4 and a synthetic LX analog (Benzo-LXA 4 ) as therapeutics in a murine model of diabetic kidney disease, ApoE -/- mice treated with streptozotocin. Results Intraperitoneal injection of LXs attenuated the development of diabetes-induced albuminuria, mesangial expansion, and collagen deposition. Notably, LXs administered 10 weeks after disease onset also attenuated established kidney disease, with evidence of preserved kidney function. Kidney transcriptome profiling defined a diabetic signature (725 genes; false discovery rate P ≤0.05). Comparison of this murine gene signature with that of human diabetic kidney disease identified shared renal proinflammatory/profibrotic signals (TNF- α , IL-1 β , NF- κ B). In diabetic mice, we identified 20 and 51 transcripts regulated by LXA 4 and Benzo-LXA 4 , respectively, and pathway analysis identified established (TGF- β 1, PDGF, TNF- α , NF- κ B) and novel (early growth response-1 [EGR-1]) networks activated in diabetes and regulated by LXs. In cultured human renal epithelial cells, treatment with LXs attenuated TNF- α -driven Egr-1 activation, and Egr-1 depletion prevented cellular responses to TGF- β 1 and TNF- α Conclusions These data demonstrate that LXs can reverse established diabetic complications and support a therapeutic paradigm to promote the resolution of inflammation. Copyright © 2018 by the American Society of Nephrology.

  8. Intravenous calcitriol therapy in an early stage prevents parathyroid gland growth

    PubMed Central

    Taniguchi, Masatomo; Tokumoto, Masanori; Tsuruya, Kazuhiko; Hirakata, Hideki; Iida, Mitsuo

    2008-01-01

    Background. Both the phenotypic alterations of parathyroid (PT) cells, e.g. down-regulation of the calcium-sensing receptor, and the increase of the PT cell number in nodular hyperplasia are the main causes of refractory secondary hyperparathyroidism. It is of great importance to prevent PT growth in an early stage. Methods. To examine a more effective method of calcitriol therapy for the prevention of PT hyperplasia, we randomized haemodialysis patients with mild hyperparathyroidism to receive either daily orally administered calcitriol (n = 33) or intravenous calcitriol (n = 27) over a 12-month study period. Calcitriol was modulated so as to keep the serum intact PTH level between 100 and 150 pg/ml. Results. Both groups showed similar reductions of the serum PTH level and similar increases in serum calcium. In both groups, there were no significant changes in the serum phosphate level. Long-term daily oral calcitriol therapy failed to prevent the increase of both maximum PT volume and total volume, as assessed by ultrasonography; however, intravenous calcitriol therapy successfully suppressed this progression. In the daily, oral group, both the bone-specific alkaline phosphatase (BAP) and the N-telopeptide cross-linked of type I collagen (NTX) significantly decreased, which was probably due to the PTH suppression. However, these bone metabolism markers remained stable in the intravenous group. The total dosage of calcitriol during the study was comparable in both groups. Conclusions. These data indicate that intravenous calcitriol therapy in an early stage of secondary hyperparathyroidism is necessary to prevent PT growth and to keep a good condition of bone metabolism. PMID:18515308

  9. The effects of HIV/AIDS on economic growth and human capitals: a panel study evidence from Asian countries.

    PubMed

    Roy, Shongkour

    2014-01-01

    Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) affects economic growths by reducing the human capitals are among the most poorly understood aspect of the AIDS epidemic. This article analyzes the effects of the prevalence of HIV and full-blown AIDS on a country's human capitals and economic growths. Using a fixed effect model for panel data 1990-2010 from the Asia, I explored the dynamic relationships among HIV/AIDS, economic growths, and human capitals within countries over time. The econometric effects concerned that HIV/AIDS plays an important role in the field of economic growths and it is measured as a change in real gross domestic product (GDP) per capita and human capitals. The modeling results for the Asian countries indicates HIV/AIDS prevalence that has a hurtful effect on GDP per capita by reducing human capitals within countries over time.

  10. Antenatal and early infant predictors of postnatal growth in rural Vietnam: a prospective cohort study.

    PubMed

    Hanieh, Sarah; Ha, Tran T; De Livera, Alysha M; Simpson, Julie A; Thuy, Tran T; Khuong, Nguyen C; Thoang, Dang D; Tran, Thach D; Tuan, Tran; Fisher, Jane; Biggs, Beverley-Ann

    2015-02-01

    To determine which antenatal and early-life factors were associated with infant postnatal growth in a resource-poor setting in Vietnam. Prospective longitudinal study following infants (n=1046) born to women who had previously participated in a cluster randomised trial of micronutrient supplementation (ANZCTR:12610000944033), Ha Nam province, Vietnam. Antenatal and early infant factors were assessed for association with the primary outcome of infant length-for-age z scores at 6 months of age using multivariable linear regression and structural equation modelling. Mean length-for-age z score was -0.58 (SD 0.94) and stunting prevalence was 6.4%. Using structural equation modelling, we highlighted the role of infant birth weight as a predictor of infant growth in the first 6 months of life and demonstrated that maternal body mass index (estimated coefficient of 45.6 g/kg/m(2); 95% CI 34.2 to 57.1), weight gain during pregnancy (21.4 g/kg; 95% CI 12.6 to 30.1) and maternal ferritin concentration at 32 weeks' gestation (-41.5 g per twofold increase in ferritin; 95% CI -78 to -5.0) were indirectly associated with infant length-for-age z scores at 6 months of age via birth weight. A direct association between 25-(OH) vitamin D concentration in late pregnancy and infant length-for-age z scores (estimated coefficient of -0.06 per 20 nmol/L; 95% CI -0.11 to -0.01) was observed. Maternal nutritional status is an important predictor of early infant growth. Elevated antenatal ferritin levels were associated with suboptimal infant growth in this setting, suggesting caution with iron supplementation in populations with low rates of iron deficiency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Visualization of early influenza A virus trafficking in human dendritic cells using STED microscopy.

    PubMed

    Baharom, Faezzah; Thomas, Oliver S; Lepzien, Rico; Mellman, Ira; Chalouni, Cécile; Smed-Sörensen, Anna

    2017-01-01

    Influenza A viruses (IAV) primarily target respiratory epithelial cells, but can also replicate in immune cells, including human dendritic cells (DCs). Super-resolution microscopy provides a novel method of visualizing viral trafficking by overcoming the resolution limit imposed by conventional light microscopy, without the laborious sample preparation of electron microscopy. Using three-color Stimulated Emission Depletion (STED) microscopy, we visualized input IAV nucleoprotein (NP), early and late endosomal compartments (EEA1 and LAMP1 respectively), and HLA-DR (DC membrane/cytosol) by immunofluorescence in human DCs. Surface bound IAV were internalized within 5 min of infection. The association of virus particles with early endosomes peaked at 5 min when 50% of NP+ signals were also EEA1+. Peak association with late endosomes occurred at 15 min when 60% of NP+ signals were LAMP1+. At 30 min of infection, the majority of NP signals were in the nucleus. Our findings illustrate that early IAV trafficking in human DCs proceeds via the classical endocytic pathway.

  12. Growth in children with chronic kidney disease: role of nutrition, growth hormone, dialysis, and steroids.

    PubMed

    Ingulli, Elizabeth G; Mak, Robert H

    2014-04-01

    Children with chronic kidney disease (CKD) have impaired growth that leads to short stature in adulthood. The problem persists even with successful transplantation and steroid withdrawal protocols. The aim of this review is to provide an overview of the pressing issues related to growth failure in children with CKD both before and after transplantation. Although great strides have been made in dialysis and transplantation, the incidence of abnormal adult height in children growing up with CKD remains as high as 45-60%. The lack of catch-up growth and resultant short stature is a critical issue for self-esteem and quality of life in many children with CKD. Aggressive daily dialysis, improved nutrition, treatment of metabolic bone disease, and the use of recombinant human growth hormone provide some hope for catch-up growth in select patients. The causes of growth failure in the setting of CKD are multifactorial. Attention to all the details by optimizing nutritional, bone and mineral metabolism, correcting metabolic acidosis and anemia, achieving excellent blood pressure control, reversing cardiovascular complications such as left ventricular hypertrophy, and minimizing the use of corticosteroids is the current standard of care. Aggressive daily dialysis can reverse many of the uremic derangements. For patients not yet on dialysis or for those after renal transplant, early institution of recombinant human growth hormone can promote growth. Improved understanding of the mechanisms of hormone resistance may offer novel targets or measurements of treatment effectiveness.

  13. Postnatal changes in the growth dynamics of the human face revealed from bone modelling patterns.

    PubMed

    Martinez-Maza, Cayetana; Rosas, Antonio; Nieto-Díaz, Manuel

    2013-09-01

    Human skull morphology results from complex processes that involve the coordinated growth and interaction of its skeletal components to keep a functional and structural balance. Previous histological works have studied the growth of different craniofacial regions and their relationship to functional spaces in humans up to 14 years old. Nevertheless, how the growth dynamics of the facial skeleton and the mandible are related and how this relationship changes through the late ontogeny remain poorly understood. To approach these two questions, we have compared the bone modelling activities of the craniofacial skeleton from a sample of subadult and adult humans. In this study, we have established for the first time the bone modelling pattern of the face and the mandible from adult humans. Our analyses reveal a patchy distribution of the bone modelling fields (overemphasized by the presence of surface islands with no histological information) reflecting the complex growth dynamics associated to the individual morphology. Subadult and adult specimens show important differences in the bone modelling patterns of the anterior region of the facial skeleton and the posterior region of the mandible. These differences indicate developmental changes in the growth directions of the whole craniofacial complex, from a predominantly downward growth in subadults that turns to a forward growth observed in the adult craniofacial skeleton. We hypothesize that these ontogenetic changes would respond to the physiological and physical requirements to enlarge the oral and nasal cavities once maturation of the brain and the closure of the cranial sutures have taken place during craniofacial development. © 2013 Anatomical Society.

  14. Starch grains on human teeth reveal early broad crop diet in northern Peru

    PubMed Central

    Piperno, Dolores R.; Dillehay, Tom D.

    2008-01-01

    Previous research indicates that the Ñanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 14C yr B.P. the valley inhabitants adopted major crop plants such as squash (Cucurbita moschata), peanuts (Arachis sp.), and cotton (Gossypium barbadense). We report here an examination of starch grains preserved in the calculus of human teeth from these sites that provides direct evidence for the early consumption of cultivated squash and peanuts along with two other major food plants not previously detected. Starch from the seeds of Phaseolus and Inga feuillei, the flesh of Cucurbita moschata fruits, and the nuts of Arachis was routinely present on numerous teeth that date to between 8210 and 6970 14C yr B.P. Early plant diets appear to have been diverse and stable through time and were rich in cultivated foods typical of later Andean agriculture. Our data provide early archaeological evidence for Phaseolus beans and I. feuillei, an important tree crop, and indicate that effective food production systems that contributed significant dietary inputs were present in the Ñanchoc region by 8000 14C yr B.P. Starch grain studies of dental remains document plants and edible parts of them not normally preserved in archaeological records and can assume primary roles as direct indicators of ancient human diets and agriculture. PMID:19066222

  15. European early modern humans and the fate of the Neandertals

    PubMed Central

    Trinkaus, Erik

    2007-01-01

    A consideration of the morphological aspects of the earliest modern humans in Europe (more than ≈33,000 B.P.) and the subsequent Gravettian human remains indicates that they possess an anatomical pattern congruent with the autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African modern humans. However, they exhibit a variable suite of features that are either distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had been lost among the African Middle Paleolithic modern humans. These features include aspects of neurocranial shape, basicranial external morphology, mandibular ramal and symphyseal form, dental morphology and size, and anteroposterior dental proportions, as well as aspects of the clavicles, scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable presence of these morphological features in the European earlier modern human samples can only be parsimoniously explained as a product of modest levels of assimilation of Neandertals into early modern human populations as the latter dispersed across Europe. This interpretation is in agreement with current analyses of recent and past human molecular data. PMID:17452632

  16. Early childhood development in Rwanda: a policy analysis of the human rights legal framework.

    PubMed

    Binagwaho, Agnes; Scott, Kirstin W; Harward, Sardis H

    2016-01-12

    Early childhood development (ECD) is a critical period that continues to impact human health and productivity throughout the lifetime. Failing to provide policies and programs that support optimal developmental attainment when such services are financially and logistically feasible can result in negative population health, education and economic consequences that might otherwise be avoided. Rwanda, with its commitment to rights-based policy and program planning, serves as a case study for examination of the national, regional, and global human rights legal frameworks that inform ECD service delivery. In this essay, we summarize key causes and consequences of the loss of early developmental potential and how this relates to the human rights legal framework in Rwanda. We contend that sub-optimal early developmental attainment constitutes a violation of individuals' rights to health, education, and economic prosperity. These rights are widely recognized in global, regional and national human rights instruments, and are guaranteed by Rwanda's constitution. Recent policy implementation by several Rwandan ministries has increased access to health and social services that promote achievement of full developmental potential. These ECD-centric activities are characterized by an integrated approach to strengthening the services provided by several public sectors. Combining population level activities with those at the local level, led by local community health workers and women's councils, can bolster community education and ensure uptake of ECD services. Realization of the human rights to health, education, and economic prosperity requires and benefits from attention to the period of ECD, as early childhood has the potential to be an opportunity for expedient intervention or the first case of human rights neglect in a lifetime of rights violations. Efforts to improve ECD services and outcomes at the population level require multisector collaboration at the highest echelons

  17. Excess iron: considerations related to development and early growth.

    PubMed

    Wessling-Resnick, Marianne

    2017-12-01

    What effects might arise from early life exposures to high iron? This review considers the specific effects of high iron on the brain, stem cells, and the process of erythropoiesis and identifies gaps in our knowledge of what molecular damage may be incurred by oxidative stress that is imparted by high iron status in early life. Specific areas to enhance research on this topic include the following: longitudinal behavioral studies of children to test associations between iron exposures and mood, emotion, cognition, and memory; animal studies to determine epigenetic changes that reprogram brain development and metabolic changes in early life that could be followed through the life course; and the establishment of human epigenetic markers of iron exposures and oxidative stress that could be monitored for early origins of adult chronic diseases. In addition, efforts to understand how iron exposure influences stem cell biology could be enhanced by establishing platforms to collect biological specimens, including umbilical cord blood and amniotic fluid, to be made available to the research community. At the molecular level, there is a need to better understand stress erythropoiesis and changes in iron metabolism during pregnancy and development, especially with respect to regulatory control under high iron conditions that might promote ineffective erythropoiesis and iron-loading anemia. These investigations should focus not only on factors such as hepcidin and erythroferrone but should also include newly identified interactions between transferrin receptor-2 and the erythropoietin receptor. Finally, despite our understanding that several key micronutrients (e.g., vitamin A, copper, manganese, and zinc) support iron's function in erythropoiesis, how these nutrients interact remains, to our knowledge, unknown. It is necessary to consider many factors when formulating recommendations on iron supplementation. © 2017 American Society for Nutrition.

  18. Early development of physical aggression and early risk factors for chronic physical aggression in humans.

    PubMed

    Tremblay, Richard E

    2014-01-01

    This chapter describes the state of knowledge on the development of physical aggression from early childhood to adulthood, the long term outcomes of chronic physical aggression during childhood and the risk factors for chronic physical aggression. Unraveling the development of physical aggression is important to understand when and why humans start using physical aggression, to understand why some humans suffer from chronic physical aggression and to understand how to prevent the development of this disorder which causes much distress to the aggressors and their victims. The study of the developmental origins of aggression also sheds light on the reasons why situational prevention of aggression is important at all ages and in all cultures.

  19. Random Secretion of Growth Hormone in Humans

    NASA Astrophysics Data System (ADS)

    Prank, Klaus; Kloppstech, Mirko; Nowlan, Steven J.; Sejnowski, Terrence J.; Brabant, Georg

    1996-08-01

    In normal humans, growth hormone (GH) is secreted from a gland located adjacent to the brain (pituitary) into the blood in distinct pulses, but in patients bearing a tumor within the pituitary (acromegaly) GH is excessively secreted in an irregular manner. It has been hypothesized that GH secretion in the diseased state becomes random. This hypothesis is supported by demonstrating that GH secretion in patients with acromegaly cannot be distinguished from a variety of linear stochastic processes based on the predictability of the fluctuations of GH concentration in the bloodstream.

  20. Enteral nutrition for optimal growth in preterm infants

    PubMed Central

    2016-01-01

    Early, aggressive nutrition is an important contributing factor of long-term neurodevelopmental outcomes. To ensure optimal growth in premature infants, adequate protein intake and optimal protein/energy ratio should be emphasized rather than the overall energy intake. Minimal enteral nutrition should be initiated as soon as possible in the first days of life, and feeding advancement should be individualized according to the clinical course of the infant. During hospitalization, enteral nutrition with preterm formula and fortified human milk represent the best feeding practices for facilitating growth. After discharge, the enteral nutrition strategy should be individualized according to the infant's weight at discharge. Infants with suboptimal weight for their postconceptional age at discharge should receive supplementation with human milk fortifiers or nutrient-enriched feeding, and the enteral nutrition strategy should be reviewed and modified continuously to achieve the target growth parameters. PMID:28194211

  1. Impaired STING Pathway in Human Osteosarcoma U2OS Cells Contributes to the Growth of ICP0-Null Mutant Herpes Simplex Virus.

    PubMed

    Deschamps, Thibaut; Kalamvoki, Maria

    2017-05-01

    Human herpes simplex virus 1 (HSV-1) is a widespread pathogen, with 80% of the population being latently infected. To successfully evade the host, the virus has evolved strategies to counteract antiviral responses, including the gene-silencing and innate immunity machineries. The immediately early protein of the virus, infected cell protein 0 (ICP0), plays a central role in these processes. ICP0 blocks innate immunity, and one mechanism is by degrading hostile factors with its intrinsic E3 ligase activity. ICP0 also functions as a promiscuous transactivator, and it blocks repressor complexes to enable viral gene transcription. For these reasons, the growth of a ΔICP0 virus is impaired in most cells, except cells of the human osteosarcoma cell line U2OS, and it is only partially impaired in cells of the human osteosarcoma cell line Saos-2. We found that the two human osteosarcoma cell lines that supported the growth of the ΔICP0 virus failed to activate innate immune responses upon treatment with 2'3'-cyclic GAMP (2'3'-cGAMP), the natural agonist of STING (i.e., stimulator of interferon genes) or after infection with the ΔICP0 mutant virus. Innate immune responses were restored in these cells by transient expression of the STING protein but not after overexpression of interferon-inducible protein 16 (IFI16). Restoration of STING expression resulted in suppression of ΔICP0 virus gene expression and a decrease in viral yields. Overexpression of IFI16 also suppressed ΔICP0 virus gene expression, albeit to a lesser extent than STING. These data suggest that the susceptibility of U2OS and Saos-2 cells to the ΔICP0 HSV-1 is in part due to an impaired STING pathway. IMPORTANCE The DNA sensor STING plays pivotal role in controlling HSV-1 infection both in cell culture and in mice. The HSV-1 genome encodes numerous proteins that are dedicated to combat host antiviral responses. The immediate early protein of the virus ICP0 plays major role in this process as it targets

  2. Impaired STING Pathway in Human Osteosarcoma U2OS Cells Contributes to the Growth of ICP0-Null Mutant Herpes Simplex Virus

    PubMed Central

    Deschamps, Thibaut

    2017-01-01

    ABSTRACT Human herpes simplex virus 1 (HSV-1) is a widespread pathogen, with 80% of the population being latently infected. To successfully evade the host, the virus has evolved strategies to counteract antiviral responses, including the gene-silencing and innate immunity machineries. The immediately early protein of the virus, infected cell protein 0 (ICP0), plays a central role in these processes. ICP0 blocks innate immunity, and one mechanism is by degrading hostile factors with its intrinsic E3 ligase activity. ICP0 also functions as a promiscuous transactivator, and it blocks repressor complexes to enable viral gene transcription. For these reasons, the growth of a ΔICP0 virus is impaired in most cells, except cells of the human osteosarcoma cell line U2OS, and it is only partially impaired in cells of the human osteosarcoma cell line Saos-2. We found that the two human osteosarcoma cell lines that supported the growth of the ΔICP0 virus failed to activate innate immune responses upon treatment with 2′3′-cyclic GAMP (2′3′-cGAMP), the natural agonist of STING (i.e., stimulator of interferon genes) or after infection with the ΔICP0 mutant virus. Innate immune responses were restored in these cells by transient expression of the STING protein but not after overexpression of interferon-inducible protein 16 (IFI16). Restoration of STING expression resulted in suppression of ΔICP0 virus gene expression and a decrease in viral yields. Overexpression of IFI16 also suppressed ΔICP0 virus gene expression, albeit to a lesser extent than STING. These data suggest that the susceptibility of U2OS and Saos-2 cells to the ΔICP0 HSV-1 is in part due to an impaired STING pathway. IMPORTANCE The DNA sensor STING plays pivotal role in controlling HSV-1 infection both in cell culture and in mice. The HSV-1 genome encodes numerous proteins that are dedicated to combat host antiviral responses. The immediate early protein of the virus ICP0 plays major role in this

  3. Human Growth Hormone Adsorption Kinetics and Conformation on Self-Assembled Monolayers

    PubMed Central

    Buijs, Jos; Britt, David W.; Hlady, Vladimir

    2012-01-01

    The adsorption process of the recombinant human growth hormone on organic films, created by self-assembly of octadecyltrichlorosilane, arachidic acid, and dipalmitoylphosphatidylcholine, is investigated and compared to adsorption on silica and methylated silica substrates. Information on the adsorption process of human growth hormone (hGH) is obtained by using total internal reflection fluorescence (TIRF). The intensity, spectra, and quenching of the intrinsic fluorescence emitted by the growth hormone’s single tryptophan are monitored and related to adsorption kinetics and protein conformation. For the various alkylated hydrophobic surfaces with differences in surface density and conformational freedom it is observed that the adsorbed amount of growth hormone is relatively large if the alkyl chains are in an ordered structure while the amounts adsorbed are considerably lower for adsorption onto less ordered alkyl chains of fatty acid and phospholipid layers. Adsorption on methylated surfaces results in a relatively large conformational change in the growth hormone’s structure, as displayed by a 7 nm blue shift in emission wavelength and a large increase in the effectiveness of fluorescence quenching. Conformational changes are less evident for hGH adsorption onto the fatty acid and phospholipid alkyl chains. Adsorption kinetics on the hydrophilic head groups of the self-assembled monolayers are similar to those on solid hydrophilic surfaces. The relatively small conformational changes in the hGH structure observed for adsorption on silica are even further reduced for adsorption on fatty acid head groups. PMID:25125795

  4. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suzuki, Kanayo; Sakaguchi, Minoru, E-mail: sakaguti@gly.oups.ac.jp; Tanaka, Satoshi

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDKmore » inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.« less

  5. Environmental influences on human growth and development: historical review and case study of contemporary influences.

    PubMed

    Schell, Lawrence M; Gallo, Mia V; Ravenscroft, Julia

    2009-01-01

    Over the past 100 years, the study of environmental influences on human physical growth and development has focused on the influences of social and economic factors; family and household characteristics; urbanization/modernization; nutrition; and features of the physical environment such as altitude, temperature and climate. Continuing in this tradition are current investigations into the roles of pollutants and other aspects of the human-made environment in affecting patterns of human growth and development, specifically the timing of sexual maturation and the development of obesity. Some of the methodological problems in conducting such studies are presented, as are results from an ongoing investigation among one Native American community that show relationships of pollutants to sexual maturation, overweight/obesity and thyroid system function which can impact growth and maturation.

  6. Postnatal growth of the human pons: a morphometric and immunohistochemical analysis.

    PubMed

    Tate, Matthew C; Lindquist, Robert A; Nguyen, Thuhien; Sanai, Nader; Barkovich, A James; Huang, Eric J; Rowitch, David H; Alvarez-Buylla, Arturo

    2015-02-15

    Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)-based morphometric analyses of the postnatal human pons (0-18 years; n = 6-14/timepoint). Pons volume increased 6-fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2-based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67(+) cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2(+) was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67(+) cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67(+) cells observed throughout childhood. In addition, two populations of vimentin/nestin-expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases. © 2014 Wiley Periodicals, Inc.

  7. Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

    PubMed

    Mathews, D J H; Sugarman, J; Bok, H; Blass, D M; Coyle, J T; Duggan, P; Finkel, J; Greely, H T; Hillis, A; Hoke, A; Johnson, R; Johnston, M; Kahn, J; Kerr, D; Kurtzberg, J; Liao, S M; McDonald, J W; McKhann, G; Nelson, K B; Rao, M; Regenberg, A; Siegel, A W; Smith, K; Solter, D; Song, H; Vescovi, A; Young, W; Gearhart, J D; Faden, R

    2008-07-22

    Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

  8. Effect of exogenous transforming growth factor β1 (TGF-β1) on early bovine embryo development.

    PubMed

    Barrera, Antonio D; García, Elina V; Miceli, Dora C

    2018-06-08

    SummaryDuring preimplantation development, embryos are exposed and have the capacity to respond to different growth factors present in the maternal environment. Among these factors, transforming growth factor β1 (TGF-β1) is a well known modulator of embryonic growth and development. However, its action during the first stages of development, when the embryo transits through the oviduct, has not been yet elucidated. The objective of the present study was to examine the effect of early exposure to exogenous TGF-β1 on embryo development and expression of pluripotency (OCT4, NANOG) and DNA methylation (DNMT1, DNMT3A, DNMT3B) genes in bovine embryos produced in vitro. First, gene expression analysis of TGF-β receptors confirmed a stage-specific expression pattern, showing greater mRNA abundance of TGFBR1 and TGFBR2 from the 2- to the 8-cell stage, before embryonic genome activation. Second, embryo culture for the first 48 h in serum-free CR1aa medium supplemented with 50 or 100 ng/ml recombinant TGF-β1 did not affect the cleavage and blastocyst rate (days 7 and 8). However, RT-qPCR analysis showed a significant increase in the relative abundance of NANOG and DNMT3A in the 8-cell stage embryos and expanded blastocysts (day 8) derived from TGF-β1 treated embryos. These results suggest an early action of exogenous TGF-β1 on the bovine embryo, highlighting the importance to provide a more comprehensive understanding of the role of TGF-β signalling during early embryogenesis.

  9. Group-Based Modeling of Time Spent in Structured Activity Trajectories from Middle Childhood into Early Adolescence

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    This study investigated trajectories of time spent in structured activities from middle childhood to early adolescence by using data from the National Institute of Child Health & Human Development (NICHD) Study of Early Child Care. We used latent class growth analyses and identified five trajectories (stable low, increasing high, decreasing low,…

  10. Are Birth Weight, Early Growth, and Motor Development Determinants of Physical Activity in Children and Youth? A Systematic Review and Meta-Analysis.

    PubMed

    Øglund, Guro Pauck; Hildebrand, Maria; Ekelund, Ulf

    2015-11-01

    The purpose of this systematic review was to explore whether birth weight, early growth and motor development act as determinants of physical activity in children and youth. We performed a systematic literature search on the possible early life determinants. A meta-analysis was performed on the association between birthweight and objectively measured physical activity. We identified 9 studies examining birth weight, in which none of the studies with objectively measured physical activity observed an association between birth weight and physical activity. The meta-analysis confirmed this result (b=-3.08, 95% CI -10.20, 4.04). The 3 studies examining early growth and physical activity in youth differ in methodology and the results are inconsistent. Two studies suggest an association between earlier motor development and physical activity and sport participation in youth. This was not confirmed in a third study. Our meta-analysis suggests that birth weight is not an important determinant of physical activity in youth. Available data does not allow firm conclusions whether early growth and motor development act as determinants of physical activity in youth.

  11. Hexamethylenebisacetamide (HMBA) is a growth factor for human, ovine and porcine thyroid cells.

    PubMed

    Fayet, G; Amphoux-Fazekas, T; Aouani, A; Hovsépian, S

    1996-03-01

    Hexamethylenebisacetamide (HMBA) provokes in murine erythroleukemia cells (MELC) a commitment to terminal differentiation leading to the activation of the expression of hemoglobin. HMBA has been tested also in other cells from colon cancer, melanoma or lung cancer. However it has not yet been tested in the thyroid. We demonstrate in this paper that HMBA in kinetics and concentration-response experiments increases the proliferation of human thyroid cells isolated from Graves'-Basedow patients. It also acts like a growth factor for ovine and porcine thyroid cells, respectively, from the OVNIS line and the ATHOS line. This molecule which is a differentiating factor in the MELC system and a growth factor in human thyroid cell cultures represents a potential to get human thyroid cell lines expressing specialized functions.

  12. The Association of Birth Weight and Infant Growth with Energy Balance-Related Behavior – A Systematic Review and Best-Evidence Synthesis of Human Studies

    PubMed Central

    Chinapaw, Mai J. M.; Jansma, Elise P.; Vrijkotte, Tanja G. M.; Gemke, Reinoud J. B. J.

    2017-01-01

    Background Suboptimal prenatal and early postnatal growths are associated with obesity in later life, but the underlying mechanisms are unknown. The aim of this study was to systematically review the literature that reports on the longitudinal association of (i) birth size or (ii) infant growth with later (i) energy intake, (ii) eating behaviors, (iii) physical activity or (iv) sedentary behavior in humans. Methods A comprehensive search of MEDLINE, EMBASE, PsycINFO and The Cochrane Library was conducted to identify relevant publications. We appraised the methodological quality of the studies and synthesized the extracted data through a best-evidence synthesis. Results Data from 41 publications were included. The quality of the studies was high in three papers, moderate in 11 and low in the large majority (n = 27) of papers appraised. Our best-evidence synthesis indicates that there is no evidence for an association of birth weight with later energy intake, eating behavior, physical activity or sedentary behavior. We found moderate evidence for an association of extreme birth weights (at both ends of the spectrum) with lower physical activity levels at a later age. Evidence for the association of infant growth with energy balance-related behavior was generally insufficient. Conclusions We conclude that current evidence does not support an association of early-life growth with energy balance-related behaviors in later life, except for an association of extreme birth weights with later physical activity. PMID:28081150

  13. Human osteoblast cells: isolation, characterization, and growth on polymers for musculoskeletal tissue engineering.

    PubMed

    El-Amin, Saadiq F; Botchwey, Edward; Tuli, Richard; Kofron, Michelle D; Mesfin, Addisu; Sethuraman, Swaminathan; Tuan, Rocky S; Laurencin, Cato T

    2006-03-01

    We performed a detailed examination of the isolation, characterization, and growth of human osteoblast cells derived from trabecular bone. We further examined the morphology, phenotypic gene expression, mineralization,and growth of these human osteoblasts on polyester polymers used for musculoskeletal tissue engineering. Polylactic-co-glycolic acid [PLAGA (85:15, 50:50, 75:25)], and poly-lactic acid (L-PLA, D,L-PLA) were examined. The osteoblastic expression of key phenotypic markers osteocalcin, alkaline phosphatase, collagen, and bone sialoprotein at 4 and 8 weeks was examined. Reverse transcription-polymerase chain reaction studies revealed that trabecular-derived osteoblasts were positive for all markers evaluated with higher levels expressed over long-term culture. These cells also revealed mineralization and maturation as evidenced by energy dispersive X-ray analysis and scanning electron microscopy. Growth studies on PLAGA at 50:50,75:25, and 85:15 ratios and PLA in the L and DL isoforms revealed that human osteoblasts actively grew, with significantly higher cell numbers attached to scaffolds composed of PLAGA 50:50 in the short term and PLAGA 85:15 in the long term compared with PLA (p < 0.05). We believe human cell adhesion among these polymeric materials may be dependent on differences in cellular integrin expression and extracellular matrix protein elaboration. (c) 2005 Wiley Periodicals, Inc.

  14. Early childhood growth patterns and school-age respiratory resistance, fractional exhaled nitric oxide and asthma.

    PubMed

    Casas, Maribel; den Dekker, Herman T; Kruithof, Claudia J; Reiss, Irwin K; Vrijheid, Martine; de Jongste, Johan C; Jaddoe, Vincent W V; Duijts, Liesbeth

    2016-12-01

    Greater infant weight gain is associated with lower lung function and increased risk of childhood asthma. The role of early childhood peak growth patterns is unclear. We assessed the associations of individually derived early childhood peak growth patterns with respiratory resistance, fractional exhaled nitric oxide, wheezing patterns, and asthma until school-age. We performed a population-based prospective cohort study among 5364 children. Repeated growth measurements between 0 and 3 years of age were used to derive standard deviation scores (s.d.s) of peak height and weight velocities (PHV and PWV, respectively), and body mass index (BMI) and age at adiposity peak. Respiratory resistance and fractional exhaled nitric oxide were measured at 6 years of age. Wheezing patterns and asthma were prospectively assessed by annual questionnaires. We also assessed whether any association was explained by childhood weight status. Greater PHV was associated with lower respiratory resistance [Z-score (95% CI): -0.03 (-0.04, -0.01) per s.d.s increase] (n = 3382). Greater PWV and BMI at adiposity peak were associated with increased risks of early wheezing [relative risk ratio (95% CI): 1.11 (1.06, 1.16), 1.26 (1.11, 1.43), respectively] and persistent wheezing [relative risk ratio (95% CI): 1.09 (1.03, 1.16), 1.37 (1.17, 1.60), respectively] (n = 3189 and n = 3005, respectively). Childhood weight status partly explained these associations. No other associations were observed. PWV and BMI at adiposity peak are critical for lung developmental and risk of school-age wheezing. Follow-up studies at older ages are needed to elucidate whether these effects persist at later ages. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Early modern human lithic technology from Jerimalai, East Timor.

    PubMed

    Marwick, Ben; Clarkson, Chris; O'Connor, Sue; Collins, Sophie

    2016-12-01

    Jerimalai is a rock shelter in East Timor with cultural remains dated to 42,000 years ago, making it one of the oldest known sites of modern human activity in island Southeast Asia. It has special global significance for its record of early pelagic fishing and ancient shell fish hooks. It is also of regional significance for its early occupation and comparatively large assemblage of Pleistocene stone artefacts. Three major findings arise from our study of the stone artefacts. First, there is little change in lithic technology over the 42,000 year sequence, with the most noticeable change being the addition of new artefact types and raw materials in the mid-Holocene. Second, the assemblage is dominated by small chert cores and implements rather than pebble tools and choppers, a pattern we argue pattern, we argue, that is common in island SE Asian sites as opposed to mainland SE Asian sites. Third, the Jerimalai assemblage bears a striking resemblance to the assemblage from Liang Bua, argued by the Liang Bua excavation team to be associated with Homo floresiensis. We argue that the near proximity of these two islands along the Indonesian island chain (c.100 km apart), the long antiquity of modern human occupation in the region (as documented at Jerimalai), and the strong resemblance of distinctive flake stone technologies seen at both sites, raises the intriguing possibility that both the Liang Bua and Jerimalai assemblages were created by modern humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Formononetin accelerates wound repair by the regulation of early growth response factor-1 transcription factor through the phosphorylation of the ERK and p38 MAPK pathways.

    PubMed

    Huh, Jeong-Eun; Nam, Dong-Woo; Baek, Young-Hyun; Kang, Jung Won; Park, Dong-Suk; Choi, Do-Young; Lee, Jae-Dong

    2011-01-01

    Formononetin, a phytoestrogen from the root of Astragalus membranaceus, is used as a blood enhancer and to improve blood microcirculation in complementary and alternative medicine. The present study investigated the influence of formononetin on the expression of early growth response factor-1 (Egr-1) and growth factors contributing to wound healing. Formononetin significantly increased growth factors such as transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) in human umbilical vein endothelial cells (HUVECs). Formononetin also increased the expression of Egr-1 transcription factor by 3.2- and 10.5-fold, compared with recombinant VEGF(125) in HUVECs. The formononetin-mediated 12%-43% increase induced endothelial cell proliferation and recovered the migration of wounded HUVECs. In an ex vivo angiogenesis assay, formononetin produced a larger capillary sprouting area than produced using recombinant VEGF(125). Cell proliferation and migration of HUVECs were also greater in the presence of formonectin than VEGF(125). Western blot analysis of scratch-wounded confluent HUVECs showed that formononetin induced the phosphorylation of extracellular signal-regulated kinase (ERK) and slightly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK). The formononetin-mediated sustained activation of Egr-1 was suppressed by the ERK inhibitor PD98059 and the p38 inhibitor SB203580. PD98059 inhibited the formononetin-induced endothelial proliferation and repair in scratch-wounded HUVECs, SB203580 increased the cell proliferation and wound healing. Formononetin accelerate wound closure rate as early as day 3 after surgery and consistently observed until day 10 after in wound animal model. These data suggest that formononetin promotes endothelial repair and wound healing in a process involving the over-expression of Egr-1 transcription factor

  17. Cortical bone growth and maturational changes in dwarf rats induced by recombinant human growth hormone

    NASA Technical Reports Server (NTRS)

    Martinez, D. A.; Orth, M. W.; Carr, K. E.; Vanderby, R. Jr; Vailas, A. C.

    1996-01-01

    The growth hormone (GH)-deficient dwarf rat was used to investigate recombinant human (rh) GH-induced bone formation and to determine whether rhGH facilitates simultaneous increases in bone formation and bone maturation during rapid growth. Twenty dwarf rats, 37 days of age, were randomly assigned to dwarf plus rhGH (GH; n = 10) and dwarf plus vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt two times daily for 14 days. Biochemical, morphological, and X-ray diffraction measurements were performed on the femur middiaphysis. rhGH stimulated new bone growth in the GH group, as demonstrated by significant increases (P < 0.05) in longitudinal bone length (6%), middiaphyseal cross-sectional area (20%), and the amount of newly accreted bone collagen (28%) in the total pool of middiaphyseal bone collagen. Cortical bone density, mean hydroxyapatite crystal size, and the calcium and collagen contents (microgram/mm3) were significantly smaller in the GH group (P < 0.05). Our findings suggest that the processes regulating new collagen accretion, bone collagen maturation, and mean hydroxyapatite crystal size may be independently regulated during rapid growth.

  18. Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction.

    PubMed

    van Ginkel, Paul R; Darjatmoko, Soesiawati R; Sareen, Dhruv; Subramanian, Lalita; Bhattacharya, Saswati; Lindstrom, Mary J; Albert, Daniel M; Polans, Arthur S

    2008-04-01

    To test the efficacy of resveratrol, a nontoxic plant product, in the treatment of uveal melanoma. The effect of oral administration and peritumor injection of resveratrol was tested on tumor growth in two animal models of uveal melanoma. The mechanism of resveratrol action on uveal melanoma cells was studied in vitro in a cell-viability assay: with JC-1 dye, to measure mitochondrial membrane potential; by Western blot analysis, to analyze the cellular redistribution of cytochrome c and Smac/diablo; and in a fluorescence assay with specific substrates, to measure activation of different caspases. Resveratrol treatment inhibited tumor growth in animal models of uveal melanoma. Since oral administration resulted in relatively low bioavailability of resveratrol, the effect of increased local levels was tested by peritumor injection of the drug. This method resulted in tumor cell death and tumor regression. In vitro experiments with multiple uveal melanoma cell lines demonstrate that resveratrol causes a decrease in cell viability, resulting at least in part from an increase in apoptosis through a mitochondrial pathway. An early event in drug action is the direct targeting of mitochondria by resveratrol, which leads to a decrease in mitochondrial membrane potential and the eventual activation of caspase-3. These data suggest that resveratrol can inhibit tumor growth and can induce apoptosis via the intrinsic mitochondrial pathway and that by further increasing bioavailability of resveratrol the potency of the drug can be increased, leading to tumor regression. The nontoxic nature of the drug at levels needed for therapy make resveratrol an attractive candidate for the treatment of uveal melanoma.

  19. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner.

    PubMed

    Vasilopoulou, E; Loubière, L S; Lash, G E; Ohizua, O; McCabe, C J; Franklyn, J A; Kilby, M D; Chan, S Y

    2014-06-01

    Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. This laboratory-based study used human decidua from first (8-11 weeks; n = 18) and second (12-16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10-) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel(®) was evaluated. Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1, TRβ1) required for thyroid hormone-responsiveness in uNK cells and macrophages from the first trimester. The viability of total decidual cells and the different

  20. Human growth hormone may be detrimental when used to accelerate recovery from acute tendon-bone interface injuries.

    PubMed

    Baumgarten, Keith M; Oliver, Harvey A; Foley, Jack; Chen, Ding-Geng; Autenried, Peter; Duan, Shanzhong; Heiser, Patrick

    2013-05-01

    There have been few scientific studies that have examined usage of human growth hormone to accelerate recovery from injury. The hypothesis of this study was that human growth hormone would accelerate tendon-to-bone healing compared with control animals treated with placebo in a rat model of acute rotator cuff injury repair. Seventy-two rats underwent repair of acute rotator cuff injuries and were randomized into the following postoperative dosing regimens: placebo, and human growth hormone at 0.1, 1, 2, 5, and 10 mg/kg/day, administered subcutaneously once per day for fourteen days (Protocol 1). An additional twenty-four rats were randomized to receive either (1) placebo or (2) human growth hormone at 5 mg/kg, administered subcutaneously twice per day for seven days preoperatively and twenty-eight days postoperatively (Protocol 2). All rats were killed twenty-eight days postoperatively. Mechanical testing was performed. Ultimate stress, ultimate force, stiffness, energy to failure, and ultimate distension were determined. For Protocol 1, analysis of variance testing showed no significant difference between the groups with regard to ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension. In Protocol 2, ultimate force to failure was significantly worse in the human growth hormone group compared with the placebo group (21.1 ± 5.85 versus 26.3 ± 5.47 N; p = 0.035). Failure was more likely to occur through the bone than the tendon-bone interface in the human growth hormone group compared with the placebo group (p = 0.001). No significant difference was found for ultimate stress, ultimate force, stiffness, energy to failure, or ultimate distension between the groups in Protocol 2. In this rat model of acute tendon-bone injury repair, daily subcutaneous postoperative human growth hormone treatment for fourteen days failed to demonstrate a significant difference in any biomechanical parameter compared with placebo. Furthermore, subcutaneous

  1. Discontinuity of Human Presence at Atapuerca during the Early Middle Pleistocene: A Matter of Ecological Competition?

    PubMed Central

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7−0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7−0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene. PMID:25054305

  2. Discontinuity of human presence at Atapuerca during the early Middle Pleistocene: a matter of ecological competition?

    PubMed

    Rodríguez-Gómez, Guillermo; Mateos, Ana; Martín-González, Jesús Angel; Blasco, Ruth; Rosell, Jordi; Rodríguez, Jesús

    2014-01-01

    Increasing evidence suggests that the European human settlement is older than 1.2 Ma. However, there is a fierce debate about the continuity or discontinuity of the early human settlement of Europe. In particular, evidence of human presence in the interval 0.7-0.5 Ma is scarce in comparison with evidence for the previous and later periods. Here, we present a case study in which the environmental conditions at Sierra de Atapuerca in the early Middle Pleistocene, a period without evidence of human presence, are compared with the conditions in the previous period, for which a relatively intense human occupation is documented. With this objective in mind, the available resources for a human population and the intensity of competition between secondary consumers during the two periods are compared using a mathematical model. The Gran Dolina site TD8 level, dated to 0.7-0.6 Ma, is taken as representative of the period during which Atapuerca was apparently not occupied by humans. Conditions at TD8 are compared with those of the previous period, represented by the TD6-2 level, which has yielded abundant evidence of intense human occupation. The results show that survival opportunities for a hypothetical human population were lower at TD8 than they were at TD6-2. Increased resource competition between secondary consumers arises as a possible explanation for the absence of human occupation at Atapuerca in the early Middle Pleistocene.

  3. Topical Human Epidermal Growth Factor in the Treatment of Senile Purpura and the Prevention of Dermatoporosis.

    PubMed

    McKnight, Braden; Seidel, Rachel; Moy, Ron

    2015-10-01

    Senile purpura presents itself as a largely unexplored challenge as it has been long thought of as a benign condition without long-term health sequelae. It is becoming increasingly accepted that skin aging not only results in cosmetic disturbances, but as a functional ones. With modern increases in lifespan, skin atrophy associated with solar damage is presenting as a clinically significant inability to mechanically protect patients. This chronic cutaneous insufficiency/fragility syndrome was recently termed dermatoporosis and senile purpura appears to be a visible marker of early stage dysfunction. To examine the effects of topically human epidermal growth factor on the clinical presence of senile purpura and its effect on skin thickness as measured via cutaneous ultrasound. Six subjects applied human epidermal growth factor morning and night for six weeks. Clinical outcomes were evaluated by comparing initial clinical photos to 6-week photos and performing a blinded investigator's global assessment (IGA). Skin thickness was evaluated via cutaneous ultrasound measurement. Ultrasound measurements indicated a mean skin thickening of 195.2 ± 35.7 um (SEM) over 6 weeks. The average number of purpuric lesions decreased from 15 ± 4.6 (SEM) to 2.3 ± 0.7 (SEM) over that same period. Senile purpura presents itself as a cosmetic disturbance posing significant psychological distress and serves as a marker of the severity of skin thinning. In this study, we demonstrate that topical h-EGF diminishes the appearance of senile purpura by thickening skin and may help prevent the development of late stage dermatoporosis.

  4. Human Endometrial Adenocarcinoma Transplanted into Nude Mice: Growth Regulation by Estradiol

    NASA Astrophysics Data System (ADS)

    Satyaswaroop, P. G.; Zaino, R. J.; Mortel, R.

    1983-01-01

    A model for studying the growth of primary tumors of human endometrium and its regulation by 17β -estradiol has been developed in which ovariectomized nude mice are used as recipients. The receptors for sex steroids are maintained during serial transplantation of the tumor in this system. Although the rate of growth of receptor-negative endometrial tumors transplanted into ovariectomized nude mice is unaffected by the sustained presence or absence of estradiol, the growth of receptor-positive tumors is significantly increased by estradiol. Receptor-positive tumors treated with estradiol produced elevated concentrations of progesterone receptor. That the progesterone receptor is functional in this tumor is evident from the induction of estradiol 17β -dehydrogenase activity upon progestin administration. These findings are consistent with receptor-mediated regulation of growth of endometrial carcinoma.

  5. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells

    PubMed Central

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen

    2015-01-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. PMID:25986608

  6. Experimental vitrification of human compacted morulae and early blastocysts using fine diameter plastic micropipettes.

    PubMed

    Cremades, N; Sousa, M; Silva, J; Viana, P; Sousa, S; Oliveira, C; Teixeira da Silva, J; Barros, A

    2004-02-01

    Vitrification of human blastocysts has been successfully applied using grids, straws and cryoloops. We assessed the survival rate of human compacted morulae and early blastocysts vitrified in pipette tips with a smaller inner diameter and solution volume than the previously described open pulled straw (OPS) method. Excess day 5 human embryos (n = 63) were experimentally vitrified in vessels. Embryos were incubated at 37 degrees C with sperm preparation medium (SPM) for 1 min, SPM + 7.5% ethylene glycol (EG)/dimethylsulphoxide (DMSO) for 3 min, and SPM + 16.5% EG + 16.5% DMSO + 0.67 mol/l sucrose for 25 s. They were then aspirated (0.5 microl) into a plastic micropipette tip (0.36 mm inner diameter), exposed to liquid nitrogen (LN(2)) vapour for 2 min before being placed into a pre-cooled cryotube, which was then closed and plunged into LN(2). Embryos were warmed and diluted using 0.33 mol/l and 0.2 mol/l sucrose. The survival rate for compacted morulae was 73% (22/30) and 82% (27/33) for early blastocysts. The survival rates of human compacted morulae and early blastocysts after vitrification with this simple technique are similar to those reported in the literature achieved by slow cooling and other vitrification protocols.

  7. New Predictive Model at 11+0 to 13+6 Gestational Weeks for Early-Onset Preeclampsia With Fetal Growth Restriction.

    PubMed

    Chang, Ying; Chen, Xu; Cui, Hong-Yan; Li, Xing; Xu, Ya-Ling

    2017-05-01

    The aim of the present study was to determine a predictive model for early-onset preeclampsia with fetal growth restriction (FGR) to be used at 11 +0 to 13 +6 gestational weeks, by combining the maternal serum level of pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PLGF), placental protein 13 (PP13), soluble endoglin (sEng), mean arterial pressure (MAP), and uterine artery Doppler. This was a retrospective cohort study of 4453 pregnant women. Uterine artery Doppler examination was conducted in the first trimester. Maternal serum PAPP-A, PLGF, PP13, and sEng were measured. Mean arterial pressure was obtained. Women were classified as with/without early-onset preeclampsia, and women with preeclampsia were classified as with/without FGR. Receiver operating characteristic analysis was performed to determine the value of the model. There were 30 and 32 pregnant women with early-onset preeclampsia with and without FGR. The diagnosis rate of early-onset preeclampsia with FGR was 67.4% using the predictive model when the false positive rate was set at 5% and 73.2% when the false positive rate was 10%. The predictive model (MAP, uterine artery Doppler measurements, and serum biomarkers) had some predictive value for the early diagnosis (11 +0 to 13 +6 gestational weeks) of early-onset preeclampsia with FGR.

  8. Effects of combined treatment with interferon and mezerein on melanogenesis and growth in human melanoma cells.

    PubMed

    Fisher, P B; Prignoli, D R; Hermo, H; Weinstein, I B; Pestka, S

    1985-01-01

    We have analyzed the effects of various human interferons produced in bacteria and the antileukemic compound mezerein (MEZ) on growth and melanogenesis in human melanoma cells. In four human melanoma cell lines, recombinant human fibroblast interferon (IFN-beta) was more active than recombinant human leukocyte interferons (IFN-alpha A, IFN-alpha D, or IFN-alpha A/D (Bgl] in inhibiting cellular proliferation. When monolayer cultures were exposed to 1000 IU/ml IFN-beta for four days the degree of growth inhibition in the different melanoma cell lines varied between 94 and 26%. Similarly, four days growth in medium containing 10 ng/ml MEZ resulted in either no inhibition of growth or as much as 53% inhibition of growth, depending on the specific melanoma cell line tested. MEZ induced dendrite-like processes, cytoplasmic projections morphologically similar to those normally found in neurons and melanocytes, in all four melanoma cell lines, whereas none of the interferons tested had this effect. The combination of interferon and MEZ resulted in a dramatic inhibition in cellular proliferation in all four melanoma cell lines. When cell extracts were assayed for melanin content, a marker of melanoma cell differentiation, the combination of IFN-beta and MEZ resulted in higher levels of melanin than with either agent alone. Dendrite-like formation was also prominent in the cultures treated with this combination. These results indicate that the antiproliferative effect of interferon toward human melanoma dells can be enhanced by treatment with MEZ and that this effect is associated with an enhancement of terminal differentiation.

  9. Exploring the association between maternal prenatal multivitamin use and early infant growth: The Healthy Start Study.

    PubMed

    Sauder, K A; Starling, A P; Shapiro, A L; Kaar, J L; Ringham, B M; Glueck, D H; Dabelea, D

    2016-10-01

    Prenatal multivitamin supplementation is recommended to improve offspring outcomes, but effects on early infant growth are unknown. We examined whether multivitamin supplementation in the year before delivery predicts offspring mass, body composition and early infant growth. Multivitamin use was assessed longitudinally in 626 women from the Healthy Start Study. Offspring body size and composition was measured with air displacement plethysmography at birth (<3 days) and postnatally (median 5.2 months). Separate multiple linear regressions assessed the relationship of weeks of daily multivitamin use with offspring mass, body composition and postnatal growth, after adjustment for potential confounders (maternal age, race, pre-pregnant body mass index; offspring gestational age at birth, sex; breastfeeding exclusivity). Maternal multivitamin use was not related to offspring mass or body composition at birth, or rate of change in total or fat-free mass in the first 5 months. Multivitamin use was inversely associated with average monthly growth in offspring percent fat mass (β = -0.009, p = 0.049) between birth and postnatal exam. Offspring of non-users had a monthly increase in percent fat mass of 3.45%, while offspring at the top quartile of multivitamin users had a monthly increase in percent fat mass of 3.06%. This association was not modified by exclusive breastfeeding. Increased multivitamin use in the pre-conception and prenatal periods was associated with a slower rate of growth in offspring percent fat mass in the first 5 months of life. This study provides further evidence that in utero nutrient exposures may affect offspring adiposity beyond birth. © 2015 World Obesity.

  10. Galangin inhibits human osteosarcoma cells growth by inducing transforming growth factor-β1-dependent osteogenic differentiation.

    PubMed

    Liu, Chunhong; Ma, Mingming; Zhang, Junde; Gui, Shaoliu; Zhang, Xiaohai; Xue, Shuangtao

    2017-05-01

    Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo. These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts.

    PubMed

    Anitua, Eduardo; de la Fuente, María; Ferrando, Marcos; Quintana, Fernando; Larreategui, Zaloa; Matorras, Roberto; Orive, Gorka

    2016-11-01

    To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation (T-test or Mann-Whitney U-test). We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro, enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in "in vivo" endometrial development and especially in human embryo implantation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology

    PubMed Central

    Ward, Carol V.; Tocheri, Matthew W.; Plavcan, J. Michael; Brown, Francis H.; Manthi, Fredrick Kyalo

    2014-01-01

    Despite discoveries of relatively complete hands from two early hominin species (Ardipithecus ramidus and Australopithecus sediba) and partial hands from another (Australopithecus afarensis), fundamental questions remain about the evolution of human-like hand anatomy and function. These questions are driven by the paucity of hand fossils in the hominin fossil record between 800,000 and 1.8 My old, a time interval well documented for the emergence and subsequent proliferation of Acheulian technology (shaped bifacial stone tools). Modern and Middle to Late Pleistocene humans share a suite of derived features in the thumb, wrist, and radial carpometacarpal joints that is noticeably absent in early hominins. Here we show that one of the most distinctive features of this suite in the Middle Pleistocene to recent human hand, the third metacarpal styloid process, was present ∼1.42 Mya in an East African hominin from Kaitio, West Turkana, Kenya. This fossil thus provides the earliest unambiguous evidence for the evolution of a key shared derived characteristic of modern human and Neandertal hand morphology and suggests that the distinctive complex of radial carpometacarpal joint features in the human hand arose early in the evolution of the genus Homo and probably in Homo erectus sensu lato. PMID:24344276

  13. A late Pleistocene human presence at Huaca Prieta, Peru, and early Pacific Coastal adaptations

    NASA Astrophysics Data System (ADS)

    Dillehay, Tom D.; Bonavia, Duccio; Goodbred, Steve L.; Pino, Mario; Vásquez, Victor; Tham, Teresa Rosales

    2012-05-01

    Archaeological excavations in deep pre-mound levels at Huaca Prieta in northern Peru have yielded new evidence of late Pleistocene cultural deposits that shed insights into the early human occupation of the Pacific coast of South America. Radiocarbon dates place this occupation between ~ 14,200 and 13,300 cal yr BP. The cultural evidence shares certain basic technological and subsistence traits, including maritime resources and simple flake tools, with previously discovered late Pleistocene sites along the Pacific coast of Peru and Chile. The results help to expand our knowledge of early maritime societies and human adaption to changing coastal environments.

  14. The Effect of Additives on the Early Stages of Growth of Calcite Single Crystals

    PubMed Central

    Freeman, Colin L.; Gong, Xiuqing; Levenstein, Mark A.; Wang, Yunwei; Kulak, Alexander; Anduix‐Canto, Clara; Lee, Phillip A.; Li, Shunbo; Chen, Li; Christenson, Hugo K.

    2017-01-01

    Abstract As crystallization processes are often rapid, it can be difficult to monitor their growth mechanisms. In this study, we made use of the fact that crystallization proceeds more slowly in small volumes than in bulk solution to investigate the effects of the soluble additives Mg2+ and poly(styrene sulfonate) (PSS) on the early stages of growth of calcite crystals. Using a “Crystal Hotel” microfluidic device to provide well‐defined, nanoliter volumes, we observed that calcite crystals form via an amorphous precursor phase. Surprisingly, the first calcite crystals formed are perfect rhombohedra, and the soluble additives have no influence on the morphology until the crystals reach sizes of 0.1–0.5 μm for Mg2+ and 1–2 μm for PSS. The crystals then continue to grow to develop morphologies characteristic of these additives. These results can be rationalized by considering additive binding to kink sites, which is consistent with crystal growth by a classical mechanism. PMID:28767197

  15. Contrasting Strategies of Alfalfa Stem Elongation in Response to Fall Dormancy in Early Growth Stage: The Tradeoff between Internode Length and Internode Number

    PubMed Central

    Wang, Zongli; Sun, Qizhong

    2015-01-01

    Fall dormancy (FD) in alfalfa (Medicago sativa L.) can be described using 11 FD ratings, is widely used as an important indicator of stress resistance, productive performance and spring growth. However, the contrasting growth strategies in internode length and internode number in alfalfa cultivars with different FD rating are poorly understood. Here, a growth chamber study was conducted to investigate the effect of FD on plant height, aboveground biomass, internode length, and internode number in alfalfa individuals in the early growth stages. In order to simulate the alfalfa growth environment in the early stage, 11 alfalfa cultivars with FD ratings from one to 11 were chosen and seeded at the greenhouse, and then were transplanted into an artificial growth chamber. The experimental design was a randomized complete block in a split-plot arrangement with three replicates. Plant height, above-ground biomass, internode length, and internode number were measured in early growth stage in all individuals. Our findings showed that plant height and the aboveground biomass of alfalfa did not significantly differ among 11 different FD rated cultivars. Also, internode length and internode number positively affected plant height and the aboveground biomass of alfalfa individuals and the average internode length significantly increased with increasing FD rating. However, internode number tended to sharply decline when the FD rating increased. Moreover, there were no correlations, slightly negative correlations, and strongly negative correlations between internode length and internode number in alfalfa individuals among the three scales, including within-FD ratings, within-FD categories and inter-FD ratings, respectively. Therefore, our results highlighted that contrasting growth strategies in stem elongation were adopted by alfalfa with different FD ratings in the early growth stage. Alfalfa cultivars with a high FD rating have longer internodes, whereas more dormant alfalfa

  16. The early inflorescence of Arabidopsis thaliana demonstrates positional effects in floral organ growth and meristem patterning.

    PubMed

    Plackett, Andrew R G; Powers, Stephen J; Phillips, Andy L; Wilson, Zoe A; Hedden, Peter; Thomas, Stephen G

    2018-06-01

    Linear modelling approaches detected significant gradients in organ growth and patterning across early flowers of the Arabidopsis inflorescence and uncovered evidence of new roles for gibberellin in floral development. Most flowering plants, including the genetic model Arabidopsis thaliana, produce multiple flowers in sequence from a reproductive shoot apex to form a flower spike (inflorescence). The development of individual flowers on an Arabidopsis inflorescence has typically been considered as highly stereotypical and uniform, but this assumption is contradicted by the existence of mutants with phenotypes visible in early flowers only. This phenomenon is demonstrated by mutants partially impaired in the biosynthesis of the phytohormone gibberellin (GA), in which floral organ growth is retarded in the first flowers to be produced but has recovered spontaneously by the 10th flower. We presently lack systematic data from multiple flowers across the Arabidopsis inflorescence to explain such changes. Using mutants of the GA 20-OXIDASE (GA20ox) GA biosynthesis gene family to manipulate endogenous GA levels, we investigated the dynamics of changing floral organ growth across the early Arabidopsis inflorescence (flowers 1-10). Modelling of floral organ lengths identified a significant, GA-independent gradient of increasing stamen length relative to the pistil in the wild-type inflorescence that was separable from other, GA-dependent effects. It was also found that the first flowers exhibited unstable organ patterning in contrast to later flowers and that this instability was prolonged by exogenous GA treatment. These findings indicate that the development of individual flowers is influenced by hitherto unknown factors acting across the inflorescence and also suggest novel functions for GA in floral patterning.

  17. An early history of human breast cancer: West meets East.

    PubMed

    Yan, Shou-He

    2013-09-01

    Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

  18. Early Growth Response Gene 1 ("EGR-1") Is Required for New and Reactivated Fear Memories in the Lateral Amygdala

    ERIC Educational Resources Information Center

    Maddox, Stephanie A.; Monsey, Melissa S.; Schafe, Glenn E.

    2011-01-01

    The immediate-early gene early growth response gene-1 (EGR-1, zif-268) has been extensively studied in synaptic plasticity and memory formation in a variety of memory systems. However, a convincing role for EGR-1 in amygdala-dependent memory consolidation processes has yet to emerge. In the present study, we have examined the role of EGR-1 in the…

  19. Implications of Nubian-Like Core Reduction Systems in Southern Africa for the Identification of Early Modern Human Dispersals

    PubMed Central

    Phillips, Natasha

    2015-01-01

    Lithic technologies have been used to trace dispersals of early human populations within and beyond Africa. Convergence in lithic systems has the potential to confound such interpretations, implying connections between unrelated groups. Due to their reductive nature, stone artefacts are unusually prone to this chance appearance of similar forms in unrelated populations. Here we present data from the South African Middle Stone Age sites Uitpanskraal 7 and Mertenhof suggesting that Nubian core reduction systems associated with Late Pleistocene populations in North Africa and potentially with early human migrations out of Africa in MIS 5 also occur in southern Africa during early MIS 3 and with no clear connection to the North African occurrence. The timing and spatial distribution of their appearance in southern and northern Africa implies technological convergence, rather than diffusion or dispersal. While lithic technologies can be a critical guide to human population flux, their utility in tracing early human dispersals at large spatial and temporal scales with stone artefact types remains questionable. PMID:26125972

  20. Exploring Human Growth: Using a Calculator to Integrate Mathematics and Science.

    ERIC Educational Resources Information Center

    Wandersee, James H.

    1992-01-01

    Presents integrated activities for mathematics and biology appropriate for various levels from grades five through eight. Explores interesting aspects of human fingernails and hair growth and their mathematical relationship to time. Provides suggestions to integrate the activities with technology. (MDH)

  1. Profiles of mRNA expression of related genes in the duck hypothalamus-pituitary growth axis during embryonic and early post-hatch development.

    PubMed

    Hu, Yan; Liu, Hongxiang; Song, Chi; Xu, Wenjuan; Ji, Gaige; Zhu, Chunhong; Shu, Jingting; Li, Huifang

    2015-03-15

    In this study, the ontogeny of body and liver weight and the pattern of related gene mRNA expression in the hypothalamus-pituitary growth axis (HPGA) of two different duck breeds (Anas platyrhynchos domestica) were compared during embryonic and post-hatch development. Duck hypothalamic growth hormone release hormone (GHRH), somatostatin (SS), pituitary growth hormone (GH), liver growth hormone receptor (GHR) and insulin-like growth factor-I (IGF-1) mRNA were first detected on the 13th embryonic day. During early duck development, SS maintained a lower expression status, whereas the other four genes exhibited highly significant variations in an age-specific manner. Highly significant breed specificity was observed with respect to hepatic IGF-1 mRNA expression, which showed a significant breed-age interaction effect. Compared with previous studies on chickens, significant species differences were observed regarding the mRNA expression of bird embryonic HPGA-related genes. During early development, highly significant breed and age specificity were observed with respect to developmental changes in body and liver weight, and varying degrees of significant linear correlation were found between these performances and the mRNA expression of HPGA-related genes in the duck HPGA. These results suggest that different genetic backgrounds may lead to differences in duck growth and HPGA-related gene mRNA expression, and the differential mRNA expression of related genes in the duck HPGA may be particularly important in the early growth of ducks. Furthermore, hepatic IGF-1 mRNA expression presented highly significant breed specificity, and evidence suggests the involvement of hepatic IGF-1 in mediating genetic effects on embryo and offspring growth in ducks. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Postnatal penile growth concurrent with mini-puberty predicts later sex-typed play behavior: Evidence for neurobehavioral effects of the postnatal androgen surge in typically developing boys.

    PubMed

    Pasterski, Vickie; Acerini, Carlo L; Dunger, David B; Ong, Ken K; Hughes, Ieuan A; Thankamony, Ajay; Hines, Melissa

    2015-03-01

    The masculinizing effects of prenatal androgens on human neurobehavioral development are well established. Also, the early postnatal surge of androgens in male infants, or mini-puberty, has been well documented and is known to influence physiological development, including penile growth. However, neurobehavioral effects of androgen exposure during mini-puberty are largely unknown. The main aim of the current study was to evaluate possible neurobehavioral consequences of mini-puberty by relating penile growth in the early postnatal period to subsequent behavior. Using multiple linear regression, we demonstrated that penile growth between birth and three months postnatal, concurrent with mini-puberty, significantly predicted increased masculine/decreased feminine behavior assessed using the Pre-school Activities Inventory (PSAI) in 81 healthy boys at 3 to 4years of age. When we controlled for other potential influences on masculine/feminine behavior and/or penile growth, including variance in androgen exposure prenatally and body growth postnally, the predictive value of penile growth in the early postnatal period persisted. More specifically, prenatal androgen exposure, reflected in the measurement of anogenital distance (AGD), and early postnatal androgen exposure, reflected in penile growth from birth to 3months, were significant predictors of increased masculine/decreased feminine behavior, with each accounting for unique variance. Our findings suggest that independent associations of PSAI with AGD at birth and with penile growth during mini-puberty reflect prenatal and early postnatal androgen exposures respectively. Thus, we provide a novel and readily available approach for assessing effects of early androgen exposures, as well as novel evidence that early postnatal aes human neurobehavioral development. Copyright © 2015. Published by Elsevier Inc.

  3. Pre-sowing Seed Treatments in Direct-seeded Early Rice: Consequences for Emergence, Seedling Growth and Associated Metabolic Events under Chilling Stress

    NASA Astrophysics Data System (ADS)

    Wang, Weiqin; Chen, Qian; Hussain, Saddam; Mei, Junhao; Dong, Huanglin; Peng, Shaobing; Huang, Jianliang; Cui, Kehui; Nie, Lixiao

    2016-01-01

    Double direct-seeding for double rice cropping is a simplified, labor saving, and efficient cropping system to improve multiple-crop index and total rice production in central China. However, poor crop establishment of direct-seeded early rice due to chilling stress is the main obstacle to wide spread of this system. A series of experiments were conducted to unravel the effects of pre-sowing seed treatments on emergence, seedling growth and associated metabolic events of direct-seeded early rice under chilling stress. Two seed priming treatments and two seed coating treatments were used in all the experiments. A non-treated control treatment was also maintained for comparison. In both the field and growth chamber studies, seed priming with selenium or salicylic acid significantly enhanced the emergence and seedling growth of rice compared with non-treated control. Nevertheless, such positive effects were not apparent for seed coating treatments. Better emergence and vigorous seedling growth of rice after seed priming was associated with enhanced α-amylase activity, higher soluble sugars contents, and greater respiration rate in primed rice seedlings under chilling stress. Taking together, these findings may provide new avenues for understanding and advancing priming-induced chilling tolerance in direct-seeded early rice in double rice cropping system.

  4. Conceptual basis for prescriptive growth standards from conception to early childhood: present and future.

    PubMed

    Uauy, R; Casanello, P; Krause, B; Kuzanovic, J P; Corvalan, C

    2013-09-01

    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.

  5. Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

    PubMed Central

    Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

    2013-01-01

    The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

  6. Rapid Growth of Uropathogenic Escherichia coli during Human Urinary Tract Infection.

    PubMed

    Forsyth, Valerie S; Armbruster, Chelsie E; Smith, Sara N; Pirani, Ali; Springman, A Cody; Walters, Matthew S; Nielubowicz, Greta R; Himpsl, Stephanie D; Snitkin, Evan S; Mobley, Harry L T

    2018-03-06

    Uropathogenic Escherichia coli (UPEC) strains cause most uncomplicated urinary tract infections (UTIs). These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC) strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical sites. Here, we hypothesize that UPEC isolates adapt to and grow more rapidly within the urinary tract than other E. coli isolates and survive in that niche. To date, there has not been a reliable method available to measure their growth rate in vivo Here we used two methods: segregation of nonreplicating plasmid pGTR902, and peak-to-trough ratio (PTR), a sequencing-based method that enumerates bacterial chromosomal replication forks present during cell division. In the murine model of UTI, UPEC strain growth was robust in vivo , matching or exceeding in vitro growth rates and only slowing after reaching high CFU counts at 24 and 30 h postinoculation (hpi). In contrast, asymptomatic bacteriuria (ABU) strains tended to maintain high growth rates in vivo at 6, 24, and 30 hpi, and population densities did not increase, suggesting that host responses or elimination limited population growth. Fecal strains displayed moderate growth rates at 6 hpi but did not survive to later times. By PTR, E. coli in urine of human patients with UTIs displayed extraordinarily rapid growth during active infection, with a mean doubling time of 22.4 min. Thus, in addition to traditional virulence determinants, including adhesins, toxins, iron acquisition, and motility, very high growth rates in vivo and resistance to the innate immune response appear to be critical phenotypes of UPEC strains. IMPORTANCE Uropathogenic Escherichia coli (UPEC) strains cause most urinary tract infections in otherwise healthy women. While we understand numerous virulence factors are utilized by E. coli to colonize and persist within the urinary tract, these properties are inconsequential unless bacteria can divide

  7. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells.

    PubMed

    Lee, Jieun; Taylor, Sarah E B; Smeriglio, Piera; Lai, Janice; Maloney, William J; Yang, Fan; Bhutani, Nidhi

    2015-08-01

    Regeneration of human cartilage is inherently inefficient; an abundant autologous source, such as human induced pluripotent stem cells (hiPSCs), is therefore attractive for engineering cartilage. We report a growth factor-based protocol for differentiating hiPSCs into articular-like chondrocytes (hiChondrocytes) within 2 weeks, with an overall efficiency >90%. The hiChondrocytes are stable and comparable to adult articular chondrocytes in global gene expression, extracellular matrix production, and ability to generate cartilage tissue in vitro and in immune-deficient mice. Molecular characterization identified an early SRY (sex-determining region Y) box (Sox)9(low) cluster of differentiation (CD)44(low)CD140(low) prechondrogenic population during hiPSC differentiation. In addition, 2 distinct Sox9-regulated gene networks were identified in the Sox9(low) and Sox9(high) populations providing novel molecular insights into chondrogenic fate commitment and differentiation. Our findings present a favorable method for generating hiPSC-derived articular-like chondrocytes. The hiChondrocytes are an attractive cell source for cartilage engineering because of their abundance, autologous nature, and potential to generate articular-like cartilage rather than fibrocartilage. In addition, hiChondrocytes can be excellent tools for modeling human musculoskeletal diseases in a dish and for rapid drug screening. © FASEB.

  8. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity.

    PubMed

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B

    2016-10-01

    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. © 2015 John Wiley & Sons Ltd.

  9. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity

    PubMed Central

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B.; King, Janet; Fung, Ellen B.

    2015-01-01

    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children’s Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency. PMID:25850574

  10. Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving very early full human milk feeding.

    PubMed

    Rønnestad, Arild; Abrahamsen, Tore G; Medbø, Sverre; Reigstad, Hallvard; Lossius, Kristin; Kaaresen, Per I; Egeland, Thore; Engelund, Inger E; Irgens, Lorentz M; Markestad, Trond

    2005-03-01

    To investigate the occurrence of and risk factors for late-onset septicemia (LOS) in a national cohort of extremely premature infants who received very early full human milk feeding. A prospective study of all infants born in Norway in 1999 and 2000 with gestational age of <28 weeks or birth weight of <1000 g was performed. Extensive clinical information, including data on feeding practices and episodes of septicemia, was collected on predefined forms. LOS was defined as growth of bacteria or fungi in blood cultures in conjunction with clinical symptoms consistent with systemic infection occurring after day 6 of life. Cox regression models, including models allowing for time-dependent covariates, were applied in the analysis of LOS. Of 464 eligible infants, 462 (99.6%) were enrolled and 405 (87.7%) survived until day 7. LOS was diagnosed for 80 (19.7%). The predominant pathogens were coagulase-negative staphylococci, followed by Candida spp. Case fatality rates associated with septicemia were 10% in general and 43% for Candida spp septicemia. Necrotizing enterocolitis or bowel perforation was diagnosed for 19 infants (4%). Enteral feeding with human milk was initiated within the third day for 98% of patients, and 92% were receiving full enteral feeding (FEF) with human milk within the third week. Both high Clinical Risk Index for Babies scores and an umbilical venous catheter in situ at 7 days of age significantly predicted LOS. However, the overall most influential risk factor for LOS was the number of days without establishment of FEF with human milk, with an adjusted relative risk of 3.7 (2.0-6.9) for LOS if FEF was not established within the second week of life. The incidence and case fatality rate of septicemia for this cohort of extremely preterm infants were lower than values in comparable studies. The main difference, compared with other studies, was the feeding practice, and the data suggest that very early FEF with human milk significantly reduces the

  11. Longitudinal regression analysis of spatial-temporal growth patterns of geometrical diffusion measures in early postnatal brain development with diffusion tensor imaging

    PubMed Central

    Chen, Yasheng; An, Hongyu; Zhu, Hongtu; Jewells, Valerie; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili

    2011-01-01

    Although diffusion tensor imaging (DTI) has provided substantial insights into early brain development, most DTI studies based on fractional anisotropy (FA) and mean diffusivity (MD) may not capitalize on the information derived from the three principal diffusivities (e.g. eigenvalues). In this study, we explored the spatial and temporal evolution of white matter structures during early brain development using two geometrical diffusion measures, namely, linear (Cl) and planar (Cp) diffusion anisotropies, from 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects. The growth trajectories were estimated with generalized estimating equations (GEE) using linear fitting with logarithm of age (days). The presence of the white matter structures in Cl and Cp was observed in neonates, suggesting that both the cylindrical and fanning or crossing structures in various white matter regions may already have been formed at birth. Moreover, we found that both Cl and Cp evolved in a temporally nonlinear and spatially inhomogeneous manner. The growth velocities of Cl in central white matter were significantly higher when compared to peripheral, or more laterally located, white matter: central growth velocity Cl = 0.0465±0.0273/log(days), versus peripheral growth velocity Cl=0.0198±0.0127/log(days), p<10−6. In contrast, the growth velocities of Cp in central white matter were significantly lower than that in peripheral white matter: central growth velocity Cp= 0.0014±0.0058/log(days), versus peripheral growth velocity Cp = 0.0289±0.0101/log(days), p<10−6. Depending on the underlying white matter site which is analyzed, our findings suggest that ongoing physiologic and microstructural changes in the developing brain may exert different effects on the temporal evolution of these two geometrical diffusion measures. Thus, future studies utilizing DTI with correlative histological analysis in the study of early brain development are warranted. PMID

  12. Effect of soy saponin on the growth of human colon cancer cells

    PubMed Central

    Tsai, Cheng-Yu; Chen, Yue-Hwa; Chien, Yi-Wen; Huang, Wen-Hsuan; Lin, Shyh-Hsiang

    2010-01-01

    AIM: To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells. METHODS: WiDr human colon cancer cells were treated with 150, 300, 600 or 1200 ppm of soy saponin to determine the effect on cell growth, cell morphology, alkaline phosphatase (AP) and protein kinase C (PKC) activities, and P53 protein, c-Fos and c-Jun gene expression. RESULTS: Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-O-tetradecanol-phorbol-13-acetate-stimulated PKC activity (P < 0.05). Cells treated with saponins developed cytoplasmic vesicles and the cell membrane became rougher and more irregular in a dose-dependent manner, and eventually disassembled. At 600 and 1200 ppm, the activity of AP was increased (P < 0.05). However, the apoptosis markers such as c-Jun and c-Fos were not significantly affected by saponin. CONCLUSION: Soy saponin may be effective in preventing colon cancer by affecting cell morphology, cell proliferation enzymes, and cell growth. PMID:20632438

  13. Early nutrition, growth and cognitive development of infants from birth to 2 years in Malaysia: a study protocol.

    PubMed

    Nurliyana, Abdul Razak; Mohd Shariff, Zalilah; Mohd Taib, Mohd Nasir; Gan, Wan Ying; Tan, Kit-Aun

    2016-09-29

    The first 2 years of life is a critical period of rapid growth and brain development. During this period, nutrition and environmental factors play important roles in growth and cognitive development of a child. This report describes the study protocol of early nutrition, growth and cognitive development of infants from birth to 2 years of age. This is a prospective cohort study of mothers and infants recruited from government health clinics in Seremban district in Negeri Sembilan, Malaysia. Infants are followed-up at 6, 12, 18 and 24 months of age. Pre-natal factors that include mother's pre-pregnancy body mass index, gestational weight gain, blood glucose and blood pressure during pregnancy, infant's gestational age, birth weight and head circumference at birth are obtained from patient card. Post-natal factors assessed at each follow-up are feeding practices, dietary intake, anthropometric measurements and cognitive development of infants. Iron status is assessed at 6 months, while infant temperament and home environment are assessed at 12 months. Maternal intelligence is assessed at 18 months. Early life nutritional programming is of current interest as many longitudinal studies are actively being conducted in developed countries to investigate this concept. The concept however is relatively new in developing countries such as Malaysia. This study will provide useful information on early nutrition and infant development in the first two years of life which can be further followed up to identify factors that track into childhood and contribute to growth and cognitive deviations.

  14. Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth?

    PubMed Central

    Devesa, Jesús; Almengló, Cristina; Devesa, Pablo

    2016-01-01

    In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown. PMID:27773998

  15. Early subtropical forest growth is driven by community mean trait values and functional diversity rather than the abiotic environment.

    PubMed

    Kröber, Wenzel; Li, Ying; Härdtle, Werner; Ma, Keping; Schmid, Bernhard; Schmidt, Karsten; Scholten, Thomas; Seidler, Gunnar; von Oheimb, Goddert; Welk, Erik; Wirth, Christian; Bruelheide, Helge

    2015-09-01

    While functional diversity (FD) has been shown to be positively related to a number of ecosystem functions including biomass production, it may have a much less pronounced effect than that of environmental factors or species-specific properties. Leaf and wood traits can be considered particularly relevant to tree growth, as they reflect a trade-off between resources invested into growth and persistence. Our study focussed on the degree to which early forest growth was driven by FD, the environment (11 variables characterizing abiotic habitat conditions), and community-weighted mean (CWM) values of species traits in the context of a large-scale tree diversity experiment (BEF-China). Growth rates of trees with respect to crown diameter were aggregated across 231 plots (hosting between one and 23 tree species) and related to environmental variables, FD, and CWM, the latter two of which were based on 41 plant functional traits. The effects of each of the three predictor groups were analyzed separately by mixed model optimization and jointly by variance partitioning. Numerous single traits predicted plot-level tree growth, both in the models based on CWMs and FD, but none of the environmental variables was able to predict tree growth. In the best models, environment and FD explained only 4 and 31% of variation in crown growth rates, respectively, while CWM trait values explained 42%. In total, the best models accounted for 51% of crown growth. The marginal role of the selected environmental variables was unexpected, given the high topographic heterogeneity and large size of the experiment, as was the significant impact of FD, demonstrating that positive diversity effects already occur during the early stages in tree plantations.

  16. Early subtropical forest growth is driven by community mean trait values and functional diversity rather than the abiotic environment

    PubMed Central

    Kröber, Wenzel; Li, Ying; Härdtle, Werner; Ma, Keping; Schmid, Bernhard; Schmidt, Karsten; Scholten, Thomas; Seidler, Gunnar; von Oheimb, Goddert; Welk, Erik; Wirth, Christian; Bruelheide, Helge

    2015-01-01

    While functional diversity (FD) has been shown to be positively related to a number of ecosystem functions including biomass production, it may have a much less pronounced effect than that of environmental factors or species-specific properties. Leaf and wood traits can be considered particularly relevant to tree growth, as they reflect a trade-off between resources invested into growth and persistence. Our study focussed on the degree to which early forest growth was driven by FD, the environment (11 variables characterizing abiotic habitat conditions), and community-weighted mean (CWM) values of species traits in the context of a large-scale tree diversity experiment (BEF-China). Growth rates of trees with respect to crown diameter were aggregated across 231 plots (hosting between one and 23 tree species) and related to environmental variables, FD, and CWM, the latter two of which were based on 41 plant functional traits. The effects of each of the three predictor groups were analyzed separately by mixed model optimization and jointly by variance partitioning. Numerous single traits predicted plot-level tree growth, both in the models based on CWMs and FD, but none of the environmental variables was able to predict tree growth. In the best models, environment and FD explained only 4 and 31% of variation in crown growth rates, respectively, while CWM trait values explained 42%. In total, the best models accounted for 51% of crown growth. The marginal role of the selected environmental variables was unexpected, given the high topographic heterogeneity and large size of the experiment, as was the significant impact of FD, demonstrating that positive diversity effects already occur during the early stages in tree plantations. PMID:26380685

  17. Three-dimensional growth dynamics of the liver in the human fetus.

    PubMed

    Szpinda, Michał; Paruszewska-Achtel, Monika; Woźniak, Alina; Badura, Mateusz; Mila-Kierzenkowska, Celestyna; Wiśniewski, Marcin

    2015-07-01

    The fetal liver is indubitably the earliest and the most severely affected organ by abnormal fetal growth. The size of the fetal liver assessed by three-dimensional ultrasonography is indispensable in determining the status of fetal growth, nutrition and maturity, and in the early recognition and monitoring fetal micro- and macrosomias. The aim of the present study was to measure the human fetal liver length, transverse and sagittal diameters to establish their age-specific reference intervals, the 3rd, 10th, 50th, 90th, and 97th smoothed centile curves, and the relative growth of the liver calculated for the 50th centile. Using anatomical, digital (NIS-Elements AR 3.0, Nikon) and statistical methods (one-way ANOVA test for paired data and post hoc RIR Tukey test, Shapiro-Wilk test, Fisher's test, Student's t test, the Altman-Chitty method), length, transverse and sagittal diameters of the liver for the 3rd, 10th, 50th, 90th, and 97th centiles were assessed in 69 human fetuses of both sexes (32 males and 37 females) aged 18-30 weeks, derived from spontaneous abortions or stillbirths. No male-female differences (P > 0.05) concerning the three parameters studied were found. During the study period, the fetal liver increased tri-dimensionally: in length from 19.51 ± 1.02 to 39.65 ± 7.05 mm, in transverse diameter from 29.44 ± 3.73 to 53.13 ± 5.31 mm, and in sagittal diameter from 22.97 ± 3.79 to 43.22 ± 5.49 mm. The natural logarithmic models were found to fit the data with gestational age (P < 0.001) in the following five cutoff points: 3rd, 10th, 50th, 90th and 97th centiles. The values of liver parameters in relation to gestational age in weeks were calculated by the following logarithmic regressions: y = -82.778 + 35.752 × ln(age) ± Z × (-2.778 + 0.308 × age) for liver length, y = -123.06 + 52.668 × ln(age) ± Z × (3.156 + 0.049 × age) for liver transverse diameter, and y = -108.94 + 46.052 × ln(age) ± Z × (-0.541 + 0.188 × age) for liver sagittal

  18. Ancient gene flow from early modern humans into Eastern Neanderthals

    PubMed Central

    Kuhlwilm, Martin; Gronau, Ilan; Hubisz, Melissa J.; de Filippo, Cesare; Prado-Martinez, Javier; Kircher, Martin; Fu, Qiaomei; Burbano, Hernán A.; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Rudan, Pavao; Brajkovic, Dejana; Kucan, Željko; Gušic, Ivan; Marques-Bonet, Tomas; Andrés, Aida M.; Viola, Bence; Pääbo, Svante; Meyer, Matthias; Siepel, Adam; Castellano, Sergi

    2016-01-01

    It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000–65,000 years ago. Here, we analyze the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a population that diverged early from other modern humans in Africa contributed genetically to the ancestors of Neanderthals from the Altai Mountains roughly 100,000 years ago. By contrast, we do not detect such a genetic contribution in the Denisovan or the two European Neanderthals. We conclude that in addition to later interbreeding events, the ancestors of Neanderthals from the Altai Mountains and of modern humans met and interbred, possibly in the Near East, many thousands of years earlier than previously reported. PMID:26886800

  19. Innovative virtual reality measurements for embryonic growth and development.

    PubMed

    Verwoerd-Dikkeboom, C M; Koning, A H J; Hop, W C; van der Spek, P J; Exalto, N; Steegers, E A P

    2010-06-01

    Innovative imaging techniques, using up-to-date ultrasonic equipment, necessitate specific biometry. The aim of our study was to test the possibility of detailed human embryonic biometry using a virtual reality (VR) technique. In a longitudinal study, three-dimensional (3D) measurements were performed from 6 to 14 weeks gestational age in 32 pregnancies (n = 16 spontaneous conception, n = 16 IVF/ICSI). A total of 125 3D volumes were analysed in the I-Space VR system, which allows binocular depth perception, providing a realistic 3D illusion. Crown-rump length (CRL), biparietal diameter (BPD), occipito-frontal diameter (OFD), head circumference (HC) and abdominal circumference (AC) were measured as well as arm length, shoulder width, elbow width, hip width and knee width. CRL, BPD, OFD and HC could be measured in more than 96% of patients, and AC in 78%. Shoulder width, elbow width, hip width and knee width could be measured in more than 95% of cases, and arm length in 82% of cases. Growth curves were constructed for all variables. Ear and foot measurements were only possible beyond 9 weeks gestation. This study provides a detailed, longitudinal description of normal human embryonic growth, facilitated by a VR system. Growth curves were created for embryonic biometry of the CRL, BPD, HC and AC early in pregnancy and also of several 'new' biometric measurements. Applying virtual embryoscopy will enable us to diagnose growth and/or developmental delay earlier and more accurately. This is especially important for pregnancies at risk of severe complications, such as recurrent late miscarriage and early growth restriction.

  20. The effects of genetic polymorphism on treatment response of recombinant human growth hormone.

    PubMed

    Chen, Shi; You, Hanxiao; Pan, Hui; Zhu, Huijuan; Yang, Hongbo; Gong, Fengying; Wang, Linjie; Jiang, Yu; Yan, Chengsheng

    2017-12-06

    Recombinant human growth hormone (rhGH) has been widely used in clinical treatment of growth hormone deficiency (GHD) or non GHD since 1985 and technology have achieved a great development in different long-acting formulations. Although the mathematical models for predicting the growth hormone response could help clinicians get to an individual personalized growth dose, many patients just can't reach the target height and the growth hormone responses differed.Genetic polymorphisms may play a role in the varies of individual responses in this treatment process.This article gives an overview of the genetic polymorphisms research of growth hormone in recent years, in order to give some potential suggestion and guide for the dose titration during treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Facilitated early cortical processing of nude human bodies.

    PubMed

    Alho, Jussi; Salminen, Nelli; Sams, Mikko; Hietanen, Jari K; Nummenmaa, Lauri

    2015-07-01

    Functional brain imaging has identified specialized neural systems supporting human body perception. Responses to nude vs. clothed bodies within this system are amplified. However, it remains unresolved whether nude and clothed bodies are processed by same cerebral networks or whether processing of nude bodies recruits additional affective and arousal processing areas. We recorded simultaneous MEG and EEG while participants viewed photographs of clothed and nude bodies. Global field power revealed a peak ∼145ms after stimulus onset to both clothed and nude bodies, and ∼205ms exclusively to nude bodies. Nude-body-sensitive responses were centered first (100-200ms) in the extrastriate and fusiform body areas, and subsequently (200-300ms) in affective-motivational areas including insula and anterior cingulate cortex. We conclude that visibility of sexual features facilitates early cortical processing of human bodies, the purpose of which is presumably to trigger sexual behavior and ultimately ensure reproduction. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. In vitro 3D regeneration-like growth of human patient brain tissue.

    PubMed

    Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

    2018-05-01

    In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

  3. Evolution and the Growth Process: Natural Selection of Entrepreneurial Traits.

    PubMed

    Galor, Oded; Michalopoulos, Stelios

    2012-03-01

    This research suggests that a Darwinian evolution of entrepreneurial spirit played a significant role in the process of economic development and the dynamics of inequality within and across societies. The study argues that entrepreneurial spirit evolved non-monotonically in the course of human history. In early stages of development, risk-tolerant, growth promoting traits generated an evolutionary advantage and their increased representation accelerated the pace of technological progress and the process of economic development. In mature stages of development, however, risk-averse traits gained an evolutionary advantage, diminishing the growth potential of advanced economies and contributing to convergence in economic growth across countries.

  4. Input Subject Diversity Enhances Early Grammatical Growth: Evidence from a Parent-Implemented Intervention

    PubMed Central

    Hadley, Pamela A.; Rispoli, Matthew; Holt, Janet K.; Papastratakos, Theodora; Hsu, Ning; Kubalanza, Mary; McKenna, Megan M.

    2016-01-01

    Purpose The current study used an intervention design to test the hypothesis that parent input sentences with diverse lexical noun phrase (NP) subjects would accelerate growth in children’s sentence diversity. Method Child growth in third person sentence diversity was modeled from 21 to 30 months (n = 38) in conversational language samples obtained at 21, 24, 27, and 30 months. Treatment parents (n = 19) received instruction on strategies designed to increase lexical NP subjects (e.g., The baby is sleeping.). Instruction consisted of one group education session and two individual coaching sessions which took place when children were approximately 22 to 23 months of age. Results Treatment substantially increased parents’ lexical NP subject tokens and types (ηp2 ≥ .45) compared to controls. Children’s number of different words was a significant predictor of sentence diversity in the analyses of group treatment effects and individual input effects. Treatment condition was not a significant predictor of treatment effects on children’s sentence diversity, but parents’ lexical NP subject types was a significant predictor of children’s sentence diversity growth, even after controlling for children’s number of different words over time. Conclusions These findings establish a link between subject diversity in parent input and children’s early grammatical growth, and the feasibility of using relatively simple strategies to alter this specific grammatical property of parent language input. PMID:28286431

  5. Early warning signals of regime shifts in coupled human–environment systems

    PubMed Central

    Bauch, Chris T.; Sigdel, Ram; Pharaon, Joe; Anand, Madhur

    2016-01-01

    In complex systems, a critical transition is a shift in a system’s dynamical regime from its current state to a strongly contrasting state as external conditions move beyond a tipping point. These transitions are often preceded by characteristic early warning signals such as increased system variability. However, early warning signals in complex, coupled human–environment systems (HESs) remain little studied. Here, we compare critical transitions and their early warning signals in a coupled HES model to an equivalent environment model uncoupled from the human system. We parameterize the HES model, using social and ecological data from old-growth forests in Oregon. We find that the coupled HES exhibits a richer variety of dynamics and regime shifts than the uncoupled environment system. Moreover, the early warning signals in the coupled HES can be ambiguous, heralding either an era of ecosystem conservationism or collapse of both forest ecosystems and conservationism. The presence of human feedback in the coupled HES can also mitigate the early warning signal, making it more difficult to detect the oncoming regime shift. We furthermore show how the coupled HES can be “doomed to criticality”: Strategic human interactions cause the system to remain perpetually in the vicinity of a collapse threshold, as humans become complacent when the resource seems protected but respond rapidly when it is under immediate threat. We conclude that the opportunities, benefits, and challenges of modeling regime shifts and early warning signals in coupled HESs merit further research. PMID:27815533

  6. Growth and development of premature infants fed predominantly human milk, predominantly premature infant formula, or a combination of human milk and premature formula.

    PubMed

    O'Connor, Deborah L; Jacobs, Joan; Hall, Robert; Adamkin, David; Auestad, Nancy; Castillo, Marcella; Connor, William E; Connor, Sonja L; Fitzgerald, Kathleen; Groh-Wargo, Sharon; Hartmann, E Eugenie; Janowsky, Jeri; Lucas, Alan; Margeson, Dean; Mena, Patricia; Neuringer, Martha; Ross, Gail; Singer, Lynn; Stephenson, Terence; Szabo, Joanne; Zemon, Vance

    2003-10-01

    had larger head circumferences (0.3-1.1 cm) than both PHM-T and >/= 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed >/= 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model). Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

  7. Phosphorylation of hepatocyte growth factor receptor and epidermal growth factor receptor of human hepatocytes can be maintained in a (3D) collagen sandwich culture system.

    PubMed

    Engl, Tobias; Boost, Kim A; Leckel, Kerstin; Beecken, Wolf-Dietrich; Jonas, Dietger; Oppermann, Elsie; Auth, Marcus K H; Schaudt, André; Bechstein, Wolf-Otto; Blaheta, Roman A

    2004-08-01

    In vitro culture models that employ human liver cells could be potent tools for predictive studies on drug toxicity and metabolism in the pharmaceutical industry. However, an adequate receptor responsiveness is necessary to allow intracellular signalling and metabolic activity. We tested the ability of three-dimensionally arranged human hepatocytes to respond to the growth factors hepatocyte growth factor (HGF) or epidermal growth factor (EGF). Isolated adult human hepatocytes were cultivated within a three-dimensional collagen gel (sandwich) or on a two-dimensional collagen matrix. Cells were treated with HGF or EGF and expression and phosphorylative activity of HGF receptors (HGFr, c-met) or EGF receptors (EGFr) were measured by flow cytometry and Western blot. Increasing HGFr and EGFr levels were detected in hepatocytes growing two-dimensionally. However, both receptors were not activated in presence of growth factors. In contrast, when hepatocytes were plated within a three-dimensional matrix, HGFr and EGFr levels remained constantly low. However, both receptors became strongly phosphorylated by soluble HGF or EGF. We conclude that cultivation of human hepatocytes in a three-dimensionally arranged in vitro system allows the maintenance of specific functional activities. The necessity of cell dimensionality for HGFr and EGFr function should be considered when an adequate in vitro system has to be introduced for drug testing.

  8. Treatment With Recombinant Human Insulin-Like Growth Factor-1 Improves Growth in Patients With PAPP-A2 Deficiency

    PubMed Central

    Muñoz-Calvo, María T.; Barrios, Vicente; Pozo, Jesús; Chowen, Julie A.; Martos-Moreno, Gabriel Á.; Hawkins, Federico; Dauber, Andrew; Domené, Horacio M.; Yakar, Shoshana; Rosenfeld, Ron G.; Pérez-Jurado, Luis A.; Oxvig, Claus; Frystyk, Jan

    2016-01-01

    Context: Pregnancy-associated plasma protein-A2 (PAPP-A2) is a metalloproteinase that specifically cleaves IGFBP-3 and IGFBP-5. Mutations in the PAPP-A2 gene have recently been shown to cause postnatal growth failure in humans, with specific skeletal features, due to the resulting decrease in IGF-1 bioavailability. However, a pharmacological treatment of this entity is yet to be established. Case Description: A 10.5-year-old girl and a 6-year-old boy, siblings from a Spanish family, with short stature due to a homozygous loss-of-function mutation in the PAPP-A2 gene (p.D643fs25*) and undetectable PAPP-A2 activity, were treated with progressive doses (40, 80, 100, and 120 μg/kg) of recombinant human IGF-1 (rhIGF-1) twice daily for 1 year. There was a clear increase in growth velocity and height in both siblings. Bioactive IGF-1 was increased, and spontaneous GH secretion was diminished after acute administration of rhIGF-1, whereas serum total IGF-1 and IGFBP-3 levels remained elevated. No episodes of hypoglycemia or any other secondary effects were observed during treatment. Conclusion: Short-term treatment with rhIGF-1 improves growth in patients with PAPP-A2 deficiency. PMID:27648969

  9. Fortifying fresh human milk with commercial powdered human milk fortifiers does not affect bacterial growth during 6 hours at room temperature.

    PubMed

    Telang, Sucheta; Berseth, Carol Lynn; Ferguson, Paul W; Kinder, Julie M; DeRoin, Mark; Petschow, Bryon W

    2005-10-01

    To evaluate the growth of resident aerobic mesophilic flora and added Enterobacter sakazakii in fresh, unfortified human milk; fresh human milk fortified with two commercial powdered fortifiers differing in iron content; and infant formula prepared from powder. Eight mothers provided preterm breast milk samples. Breast milk samples were divided into three aliquots: unfortified, fortified with fortifier containing 1.44 mg iron/14 kcal, and fortified with fortifier containing 0.4 mg iron/14 kcal. Aliquots of formula were prepared. Breast milk and formula aliquots were divided into two test samples. Half were inoculated with low amounts of E sakazakii; half were not. All test samples were maintained at room temperature (22 degrees C), serially diluted, and plated onto agars after 0, 2, 4, and 6 hours. Plates were incubated at 35 degrees C and enumerated. Data were analyzed using repeated measures analysis of variance. P<.05 was considered significant. There were no differences in colony counts of aerobic bacteria among uninoculated or among inoculated human milk samples at any time; counts did not increase significantly over 6 hours. There were no differences in colony counts of E sakazakii among inoculated human milk samples at any time; counts did not increase significantly over 6 hours. Aerobic bacteria and E sakazakii colony counts from infant formula did not increase significantly over 6 hours. During 6 hours at 22 degrees C, fresh human milk and formula had negligible bacterial growth; fortifying human milk with powdered fortifiers did not affect bacterial growth.

  10. Expression of growth differentiation factor 6 in the human developing fetal spine retreats from vertebral ossifying regions and is restricted to cartilaginous tissues.

    PubMed

    Wei, Aiqun; Shen, Bojiang; Williams, Lisa A; Bhargav, Divya; Gulati, Twishi; Fang, Zhimin; Pathmanandavel, Sarennya; Diwan, Ashish D

    2016-02-01

    During embryogenesis vertebral segmentation is initiated by sclerotomal cell migration and condensation around the notochord, forming anlagen of vertebral bodies and intervertebral discs. The factors that govern the segmentation are not clear. Previous research demonstrated that mutations in growth differentiation factor 6 resulted in congenital vertebral fusion, suggesting this factor plays a role in development of vertebral column. In this study, we detected expression and localization of growth differentiation factor 6 in human fetal spinal column, especially in the period of early ossification of vertebrae and the developing intervertebral discs. The extracellular matrix proteins were also examined. Results showed that high levels of growth differentiation factor 6 were expressed in the nucleus pulposus of intervertebral discs and the hypertrophic chondrocytes adjacent to the ossification centre in vertebral bodies, where strong expression of proteoglycan and collagens was also detected. As fetal age increased, the expression of growth differentiation factor 6 was decreased correspondingly with the progress of ossification in vertebral bodies and restricted to cartilaginous regions. This expression pattern and the genetic link to vertebral fusion suggest that growth differentiation factor 6 may play an important role in suppression of ossification to ensure proper vertebral segmentation during spinal development. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  11. Endocrine and Metabolic Biomarkers Predicting Early Childhood Obesity Risk.

    PubMed

    Socha, Piotr; Hellmuth, Christian; Gruszfeld, Dariusz; Demmelmair, Hans; Rzehak, Peter; Grote, Veit; Weber, Martina; Escribano, Joaquin; Closa-Monasterolo, Ricardo; Dain, Elena; Langhendries, Jean-Paul; Riva, Enrica; Verduci, Elvira; Koletzko, Berthold

    2016-01-01

    There is growing evidence of long-term effects of early dietary intervention in infancy on later obesity risk. Many studies showed reduced risk of obesity with breastfeeding in infancy, which could be related to the reduced protein intake with human milk compared to infant formula. In a randomized controlled trial (Childhood Obesity Project), we were able to show that infant formula with reduced protein content results in lower BMI both at 2 and 6 years. These effects seem to be mediated mainly by branched-chain amino acids which stimulate the insulin-like growth factor (IGF)-1 axis and insulin release. In this trial, we also showed an influence of high-protein diet on larger kidney size, which seems to be partly explained by a significant effect of free IGF-1 on kidney volume. The IGF-1 axis was shown to regulate early growth, adipose tissue differentiation and early adipogenesis in animals and in humans. Leptin and adiponectin can also be regarded as important endocrine regulators of obesity. These markers were tested in observational studies. Leptin seems to be closely correlated with BMI but changes in adiponectin require further exploration. Still, there is a lack of good data or some results are contradictory to indicate the role of either leptin or adiponectin in infancy for determining later obesity risk. © 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.

  12. Human umbilical cord blood serum promotes growth, proliferation, as well as differentiation of human bone marrow-derived progenitor cells.

    PubMed

    Phadnis, Smruti M; Joglekar, Mugdha V; Venkateshan, Vijayalakshmi; Ghaskadbi, Surendra M; Hardikar, Anandwardhan A; Bhonde, Ramesh R

    2006-01-01

    Fetal calf serum (FCS) is conventionally used for animal cell cultures due to its inherent growth-promoting activities. However animal welfare issues and stringent requirements for human transplantation studies demand a suitable alternative for FCS. With this view, we studied the effect of FCS, human AB serum (ABS), and human umbilical cord blood serum (UCBS) on murine islets of Langerhans and human bone marrow-derived mesenchymal-like cells (hBMCs). We found that there was no difference in morphology and functionality of mouse islets cultured in any of these three different serum supplements as indicated by insulin immunostaining. A comparative analysis of hBMCs maintained in each of these three different serum supplements demonstrated that UCBS supplemented media better supported proliferation of hBMCs. Moreover, a modification of adipogenic differentiation protocol using UCBS indicates that it can be used as a supplement to support differentiation of hBMCs into adipocytes. Our results demonstrate that UCBS not only is suitable for maintenance of murine pancreatic islets, but also supports attachment, propagation, and differentiation of hBMCs in vitro. We conclude that UCBS can serve as a better serum supplement for growth, maintenance, and differentiation of hBMCs, making it a more suitable supplement in cell systems that have therapeutic potential in human transplantation programs.

  13. Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.

    PubMed

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M; Esguerra, Camila V; Blust, Ronny; Darras, Veerle M; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  14. Deiodinase Knockdown during Early Zebrafish Development Affects Growth, Development, Energy Metabolism, Motility and Phototransduction

    PubMed Central

    Bagci, Enise; Heijlen, Marjolein; Vergauwen, Lucia; Hagenaars, An; Houbrechts, Anne M.; Esguerra, Camila V.; Blust, Ronny; Darras, Veerle M.; Knapen, Dries

    2015-01-01

    Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance

  15. Barium distributions in teeth reveal early life dietary transitions in primates

    PubMed Central

    Austin, Christine; Smith, Tanya M.; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J.; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-01-01

    Early life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1,2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early life dietary history in fossils is hampered by the absence of prospectively-validated biomarkers that are not modified during fossilisation4. Here we show that major dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively-recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk and through the weaning process. We also document transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, suggesting an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history. PMID:23698370

  16. Barium distributions in teeth reveal early-life dietary transitions in primates.

    PubMed

    Austin, Christine; Smith, Tanya M; Bradman, Asa; Hinde, Katie; Joannes-Boyau, Renaud; Bishop, David; Hare, Dominic J; Doble, Philip; Eskenazi, Brenda; Arora, Manish

    2013-06-13

    Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother's milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.

  17. Physical Growth of the Shuar: Height, Weight, and BMI References for an Indigenous Amazonian Population

    PubMed Central

    URLACHER, SAMUEL S.; BLACKWELL, AARON D.; LIEBERT, MELISSA A.; MADIMENOS, FELICIA C.; CEPON-ROBINS, TARA J.; GILDNER, THERESA E.; SNODGRASS, J. JOSH; SUGIYAMA, LAWRENCE S.

    2015-01-01

    Objectives Information concerning physical growth among small-scale populations remains limited, yet such data are critical to local health efforts and to foster basic understandings of human life history and variation in childhood development. Using a large dataset and robust modeling methods, this study aims to describe growth from birth to adulthood among the indigenous Shuar of Amazonian Ecuador. Methods Mixed-longitudinal measures of height, weight, and BMI were collected from Shuar participants (n = 2,463; age 0–29 years). Centile growth curves and tables were created for each anthropometric variable of interest using GAMLSS. Pseudo-velocity and LMS curves were generated to further investigate Shuar patterns of growth and to facilitate comparison with U.S. CDC and multinational WHO growth references. Results The Shuar are small throughout life and exhibit complex patterns of growth that differ substantially from those of international references. Similar to other Amazonians, Shuar growth in weight compares more favorably to references than growth in height, resulting in BMI curves that approximate international medians. Several additional characteristics of Shuar development are noteworthy, including large observed variation in body size early in life, significant infant growth faltering, extended male growth into adulthood, and a markedly early female pubertal growth spurt in height. Phenotypic plasticity and genetic selection in response to local environmental factors may explain many of these patterns. Conclusions Providing a detailed reference of growth for the Shuar and other Amazonian populations, this study possesses direct clinical application and affords valuable insight into childhood health and the ecology of human growth. PMID:26126793

  18. SEM evaluation of human gingival fibroblasts growth onto CAD/CAM zirconia and veneering ceramic for zirconia

    PubMed Central

    Zizzari, Vincenzo; Borelli, Bruna; De Colli, Marianna; Tumedei, Margherita; Di Iorio, Donato; Zara, Susi; Sorrentino, Roberto; Cataldi, Amelia; Gherlone, Enrico Felice; Zarone, Fernando; Tetè, Stefano

    2013-01-01

    Summary Aim To evaluate the growth of Human Gingival Fibroblasts (HGFs) cultured onto sample discs of CAD/CAM zirconia and veneering ceramic for zirconia by means of Scanning Electron Microscope (SEM) analysis at different experimental times. Methods A total of 26 experimental discs, divided into 2 groups, were used: Group A) CAD/CAM zirconia (3Y-TZP) discs (n=13); Group B) veneering ceramic for zirconia discs (n=13). HGFs were obtained from human gingival biopsies, isolated and placed in culture plates. Subsequently, cells were seeded on experimental discs at 7,5×103/cm2 concentration and cultured for a total of 7 days. Discs were processed for SEM observation at 3h, 24h, 72h and 7 days. Results In Group A, after 3h, HGFs were adherent to the surface and showed a flattened profile. The disc surface covered by HGFs resulted to be wider in Group A than in Group B samples. At SEM observation, after 24h and 72h, differences in cell attachment were slightly noticeable between the groups, with an evident flattening of HGFs on both surfaces. All differences between Group A and group B became less significant after 7 days of culture in vitro. Conclusions SEM analysis of HGFs showed differences in terms of cell adhesion and proliferation, especially in the early hours of culture. Results showed a better adhesion and cell growth in Group A than in Group B, especially up to 72h in vitro. Differences decreased after 7 days, probably because of the rougher surface of CAD/CAM zirconia, promoting better cell adhesion, compared to the smoother surface of veneering ceramic. PMID:24611089

  19. Metabolic effects of human growth hormone in corticosteroid-treated children

    PubMed Central

    Morris, Helen G.; Jorgensen, Jacqueline R.; Elrick, Harold; Goldsmith, Richard E.

    1968-01-01

    The effects of administered human growth hormone (HGH) were evaluated in dwarfed, prepubertal children who were receiving long-term corticosteroid therapy for a chronic disease. During 11 complete metabolic balance studies, the eight corticosteroid-treated children demonstrated impaired response to large doses of HGH with minimal nitrogen and no phosphorus retention. In contrast, two hypopituitary subjects and two asthmatic children not receiving corticosteroid responded to the same preparations of HGH with nitrogen, potassium, and phosphorus retention. Six corticosteroid-treated children were given large doses of HGH (40-120 mg/wk for 4 to 8 months and showed no improvement in their retarded rate of growth, whereas the hypopituitary subjects showed accelerated growth during administration of 10-15 mg of HGH/wk. It is concluded that dwarfism in steroid-treated children results from corticosteroid-induced antagonism of the effects of HGH at the peripheral tissue level. PMID:5637134

  20. Conventional and Piecewise Growth Modeling Techniques: Applications and Implications for Investigating Head Start Children's Early Literacy Learning

    ERIC Educational Resources Information Center

    Hindman, Annemarie H.; Cromley, Jennifer G.; Skibbe, Lori E.; Miller, Alison L.

    2011-01-01

    This article reviews the mechanics of conventional and piecewise growth models to demonstrate the unique affordances of each technique for examining the nature and predictors of children's early literacy learning during the transition from preschool through first grade. Using the nationally representative Family and Child Experiences Survey…

  1. Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo-maternal interface.

    PubMed

    Baston-Buest, Dunja M; Porn, Anne C; Schanz, Andrea; Kruessel, Jan-S; Janni, Wolfgang; Hess, Alexandra P

    2011-02-01

    Angiogenesis is required for successful implantation of the invading blastocyst. Vascular endothelial growth factor (VEGF) is an important key player in angiogenesis and vascular remodeling during the implantation process. Besides its well-characterized receptors VEGFR1 and VEGFR2, neuropilin-1 (NRP-1) has been shown to play an additional role in the signaling process of angiogenesis in human endometrium during the menstrual cycle, as a co-receptor of VEGF. These findings led to the hypothesis that NRP-1 might play a role in the vascular remodeling process during embryo implantation and the establishment of a pregnancy. NRP-1 mRNA transcript and protein expression were investigated in human choriocarcinoma cell lines (JEG-3, Jar and BeWo) aiming to evaluate the expression of NRP-1 in vitro, as well as in human decidua of all three trimesters of pregnancy, by western blot analysis (three samples of each trimester of pregnancy). The localization of NRP-1 in human decidua of all three trimesters of pregnancy was analyzed by immunohistochemistry (five samples of each trimester of pregnancy). NRP-1 transcript and protein were expressed in all cell lines examined. Corresponding to the analysis of human tissue by western blot and the localization by immunohistochemistry, NRP-1 protein higher expressed in samples of early pregnancy in comparison to the end of pregnancy. NRP-1 was expressed in the decidua, villi and invading cytotrophoblast of all samples investigated. This is the first study clearly showing the expression of NRP-1 in human decidua and trophoblast, suggesting an important role for the VEGF co-receptor NRP-1 besides the established receptor VEGFR2 at the embryo-maternal interface during embryonic implantation and placentation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  2. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    NASA Astrophysics Data System (ADS)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  3. Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

    PubMed

    Miyoshi, Yuichiro; Shien, Tadahiko; Ogiya, Akiko; Ishida, Naoko; Yamazaki, Kieko; Horii, Rie; Horimoto, Yoshiya; Masuda, Norikazu; Yasojima, Hiroyuki; Inao, Touko; Osako, Tomofumi; Takahashi, Masato; Tomioka, Nobumoto; Endo, Yumi; Hosoda, Mitsuchika; Doihara, Hiroyoshi; Miyoshi, Shinichiro; Yamashita, Hiroko

    2016-07-02

    The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). Among patients with ER-positive/HER2

  4. Loss of Robustness and Addiction to IGF1 during Early Keratinocyte Transformation by Human Papilloma Virus 16

    PubMed Central

    Geiger, Tamar; Levitzki, Alexander

    2007-01-01

    Infection of keratinocytes with high risk human Papilloma virus causes immortalization, and when followed by further mutations, leads to cervical cancer and other anogenital tumors. Here we monitor the progressive loss of robustness in an in vitro model of the early stages of transformation that comprises normal keratinocytes and progressive passages of HPV16 immortalized cells. As transformation progresses, the cells acquire higher proliferation rates and gain the ability to grow in soft agar. Concurrently, the cells lose robustness, becoming more sensitive to serum starvation and DNA damage by Cisplatin. Loss of robustness in the course of transformation correlates with significant reductions in the activities of the anti-apoptotic proteins PKB/Akt, Erk, Jnk and p38 both under normal growth conditions and upon stress. In parallel, loss of robustness is manifested by the shrinkage of the number of growth factors that can rescue starving cells from apoptosis, with the emergence of dependence solely on IGF1. Treatment with IGF1 activates PKB/Akt and Jnk and through them inhibits p53, rescuing the cells from starvation. We conclude that transformation in this model induces higher susceptibility of cells to stress due to reduced anti-apoptotic signaling and hyper-activation of p53 upon stress. PMID:17622350

  5. Effect of HSP27 on Human Breast Tumor Cell Growth and Motility

    DTIC Science & Technology

    1999-08-01

    the small stress protein, HSP27 , on growth and motility characteristics of normal and tumor-derived human mammary cell lines. We hypothesized that...cells overexpressing HSP27 would show increased motility, altered chemotactic properties, increased resistance to heat killing and to certain drugs...Donna has prepared and studied 19 clonal MDA23 1 breast tumor cell lines that overexpress human HSP27 , and determined that, while heat resistance is

  6. Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hara, H.; Seon, B.K.

    1987-05-01

    In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Asciticmore » and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.« less

  7. The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

    PubMed

    Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

    2016-01-01

    Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

  8. Early Head Growth in Infants at Risk of Autism: A Baby Siblings Research Consortium Study

    PubMed Central

    Zwaigenbaum, Lonnie; Young, Gregory S.; Stone, Wendy L.; Dobkins, Karen; Ozonoff, Sally; Brian, Jessica; Bryson, Susan E.; Carver, Leslie J.; Hutman, Ted; Iverson, Jana M.; Landa, Rebecca J.; Messinger, Daniel

    2014-01-01

    Objective: While early brain overgrowth is frequently reported in autism spectrum disorder (ASD), the relationship between ASD and head circumference (HC) is less clear, with inconsistent findings from longitudinal studies that include community controls. Our aim was to examine whether head growth in the first 3 years differed between children with ASD from a high-risk (HR) sample of infant siblings of children with ASD (by definition, multiplex), HR siblings not diagnosed with ASD, and low-risk (LR) controls. Method: Participants included 442 HR and 253 LR infants from 12 sites of the international Baby Siblings Research Consortium. Longitudinal HC data were obtained prospectively, supplemented by growth records. Random effects non-linear growth models were used to compare HC in HR infants and LR infants. Additional comparisons were conducted with the HR group stratified by diagnostic status at age 3: ASD (n=77), developmental delay (DD; n=32), and typical development (TD; n=333). Nonlinear growth models were also developed for height to assess general overgrowth associated with ASD. Results: There was no overall difference in head circumference growth over the first 3 years between HR and LR infants, although secondary analyses suggested possible increased total growth in HR infants, reflected by the model asymptote. Analyses stratifying the HR group by 3-year outcomes did not detect differences in head growth or height between HR infants who developed ASD and those who did not, nor between infants with ASD and LR controls. Conclusion: Head growth was uninformative as an ASD risk marker within this HR cohort. PMID:25245349

  9. Characterization of the cell growth analysis for detection of immortal cellular impurities in human mesenchymal stem cells.

    PubMed

    Kono, Ken; Takada, Nozomi; Yasuda, Satoshi; Sawada, Rumi; Niimi, Shingo; Matsuyama, Akifumi; Sato, Yoji

    2015-03-01

    The analysis of in vitro cell senescence/growth after serial passaging can be one of ways to show the absence of immortalized cells, which are frequently tumorigenic, in human cell-processed therapeutic products (hCTPs). However, the performance of the cell growth analysis for detection of the immortalized cellular impurities has never been evaluated. In the present study, we examined the growth rates of human mesenchymal stem cells (hMSCs, passage 5 (P = 5)) contaminated with various doses of HeLa cells, and compared with that of hMSCs alone. The growth rates of the contaminated hMSCs were comparable to that of hMSCs alone at P = 5, but significantly increased at P = 6 (0.1% and 0.01% HeLa) or P = 7 (0.001% HeLa) within 30 days. These findings suggest that the cell growth analysis is a simple and sensitive method to detect immortalized cellular impurities in hCTPs derived from human somatic cells. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression.

    PubMed

    Bao, Tianhao; Ke, Yang; Wang, Yifan; Wang, Weiwei; Li, Yuehua; Wang, Yan; Kui, Xiang; Zhou, Qixin; Zhou, Han; Zhang, Cheng; Zhou, Dongming; Wang, Lin; Xiao, Chunjie

    2018-07-01

    Taraxasterol has potent anti-inflammatory and anti-tumor activity. However, the effect and potential mechanisms of Taraxasterol on the growth of human liver cancer have not been clarified. Histidine triad nucleotide-binding protein 1 (Hint1) is a tumor suppressor and its downregulated expression is associated with the development of cancer. Here, we report that Taraxasterol treatment significantly suppressed cell proliferation and induced cell cycle arrest at G0/G1 phase and apoptosis in liver cancer cells, but not in non-tumor hepatocytes. Furthermore, Taraxasterol upregulated Hint1 and Bax, but downregulated Bcl2 and cyclin D1 expression, accompanied by promoting the demethylation in the Hint1 promoter region in liver cancer cells. The effects of Taraxasterol were abrogated by Hint1 silencing and partially mitigated by Bax silencing, Bcl2 or cyclin D1 over-expression in HepG2 cells. Moreover, oral administration with Taraxasterol did not affect body weight, urinary protein levels, and the heart, liver, and kidney morphology in BALB/c mice but effectively inhibited the growth of implanted SK-Hep1 tumor in vivo. Collectively, we demonstrate that Taraxasterol inhibits the growth of liver cancer at least partially by enhancing Hint1 expression to regulate Bax, Bcl2, and cyclin D1 expression. Taraxasterol may be a drug candidate for the treatment of human liver cancer. Taraxasterol inhibits growth and induces apoptosis in human liver cancer cells. Taraxasterol enhances Hint1 expression by promoting demethylation in Hint1 promoter. Taraxasterol increases Hint1 levels to regulate Bax, Bcl2, and cyclinD1 expression. The effects of Taraxasterol are abrogated by Hint1 silencing in liver cancer cells. Taraxasterol inhibits the growth of subcutaneously implanted liver cancers in mice.

  11. Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis.

    PubMed

    Wang, Tao; Xie, Zi-ping; Huang, Zhan-sen; Li, Hao; Wei, An-yang; Di, Jin-ming; Xiao, Heng-jun; Zhang, Zhi-gang; Cai, Liu-hong; Tao, Xin; Qi, Tao; Chen, Di-ling; Chen, Jun

    2015-10-01

    In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

  12. Halofuginone suppresses growth of human uterine leiomyoma cells in a mouse xenograft model.

    PubMed

    Koohestani, Faezeh; Qiang, Wenan; MacNeill, Amy L; Druschitz, Stacy A; Serna, Vanida A; Adur, Malavika; Kurita, Takeshi; Nowak, Romana A

    2016-07-01

    Does halofuginone (HF) inhibit the growth of human uterine leiomyoma cells in a mouse xenograft model? HF suppresses the growth of human uterine leiomyoma cells in a mouse xenograft model through inhibiting cell proliferation and inducing apoptosis. Uterine leiomyomas are the most common benign tumors of the female reproductive tract. HF can suppress the growth of human uterine leiomyoma cells in vitro. The mouse xenograft model reflects the characteristics of human leiomyomas. Primary leiomyoma smooth muscle cells from eight patients were xenografted under the renal capsule of adult, ovariectomized NOD-scid IL2Rγ(null) mice (NSG). Mice were treated with two different doses of HF or vehicle for 4 weeks with six to eight mice per group. Mouse body weight measurements and immunohistochemical analysis of body organs were carried out to assess the safety of HF treatment. Xenografted tumors were measured and analyzed for cellular and molecular changes induced by HF. Ovarian steroid hormone receptors were evaluated for possible modulation by HF. Treatment of mice carrying human UL xenografts with HF at 0.25 or 0.50 mg/kg body weight for 4 weeks resulted in a 35-40% (P < 0.05) reduction in tumor volume. The HF-induced volume reduction was accompanied by increased apoptosis and decreased cell proliferation. In contrast, there was no significant change in the collagen content either at the transcript or protein level between UL xenografts in control and HF groups. HF treatment did not change the expression level of ovarian steroid hormone receptors. No adverse pathological effects were observed in other tissues from mice undergoing treatment at these doses. While this study did test the effects of HF on human leiomyoma cells in an in vivo model, HF was administered to mice whose tolerance and metabolism of the drug may differ from that in humans. Also, the longer term effects of HF treatment are yet unclear. The results of this study showing the effectiveness of HF in

  13. Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents.

    PubMed

    Ceelen, Manon; van Weissenbruch, Mirjam M; Prein, Janneke; Smit, Judith J; Vermeiden, Jan P W; Spreeuwenberg, Marieke; van Leeuwen, Flora E; Delemarre-van de Waal, Henriette A

    2009-11-01

    Little is known about post-natal growth in IVF offspring and the effects of rates of early post-natal growth on blood pressure and body fat composition during childhood and adolescence. The follow-up study comprised 233 IVF children aged 8-18 years and 233 spontaneously conceived controls born to subfertile parents. Growth data from birth to 4 years of age, available for 392 children (n = 193 IVF, n = 199 control), were used to study early post-natal growth. Furthermore, early post-natal growth velocity (weight gain) was related to blood pressure and skinfold measurements at follow-up. We found significantly lower weight, height and BMI standard deviation scores (SDSs) at 3 months, and weight SDS at 6 months of age in IVF children compared with controls. Likewise, IVF children demonstrated a greater gain in weight SDS (P < 0.001), height SDS (P = 0.013) and BMI SDS (P = 0.029) during late infancy (3 months to 1 year) versus controls. Weight gain during early childhood (1-3 years) was related to blood pressure in IVF children (P = 0.014 systolic, 0.04 diastolic) but not in controls. Growth during late infancy was not related to skinfold thickness in IVF children, unlike controls (P = 0.002 peripheral sum, 0.003 total sum). Growth during early childhood was related to skinfold thickness in both IVF and controls (P = 0.005 and 0.01 peripheral sum and P = 0.003 and 0.005 total sum, respectively). Late infancy growth velocity of IVF children was significantly higher compared with controls. Nevertheless, early childhood growth instead of infancy growth seemed to predict cardiovascular risk factors in IVF children. Further research is needed to confirm these findings and to follow-up growth and development of IVF children into adulthood.

  14. AKT delays the early-activated apoptotic pathway in UVB-irradiated keratinocytes via BAD translocation.

    PubMed

    Claerhout, Sofie; Decraene, David; Van Laethem, An; Van Kelst, Sofie; Agostinis, Patrizia; Garmyn, Marjan

    2007-02-01

    Upon irradiation with a high dose of UVB, keratinocytes undergo apoptosis as a protective mechanism. In previous work, we demonstrated the existence of an early-activated UVB-induced apoptotic pathway in growth factor-depleted human keratinocytes, which can be substantially delayed by the exclusive supplementation of IGF-1. We now show that in human keratinocytes, IGF-1 inhibits the onset of UVB-triggered apoptosis through a transcriptional independent, AKT-mediated mechanism, involving BAD serine 136 phosphorylation. Our results show that the early UVB-induced apoptosis in growth factor-depleted human keratinocytes is exclusively triggered through the mitochondrial pathway. It is accompanied by BAX translocation, cytochrome c release, and procaspase-9 cleavage, but not by procaspase-8 or BID cleavage. In human keratinocytes, IGF-1 supplementation inhibits these events in a transcription-independent manner. Both IGF-1 supplementation and the transduction of a membrane-targeted form of AKT result in a shift of the BH3-only protein BAD from the mitochondria to the cytoplasm, paralleled by an increase of AKT-specific Ser136 phospho-BAD bound to 14-3-3zeta protein. These data indicate that AKT-induced BAD phosphorylation and its subsequent cytoplasmic sequestration by 14-3-3zeta is a major mechanism responsible for the postponement of UVB-induced apoptosis in human keratinocytes.

  15. Synchrotron FTIR microspectroscopy reveals early adipogenic differentiation of human mesenchymal stem cells at single-cell level

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Zhixiao; University of Chinese Academy of Science, Beijing 100049; Tang, Yuzhao

    Human mesenchymal stem cells (hMSCs) have been used as an ideal in vitro model to study human adipogenesis. However, little knowledge of the early stage differentiation greatly hinders our understanding on the mechanism of the adipogenesis processes. In this study, synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy was applied to track the global structural and compositional changes of lipids, proteins and nucleic acids inside individual hMSCs along the time course. The multivariate analysis of the SR-FTIR spectra distinguished the dynamic and significant changes of the lipids and nucleic acid at early differentiation stage. Importantly, changes of lipid structure during early daysmore » (Day 1–3) of differentiation might serve as a potential biomarker in identifying the state in early differentiation at single cell level. These results proved that SR-FTIR is a powerful tool to study the stem cell fate determination and early lipogenesis events. - Highlights: • Molecular events occur in the early adipogenic differentiation stage of hMSCs are studied by SR-FTIR. • SR-FTIR data suggest that lipids may play an important role in hMSCs determination. • As potential biomarkers, lipids peaks can identify the state of cell in early differentiation stage at single-cell level.« less

  16. Long-term consequences of nutrition and growth in early childhood and possible preventive interventions.

    PubMed

    Adair, Linda S

    2014-01-01

    Maternal nutritional deficiencies and excesses during pregnancy, and faster infant weight gain in the first 2 years of life are associated with increased risk of noncommunicable diseases (NCDs) in adulthood. The first 1,000 days of life (from conception until the child reaches age 2 years) represent a vulnerable period for programming of NCD risk, and are an important target for prevention of adult disease. This paper takes a developmental perspective to identify periconception, pregnancy, and infancy nutritional stressors, and to discuss mechanisms through which they influence later disease risk with the goal of informing age-specific interventions. Low- and middle-income countries need to address the dual burden of under- and overnutrition by implementing interventions to promote growth and enhance survival and intellectual development without increasing chronic disease risk. In the absence of good evidence from long-term follow-up of early life interventions, current recommendations for early life prevention of adult disease presume that interventions designed to optimize pregnancy outcomes and promote healthy infant growth and development will also reduce chronic disease risk. These include an emphasis on optimizing maternal nutrition prior to pregnancy, micronutrient adequacy in the preconception period and during pregnancy, promotion of breastfeeding and high-quality complementary foods, and prevention of obesity in childhood and adolescence. © 2014 Nestec Ltd., Vevey/S. Karger AG, Basel.

  17. Deconstructing the externalizing spectrum: Growth patterns of overt aggression, covert aggression, oppositional behavior, impulsivity/inattention, and emotion dysregulation between school entry and early adolescence

    PubMed Central

    Olson, Sheryl L.; Sameroff, Arnold J.; Lansford, Jennifer E.; Sexton, Holly; Davis-Kean, Pamela; Bates, John E.; Pettit, Gregory S.; Dodge, Kenneth A.

    2013-01-01

    The purpose of this study was to determine whether five subcomponents of children's externalizing behavior showed distinctive patterns of long-term growth and predictive correlates. We examined growth in teachers' ratings of overt aggression, covert aggression, oppositional defiance, impulsivity/inattention, and emotion dysregulation across three developmental periods spanning kindergarten through Grade 8 (ages 5–13 years). We also determined whether three salient background characteristics, family socioeconomic status, child ethnicity, and child gender, differentially predicted growth in discrete categories of child externalizing symptoms across development. Participants were 543 kindergarten-age children (52% male, 81% European American, 17% African American) whose problem behaviors were rated by teachers each successive year of development through Grade 8. Latent growth curve analyses were performed for each component scale, contrasting with overall externalizing, in a piecewise fashion encompassing three developmental periods: kindergarten–Grade 2, Grades 3–5, and Grades 6–8. We found that most subconstructs of externalizing behavior increased significantly across the early school age period relative to middle childhood and early adolescence. However, overt aggression did not show early positive growth, and emotion dysregulation significantly increased across middle childhood. Advantages of using subscales were most clear in relation to illustrating different growth functions between the discrete developmental periods. Moreover, growth in some discrete subcomponents was differentially associated with variations in family socioeconomic status and ethnicity. Our findings strongly affirmed the necessity of adopting a developmental approach to the analysis of growth in children's externalizing behavior and provided unique data concerning similarities and differences in growth between subconstructs of child and adolescent externalizing behavior. PMID

  18. [Local injection of exogenous nerve growth factor improves early bone maturation of implants].

    PubMed

    Yao, Yang; Du, Yu; Gu, Xia; Guang, Meng-Kai; Huang, Bo; Gong, Ping

    2018-04-01

    To investigate the effects of nerve growth factor (NGF) in the osteogenic action of implants and the maturation and reconstruction changes in bone tissues in the early stage of osseointegration. The mouse implant model was established by placing titanium in the femoral head of the mouse and locally injecting NGF in the implant zone. On 1, 2 and 4 weeks after operation, stain samples were collected from animals using hematoxylin-eosin (HE) staining and Masson staining. The effect of NGF on the bone maturation was compared at different time points of early stage osseointegration. The results of HE and Masson staining indicated that the local injection of external NGF can up-regulate bone mass, amount of bone trabecula, and bone maturity in the mouse model. The mature bone rate in treatment group of 1 week and 4 weeks after operation were significantly higher than those in the control group (P<0.05). NGF can shorten the period of bone maturation.

  19. Neighborhood Violent Crime and Academic Growth in Chicago: Lasting Effects of Early Exposure*

    PubMed Central

    Burdick-Will, Julia

    2017-01-01

    A large body of research documents the importance of early experiences for later academic, social, and economic success. Exposure to an unsafe neighborhood is no exception. Living in a violent neighborhood can influence the stress levels, protective behaviors, and community interactions of both parents and children in ways that generate cumulative educational disadvantage. Using nine years (2002–2011) of detailed crime data from the Chicago Police Department and longitudinal administrative data from the Chicago Public Schools, I estimate the influence of early exposure to neighborhood violence on growth in standardized test scores over time. Student fixed-effects are included to remove any bias due to constant differences between students. The results show that children from more violent neighborhoods fall farther behind their peers from safer neighborhoods as they progress through school. These effects are comparable in size to the independent association with socioeconomic disadvantage and an annual measure of more recent neighborhood violence exposure. PMID:29129943

  20. The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

    PubMed Central

    Steffani, Liliana; Martínez, Sebastián; Monterde, Mercedes; Ferri, Blanca; Núñez, Maria Jose; AinhoaRomero-Espinós; Zamora, Omar; Gurrea, Marta; Sangiao-Alvarellos, Susana; Vega, Olivia; Simón, Carlos; Pellicer, Antonio; Tena-Sempere, Manuel

    2014-01-01

    Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. PMID:24498170

  1. 3D quantitative analysis of early decomposition changes of the human face.

    PubMed

    Caplova, Zuzana; Gibelli, Daniele Maria; Poppa, Pasquale; Cummaudo, Marco; Obertova, Zuzana; Sforza, Chiarella; Cattaneo, Cristina

    2018-03-01

    Decomposition of the human body and human face is influenced, among other things, by environmental conditions. The early decomposition changes that modify the appearance of the face may hamper the recognition and identification of the deceased. Quantitative assessment of those changes may provide important information for forensic identification. This report presents a pilot 3D quantitative approach of tracking early decomposition changes of a single cadaver in controlled environmental conditions by summarizing the change with weekly morphological descriptions. The root mean square (RMS) value was used to evaluate the changes of the face after death. The results showed a high correlation (r = 0.863) between the measured RMS and the time since death. RMS values of each scan are presented, as well as the average weekly RMS values. The quantification of decomposition changes could improve the accuracy of antemortem facial approximation and potentially could allow the direct comparisons of antemortem and postmortem 3D scans.

  2. Achondroplastic Dwarfism—Effects of Treatment with Human Growth Hormone

    PubMed Central

    Escamilla, Roberto F.; Hutchings, John J.; Li, Choh Hao; Forsham, Peter

    1966-01-01

    Two male patients with achondroplastic dwarfism aged 7-5/12 and 14½ years were treated with human growth hormone 5 mg daily. Both showed nitrogen retention on balance studies, the older second patient to a marked degree. In the younger patient, height increased from 95.4 to 106.3 cm on hgh 5 mg daily alone for 14 out of 24 months. The rate of growth approximately doubled during the first two treatment periods as compared with the pre-treatment rate. In the second older patient hgh was administered 5 mg daily intramuscularly for 21 out of 33 months. Growth from 129.6 cm to 137.8 cm occurred with the rate increasing following the addition of Na-1-thyroxine to the routine. This increased growth rate occurred during the post-puberty deceleration phase. Bone ages, interpreted from changes in the phalanges and metacarpals, increased from 4½ to 6 years during 16 months in Case 1, and from 13½ to 18 years in 33 months in Case 2. Transient adolescent gynecomastia appeared in Case 2. No local or general toxic effects were noted. These results are suggestive, but whether or not the eventual height of an achondroplastic dwarf can be significantly altered must await further studies. ImagesFigure 1.Figure 2. PMID:5946547

  3. Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

    PubMed

    Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

    2014-08-01

    The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

  4. Influence of establishment timing and planting stock on early rotational growth of loblolly pine plantations in Texas

    Treesearch

    M. A. Blazier; E. L. Taylor; A. G. Holley

    2010-01-01

    Planting container seedlings, which have relatively fully formed root systems encased in a soil-filled plug, may improve loblolly pine plantation productivity by increasing early survival and growth relative to that of conventionally planted bareroot seedlings. Planting seedlings in fall may also confer productivity increases to loblolly pine plantations by giving...

  5. Effects of seed weight and rate of emergence on early growth of open-pollinated Douglas-fir families.

    Treesearch

    J.B. St. Clair; W.T. Adams

    1991-01-01

    Seed weight, time of emergence, and three measures of seedling size were recorded for 39 open-pollinated Douglas-fir (Pseudotsuga menziesii var. menziesii[Mirb.] Franco) families in order to assess family variation in seed weight and emergence, and the influence of these seed traits on early growth. Families were planted both...

  6. Effects of temperature on embryonic and early larval growth and development in the rough-skinned newt (Taricha granulosa).

    PubMed

    Smith, Geoffrey D; Hopkins, Gareth R; Mohammadi, Shabnam; M Skinner, Heather; Hansen, Tyler; Brodie, Edmund D; French, Susannah S

    2015-07-01

    We investigated the effects of temperature on the growth and development of embryonic and early larval stages of a western North American amphibian, the rough-skinned newt (Taricha granulosa). We assigned newt eggs to different temperatures (7, 14, or 21°C); after hatching, we re-assigned the newt larvae into the three different temperatures. Over the course of three to four weeks, we measured total length and developmental stage of the larvae. Our results indicated a strong positive relationship over time between temperature and both length and developmental stage. Importantly, individuals assigned to cooler embryonic temperatures did not achieve the larval sizes of individuals from the warmer embryonic treatments, regardless of larval temperature. Our investigation of growth and development at different temperatures demonstrates carry-over effects and provides a more comprehensive understanding of how organisms respond to temperature changes during early development. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Early Life Conditions and Physiological Stress following the Transition to Farming in Central/Southeast Europe: Skeletal Growth Impairment and 6000 Years of Gradual Recovery

    PubMed Central

    Macintosh, Alison A.; Pinhasi, Ron; Stock, Jay T.

    2016-01-01

    Early life conditions play an important role in determining adult body size. In particular, childhood malnutrition and disease can elicit growth delays and affect adult body size if severe or prolonged enough. In the earliest stages of farming, skeletal growth impairment and small adult body size are often documented relative to hunter-gatherer groups, though this pattern is regionally variable. In Central/Southeast Europe, it is unclear how early life stress, growth history, and adult body size were impacted by the introduction of agriculture and ensuing long-term demographic, social, and behavioral change. The current study assesses this impact through the reconstruction and analysis of mean stature, body mass, limb proportion indices, and sexual dimorphism among 407 skeletally mature men and women from foraging and farming populations spanning the Late Mesolithic through Early Medieval periods in Central/Southeast Europe (~7100 calBC to 850 AD). Results document significantly reduced mean stature, body mass, and crural index in Neolithic agriculturalists relative both to Late Mesolithic hunter-gatherer-fishers and to later farming populations. This indication of relative growth impairment in the Neolithic, particularly among women, is supported by existing evidence of high developmental stress, intensive physical activity, and variable access to animal protein in these early agricultural populations. Among subsequent agriculturalists, temporal increases in mean stature, body mass, and crural index were more pronounced among Central European women, driving declines in the magnitude of sexual dimorphism through time. Overall, results suggest that the transition to agriculture in Central/Southeast Europe was challenging for early farming populations, but was followed by gradual amelioration across thousands of years, particularly among Central European women. This sex difference may be indicative, in part, of greater temporal variation in the social status afforded

  8. Effects of early human handling on the pain sensitivity of young lambs.

    PubMed

    Guesgen, Mirjam J; Beausoleil, Ngaio J; Stewart, Mairi

    2013-01-01

    Pain sensitivity of lambs changes over the first weeks of life. However, the effects of early treatments such as human handling on pain sensitivity are unknown for this species. This study investigated the effects of regular early gentle human handling on the pain sensitivity of lambs, indicated by their behavioural responses to tail docking. Prospective part-blinded experimental study. Twenty-nine singleton Coopworth lambs (females n=14, males n=15). Starting at one day of age, lambs were either handled twice daily for 2 weeks (Handled), were kept in the presence of lambs who were being handled but were not handled themselves (Presence), or were exposed to a human only during routine feeding and care (Control). At 3 weeks of age, all lambs were tail docked using rubber rings. Changes in behaviour due to docking were calculated and change data were analyzed using two-way anova with treatment and test pen as main factors. All lambs showed significant increases in the frequency and duration of behaviours indicative of pain, including 'abnormal' behaviours, and decreases in the frequency and duration of 'normal' behaviours after docking. Handled lambs showed a smaller increase in the time spent lying abnormally after docking than did Control lambs (mean transformed change in proportion of 30 minutes spent±SE: Control 0.55±0.04; Handled 0.38±0.03; Presence 0.48±0.03; C versus H t=3.45, p=0.007). These results provide some evidence that handling early in life may reduce subsequent pain sensitivity in lambs. While the behavioural effects of handling on pain behaviour were subtle, the results suggest, at the very least, that early handling does not increase pain sensitivity in lambs and suggests there is still flexibility postnatally in the pain processing system of a precocial species. © 2012 The Authors. Veterinary Anaesthesia and Analgesia. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  9. Growth and differentiation of human lens epithelial cells in vitro on matrix

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Bjornstad, K. A.; Chang, P. Y.; McNamara, M. P.; Chang, E.; Aragon, G.; Lin, S. P.; Lui, G.; Polansky, J. R.

    2000-01-01

    PURPOSE: To characterize the growth and maturation of nonimmortalized human lens epithelial (HLE) cells grown in vitro. METHODS: HLE cells, established from 18-week prenatal lenses, were maintained on bovine corneal endothelial (BCE) extracellular matrix (ECM) in medium supplemented with basic fibroblast growth factor (FGF-2). The identity, growth, and differentiation of the cultures were characterized by karyotyping, cell morphology, and growth kinetics studies, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, and Western blot analysis. RESULTS: HLE cells had a male, human diploid (2N = 46) karyotype. The population-doubling time of exponentially growing cells was 24 hours. After 15 days in culture, cell morphology changed, and lentoid formation was evident. Reverse transcription-polymerase chain reaction (RT-PCR) indicated expression of alphaA- and betaB2-crystallin, fibroblast growth factor receptor 1 (FGFR1), and major intrinsic protein (MIP26) in exponential growth. Western analyses of protein extracts show positive expression of three immunologically distinct classes of crystallin proteins (alphaA-, alphaB-, and betaB2-crystallin) with time in culture. By Western blot analysis, expression of p57(KIP2), a known marker of terminally differentiated fiber cells, was detectable in exponential cultures, and levels increased after confluence. MIP26 and gamma-crystallin protein expression was detected in confluent cultures, by using immunofluorescence, but not in exponentially growing cells. CONCLUSIONS: HLE cells can be maintained for up to 4 months on ECM derived from BCE cells in medium containing FGF-2. With time in culture, the cells demonstrate morphologic characteristics of, and express protein markers for, lens fiber cell differentiation. This in vitro model will be useful for investigations of radiation-induced cataractogenesis and other studies of lens toxicity.

  10. [Pubertal growth of 1,453 healthy children according to age at pubertal growth spurt onset. The Barcelona longitudinal growth study].

    PubMed

    Carrascosa, Antonio; Yeste, Diego; Moreno-Galdó, Antonio; Gussinyé, Miquel; Ferrández, Ángel; Clemente, María; Fernández-Cancio, Mónica

    2018-02-20

    Pubertal growth pattern differs according to age at pubertal growth spurt onset which occurs over a five years period (girls: 8-13 years, boys: 10-15 years). The need for more than one pubertal reference pattern has been proposed. We aimed to obtain five 1-year-age-interval pubertal patterns. Longitudinal (6 years of age-adult height) growth study of 1,453 healthy children to evaluate height-for-age, growth velocity-for-age and weight-for-age values. According to age at pubertal growth spurt onset girls were considered: very-early matures (8-9 years, n=119), early matures (9-10 years, n=157), intermediate matures (10-11 years, n=238), late matures (11-12 years, n=127) and very-late matures (12-13 years, n=102), and boys: very-early matures (10-11 years, n=110), early matures (11-12 years, n=139), intermediate matures (12-13 years, n=225), late matures (13-14 years, n=133) and very-late matures (14-15 years, n=103). Age at menarche and growth up to adult height were recorded. In both sexes, statistically-significant (P<.0001) and clinically-pertinent differences in pubertal growth pattern (mean height-for-age, mean growth velocity-for-age and mean pubertal height gain, values) were found among the five pubertal maturity groups and between each group and the whole population, despite similar adult height values. The same occurred for age at menarche and growth from menarche to adult height (P<.05). In both sexes, pubertal growth spurt onset is a critical milestone determining pubertal growth and sexual development. The contribution of our data to better clinical evaluation of growth according to the pubertal maturity tempo of each child will obviate the mistakes made when only one pubertal growth reference is used. Copyright © 2018. Publicado por Elsevier España, S.L.U.

  11. Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo.

    PubMed

    Chu, Sheng-Hua; Feng, Dong-Fu; Ma, Yan-Bin; Li, Zhi-Qiang

    2012-01-01

    Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU).

  12. Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo

    PubMed Central

    Chu, Sheng-Hua; Feng, Dong-Fu; Ma, Yan-Bin; Li, Zhi-Qiang

    2012-01-01

    Hydroxyapatite nanoparticles (nano-HAPs) have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). PMID:22888225

  13. Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemic colon anastomosis in rats.

    PubMed

    Yarimkaya, Ali; Apaydin, Berat; Unal, Ethem; Karabicak, Ilhan; Aydogan, Fatih; Uslu, Ezel; Erginoz, Ethem; Artis, Tarik; Eyuboglu, Erhun

    2003-12-01

    Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemic colon anastomosis in rats. Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemic colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemic colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonic anastomosis.

  14. Immunohistochemical Markers of Neural Progenitor Cells in the Early Embryonic Human Cerebral Cortex

    PubMed Central

    Vinci, L.; Ravarino, A.; Fanos, V.; Naccarato, A.G.; Senes, G.; Gerosa, C.; Bevilacqua, G.; Faa, G.; Ambu, R.

    2016-01-01

    The development of the human central nervous system represents a delicate moment of embryogenesis. The purpose of this study was to analyze the expression of multiple immunohistochemical markers in the stem/progenitor cells in the human cerebral cortex during the early phases of development. To this end, samples from cerebral cortex were obtained from 4 human embryos of 11 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including GFAP, WT1, Nestin, Vimentin, CD117, S100B, Sox2, PAX2, PAX5, Tβ4, Neurofilament, CD44, CD133, Synaptophysin and Cyclin D1. Our study shows the ability of the different immunohistochemical markers to evidence different zones of the developing human cerebral cortex, allowing the identification of the multiple stages of differentiation of neuronal and glial precursors. Three important markers of radial glial cells are evidenced in this early gestational age: Vimentin, Nestin and WT1. Sox2 was expressed by the stem/progenitor cells of the ventricular zone, whereas the postmitotic neurons of the cortical plate were immunostained by PAX2 and NSE. Future studies are needed to test other important stem/progenitor cells markers and to better analyze differences in the immunohistochemical expression of these markers during gestation. PMID:26972711

  15. Identification of Water Use Strategies at Early Growth Stages in Durum Wheat from Shoot Phenotyping and Physiological Measurements

    PubMed Central

    Nakhforoosh, Alireza; Bodewein, Thomas; Fiorani, Fabio; Bodner, Gernot

    2016-01-01

    Modern imaging technology provides new approaches to plant phenotyping for traits relevant to crop yield and resource efficiency. Our objective was to investigate water use strategies at early growth stages in durum wheat genetic resources using shoot imaging at the ScreenHouse phenotyping facility combined with physiological measurements. Twelve durum landraces from different pedoclimatic backgrounds were compared to three modern check cultivars in a greenhouse pot experiment under well-watered (75% plant available water, PAW) and drought (25% PAW) conditions. Transpiration rate was analyzed for the underlying main morphological (leaf area duration) and physiological (stomata conductance) factors. Combining both morphological and physiological regulation of transpiration, four distinct water use types were identified. Most landraces had high transpiration rates either due to extensive leaf area (area types) or both large leaf areas together with high stomata conductance (spender types). All modern cultivars were distinguished by high stomata conductance with comparatively compact canopies (conductance types). Only few landraces were water saver types with both small canopy and low stomata conductance. During early growth, genotypes with large leaf area had high dry-matter accumulation under both well-watered and drought conditions compared to genotypes with compact stature. However, high stomata conductance was the basis to achieve high dry matter per unit leaf area, indicating high assimilation capacity as a key for productivity in modern cultivars. We conclude that the identified water use strategies based on early growth shoot phenotyping combined with stomata conductance provide an appropriate framework for targeted selection of distinct pre-breeding material adapted to different types of water limited environments. PMID:27547208

  16. Aluminium chloride promotes anchorage-independent growth in human mammary epithelial cells.

    PubMed

    Sappino, André-Pascal; Buser, Raphaële; Lesne, Laurence; Gimelli, Stefania; Béna, Frédérique; Belin, Dominique; Mandriota, Stefano J

    2012-03-01

    Aluminium salts used as antiperspirants have been incriminated as contributing to breast cancer incidence in Western societies. To date, very little or no epidemiological or experimental data confirm or infirm this hypothesis. We report here that in MCF-10A human mammary epithelial cells, a well-established normal human mammary epithelial cell model, long-term exposure to aluminium chloride (AlCl(3) ) concentrations of 10-300 µ m, i.e. up to 100 000-fold lower than those found in antiperspirants, and in the range of those recently measured in the human breast, results in loss of contact inhibition and anchorage-independent growth. These effects were preceded by an increase of DNA synthesis, DNA double strand breaks (DSBs), and senescence in proliferating cultures. AlCl(3) also induced DSBs and senescence in proliferating primary human mammary epithelial cells. In contrast, it had no similar effects on human keratinocytes or fibroblasts, and was not detectably mutagenic in bacteria. MCF-10A cells morphologically transformed by long-term exposure to AlCl(3) display strong upregulation of the p53/p21(Waf1) pathway, a key mediator of growth arrest and senescence. These results suggest that aluminium is not generically mutagenic, but similar to an activated oncogene, it induces proliferation stress, DSBs and senescence in normal mammary epithelial cells; and that long-term exposure to AlCl(3) generates and selects for cells able to bypass p53/p21(Waf1) -mediated cellular senescence. Our observations do not formally identify aluminium as a breast carcinogen, but challenge the safety ascribed to its widespread use in underarm cosmetics. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner

    PubMed Central

    Vasilopoulou, E.; Loubière, L.S.; Lash, G.E.; Ohizua, O.; McCabe, C.J.; Franklyn, J.A.; Kilby, M.D.; Chan, S.Y.

    2014-01-01

    STUDY QUESTION Does triiodothyronine (T3) regulate the secretion of angiogenic growth factors and cytokines by human decidual cells isolated from early pregnancy? SUMMARY ANSWER T3 modulates the secretion of specific angiogenic growth factors and cytokines, with different regulatory patterns observed amongst various isolated subpopulations of human decidual cells and with a distinct change between the first and second trimesters of pregnancy. WHAT IS KNOWN ALREADY Maternal thyroid dysfunction during early pregnancy is associated with complications of malplacentation including miscarriage and pre-eclampsia. T3 regulates the proliferation and apoptosis of fetal-derived trophoblasts, as well as promotes the invasive capability of extravillous trophoblasts (EVT). We hypothesize that T3 may also have a direct impact on human maternal-derived decidual cells, which are known to exert paracrine regulation upon trophoblast behaviour and vascular development at the uteroplacental interface. STUDY DESIGN, SIZE, DURATION This laboratory-based study used human decidua from first (8–11 weeks; n = 18) and second (12–16 weeks; n = 12) trimester surgical terminations of apparently uncomplicated pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS Primary cultures of total decidual cells, and immunomagnetic bead-isolated populations of stromal-enriched (CD10+) and stromal-depleted (CD10−) cells, uterine natural killer cells (uNK cells; CD56+) and macrophages (CD14+) were assessed for thyroid hormone receptors and transporters by immunocytochemistry. Each cell population was treated with T3 (0, 1, 10, 100 nM) and assessments were made of cell viability (MTT assay) and angiogenic growth factor and cytokine secretion (immunomediated assay). The effect of decidual cell-conditioned media on EVT invasion through Matrigel® was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE Immunocytochemistry showed the expression of thyroid hormone transporters (MCT8, MCT10) and receptors (TRα1

  18. Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas.

    PubMed

    Singal, Sahil S; Nygard, Karen; Gratton, Robert; Jansson, Thomas; Gupta, Madhulika B

    2018-05-01

    Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.

  19. Growth rate, transmission mode and virulence in human pathogens.

    PubMed

    Leggett, Helen C; Cornwallis, Charlie K; Buckling, Angus; West, Stuart A

    2017-05-05

    The harm that pathogens cause to hosts during infection, termed virulence, varies across species from negligible to a high likelihood of rapid death. Classic theory for the evolution of virulence is based on a trade-off between pathogen growth, transmission and host survival, which predicts that higher within-host growth causes increased transmission and higher virulence. However, using data from 61 human pathogens, we found the opposite correlation to the expected positive correlation between pathogen growth rate and virulence. We found that (i) slower growing pathogens are significantly more virulent than faster growing pathogens, (ii) inhaled pathogens and pathogens that infect via skin wounds are significantly more virulent than pathogens that are ingested, but (iii) there is no correlation between symptoms of infection that aid transmission (such as diarrhoea and coughing) and virulence. Overall, our results emphasize how virulence can be influenced by mechanistic life-history details, especially transmission mode, that determine how parasites infect and exploit their hosts.This article is part of the themed issue 'Opening the black box: re-examining the ecology and evolution of parasite transmission'. © 2017 The Authors.

  20. Fertility, Human Capital, and Economic Growth over the Demographic Transition

    PubMed Central

    Mason, Andrew

    2009-01-01

    Do low fertility and population aging lead to economic decline if couples have fewer children, but invest more in each child? By addressing this question, this article extends previous work in which the authors show that population aging leads to an increased demand for wealth that can, under some conditions, lead to increased capital per worker and higher per capita consumption. This article is based on an overlapping generations (OLG) model which highlights the quantity–quality tradeoff and the links between human capital investment and economic growth. It incorporates new national level estimates of human capital investment produced by the National Transfer Accounts project. Simulation analysis is employed to show that, even in the absence of the capital dilution effect, low fertility leads to higher per capita consumption through human capital accumulation, given plausible model parameters. PMID:20495605

  1. Bidirectional enhancing activities between human T cell leukemia-lymphoma virus type I and human cytomegalovirus in human term syncytiotrophoblast cells cultured in vitro.

    PubMed

    Tóth, F D; Aboagye-Mathiesen, G; Szabó, J; Liu, X; Mosborg-Petersen, P; Kiss, J; Hager, H; Zdravkovic, M; Andirkó, I; Aranyosi, J

    1995-12-01

    The syncytiotrophoblast layer of the human placenta has an important role in limiting transplacental viral spread from mother to fetus. Human cytomegalovirus (HCMV) is capable of establishing a latent infection in syncytiotrophoblast cells, with restriction of gene expression to immediate-early and early proteins. We analyzed the extent of replication of human T cell leukemia-lymphoma virus type I (HTLV-I) in human term syncytiotrophoblasts infected with HTLV-I alone or coinfected with HTLV-I and HCMV. Although syncytiotrophoblasts could be infected with cell-free HTLV-I, no viral protein expression was found in the singly infected cells. On the contrary, coinfection of the cells with HTLV-I and HCMV resulted in simultaneous replication of both viruses. Bidirectional enhancing activities between HTLV-I and HCMV were mediated primarily by the Tax and immediate-early proteins, respectively. The stimulatory effect of HTLV-I Tax on HCMV replication appeared to be mediated partly by tumor necrosis factor beta and transforming growth factor beta-1. We observed formation of pseudotypes with HTLV-I nucleocapsids within HCMV envelopes, whereas HCMV was not pseudotyped by HTLV-I envelopes in dually infected syncytiotrophoblast cells. Our data suggest that in vivo dual infection of syncytiotrophoblast cells with HTLV-I and HCMV may facilitate the transplacental transmission of both viruses.

  2. Early-Life Telomere Dynamics Differ between the Sexes and Predict Growth in the Barn Swallow (Hirundo rustica)

    PubMed Central

    Parolini, Marco; Romano, Andrea; Khoriauli, Lela; Nergadze, Solomon G.; Caprioli, Manuela; Rubolini, Diego; Santagostino, Marco; Saino, Nicola; Giulotto, Elena

    2015-01-01

    Telomeres are conserved DNA-protein structures at the termini of eukaryotic chromosomes which contribute to maintenance of genome integrity, and their shortening leads to cell senescence, with negative consequences for organismal functions. Because telomere erosion is influenced by extrinsic and endogenous factors, telomere dynamics may provide a mechanistic basis for evolutionary and physiological trade-offs. Yet, knowledge of fundamental aspects of telomere biology under natural selection regimes, including sex- and context-dependent variation in early-life, and the covariation between telomere dynamics and growth, is scant. In this study of barn swallows (Hirundo rustica) we investigated the sex-dependent telomere erosion during nestling period, and the covariation between relative telomere length and body and plumage growth. Finally, we tested whether any covariation between growth traits and relative telomere length depends on the social environment, as influenced by sibling sex ratio. Relative telomere length declined on average over the period of nestling maximal growth rate (between 7 and 16 days of age) and differently covaried with initial relative telomere length in either sex. The frequency distribution of changes in relative telomere length was bimodal, with most nestlings decreasing and some increasing relative telomere length, but none of the offspring traits predicted the a posteriori identified group to which individual nestlings belonged. Tail and wing length increased with relative telomere length, but more steeply in males than females, and this relationship held both at the within- and among-broods levels. Moreover, the increase in plumage phenotypic values was steeper when the sex ratio of an individual’s siblings was female-biased. Our study provides evidence for telomere shortening during early life according to subtly different dynamics in either sex. Furthermore, it shows that the positive covariation between growth and relative telomere

  3. Effects of postnatal growth restriction and subsequent catch-up growth on neurodevelopment and glucose homeostasis in rats.

    PubMed

    Alexeev, Erica E; Lönnerdal, Bo; Griffin, Ian J

    2015-06-05

    There is increasing evidence that poor growth of preterm infants is a risk factor for poor long-term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine the consequences of different patterns of postnatal growth and hypothesized that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11, R pups were re-randomized into litters of 6 (R-6), 10 (R-10) or 16 (R-16) pups/dam. N pups remained in litters of 10 pups/dam (N-10). Memory and learning were examined through T-maze test. Insulin sensitivity was measured by i.p. insulin tolerance test and glucose tolerance test. By d10, N pups weighed 20% more than R pups (p < 0.001). By d15, the R-6 group caught up to the N-10 group in weight, the R-10 group showed partial catch-up growth and the R-16 group showed no catch-up growth. All R groups showed poorer scores in developmental testing when compared with the N-10 group during T-Maze test (p < 0.05). Although R-16 were more insulin sensitive than R-6 and R-10, all R groups were more glucose tolerant than N-10. In rats, differences in postnatal growth restriction leads to changes in development and in insulin sensitivity. These results may contribute to better elucidating the causes of poor developmental outcomes in human preterm infants.

  4. The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor.

    PubMed

    Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino

    2017-01-01

    Nerve growth factor is a therapeutic candidate for Alzheimer's disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-β deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNGFp), inspired by the human genetic disease hereditary sensory and autonomic neuropathy type V. hNGFp has identical neurotrophic potency as wild-type human nerve growth factor, but a 10-fold lower pain sensitizing activity. In this study we first mimicked, in the 5xFAD mouse model, the intraparenchymal delivery of hNGFp used in clinical trials and found it to be ineffective in decreasing amyloid-β plaque load. On the contrary, the same dose of hNGFp delivered intranasally, which was widely biodistributed in the brain and did not induce pain, showed a potent anti-amyloidogenic action and rescued synaptic plasticity and memory deficits. We found that hNGFp acts on glial cells, modulating inflammatory proteins such as the soluble TNFα receptor II and the chemokine CXCL12. We further established that the rescuing effect by hNGFp is mediated by CXCL12, as pharmacological inhibition of CXCL12 receptor CXCR4 occludes most of hNGFp effects. These findings have significant therapeutic implications: (i) we established that a widespread exposure of the brain is required for nerve growth factor to fully exert its neuroprotective actions; and (ii) we have identified a new anti-neurodegenerative pathway as a broad target for new therapeutic opportunities for neurodegenerative diseases. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  5. Interorgan handling of fibroblast growth factor-23 in humans.

    PubMed

    Verzola, Daniela; Ansaldo, Francesca; Milanesi, Samantha; Parodi, Emanuele Luigi; Rosa, Gian Marco; Sofia, Antonella; Bonanni, Alice; Viazzi, Francesca; Balbi, Manrico; Garibotto, Giacomo

    2017-02-01

    Fibroblast growth factor-23 (FGF-23) accumulates in blood of patients with chronic kidney disease (CKD) and is associated both with cardiovascular complications and disease progression. However, our knowledge of the sites and mechanisms that regulate plasma FGF-23 is still incomplete. We measured plasma intact FGF-23 across the kidney, splanchnic organs, and lung in 11 patients [estimated glomerular filtration rate (eGFR) 60 ± 6 ml/min] during elective diagnostic cardiac catheterizations. In these patients FGF-23 was removed by the kidney, with a fractional extraction (FE) of ∼22%. The FE of FGF-23 across the kidney was similar to that of creatinine (∼17%, P = NS). In addition, the FGF-23 FE by the kidney was significantly directly related to eGFR (r = 0.709 P = 0.018) and to kidney creatinine FE (r = 0.736 P = 0.013) but only as a trend to plasma phosphate levels (r = 0.55, P = 0.18). There was no difference in FGF-23 levels in blood perfusing splanchnic organs and cardiopulmonary bed. However, the arterial-venous difference of FGF-23 across the lung was directly related to FGF-23 pulmonary artery levels, suggesting that the lung, and possibly the heart, participate in the homeostasis of plasma FGF-23 when its systemic levels are increased. Our data show that the human kidney is the only site for FGF-23 removal from blood and suggest that FGF-23 is predominantly removed by glomerular filtration. The kidney ability to remove FGF-23 from the circulation likely accounts for the early increase in blood of FGF-23 in patients with CKD. Copyright © 2017 the American Physiological Society.

  6. Brain anatomical networks in early human brain development.

    PubMed

    Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

    2011-02-01

    Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

  7. Growth and characterization of different human rhinovirus C types in three-dimensional human airway epithelia reconstituted in vitro

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tapparel, Caroline, E-mail: Caroline.Tapparel@hcuge.ch; Sobo, Komla; Constant, Samuel

    New molecular diagnostic tools have recently allowed the discovery of human rhinovirus species C (HRV-C) that may be overrepresented in children with lower respiratory tract complications. Unlike HRV-A and HRV-B, HRV-C cannot be propagated in conventional immortalized cell lines and their biological properties have been difficult to study. Recent studies have described the successful amplification of HRV-C15, HRV-C11, and HRV-C41 in sinus mucosal organ cultures and in fully differentiated human airway epithelial cells. Consistent with these studies, we report that a panel of clinical HRV-C specimens including HRV-C2, HRV-C7, HRV-C12, HRV-C15, and HRV-C29 types were all capable of mediating productivemore » infection in reconstituted 3D human primary upper airway epithelial tissues and that the virions enter and exit preferentially through the apical surface. Similar to HRV-A and HRV-B, our data support the acid sensitivity of HRV-C. We observed also that the optimum temperature requirement during HRV-C growth may be type-dependent. - Highlights: • A 3D human upper airway epithelia reconstituted in vitro supports HRV-C growth. • HRV-Cs enter and exit preferentially at the apical side of this ALI culture system. • HRV-Cs are acid sensitive. • Temperature sensitivity may be type-dependent for HRV-Cs.« less

  8. Evolution and the Growth Process: Natural Selection of Entrepreneurial Traits*

    PubMed Central

    Galor, Oded; Michalopoulos, Stelios

    2013-01-01

    This research suggests that a Darwinian evolution of entrepreneurial spirit played a significant role in the process of economic development and the dynamics of inequality within and across societies. The study argues that entrepreneurial spirit evolved non-monotonically in the course of human history. In early stages of development, risk-tolerant, growth promoting traits generated an evolutionary advantage and their increased representation accelerated the pace of technological progress and the process of economic development. In mature stages of development, however, risk-averse traits gained an evolutionary advantage, diminishing the growth potential of advanced economies and contributing to convergence in economic growth across countries. PMID:25089059

  9. [How safe is the recombinant human growth hormone?

    PubMed

    Calzada-León, Raúl

    2017-01-01

    In this paper, several aspects related to the safety of the use of biosynthetic human growth hormone are reviewed. For example, its classification as a biosynthetic drug, the phases that need to be performed in Mexico to verify its safety (obtaining, purification, preclinical studies, clinical trials, and finally observational clinical studies), as well as the evidence that exists in relation to the association of intracranial hypertension, muscular events, scoliosis, slipped capital femoral epiphysis, obstructive sleep apnea, pancreatitis, alterations in cortisol, thyroid hormones alterations, cardiovascular disease, metabolic risk, mortality and cancer, adverse events not related to its use, and finally dosing and safety.

  10. Agriculture on Mars: Soils for Plant Growth

    NASA Technical Reports Server (NTRS)

    Ming, D. W.

    2016-01-01

    Robotic rovers and landers have enabled the mineralogical, chemical, and physical characterization of loose, unconsolidated materials on the surface of Mars. Planetary scientists refer to the regolith material as "soil." NASA is currently planning to send humans to Mars in the mid 2030s. Early missions may rely on the use of onsite resources to enable exploration and self-sufficient outposts on Mars. The martian "soil" and surface environment contain all essential plant growth elements. The study of martian surface materials and how they might react as agricultural soils opens a new frontier for researchers in the soil science community. Other potential applications for surface "soils" include (i) sources for extraction of essential plant-growth nutrients, (ii) sources of O2, H2, CO2, and H2O, (iii) substrates for microbial populations in the degradation of wastes, and (iv) shielding materials surrounding outpost structures to protect humans, plants, and microorganisms from radiation. There are many challenges that will have to be addressed by soil scientists prior to human exploration over the next two decades.

  11. Effects of recombinant human growth hormone on enterocutaneous fistula patients.

    PubMed

    Gu, Guo-Sheng; Ren, Jian-An; Li, Ning; Li, Jie-Shou

    2008-11-28

    To explore the effects of recombinant human growth hormone (rhGH) on intestinal mucosal epithelial cell proliferation and nutritional status in patients with enterocutaneous fistula. Eight patients with enterocutaneous fistulas received recombinant human growth hormone (10 microg/d) for 7 d. Image analysis and immunohistochemical techniques were used to analyse the expression of proliferating cell nuclear antigen (PCNA) in intestinal mucosal epithelial cells in biopsy samples from the patients who had undergone an endoscopic biopsy through the fistula at day 0, 4 and 7. Body weights, nitrogen excretion, serum levels of total proteins, albumin, prealbumin, transferrin and fibronectin were measured at day 0, 4 and 7. Significant improvements occurred in the expression of PCNA in the intestinal mucosal epithelial cells at day 4 and 7 compared to day 0 (24.93 +/- 3.41%, 30.46 +/- 5.24% vs 12.92 +/- 4.20%, P < 0.01). These changes were accompanied by the significant improvement of villus height (500.54 +/- 53.79 microm, 459.03 +/- 88.98 microm vs 210.94 +/- 49.16 microm, P < 0.01), serum levels of total proteins (70.52 +/- 5.13 g/L, 74.89 +/- 5.16 g/L vs 63.51 +/- 2.47 g/L, P < 0.01), albumin (39.44 +/- 1.18 g/L, 42.39 +/- 1.68 g/L vs 35.74 +/- 1.75 g/L, P < 0.01) and fibronectin (236.3 +/- 16.5 mg/L, 275.8 +/- 16.9 mg/L vs 172.5 +/- 21.4 mg/L, P < 0.01) at day 4 and 7, and prealbumin (286.38 +/- 65.61 mg/L vs 180.88 +/- 48.28 mg/L, P < 0.05), transferrin (2.61 +/- 0.12 g/L vs 2.41 +/- 0.14 g/L, P < 0.05) at day 7. Nitrogen excretion was significantly decreased at day 7 (3.40 +/- 1.65 g/d vs 7.25 +/- 3.92 g/d, P < 0.05). No change was observed in the body weight. Recombinant human growth hormone could promote intestinal mucosal epithelial cell proliferation and protein synthesis in patients with enterocutaneous fistula.

  12. The Nell-1 Growth Factor Stimulates Bone Formation by Purified Human Perivascular Cells

    PubMed Central

    Zhang, Xinli; Péault, Bruno; Chen, Weiwei; Li, Weiming; Corselli, Mirko; James, Aaron W.; Lee, Min; Siu, Ronald K.; Shen, Pang; Zheng, Zhong; Shen, Jia; Kwak, Jinny; Zara, Janette N.; Chen, Feng; Zhang, Hong; Yin, Zack; Wu, Ben; Ting, Kang

    2011-01-01

    The search for novel sources of stem cells other than bone marrow mesenchymal stem cells (MSCs) for bone regeneration and repair has been a critical endeavor. We previously established an effective protocol to homogeneously purify human pericytes from multiple fetal and adult tissues, including adipose, bone marrow, skeletal muscle, and pancreas, and identified pericytes as a primitive origin of human MSCs. In the present study, we further characterized the osteogenic potential of purified human pericytes combined with a novel osteoinductive growth factor, Nell-1. Purified pericytes grown on either standard culture ware or human cancellous bone chip (hCBC) scaffolds exhibited robust osteogenic differentiation in vitro. Using a nude mouse muscle pouch model, pericytes formed significant new bone in vivo as compared to scaffold alone (hCBC). Moreover, Nell-1 significantly increased pericyte osteogenic differentiation, both in vitro and in vivo. Interestingly, Nell-1 significantly induced pericyte proliferation and was observed to have pro-angiogenic effects, both in vitro and in vivo. These studies suggest that pericytes are a potential new cell source for future efforts in skeletal regenerative medicine, and that Nell-1 is a candidate growth factor able to induce pericyte osteogenic differentiation. PMID:21615216

  13. Early Human Evolution in the Western Palaearctic: Ecological Scenarios

    NASA Astrophysics Data System (ADS)

    Carrión, José S.; Rose, James; Stringer, Chris

    2011-06-01

    This review presents the themes of a special issue dealing with environmental scenarios of human evolution during the Early Pleistocene (2.6-0.78 Ma; MIS 103-MIS 19) and early Middle Pleistocene (0.78-0.47 Ma; MIS 19-base of MIS 12) within the western Palaearctic. This period is one of dramatic changes in the climates and the distribution of Palaearctic biota. These changes have played their role in generating adaptive and phyletic patterns within the human ancestry, involving several species such as Homo habilis, "Homo georgicus", Homo erectus, Homo antecessor and Homo heidelbergensis. In the archaeological record, these species include the Oldowan (Mode 1) and Acheulian (Mode 2) lithic technologies. Taphonomic considerations of palaeoecological research in hominin-bearing sites are provided and evaluated. Syntheses are provided for north Africa, western Asia, the Mediterranean Basin, Britain, and continental Europe. Palaeoenvironmental reconstructions based on multidisciplinary data are given for Ain Boucherit, Ain Hanech and El-Kherba in Algeria, Dmanisi in Georgia, Atapuerca, Cueva Negra, and the Orce Basin in Spain, Monte Poggiolo and Pirro Nord in Italy, Pont-de-Lavaud in France, and Mauer in Germany. The state of the art with the Out of Africa 1 dispersal model is reviewed. A source-sink dynamics model for Palaeolithic Europe is described to explain the morphological disparity of H. heidelbergensis (we will sometimes use the informal name "Heidelbergs") and early Neanderthals. Other aspects debated here are the selective value of habitat mosaics including reconstructions based on mammal and avian databases, and the role of geological instability combined with topographic complexity. This review is completed by addressing the question of whether the appearance of evolutionary trends within hominins is concentrated in regions of highest worldwide biological diversity (biodiversity hotspots). It is concluded that the keys for the activation of evolutionary

  14. Physical growth of the shuar: Height, Weight, and BMI references for an indigenous amazonian population.

    PubMed

    Urlacher, Samuel S; Blackwell, Aaron D; Liebert, Melissa A; Madimenos, Felicia C; Cepon-Robins, Tara J; Gildner, Theresa E; Snodgrass, J Josh; Sugiyama, Lawrence S

    2016-01-01

    Information concerning physical growth among small-scale populations remains limited, yet such data are critical to local health efforts and to foster basic understandings of human life history and variation in childhood development. Using a large dataset and robust modeling methods, this study aims to describe growth from birth to adulthood among the indigenous Shuar of Amazonian Ecuador. Mixed-longitudinal measures of height, weight, and body mass index (BMI) were collected from Shuar participants (n = 2,463; age: 0-29 years). Centile growth curves and tables were created for each anthropometric variable of interest using Generalized Additive Models for Location, Scale, and Shape (GAMLSS). Pseudo-velocity and Lambda-Mu-Sigma curves were generated to further investigate Shuar patterns of growth and to facilitate comparison with United States Center for Disease Control and Prevention and multinational World Health Organization growth references. The Shuar are small throughout life and exhibit complex patterns of growth that differ substantially from those of international references. Similar to other Amazonians, Shuar growth in weight compares more favorably to references than growth in height, resulting in BMI curves that approximate international medians. Several additional characteristics of Shuar development are noteworthy, including large observed variation in body size early in life, significant infant growth faltering, extended male growth into adulthood, and a markedly early female pubertal growth spurt in height. Phenotypic plasticity and genetic selection in response to local environmental factors may explain many of these patterns. Providing a detailed reference of growth for the Shuar and other Amazonian populations, this study possesses direct clinical application and affords valuable insight into childhood health and the ecology of human growth. © 2015 Wiley Periodicals, Inc.

  15. Early adolescent childbearing in low- and middle-income countries: associations with income inequity, human development and gender equality.

    PubMed

    Decker, Michele R; Kalamar, Amanda; Tunçalp, Özge; Hindin, Michelle J

    2017-03-01

    Reducing unwanted adolescent childbearing is a global priority. Little is known about how national-level economic and human development indicators relate to early adolescent childbearing. This ecological study evaluates associations of Gross Domestic Product (GDP), GINI index, Human Development Index (HDI) and Gender-related Development Index (GDI; i.e. the HDI adjusted for gender disparities) with early adolescent childbearing in 27 low- and middle-income countries (LMICs) across three time periods. Among women ages 18–24, prevalence estimates for early birth (<16 years) were calculated by nation, and weighted linear regressions evaluated associations between national indicators and early childbearing. To examine temporal trends, analyses were stratified by year groupings. Early adolescent childbearing declined over time, with the greatest change observed in Bangladesh (31.49% in 1996/7 to 19.69% in 2011). In adjusted models, GDI was negatively associated with early childbearing, i.e. early childbearing prevalence decreased as GDI increased. In the most recent time period, relative to the lowest GDI group, the average prevalence of early childbearing was significantly lower in the middle (-12.40, P < 0.00) and upper (-10.96, P = 0.03) tertiles after adjustment for the other indicators. These other indicators showed no consistent association with early childbearing. As national-level GDI increased, early adolescent childbearing declined. The GDI, which reflects human development adjusted for gender disparities in educational and economic prospects, was more consistently related to early adolescent childbearing than the absolute development prospects as given by the HDI. While creating gender equality is an important goal in and of itself, the findings emphasize the potential for improved national-level gender equitable development as a means to improve adolescents’ sexual and reproductive health.

  16. Tumor-targeted SN38 inhibits growth of early stage non-small cell lung cancer (NSCLC) in a KRas/p53 transgenic mouse model.

    PubMed

    Deneka, Alexander Y; Haber, Leora; Kopp, Meghan C; Gaponova, Anna V; Nikonova, Anna S; Golemis, Erica A

    2017-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide, with a 5-year survival of only ~16%. Potential strategies to address NSCLC mortality include improvements in early detection and prevention, and development of new therapies suitable for use in patients with early and late stage diagnoses. Controlling the growth of early stage tumors could yield significant clinical benefits for patients with comorbidities that make them poor candidates for surgery: however, many drugs that limit cancer growth are not useful in the setting of long-term use or in comorbid patients, because of associated toxicities. In this study, we explored the use of a recently described small molecule agent, STA-8666, as a potential agent for controlling early stage tumor growth. STA-8666 uses a cleavable linker to merge a tumor-targeting moiety that binds heat shock protein 90 (HSP90) with the cytotoxic chemical SN38, and has been shown to have high efficacy and low toxicity, associated with efficient tumor targeting, in preclinical studies using patient-derived and other xenograft models for pancreatic, bladder, and small cell lung cancer. Using a genetically engineered model of NSCLC arising from induced mutation of KRas and knockout of Trp53, we continuously dosed mice with STA-8666 from immediately after tumor induction for 15 weeks. STA-8666 significantly slowed the rate of tumor growth, and was well tolerated over this extended dosing period. STA-8666 induced DNA damage and apoptosis, and reduced proliferation and phosphorylation of the proliferation-associated protein ERK1/2, selectively in tumor tissue. In contrast, STA-8666 did not affect tumor features, such as degree of vimentin staining, associated with epithelial-mesenchymal transition (EMT), or downregulate tumor expression of HSP90. These data suggest STA-8666 and other similar targeted compounds may be useful additions to control the growth of early stage NSCLC in patient populations.

  17. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, Yue; Xie, Changchun; Murphy, Susan K.

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  18. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    DOE PAGES

    Li, Yue; Xie, Changchun; Murphy, Susan K.; ...

    2015-06-26

    Here, lead exposure during early development causes neurodevelopmental disorders by unknown mechanisms. Epidemiologic studies have focused recently on determining associations between lead exposure and global DNA methylation; however, such approaches preclude the identification of loci that may alter human disease risk. The objective of this study was to determine whether maternal, postnatal, and early childhood lead exposure can alter the differentially methylated regions (DMRs) that control the monoallelic expression of imprinted genes involved in metabolism, growth, and development. Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study frommore » birth to 78 months. When participants were adults, we used Sequenom EpiTYPER assays to test peripheral blood DNA to quantify CpG methylation in peripheral blood leukocytes at DMRs of 22 human imprinted genes. Statistical analyses were conducted using linear regression. Mean blood lead concentration from birth to 78 months was associated with a significant decrease in PEG3 DMR methylation (β = –0.0014; 95% CI: –0.0023, –0.0005, p = 0.002), stronger in males (β = –0.0024; 95% CI: –0.0038, –0.0009, p = 0.003) than in females (β = –0.0009; 95% CI: –0.0020, 0.0003, p = 0.1). Elevated mean childhood blood lead concentration was also associated with a significant decrease in IGF2/H19 (β = –0.0013; 95% CI: –0.0023, –0.0003, p = 0.01) DMR methylation, but primarily in females, (β = –0.0017; 95% CI: –0.0029, –0.0006, p = 0.005) rather than in males, (β = –0.0004; 95% CI: –0.0023, 0.0015, p = 0.7). Elevated blood lead concentration during the neonatal period was associated with higher PLAGL1/HYMAI DMR methylation regardless of sex (β = 0.0075; 95% CI: 0.0018, 0.0132, p = 0.01). The magnitude of associations between cumulative lead exposure and CpG methylation remained unaltered from 30 to 78 months. Our

  19. Constitutively Expressed IFITM3 Protein in Human Endothelial Cells Poses an Early Infection Block to Human Influenza Viruses

    PubMed Central

    Sun, Xiangjie; Zeng, Hui; Kumar, Amrita; Belser, Jessica A.; Maines, Taronna R.

    2016-01-01

    ABSTRACT A role for pulmonary endothelial cells in the orchestration of cytokine production and leukocyte recruitment during influenza virus infection, leading to severe lung damage, has been recently identified. As the mechanistic pathway for this ability is not fully known, we extended previous studies on influenza virus tropism in cultured human pulmonary endothelial cells. We found that a subset of avian influenza viruses, including potentially pandemic H5N1, H7N9, and H9N2 viruses, could infect human pulmonary endothelial cells (HULEC) with high efficiency compared to human H1N1 or H3N2 viruses. In HULEC, human influenza viruses were capable of binding to host cellular receptors, becoming internalized and initiating hemifusion but failing to uncoat the viral nucleocapsid and to replicate in host nuclei. Unlike numerous cell types, including epithelial cells, we found that pulmonary endothelial cells constitutively express a high level of the restriction protein IFITM3 in endosomal compartments. IFITM3 knockdown by small interfering RNA (siRNA) could partially rescue H1N1 virus infection in HULEC, suggesting IFITM3 proteins were involved in blocking human influenza virus infection in endothelial cells. In contrast, selected avian influenza viruses were able to escape IFITM3 restriction in endothelial cells, possibly by fusing in early endosomes at higher pH or by other, unknown mechanisms. Collectively, our study demonstrates that the human pulmonary endothelium possesses intrinsic immunity to human influenza viruses, in part due to the constitutive expression of IFITM3 proteins. Notably, certain avian influenza viruses have evolved to escape this restriction, possibly contributing to virus-induced pneumonia and severe lung disease in humans. IMPORTANCE Avian influenza viruses, including H5N1 and H7N9, have been associated with severe respiratory disease and fatal outcomes in humans. Although acute respiratory distress syndrome (ARDS) and progressive pulmonary

  20. Early humans' egalitarian politics: runaway synergistic competition under an adapted veil of ignorance.

    PubMed

    Harvey, Marc

    2014-09-01

    This paper proposes a model of human uniqueness based on an unusual distinction between two contrasted kinds of political competition and political status: (1) antagonistic competition, in quest of dominance (antagonistic status), a zero-sum, self-limiting game whose stake--who takes what, when, how--summarizes a classical definition of politics (Lasswell 1936), and (2) synergistic competition, in quest of merit (synergistic status), a positive-sum, self-reinforcing game whose stake becomes "who brings what to a team's common good." In this view, Rawls's (1971) famous virtual "veil of ignorance" mainly conceals politics' antagonistic stakes so as to devise the principles of a just, egalitarian society, yet without providing any means to enforce these ideals (Sen 2009). Instead, this paper proposes that human uniqueness flourished under a real "adapted veil of ignorance" concealing the steady inflation of synergistic politics which resulted from early humans' sturdy egalitarianism. This proposition divides into four parts: (1) early humans first stumbled on a purely cultural means to enforce a unique kind of within-team antagonistic equality--dyadic balanced deterrence thanks to handheld weapons (Chapais 2008); (2) this cultural innovation is thus closely tied to humans' darkest side, but it also launched the cumulative evolution of humans' brightest qualities--egalitarian team synergy and solidarity, together with the associated synergistic intelligence, culture, and communications; (3) runaway synergistic competition for differential merit among antagonistically equal obligate teammates is the single politically selective mechanism behind the cumulative evolution of all these brighter qualities, but numerous factors to be clarified here conceal this mighty evolutionary driver; (4) this veil of ignorance persists today, which explains why humans' unique prosocial capacities are still not clearly understood by science. The purpose of this paper is to start lifting