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Sample records for human early growth

  1. 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. PMID:25413647

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

    SciTech Connect

    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 human 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.

  3. 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

  4. Early production of human neutrophils and platelets posttransplant is severely compromised by growth factor exposure.

    PubMed

    Miller, Paul H; Knapp, David J H F; Beer, Philip A; MacAldaz, Margarita; Rabu, Gabrielle; Cheung, Alice M S; Wei, Lisa; Eaves, Connie J

    2016-07-01

    The critical human cells that produce neutrophils and platelets within 3 weeks in recipients of hematopoietic transplants are thought to produce these mature blood cells with the same kinetics in sublethally irradiated immunodeficient mice. Quantification of their numbers indicates their relative underrepresentation in cord blood (CB), likely explaining the clinical inadequacy of single CB units in rescuing hematopoiesis in myelosuppressed adult patients. We here describe that exposure of CD34(+) CB cells ex vivo to growth factors that markedly expand their numbers and colony-forming cell content also rapidly (within 24 hours) produce a significant and sustained net loss of their original short-term repopulating activity. This loss of short-term in vivo repopulating activity affects early platelet production faster than early neutrophil output, consistent with their origin from distinct input populations. Moreover, this growth factor-mediated loss is not abrogated by published strategies to increase progenitor homing despite evidence that the effect on rapid neutrophil production is paralleled in time and amount by a loss of the homing of their committed clonogenic precursors to the bone marrow. These results highlight the inability of in vitro or phenotype assessments to reliably predict clinical engraftment kinetics of cultured CB cells. PMID:27090409

  5. [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. PMID:26580942

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

    PubMed Central

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

    2014-01-01

    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. PMID:24603366

  7. Human telomerase reverse transcriptase (hTERT) promotes cancer invasion by modulating cathepsin D via early growth response (EGR)-1.

    PubMed

    Park, Young-Jin; Kim, Eun Kyoung; Bae, Jung Yoon; Moon, Sook; Kim, Jin

    2016-01-28

    Human telomerase reverse transcriptase (hTERT) contributes to tumor progression as well as maintaining telomere length, however, the mechanism by which hTERT promotes invasiveness is not yet completely understood. This study aims to unravel the precise mechanism through which hTERT promotes cancer invasion. We established an hTERT-overexpressed immortalized cell line (IHOK/hTERT). In orthotopic xenograft models, IHOK/hTERT harbors higher tumorigenicity than IHOK/Control. IHOK/hTERT showed much higher migration and invasion activities compared to IHOK/Control. IHOK/hTERT co-cultured with fibroblasts displayed increased invasion compared to IHOK/hTERT without fibroblasts. We screened for genes that play an important role in intermodulation between cancer cells and fibroblasts using a microarray and identified fibroblast activation protein (FAP). hTERT knockdown showed decreased expression of FAP and early growth response (EGR)-1, one of the transcriptional regulators of FAP in IHOK/hTERT and oral cancer cell line YD10B. Furthermore, EGR-1 knockdown in IHOK/hTERT and YD10B showed reduced invasion and reduced cathepsin D expression compared to Control-siRNA cells. Taken together, this study provides evidence that hTERT overexpression is responsible for the upregulation of the cysteine protease cathepsin D by regulating EGR-1 to activate invasiveness in cancer progression. PMID:26519755

  8. 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. PMID:18785651

  9. Early stage of nanocrystal growth

    SciTech Connect

    2012-01-01

    Berkeley Lab researchers at the Molecular Foundry have elucidated important mechanisms behind oriented attachment, the phenomenon that drives biomineralization and the growth of nanocrystals. This electron microscopy movie shows the early stage of nanocrystal growth. Nanoparticles make transient contact at many points and orientations until their lattices are perfectly matched. The particles then make a sudden jump-to-contact to form attached aggregates. (Movie courtesy of Jim DeYoreo)

  10. Human growth hormone.

    PubMed

    Strobl, J S; Thomas, M J

    1994-03-01

    The study of human growth hormone is a little more than 100 years old. Growth hormone, first identified for its dramatic effect on longitudinal growth, is now known to exert generalized effects on protein, lipid, and carbohydrate metabolism. Additional roles for growth hormone in human physiology are likely to be discovered in the areas of sleep research and reproduction. Furthermore, there is some indication that growth hormone also may be involved in the regulation of immune function, mental well-being, and the aging process. Recombinant DNA technology has provided an abundant and safe, albeit expensive, supply of human growth hormone for human use, but the pharmacological properties of growth hormone are poor. Most growth hormone-deficient individuals exhibit a secretory defect rather than a primary defect in growth hormone production, however, and advances in our understanding of the neuroendocrine regulation of growth hormone secretion have established the basis for the use of drugs to stimulate release of endogenously synthesized growth hormone. This promises to be an important area for future drug development. PMID:8190748

  11. Early influences of nutrition on postnatal growth.

    PubMed

    Koletzko, Berthold; Beyer, Jeanette; Brands, Brigitte; Demmelmair, Hans; Grote, Veit; Haile, Gudrun; Gruszfeld, Dariusz; Rzehak, Peter; Socha, Piotr; Weber, Martina

    2013-01-01

    Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy. PMID:23502135

  12. Human chorionic gonadotrophin in early gestation induces growth of estrogenic ovarian follicles and improves primiparous sow fertility during summer.

    PubMed

    Seyfang, Jemma; Langendijk, P; Chen, T Y; Bouwman, E; Kirkwood, R N

    2016-09-01

    Reduced summer farrowing rates may be due to inadequate corpora luteal (CL) support. Porcine CL become dependent on LH from 12 d of pregnancy and the embryonic estrogen signal for maternal recognition of pregnancy (MRP) is initiated at about 11-12 d after insemination. We hypothesised that injection of the LH analogue human chorionic gonadotropin (hCG) would induce growth of estrogenic follicles and, by mimicking the signal for MRP and stimulating progesterone secretion, increase primiparous sow fertility. In Experiment 1, during a 28 d lactation 53 mixed parity sows were full-fed either throughout lactation (n=16) or until 18 d and then feed restricted during the last 10 d of lactation (n=36). At 12 d after mating restrict-fed sows were injected with 1000IU hCG (n=17) or were not injected (n=19); the full-fed sows acted as non-treated positive controls. Transrectal ovarian ultrasound exams were performed on days 12, 16, 20, 24, and 28; blood samples were obtained on days 12, 14, and 15 for estradiol and progesterone assay. For Experiment 2, during the summer months primiparous sows received 1000IU hCG 12 d after mating (n=28) or were non-injected controls (n=27). Pregnancy status was determined at 28 d and sows allowed to go to term to determine farrowing rates and litter sizes. In Experiment 1, injection of hCG increased (P<0.001) follicle diameter and serum concentrations of estradiol (P<0.01) and progesterone (P<0.05). There were no effects of lactation feeding level on wean-estrus interval, farrowing rate or subsequent litter size. In Experiment 2, hCG injection was associated with a higher pregnancy rate (P<0.05) and farrowing rate (P<0.08). There was no effect on litter size. These data confirm that hCG stimulates growth of estrogenic follicles and CL function, and improves primiparous sow fertility during the summer months. PMID:27397793

  13. Apoptosis Induction of Human Bladder Cancer Cells by Sanguinarine through Reactive Oxygen Species-Mediated Up-Regulation of Early Growth Response Gene-1

    PubMed Central

    Han, Min Ho; Park, Cheol; Jin, Cheng-Yun; Kim, Gi-Young; Chang, Young-Chae; Moon, Sung-Kwon; Kim, Wun-Jae; Choi, Yung Hyun

    2013-01-01

    Although the effects of sanguinarine, a benzophenanthridine alkaloid, on the inhibition of some kinds of cancer cell growth have been established, the underlying mechanisms are not completely understood. This study investigated possible mechanisms by which sanguinarine exerts its anticancer action in cultured human bladder cancer cell lines (T24, EJ, and 5637). Sanguinarine treatment resulted in concentration-response growth inhibition of the bladder cancer cells by inducing apoptosis. Sanguinarine-induced apoptosis was correlated with the up-regulation of Bax, the down-regulation of Bid and XIAP, the activation of caspases (-3, -8, and -9), and the generation of increased reactive oxygen species (ROS). The ROS scavenger N-acetyl cysteine (NAC) completely reversed the sanguinarine-triggered apoptotic events. In addition, sanguinarine effectively increased the activation of the c-Jun N-terminal kinase (JNK) and the expression of the early growth response gene-1 (Egr-1), which was recovered by pretreatment with NAC. Furthermore, knockdown of Egr-1 expression by small interfering RNA attenuated sanguinarine-induced apoptosis, but not the JNK inhibitor, indicating that the interception of ROS generation blocked the sanguinarine-induced apoptotic effects via deregulation of the expression of Egr-1 proteins. Taken together, the data provide evidence that sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals. PMID:23717422

  14. Reduction of radiochemotherapy-induced early oral mucositis by recombinant human keratinocyte growth factor (palifermin): Experimental studies in mice

    SciTech Connect

    Doerr, Wolfgang . E-mail: doerr@rcs.urz.tu-dresden.de; Baessler, Stefan; Reichel, Sandra; Spekl, Kathrin

    2005-07-01

    Purpose: To study the effect of recombinant human keratinocyte growth factor (rHuKGF or palifermin) on oral mucositis induced by radiochemotherapy in a mouse model. Methods and Materials: Cis-diamminedichloroplatinum (cisplatin) and/or 5-fluorouracil were given before single dose irradiation, combined with palifermin before or after the treatment, or both. Daily fractionated irradiation for 2 weeks was followed by graded test doses. With additional chemotherapy in Week 1, palifermin was given before radiotherapy and at the end of the first week, or additionally at the end of Week 2. Radiochemotherapy in Week 2 was combined with palifermin at the end of Weeks 1 and 2, Weeks 1, 2, and 3, or additionally before radiotherapy. Ulceration of mouse tongue mucosa was analyzed as the endpoint. Results: The dose associated with ulcer induction in 50% of the mice (ED{sub 50}) for single-dose irradiation was 11.5 {+-} 0.7 Gy. Palifermin increased the ED{sub 50} to about 19 Gy in all protocols tested. Similar values were observed when chemotherapy was added before irradiation. With fractionated irradiation, palifermin increased the ED{sub 50} for test irradiation from 5.7 {+-} 1.5 Gy to 12-15 Gy, depending on the administration protocol. With chemotherapy in Week 1, two palifermin injections had no significant effect, but a third injection increased the ED{sub 50} to 13 Gy. With chemotherapy in Week 2, all palifermin protocols resulted in ED{sub 50} values of 13-14 Gy. Conclusion: A marked increase in oral mucosal radiation tolerance by palifermin was found, which was preserved in combinations with chemotherapy using cisplatin and/or 5-fluorouracil.

  15. Early recognition of growth abnormalities permitting early intervention

    PubMed Central

    Haymond, Morey; Kappelgaard, Anne-Marie; Czernichow, Paul; Biller, Beverly MK; Takano, Koji; Kiess, Wieland

    2013-01-01

    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. Conclusion This review summarizes currently available information on monitoring for short stature in children and conditions usually associated with short stature and summarizes the authors’ conclusions on the early recognition of growth disorders. PMID:23586744

  16. Early recognition of growth abnormalities permitting early intervention

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. 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. PMID:25377654

  18. Ephedrae herba stimulates hepatocyte growth factor-induced MET endocytosis and downregulation via early/late endocytic pathways in gefitinib-resistant human lung cancer cells.

    PubMed

    Nishimura, Yukio; Hyuga, Sumiko; Takiguchi, Soichi; Hyuga, Masashi; Itoh, Kazuyuki; Hanawa, Toshihiko

    2016-05-01

    The MET tyrosine kinase receptor and its ligand, hepatocyte growth factor (HGF), are known to be overexpressed in a variety of malignant tumor cells, and are implicated in the development of gefitinib-resistance in human non-small cell lung cancer (NSCLC) cells. Ephedrae herba was previously reported to prevent HGF-induced cancer cell motility by directly suppressing HGF/MET signaling through the inhibition of MET tyrosine kinase, and treatment with its extract also considerably reduced MET protein levels. To further investigate the mechanism underlying the Ephedrae herba-induced inhibition of MET phosphorylation as well as its degradation and subsequent disappearance, we examined the effect of Ephedrae herba on HGF-stimulated MET endocytosis and downregulation via early/late endocytic pathways in an NSCLC cell line. Using immunofluorescence microscopy, we found that pretreatment of cells with Ephedrae herba extract dramatically changed the intracellular distribution of plasma membrane-associated MET, and that the resultant MET staining was distributed throughout the cytoplasm. Pretreatment of the cells with Ephedrae herba extract also led to the rapid loss of MET and phosphorylated (p)-MET in HGF-stimulated cells. In contrast, inefficient endocytic delivery of MET and p-MET from early to late endosomes was observed in the absence of Ephedrae herba extract, since considerable amounts of the internalized MET accumulated in the early endosomes and were not delivered to lysosomes up to 1 h after HGF-stimulation. Furthermore, large amounts of MET and p-MET that had accumulated in late endosomes of Ephedrae herba-pretreated cells after HGF stimulation were observed along with bafilomycin A1. Therefore, we inferred that degradation of MET occurred in the late endosome/lysosome pathway. Moreover, western blot analysis revealed the accelerated degradation of MET and p-MET proceeds in cells pretreated with Ephedrae herba extract. Collectively, our results suggest that

  19. Human adenovirus early region 4 open reading frame 1 genes encode growth-transforming proteins that may be distantly related to dUTP pyrophosphatase enzymes.

    PubMed Central

    Weiss, R S; Lee, S S; Prasad, B V; Javier, R T

    1997-01-01

    An essential oncogenic determinant of subgroup D human adenovirus type 9 (Ad9), which uniquely elicits estrogen-dependent mammary tumors in rats, is encoded by early region 4 open reading frame 1 (E4 ORF1). Whereas Ad9 E4 ORF1 efficiently induces transformed foci on the established rat embryo fibroblast cell line CREF, the related subgroup A Ad12 and subgroup C Ad5 E4 ORF1s do not (R. T. Javier, J. Virol. 68:3917-3924, 1994). In this study, we found that the lack of transforming activity associated with non-subgroup D adenovirus E4 ORF1s in CREF cells correlated with significantly reduced protein levels compared to Ad9 E4 ORF1 in these cells. In the human cell line TE85, however, the non-subgroup D adenovirus E4 ORF1s produced protein levels higher than those seen in CREF cells as well as transforming activities similar to that of Ad9 E4 ORF1, suggesting that all adenovirus E4 ORF1 polypeptides possess comparable cellular growth-transforming activities. In addition, searches for known proteins related to these novel viral transforming proteins revealed that the E4 ORF1 proteins had weak sequence similarity, over the entire length of the E4 ORF1 polypeptides, with a variety of organismal and viral dUTP pyrophosphatase (dUTPase) enzymes. Even though adenovirus E4 ORF1 proteins lacked conserved protein motifs of dUTPase enzymes or detectable enzymatic activity, E4 ORF1 and dUTPase proteins were predicted to possess strikingly similar secondary structure arrangements. It was also established that an avian adenovirus protein, encoded within a genomic location analogous to that of the human adenovirus E4 ORF1s, was a genuine dUTPase enzyme. Although no functional similarity was found for the E4 ORF1 and dUTPase proteins, we propose that human adenovirus E4 ORF1 genes have evolved from an ancestral adenovirus dUTPase and, from this structural framework, developed novel transforming properties. PMID:9032316

  20. Stochastic Models of Human Growth.

    ERIC Educational Resources Information Center

    Goodrich, Robert L.

    Stochastic difference equations of the Box-Jenkins form provide an adequate family of models on which to base the stochastic theory of human growth processes, but conventional time series identification methods do not apply to available data sets. A method to identify structure and parameters of stochastic difference equation models of human…

  1. 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)

  2. Synergistic induction of early stage of bone formation by combination of recombinant human bone morphogenetic protein-2 and epidermal growth factor

    PubMed Central

    Lee, Jae Hyup; Jang, Soo-Jeong; Baek, Hae-Ri; Lee, Kyung Mee; Chang, Bong-Soon; Lee, Choon-Ki

    2015-01-01

    This study evaluates whether the combination of the rhBMP-2 and various types of growth factors including EGF, FGF, PDGF and VEGF increases osteoinductivity compared to the single use of rhBMP-2 through in vitro and in vivo study. Cultured human MSCs were treated with rhBMP-2 only or in combination with growth factors. For in vivo evaluation, rhBMP-2 only or with growth factors was implanted into the calvarial defect made on SD rats. Both EGF and PDGF significantly increased both ALP activity and expression level in hMSCs when treated in combination with rhBMP-2 at 3 and 7 days of differentiation and significantly raised the accumulation of the calcium at day 14. Furthermore, micro-CT scanning revealed that the EGF an FGF groups show significantly increased new bone surface ratio compared to the rhBMP-2 only group and, the EGF treatment significantly up regulated percent bone volume and trabecular number at two weeks after the surgery. VEGF treatment also significantly raised trabecular number and FGF treatment significantly increased the trabecular thickness. Histological examination revealed that the EGF combination group showed enhanced bone regeneration than the rhBMP-2 only group two weeks after the implantation. Even though the treatment of rhBMP-2 with PDGF and FGF failed to show enhanced osteogenesis in vitro and in vivo simultaneously, these results suggest that the positive effect of the combination of EGF and rhBMP-2 is expected to induce the bone formation earlier compared to the single use of rhBMP-2 in vitro and in vivo. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd. PMID:24764222

  3. Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor.

    PubMed

    Suzuki, Takashi; Inoue, Akio; Miki, Yasuhiro; Moriya, Takuya; Akahira, Jun-ichi; Ishida, Takanori; Hirakawa, Hisashi; Yamaguchi, Yuri; Hayashi, Shin-ichi; Sasano, Hironobu

    2007-06-01

    Early growth responsive gene 3 (EGR3) is a zinc-finger transcription factor and plays important roles in cellular growth and differentiation. We recently demonstrated estrogen-mediated induction of EGR3 in breast carcinoma cells. However, EGR3 has not yet been examined in breast carcinoma tissues and its significance remains unknown. Therefore, in this study, we examined biological functions of EGR3 in the breast carcinoma by immunohistochemistry, in vitro study, and nude mouse xenograft model. EGR3 immunoreactivity was detected in carcinoma cells in 99 (52%) out of 190 breast carcinoma tissues and was associated with the mRNA level. EGR3 immunoreactivity was positively associated with lymph node status, distant metastasis into other organs, estrogen receptor alpha, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negatively correlated with tubule formation. EGR3 immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- and multivariate analyses. Egr3-expressing transformant cell lines derived from MCF-7 Tet-Off cells (Eg-10 and Eg-11) significantly enhanced the migration and invasion properties according to the treatment of doxycyclin, but did not significantly change the cell proliferation. Moreover, Eg-11 cells injected into athymic mice irregularly invaded into the adjacent peritumoral tissues, although Clt-7, which was stably transfected with empty vector as a control, demonstrated a well-circumscribed tumor. Eg-11 cells were significantly associated with invasive components and less tubule formation in the xenograft model. These results suggest that EGR3 plays an important role in estrogen-meditated invasion and is an independent prognostic factor in breast carcinoma. PMID:17639044

  4. Transcriptome Encyclopedia of Early Human Development.

    PubMed

    Sahakyan, Anna; Plath, Kathrin

    2016-05-01

    Our understanding of human pre-implantation development is limited by the availability of human embryos and cannot completely rely on mouse studies. Petropoulos et al. now provide an extensive transcriptome analysis of a large number of human pre-implantation embryos at single-cell resolution, revealing previously unrecognized features unique to early human development. PMID:27153491

  5. Early growth response-1 in the pathogenesis of cardiovascular disease.

    PubMed

    Khachigian, Levon M

    2016-07-01

    This article reviews the regulatory roles of the immediate-early gene product and prototypic zinc finger transcription factor, early growth response-1 in models of cardiovascular pathobiology, focusing on insights using microRNA, DNAzymes, small hairpin RNA, small interfering RNA, oligonucleotide decoy strategies and mice deficient in early growth response-1. PMID:27251707

  6. Markers of early endothelial dysfunction in intrauterine growth restriction-derived human umbilical vein endothelial cells revealed by 2D-DIGE and mass spectrometry analyses.

    PubMed

    Caniuguir, Andres; Krause, Bernardo J; Hernandez, Cherie; Uauy, Ricardo; Casanello, Paola

    2016-05-01

    Intrauterine growth restriction (IUGR) associates with fetal and placental vascular dysfunction, and increased cardiovascular risk later on life. We hypothesize that endothelial cells derived from IUGR umbilical veins present significant changes in the proteome which could be involved in the endothelial dysfunction associated to this conditions. To address this the proteome profile of human umbilical endothelial cells (HUVEC) isolated from control and IUGR pregnancies was compared by 2D-Differential In Gel Electrophoresis (DIGE) and further protein identification by MALDI-TOF MS. Using 2D-DIGE 124 spots were identified as differentially expressed between control and IUGR HUVEC, considering a cut-off of 2 fold change, which represented ∼10% of the total spots detected. Further identification by MALDI-TOF MS and in silico clustering of the proteins showed that those differentially expressed proteins between control and IUGR HUVEC were mainly related with cytoskeleton organization, proteasome degradation, oxidative stress response, mRNA processing, chaperones and vascular function. Finally Principal Component analysis of the identified proteins showed that differentially expressed proteins allow distinguishing between control and IUGR HUVEC based on their proteomic profile. This study demonstrates for the first time that IUGR-derived HUVEC maintained in primary culture conditions present an altered proteome profile, which could reflect an abnormal programming of endothelial function in this fetal condition. PMID:27208404

  7. Treatment of early-stage human epidermal growth factor 2-positive cancers among medicare enrollees: age and race strongly associated with non-use of trastuzumab.

    PubMed

    Vaz-Luis, Ines; Lin, Nancy U; Keating, Nancy L; Barry, William T; Lii, Joyce; Burstein, Harold J; Winer, Eric P; Freedman, Rachel A

    2016-08-01

    Adjuvant trastuzumab for human epidermal growth factor receptor-2 (HER2)-positive breast cancer is highly efficacious regardless of age. Recent data suggested that many older patients with HER2-positive disease do not receive adjuvant trastuzumab. Nevertheless, some of this 'under-treatment' may be clinically appropriate. We used Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify patients aged ≥ 66 with stage ≥ Ib-III, HER2-positive breast cancer diagnosed during 2010-2011 (HER2 status available) who did not have a history of congestive heart failure. We described all systemic treatments received and sociodemographic and clinical characteristics associated with treatment patterns. Among 770 women 44.4 % did not receive trastuzumab, including 21.8 % who received endocrine therapy only, 6.3 % who received chemotherapy (±endocrine therapy) and 16.2 % who did not receive any systemic therapy. In addition to age and grade, race was strongly associated with non-use of trastuzumab (64.4 % of Non-Hispanic blacks vs. 43.6 % of whites did not receive trastuzumab, adjusted ORNon-Hispanic black vs. white = 3.14, 95 %CI = 1.38-7.17), and many patients with stage III disease did not receive trastuzumab. Further, 16.2 % of patients did not receive any systemic treatment and this occurred more frequently for black patients. Over 40 % of older patients with indication to receive adjuvant trastuzumab did not receive it and nearly 20 % of these patients did not receive any other treatment. Although treatment omission may be appropriate in some cases, we observed concerning differences in trastuzumab receipt, particularly for black women. Strategies to optimize care for older patients and to eliminate treatment disparities are urgently needed. PMID:27484879

  8. The progress of early growth response factor 1 and leukemia

    PubMed Central

    Tian, Jing; Li, Ziwei; Han, Yang; Jiang, Tao; Song, Xiaoming; Jiang, Guosheng

    2016-01-01

    Summary Early growth response gene-1 (EGR1) widely exists in the cell nucleus of such as, zebrafish, mice, chimpanzees and humans, an it also can be observed in the cytoplasm of some tumors. EGR1 was named just after its brief and rapid expression of different stimuli. Accumulating studies have extensively demonstrated that the widespread dysregulation of EGR1 is involved in hematological malignancies such as human acute myeloid leukemia (AML), chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B cell lymphoma. With the deep research on EGR1, its expression, function and regulatory mechanism has been gradually elucidated, and provides more possibilities for treatment strategies of patients with leukemia. Herein, we summarize the roles of EGR1 in its biological function and relationship with leukemia. PMID:27195189

  9. The progress of early growth response factor 1 and leukemia.

    PubMed

    Tian, Jing; Li, Ziwei; Han, Yang; Jiang, Tao; Song, Xiaoming; Jiang, Guosheng

    2016-05-01

    Early growth response gene-1 (EGR1) widely exists in the cell nucleus of such as, zebrafish, mice, chimpanzees and humans, an it also can be observed in the cytoplasm of some tumors. EGR1 was named just after its brief and rapid expression of different stimuli. Accumulating studies have extensively demonstrated that the widespread dysregulation of EGR1 is involved in hematological malignancies such as human acute myeloid leukemia (AML), chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B cell lymphoma. With the deep research on EGR1, its expression, function and regulatory mechanism has been gradually elucidated, and provides more possibilities for treatment strategies of patients with leukemia. Herein, we summarize the roles of EGR1 in its biological function and relationship with leukemia. PMID:27195189

  10. Early rapid growth, early birth: Accelerated fetal growth and spontaneous late preterm birth

    PubMed Central

    Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Gotsch, Francesca; Goncalves, Luis; Hassan, Sonia; Gomez, Ricardo; Nien, Jyh Kae; Frongillo, Edward A.; Romero, Roberto

    2011-01-01

    The past two decades in the United States have seen a 24 % rise in spontaneous late preterm delivery (34 to 36 weeks) of unknown etiology. This study tested the hypothesis that fetal growth was identical prior to spontaneous preterm (n=221, median gestational age at birth 35.6 weeks) and term (n=3706) birth among pregnancies followed longitudinally in Santiago, Chile. The hypothesis was not supported: Preterm-delivered fetuses were significantly larger than their term-delivered peers by mid-second trimester in estimated fetal weight, head, limb and abdominal dimensions, and they followed different growth trajectories. Piecewise regression assessed time-specific differences in growth rates at 4-week intervals from 16 weeks. Estimated fetal weight and abdominal circumference growth rates faltered at 20 weeks among the preterm-delivered, only to match and/or exceed their term-delivered peers at 24–28 weeks. After an abrupt decline at 28 weeks attenuating growth rates in all dimensions, fetuses delivered preterm did so at greater population-specific sex and age-adjusted weight than their peers from uncomplicated pregnancies (p<0.01). Growth rates predicted birth timing: one standard score of estimated fetal weight increased the odds ratio for preterm birth from 2.8 prior to 23 weeks, to 3.6 (95% confidence interval, 1.82–7.11, p<0.05) between 23 and 27 weeks. After 27 weeks, increasing size was protective (OR: 0.56, 95% confidence interval, 0.38–0.82, p=0.003). These data document, for the first time, a distinctive fetal growth pattern across gestation preceding spontaneous late preterm birth, identify the importance of mid-gestation for alterations in fetal growth, and add perspective on human fetal biological variability. PMID:18988282

  11. Up-regulation of early growth response gene 1 (EGR-1) via ERK1/2 signals attenuates sulindac sulfide-mediated cytotoxicity in the human intestinal epithelial cells

    SciTech Connect

    Moon, Yuseok Yang, Hyun; Kim, Yung Bu

    2007-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are used to relieve pain and inflammation and have also received considerable attention because of their preventive effects against human cancer. However, the drug application is sometimes limited by the severe gastrointestinal ulcers and mucosal complications. In the present study, NSAID sulindac sulfide was investigated for the cytotoxic injury in the intestinal epithelial cells in association with an immediate inducible factor, early growth response gene 1 (EGR-1). Previously we reported that sulindac sulfide can suppress tumor cell invasion by inducing EGR-1. Extending the previous study, EGR-1 induction by sulindac sulfide was observed both in the non-transformed and transformed human intestinal epithelial cell lines. In terms of signaling pathway, ERK1/2 MAP kinases and its substrate Elk-1 transcription factor were involved in the sulindac sulfide-induced EGR-1 gene expression. Moreover, sulindac sulfide stimulated the nuclear translocation of the transcription factor EGR-1, which was also mediated by ERK1/2 signaling pathway. The roles of EGR-1 signals in the apoptotic cell death were assessed in the intestinal epithelial cells. Suppression of EGR-1 expression retarded cellular growth and colony forming activity in the intestinal epithelial cells. Moreover, induced EGR-1 ameliorated sulindac sulfide-mediated apoptotic cell death and enhanced the cellular survival. Taken all together, sulindac sulfide activated ERK1/2 MAP kinases which then mediated EGR-1 induction and nuclear translocation, all of which played important roles in the cellular survival from NSAID-mediated cytotoxicity in the human intestinal epithelial cells, implicating the protective roles of EGR-1 in the NSAID-mediated mucosal injuries.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26876605

  13. 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 44weeks, 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. PMID:26876605

  14. 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. PMID:25665006

  15. Safety and Tolerability of Docetaxel, Cyclophosphamide, and Trastuzumab Compared to Standard Trastuzumab-Based Chemotherapy Regimens for Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

    PubMed Central

    Jitawatanarat, Potjana; O'Connor, Tracey L.; Kossoff, Ellen B.; Levine, Ellis G.; Chittawatanarat, Kaweesak

    2014-01-01

    Purpose We evaluated the tolerability and cardiac safety of docetaxel, cyclophosphamide, and trastuzumab (TCyH) for the treatment of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared to the standard trastuzumab-based chemotherapy regimens doxorubicin with cyclophosphamide followed by paclitaxel and trastuzumab (AC-TH) and docetaxel, carboplatin, and trastuzumab (TCaH). Methods We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-based chemotherapy at a single comprehensive cancer center between 2004 and 2011. Patient characteristics, comorbidities, relative dose intensity (RDI) of each regimen, tolerability, and cardiac toxicity were evaluated. Results One hundred seventy-seven patients were included in the study (AC-TH, n=114; TCaH, n=39; TCyH, n=24). TCyH was solely administered in the adjuvant setting, whereas two-thirds of the AC-TH and TCaH groups were administered postoperatively. Patients treated with TCyH tended to have a more significant underlying cardiac history, higher Charlson comorbidity index, and were of an earlier stage. All patients treated with TCyH received granulocyte colony stimulating factor primary prophylaxis. No febrile neutropenia or grade ≥3 hematologic toxicity was observed in the TCyH group as compared to the AC-TH and TCaH groups. There were no significant differences in the rates of early termination, hospitalization, dose reduction, or RDI between the regimens. The symptomatic congestive heart failure rate between AC-TH, TCaH, and TCyH groups was not significantly different (4.4% vs. 2.6% vs. 8.3%, respectively, p=0.57). There was also no significant difference in the rate of early trastuzumab termination between patients treated with each regimen. Conclusion TCyH is well tolerated and should be investigated as an alternative adjuvant chemotherapy option for patients who are not candidates for standard trastuzumab

  16. Studying Children's Early Literacy Development: Confirmatory Multidimensional Scaling Growth Modeling

    ERIC Educational Resources Information Center

    Ding, Cody

    2012-01-01

    There has been considerable debate over the ways in which children's early literacy skills develop over time. Using confirmatory multidimensional scaling (MDS) growth analysis, this paper directly tested the hypothesis of a cumulative trajectory versus a compensatory trajectory of development in early literacy skills among a group of 1233…

  17. Growth monitoring as an early detection tool: a systematic review.

    PubMed

    Scherdel, Pauline; Dunkel, Leo; van Dommelen, Paula; Goulet, Olivier; Salaün, Jean-François; Brauner, Raja; Heude, Barbara; Chalumeau, Martin

    2016-05-01

    Growth monitoring of apparently healthy children aims at early detection of serious underlying disorders. However, existing growth-monitoring practices are mainly based on suboptimal methods, which can result in delayed diagnosis of severe diseases and inappropriate referrals. We did a systematic review to address two key and interconnected questions underlying growth monitoring: which conditions should be targeted, and how should abnormal growth be defined? We systematically searched for studies reporting algorithms for growth monitoring in children and studies comparing the performance of new WHO growth charts with that of other growth charts. Among 1556 identified citations, 69 met the inclusion criteria. Six target conditions have mainly been studied: Turner syndrome, coeliac disease, cystic fibrosis, growth hormone deficiency, renal tubular acidosis, and small for gestational age with no catch-up after 2 or 3 years. Seven algorithms to define abnormal growth have been proposed in the past 20 years, but their level of validation is low, and their overall sensitivities and specificities vary substantially; however, the Grote and Saari clinical decision rules seem the most promising. Two studies reported that WHO growth charts had poorer performance compared with other existing growth charts for early detection of target conditions. Available data suggest a large gap between the widespread implementation of growth monitoring and its level of evidence or the clinical implications of early detection of serious disorders in children. Further investigations are needed to standardise the practice of growth monitoring, with a consensus on a few priority target conditions and with internationally validated clinical decision rules to define abnormal growth, including the selection of appropriate growth charts. PMID:26777129

  18. 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...

  19. 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...

  20. 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... 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...

  1. 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... 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...

  2. Peroxisome proliferator-activated receptor-γ agonist inhibits collagen synthesis in human keloid fibroblasts by suppression of early growth response-1 expression through upregulation of miR-543 expression

    PubMed Central

    Zhu, Hua-Yu; Bai, Wen-Dong; Wang, Hong-Tao; Xie, Song-Tao; Tao, Ke; Su, Lin-Lin; Liu, Jia-Qi; Yang, Xue-Kang; Li, Jun; Wang, Yun-Chuan; He, Ting; Han, Jun-Tao; Hu, Da-Hai

    2016-01-01

    A keloid is a benign skin tumor formed by an overgrowth of granulation tissue in affected patients. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists were reported to be able to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanism of PPAR-γ agonist troglitazone treatment for fibroblasts obtained from keloid patients. The data revealed that troglitazone treatment of keloid fibroblasts (KFs) downregulated the expression of early growth response-1 (Egr1) and collagen-1 (Col1). Level of Egr1 were closely associated with KF-induced fibrosis. The miRNA profiling data revealed that miR-543 was transcriptionally activated after troglitazone treatment. Bioinformatic analysis and experimental data showed that miR-543 was able to target Egr1. ELISA data confirmed that Col1 protein in the supernatant were modulated by the feedback regulatory axis of PPAR-γ agonist-induced miR-543 to inhibit Egr1 expression, whereas PPAR-γ antagonist treatment abolished such effect on Col1 suppression in KFs. This study demonstrated that the PPAR-γ agonist-mediated miR-543 and Egr1 signaling plays an important role in the suppression of collagen synthesis in KFs. Future in vivo studies are needed to confirm these in vitro data. PMID:27429849

  3. Peroxisome proliferator-activated receptor-γ agonist inhibits collagen synthesis in human keloid fibroblasts by suppression of early growth response-1 expression through upregulation of miR-543 expression.

    PubMed

    Zhu, Hua-Yu; Bai, Wen-Dong; Wang, Hong-Tao; Xie, Song-Tao; Tao, Ke; Su, Lin-Lin; Liu, Jia-Qi; Yang, Xue-Kang; Li, Jun; Wang, Yun-Chuan; He, Ting; Han, Jun-Tao; Hu, Da-Hai

    2016-01-01

    A keloid is a benign skin tumor formed by an overgrowth of granulation tissue in affected patients. Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists were reported to be able to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanism of PPAR-γ agonist troglitazone treatment for fibroblasts obtained from keloid patients. The data revealed that troglitazone treatment of keloid fibroblasts (KFs) downregulated the expression of early growth response-1 (Egr1) and collagen-1 (Col1). Level of Egr1 were closely associated with KF-induced fibrosis. The miRNA profiling data revealed that miR-543 was transcriptionally activated after troglitazone treatment. Bioinformatic analysis and experimental data showed that miR-543 was able to target Egr1. ELISA data confirmed that Col1 protein in the supernatant were modulated by the feedback regulatory axis of PPAR-γ agonist-induced miR-543 to inhibit Egr1 expression, whereas PPAR-γ antagonist treatment abolished such effect on Col1 suppression in KFs. This study demonstrated that the PPAR-γ agonist-mediated miR-543 and Egr1 signaling plays an important role in the suppression of collagen synthesis in KFs. Future in vivo studies are needed to confirm these in vitro data. PMID:27429849

  4. 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

  5. Human growth hormone doping in sport

    PubMed Central

    Saugy, M; Robinson, N; Saudan, C; Baume, N; Avois, L; Mangin, P

    2006-01-01

    Background and objectives Recombinant human growth hormone (rhGH) has been on the list of forbidden substances since availability of its recombinant form improved in the early 1990s. Although its effectiveness in enhancing physical performance is still unproved, the compound is likely used for its potential anabolic effect on the muscle growth, and also in combination with other products (androgens, erythropoietin, etc.). The degree of similarity between the endogenous and the recombinant forms, the pulsatile secretion and marked interindividual variability makes detection of doping difficult. Two approaches proposed to overcome this problem are: the indirect method, which measures a combination of several factors in the biological cascade affected by administration of GH; and the direct method, which measures the difference between the circulating and the recombinant (represented by the unique 22 kD molecule) forms of GH. This article gives an overview of what is presently known about hGH in relation to sport. The available methods of detection are also evaluated. Methods Review of the literature on GH in relation to exercise, and its adverse effects and methods of detection when used for doping. Results and conclusion The main effects of exercise on hGH production and the use and effects of rhGH in athletes are discussed. Difficulties encountered by laboratories to prove misuse of this substance by both indirect and direct analyses are emphasised. The direct method currently seems to have the best reliability, even though the time window of detection is too short. hGH doping is a major challenge in the fight against doping. The effect of exercise on hGH and its short half‐life are still presenting difficulties during doping analysis. To date the most promising method appears to be the direct approach utilising immunoassays. PMID:16799101

  6. Early intestinal growth and development in poultry.

    PubMed

    Lilburn, M S; Loeffler, S

    2015-07-01

    While there are many accepted "facts" within the field of poultry science that are in truth still open for discussion, there is little debate with respect to the tremendous genetic progress that has been made with commercial broilers and turkeys (Havenstein et al., 2003, 2007). When one considers the changes in carcass development in poultry meat strains, these genetic "improvements" have not always been accompanied by correlated changes in other physiological systems and this can predispose some birds to developmental anomalies (i.e. ascites; Pavlidis et al., 2007; Wideman et al., 2013). Over the last decade, there has been increased interest in intestinal growth/health as poultry nutritionists have attempted to adopt new approaches to deal with the broader changes in the overall nutrition landscape. This landscape includes not only the aforementioned genetic changes but also a raft of governmental policies that have focused attention on the environment (phosphorus and nitrogen excretion), consumer pressure on the use of antibiotics, and renewable biofuels with its consequent effects on ingredient costs. Intestinal morphology has become a common research tool for assessing nutritional effects on the intestine but it is only one metric among many that can be used and histological results can often be interpreted in a variety of ways. This study will address the broader body of research on intestinal growth and development in commercial poultry and will attempt to integrate the topics of the intestinal: microbial interface and the role of the intestine as an immune tissue under the broad umbrella of intestinal physiology. PMID:25910905

  7. 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…

  8. Magnetochronology of early humans in China

    NASA Astrophysics Data System (ADS)

    Deng, C.; Zhu, R.; Pan, Y.

    2009-12-01

    China is a key area for probing into human occupation in the Old World after the initial expansion of early humans out of Africa. Chronology of Chinese Paleolithic/hominin sites in different paleoclimatic and paleoenvironmental settings is paramount for understanding early human migration and adaptation. In recent years, we conducted detailed magnetostratigraphic investigations on the Nihewan Basin in temperate northern China and the Yuanmou Basin in subtropical southern China, both of which contained abundant sites of early humans and mammalian faunas. The age of the sedimentary sequence of the eastern Nihewan Basin can be magnetostratigraphically constrained to an interval from late Pliocene to late Pleistocene. The basal age of the Nihewan Formation in the eastern basin is constrained just prior to the Gauss-Matuyama geomagnetic reversal, that is, between ~2.6 Ma and ~3.0 Ma. The fluvio-lacustrine sequences in this basin were deposited from the late Gauss chron into the late Brunhes chron, and are capped by the last interglacial soil and the last glacial loess , or by the late Pleistocene or Holocene loess sediments. As a result, the Nihewan faunas (sensu lato) can be placed between the Matuyama-Brunhes geomagnetic reversal and the onset of the Olduvai subchron (0.78-1.95 Ma), and a robust chronological sequence of early human colonization in this basin has been established: Maliang (0.8 Ma), Huojiadi (1.0 Ma), Donggutuo and Cenjiawan (1.1 Ma), Feiliang (1.2 Ma), Banshan (1.32 Ma), Xiaochangliang and Xiantai (1.36 Ma), MJG-I (1.55 Ma), MJG-II (1.64 Ma), and MJG-III (1.66 Ma). The age of the sedimentary sequence of the Yuanmou Basin can be magnetostratigraphically constrained to an interval from early Pliocene to Pleistocene. The basal age of this basin sedimentary sequence is constrained just prior to the onset of the Sidufjall subchron, that is, ~4.9 Ma. Accumulation of the Yuanmou sequence was terminated during the Matuyama chron bracketed by the Olduvai and

  9. Endogenous cholecystokinin regulates growth of human cholangiocarcinoma.

    PubMed Central

    Evers, B M; Gomez, G; Townsend, C M; Rajaraman, S; Thompson, J C

    1989-01-01

    Exogenous administration of cholecystokinin (CCK) or caerulein inhibits growth of SLU-132, a human cholangiocarcinoma that we have shown to possess receptors for CCK. Chronic administration of cholestyramine, a resin that binds bile salts, increases release of CCK and growth of the pancreas in guinea pigs. Feeding the bile salt, taurocholate, inhibits meal-stimulated release of CCK. The purpose of this study was to determine whether endogenous CCK affects growth of the human cholangiocarcinoma, SLU-132. We implanted SLU-132 subcutaneously into athymic nude mice. The bile salt pool was depleted by feeding 4% cholestyramine for 40 days, either alone or enriched with 0.5% taurocholate for 32 days. When the mice were killed, tumors and pancreas were removed. Cholestyramine significantly inhibited the growth of SLU-132 and stimulated growth of the normal pancreas. Feeding of taurocholate acted to stimulate tumor growth. These results demonstrate that endogenous levels of CCK regulate growth of this human cholangiocarcinoma. Our findings suggest that manipulation of levels of endogenous gut hormones may, in the future, play a role in management of patients with certain gastrointestinal cancers. Images Fig. 1. PMID:2476084

  10. Magnetostratigraphic dating of early humans in China

    NASA Astrophysics Data System (ADS)

    Zhu, Rixiang; An, Zhisheng; Potts, Richard; Hoffman, Kenneth A.

    2003-06-01

    China is a key area for research into human occupation in the Old World after the initial expansion of early humans out of Africa. Reliable age determinations are pivotal for assessing the patterns of human evolution and dispersal in this region. This paper reviews magnetostratigraphic studies of some early Pleistocene strata bearing hominin remains and/or artifact stone tools from northern to southern China. The quality and reliability of the paleomagnetic dates are also evaluated. New magnetostratigraphic results for the Xihoudu Paleolithic site in north-central China are also presented. Among the few hominin or Paleolithic sites in China from the early Pleistocene, five have been well investigated. Three of these are in northern China at Xiaochangliang, Donggutuo and Gongwangling; the remaining two in southern China at Longgupo and Yuanmou. Considerable progress has been made during the past three decades towards paleomagnetically dating these sites. Indeed, the age estimates at Xiaochangliang and Gongwangling have been widely accepted. Magnetostratigraphic consensus about the age of the Donggutuo site has also been reached. However, the age determination for the two sites in southern China is still contested. The integration of rock-magnetic stratigraphy with magnetic polarity stratigraphy has resulted in a determined age of 1.36 Ma for a stone tool-containing layer of lacustrine sediments at the Xiaochangliang site in the Nihewan Basin. Lithostratigraphic constraints have significantly contributed to determining the age of Lantian Homo erectus at Gongwangling, which occurred in a loess-paleosol sequence of the southern Loess Plateau. Its age, paleomagnetically derived, is about 1.15 Ma. These two paleomagnetic ages suggest an expansion and flourishing of human groups from northern to north-central China during the early Pleistocene. This suggestion has been reinforced by our new magnetostratigraphic age estimate of about 1.27 Ma for the Xihoudu site as will be

  11. 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.

  12. The early growth of the first black holes

    DOE PAGESBeta

    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. Human Growth Hormone: The Latest Ergogenic Aid?

    ERIC Educational Resources Information Center

    Cowart, Virginia S.

    1988-01-01

    Believing that synthetic human growth hormone (hGH) will lead to athletic prowess and fortune, some parents and young athletes wish to use the drug to enhance sports performance. Should hGH become widely available, its abuse could present many problems, from potential health risks to the ethics of drug-enhanced athletic performance. (JL)

  14. Early Defensive Mechanisms against Human Papillomavirus Infection.

    PubMed

    Moerman-Herzog, Andrea; Nakagawa, Mayumi

    2015-08-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  15. Early Defensive Mechanisms against Human Papillomavirus Infection

    PubMed Central

    Moerman-Herzog, Andrea

    2015-01-01

    Cervical cancer is the fourth most common cancer in women and is almost exclusively caused by human papillomavirus (HPV) infection. HPV is also frequently associated with other cancers arising from mucosal epithelium, including anal and oropharyngeal cancers, which are becoming more common in both men and women. Viral persistence and progression through precancerous lesion stages are prerequisites for HPV-associated cancer and reflect the inability of cell-mediated immune mechanisms to clear infections and eliminate abnormal cells in some individuals. Cell-mediated immune responses are initiated by innate pathogen sensing and subsequent secretion of soluble immune mediators and amplified by the recruitment and activation of effector T lymphocytes. This review discusses early defensive mechanisms of innate responders to natural HPV infection, their influence on response polarization, and the underappreciated role of keratinocytes in this process. PMID:26063238

  16. Growth of gold nanoparticles in human cells.

    PubMed

    Anshup, Anshup; Venkataraman, J Sai; Subramaniam, Chandramouli; Kumar, R Rajeev; Priya, Suma; Kumar, T R Santhosh; Omkumar, R V; John, Annie; Pradeep, T

    2005-12-01

    Gold nanoparticles of 20-100 nm diameter were synthesized within HEK-293 (human embryonic kidney), HeLa (human cervical cancer), SiHa (human cervical cancer), and SKNSH (human neuroblastoma) cells. Incubation of 1 mM tetrachloroaurate solution, prepared in phosphate buffered saline (PBS), pH 7.4, with human cells grown to approximately 80% confluency yielded systematic growth of nanoparticles over a period of 96 h. The cells, stained due to nanoparticle growth, were adherent to the bottom of the wells of the tissue culture plates, with their morphology preserved, indicating that the cell membrane was intact. Transmission electron microscopy of ultrathin sections showed the presence of nanoparticles within the cytoplasm and in the nucleus, the latter being much smaller in dimension. Scanning near field microscopic images confirmed the growth of large particles within the cytoplasm. Normal cells gave UV-visible signatures of higher intensity than the cancer cells. Differences in the cellular metabolism of cancer and noncancer cells were manifested, presumably in their ability to carry out the reduction process. PMID:16316080

  17. 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

  18. TBCRC 008: Early Change in 18F-FDG Uptake on PET Predicts Response to Preoperative Systemic Therapy in Human Epidermal Growth Factor Receptor 2–Negative Primary Operable Breast Cancer

    PubMed Central

    Connolly, Roisin M.; Leal, Jeffrey P.; Goetz, Matthew P.; Zhang, Zhe; Zhou, Xian C.; Jacobs, Lisa K.; Mhlanga, Joyce; Joo, H O; Carpenter, John; Storniolo, Anna Maria; Watkins, Stanley; Fetting, John H.; Miller, Robert S.; Sideras, Kostandinos; Jeter, Stacie C.; Walsh, Bridget; Powers, Penny; Zorzi, Jane; Boughey, Judy C.; Davidson, Nancy E.; Carey, Lisa A.; Wolff, Antonio C.; Khouri, Nagi; Gabrielson, Edward; Wahl, Richard L.; Stearns, Vered

    2015-01-01

    Epigenetic modifiers, including the histone deacetylase inhibitor vorinostat, may sensitize tumors to chemotherapy and enhance outcomes. We conducted a multicenter randomized phase II neo-adjuvant trial of carboplatin and nanoparticle albumin-bound paclitaxel (CP) with vorinostat or placebo in women with stage II/III, human epidermal growth factor receptor 2 (HER2)–negative breast cancer, in which we also examined whether change in maximum standardized uptake values corrected for lean body mass (SULmax) on 18F-FDG PET predicted pathologic complete response (pCR) in breast and axillary lymph nodes. Methods Participants were randomly assigned to 12 wk of preoperative carboplatin (area under the curve of 2, weekly) and nab-paclitaxel (100 mg/m2 weekly) with vorinostat (400 mg orally daily, days 1–3 of every 7-d period) or placebo. All patients underwent 18F-FDG PET and research biopsy at baseline and on cycle 1 day 15. The primary endpoint was the pCR rate. Secondary objectives included correlation of change in tumor SULmax on 18F-FDG PET by cycle 1 day 15 with pCR and correlation of baseline and change in Ki-67 with pCR. Results In an intent-to-treat analysis (n = 62), overall pCR was 27.4% (vorinostat, 25.8%; placebo, 29.0%). In a pooled analysis (n = 59), we observed a significant difference in median change in SULmax 15 d after initiating preoperative therapy between those achieving pCR versus not (percentage reduction, 63.0% vs. 32.9%; P = 0.003). Patients with 50% or greater reduction in SULmax were more likely to achieve pCR, which remained statistically significant in multivariable analysis including estrogen receptor status (odds ratio, 5.1; 95% confidence interval, 1.3–22.7; P = 0.023). Differences in baseline and change in Ki-67 were not significantly different between those achieving pCR versus not. Conclusion Preoperative CP with vorinostat or placebo is associated with similar pCR rates. Early change in SULmax on 18F-FDG PET 15 d after the

  19. Potential role of human growth hormone in melanoma growth promotion.

    PubMed

    Handler, Marc Z; Ross, Andrew L; Shiman, Michael I; Elgart, George W; Grichnik, James M

    2012-10-01

    BACKGROUND Human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the malignant transformation and progression of a variety of cancers. HGH is also known to upregulate molecular signaling pathways implicated in the pathogenesis of melanoma. Although HGH has previously been implicated in promoting the clinical growth of both benign and malignant melanocytic neoplasms, to our knowledge there are no conclusive studies demonstrating an increased risk of melanoma following HGH therapy. Nevertheless, there are reports of melanoma developing subsequent to HGH coadministered with either other hormones or following irradiation. OBSERVATION A 49-year-old white man presented with a new pigmented papule that was diagnosed as melanoma. The patient reported using HGH for 3 months prior to the diagnosis. His 51-year-old wife, who also was white, had also been using exogenous HGH for 3 months and had been diagnosed as having a melanoma 2 weeks prior. CONCLUSIONS Given the unlikelihood of 2 unrelated people developing melanoma within a short time span, it is reasonable to assume that a common environmental component (HGH or other shared exposure) contributed to the development of both melanomas. Because of the increased use of exogenous HGH as an antiaging agent, it is important to be aware of the growth-promoting effects of this hormone. Until better data are available that determines the true risk of exogenous HGH, its use as an antiaging agent merits increased surveillance. PMID:23069955

  20. Improved clonal and nonclonal growth of human, rat and bovine adrenocortical cells in culture.

    PubMed

    McAllister, J M; Hornsby, P J

    1987-10-01

    This report describes the development of a culture system for long-term growth and cloning of human fetal adrenocortical cells. Optimal conditions for stimulating clonal growth were determined by testing the efficacy of horse serum (HS), fetal bovine serum (FBS), fibroblast growth factor (FGF), epidermal growth factor (EGF), fibronectin, and a combination of growth factors, UltroSer G, in stimulating growth from low density. Optimal conditions for clonal growth were achieved using fibronectin-coated dishes and DME/F12 medium with 10% FBS, 10% HS, 2% UltroSer G, and 100 ng/ml FGF or 100 pM EGF. Conditions for growth at clonal density were found to be optimal for growth of early passage, nonclonal cultures at higher densities. The improved growth conditions used for cloning were shown to allow continued long-term growth of nonclonal human adrenocortical cells without fibroblast overgrowth. All cells in cultures grown in HS, FBS, and UltroSer G had morphologic characteristics of adrenocortical cells, whereas cells grown in FBS only rapidly became overgrown with fibroblasts. Clonal and nonclonal early passage human adrenocortical cells had similar mitogenic responses to FGF and EGF. Whereas FGF, EGF, and UltroSer G showed similar stimulation of DNA synthesis and clonal growth in human adrenocortical cells and human adrenal gland fibroblasts, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate stimulated growth only in adrenocortical cells and was strongly inhibitory to growth in fibroblasts. In both cell types, forskolin inhibited DNA synthesis. Human adrenocortical cell cultures were functional and synthesized cortisol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. The improved growth conditions for clonal growth of human adrenocortical cells also provided optimal conditions for long-term growth of cultured rat adrenocortical cells and increased the cloning efficiency of cultured bovine adrenocortical cells. PMID:3667487

  1. Ventilation Homogeneity Improves with Growth Early in Life

    PubMed Central

    Chakr, Valentina C.; Llapur, Conrado J.; Sarria, Edgar E.; Mattiello, Rita; Kisling, Jeffrey; Tiller, Christina; Kimmel, Risa; Poindexter, Brenda; Tepper, Robert S.

    2011-01-01

    Some studies have suggested that lung clearance index (LCI) is age-independent among healthy subjects early in life, which implies that ventilation distribution does not vary with growth. However, other studies of older children and adolescents suggest that ventilation becomes more homogenous with somatic growth. We describe a new technique to obtain multiple breath washout (MBWO) in sedated infants and toddlers using slow augmented inflation breaths that yields an assessment of LCI and the slope of phase III, which is another index of ventilation inhomogeneity. We evaluated whether ventilation becomes more homogenous with increasing age early in life, and whether infants with chronic lung disease of infancy (CLDI) have increased ventilation inhomogeneity relative to full term controls. Fullterm controls (N = 28) and CLDI (N = 22) subjects between 3 and 28 months corrected-age were evaluated. LCI decreased with increasing age; however, there was no significant difference between the two groups (9.3 vs. 9.5; p = 0.56). Phase III slopes adjusted for expired volume (SND) increased with increasing breath number during the washout and decreased with increasing age. There was no significant difference in SND between fullterm and CLDI subjects (211 vs. 218; P = 0.77). Our findings indicate that ventilation becomes more homogenous with lung growth and maturation early in life; however, there is no evidence that ventilation inhomogeneity is a significant component of the pulmonary pathophysiology of CLDI. PMID:21901860

  2. (PCG) Protein Crystal Growth Human Serum Albumin

    NASA Technical Reports Server (NTRS)

    1989-01-01

    (PCG) Protein Crystal Growth Human Serum Albumin. Contributes to many transport and regulatory processes and has multifunctional binding properties which range from various metals, to fatty acids, hormones, and a wide spectrum of therapeutic drugs. The most abundant protein of the circulatory system. It binds and transports an incredible variety of biological and pharmaceutical ligands throughout the blood stream. Principal Investigator on STS-26 was Larry DeLucas.

  3. 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

  4. 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. PMID:24378592

  5. Germination and early growth of Brassica juncea in copper mine tailings amended with technosol and compost.

    PubMed

    Novo, Luís A B; 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

  6. 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

  7. Near-criticality underlies the behavior of early tumor growth.

    PubMed

    Remy, Guillaume; Cluzel, Philippe

    2016-01-01

    The controlling factors that underlie the growth of tumors have often been hard to identify because of the presence in this system of a large number of intracellular biochemical parameters. Here, we propose a simplifying framework to identify the key physical parameters that govern the early growth of tumors. We model growth by means of branching processes where cells of different types can divide and differentiate. First, using this process that has only one controlling parameter, we study a one cell type model and compute the probability for tumor survival and the time of tumor extinction. Second, we show that when cell death and cell division are perfectly balanced, stochastic effects dominate the growth dynamics and the system exhibits a near-critical behavior that resembles a second-order phase transition. We show, in this near-critical regime, that the time interval before tumor extinction is power-law distributed. Finally, we apply this branching formalism to infer, from experimental growth data, the number of different cell types present in the observed tumor. PMID:27043180

  8. Near-criticality underlies the behavior of early tumor growth

    NASA Astrophysics Data System (ADS)

    Remy, Guillaume; Cluzel, Philippe

    2016-04-01

    The controlling factors that underlie the growth of tumors have often been hard to identify because of the presence in this system of a large number of intracellular biochemical parameters. Here, we propose a simplifying framework to identify the key physical parameters that govern the early growth of tumors. We model growth by means of branching processes where cells of different types can divide and differentiate. First, using this process that has only one controlling parameter, we study a one cell type model and compute the probability for tumor survival and the time of tumor extinction. Second, we show that when cell death and cell division are perfectly balanced, stochastic effects dominate the growth dynamics and the system exhibits a near-critical behavior that resembles a second-order phase transition. We show, in this near-critical regime, that the time interval before tumor extinction is power-law distributed. Finally, we apply this branching formalism to infer, from experimental growth data, the number of different cell types present in the observed tumor.

  9. Information for People Treated with Human Growth Hormone (Summary)

    MedlinePlus

    ... Program (NHPP): Information for People Treated with Pituitary Human Growth Hormone (Summary) Page Content On this page: ... disease (CJD) occur in people treated with pituitary human growth hormone (hGH)? How many people treated with ...

  10. Humans at high altitude: hypoxia and fetal growth

    PubMed Central

    Moore, Lorna G.; Charles, Shelton M.; Julian, Colleen G.

    2011-01-01

    High-altitude studies offer insight into the evolutionary processes and physiological mechanisms affecting the early phases of the human lifespan. Chronic hypoxia slows fetal growth and reduces the pregnancy-associated rise in uterine artery (UA) blood flow. Multigenerational vs. shorter-term high-altitude residents are protected from the altitude-associated reductions in UA flow and fetal growth. Presently unknown is whether this fetal-growth protection is due to the greater delivery or metabolism of oxygen, glucose or other substrates or to other considerations such as mechanical factors protecting fragile fetal villi, the creation of a reserve protecting against ischemia/reperfusion injury, or improved placental O2 transfer as the result of narrowing the A-V O2 difference and raising uterine PvO2. Placental growth and development appear to be normal or modified at high altitude in ways likely to benefit diffusion. Much remains to be learned concerning the effects of chronic hypoxia on embryonic development. Further research is required for identifying the fetoplacental and maternal mechanisms responsible for transforming the maternal vasculature and regulating UA blood flow and fetal growth. Genomic as well as epigenetic studies are opening new avenues of investigation that can yield insights into the basic pathways and evolutionary processes involved. PMID:21536153

  11. The Growth of Early Galaxies and Reionization of Hydrogen

    NASA Astrophysics Data System (ADS)

    Ram Chary, Ranga

    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.

  12. Dissolved iron supply limits early growth of estuarine mangroves.

    PubMed

    Alongi, Daniel M

    2010-11-01

    Three mesocosm experiments were performed in an outdoor facility to quantify the responses of five mangrove species grown from seedling to sapling stage to increasing rates of dissolved iron supply. Stem extension and biomass of mangroves were measured in the first two experiments, and in the third experiment, rates of microbial iron reduction were measured in relation to stem extension of two mangrove species. In all experiments, mangrove growth was enhanced by increasing iron supply, although some species showed iron toxicity at the higher supply rates. In the first two experiments, stem extension rates of Rhizophora apiculata, Bruguiera gymnorrhiza, and Xylocarpus moluccensis best fit Gaussian curves with maximal growth at supply rates of 50-60 mmol Fe x m(-2) x d(-1), whereas growth of Avicennia marina and Ceriops tagal increased to the highest rate (100 mmol Fe x m(-2) x d(-1)) of iron supply. Changes in leaf chlorophyll concentrations and iron content of roots mirrored the growth responses. In the third experiment, rates of microbial iron reduction were greater with R. apiculata and A. marina than in controls without plants; for both species, there was a positive relationship between stem extension and iron reduction. The rates of iron reduction and rates of iron supplied to the plants were well within the range of interstitial iron concentrations and rates of iron reduction found in the natural mangrove soils from which the seedlings were obtained. The responses of these species show that mangroves growing from seedling to sapling stage have a strong nutritional requirement for iron, and that there is a close relationship between plant roots and the activities of iron-reducing bacteria. These results suggest that mangrove growth may be limited in some natural forests by the rate at which iron is solubilized by iron-reducing bacteria. Such biogeochemical conditions have significant implications for successful recruitment, establishment, and early growth of

  13. 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.

  14. Environmental noise and human prenatal growth

    SciTech Connect

    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 exposure 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.

  15. 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. PMID:25698140

  16. Significance of the disulphide bonds of human growth hormone.

    PubMed

    Junnila, Riia K; Kopchick, John J

    2013-01-01

    Growth hormone (GH) structure is stabilised by two disulphide bonds, C53-C165 and C182-C189 in human GH. Researchers have investigatedthe role of these structural features since the late 1960s. Early studies implied that the disulphide bonds would not be importantfor biological activity of GH. However, more advanced techniques, as well as clues from patients carrying mutations in their GH1 gene,have demonstrated that the integrity of the disulphide bond between cysteines C53 and C165 is required for biological activity of GH.In contrast, disruption of the C-terminal disulphide bond (C182-C189) has only modest effects on the biological potency of GH, despitedecreased binding affinity to GH receptor and reduced stability as shown by a comprehensive in vitro study.To confirm these results, we generated transgenic mice that express a human GH analogue, C189A, and observed normal growth-promotingand lipolytic activities. In this article, we present new data and review old results concerning the disulphide bonds of GH. We also discussrelevant mutations found in patients with growth disorders. PMID:24002958

  17. The Rapid Growth of Fibroids during Early Pregnancy

    PubMed Central

    Benaglia, Laura; Cardellicchio, Lucia; Filippi, Francesca; Paffoni, Alessio; Vercellini, Paolo; Somigliana, Edgardo; Fedele, Luigi

    2014-01-01

    Several studies aimed to disentangle whether pregnancy influences the growth of uterine fibroids but results were inconsistent. In this study, we speculated that fibroid enlargement during pregnancy may not be linear and we hypothesized that this phenomenon may mainly occur during initial pregnancy. To test this hypothesis, we set up a prospective cohort study of women with fibroids undergoing IVF. Cases were women achieving a viable pregnancy. Controls were the subsequent women with fibroids but failing to become pregnant. Twenty-five cases and 25 controls were recruited. The total number of fibroids in the two groups was 46 and 41, respectively. The mean ± SD diameter of the fibroids was 17±10 and 20±11 mm, respectively (p = 0.18). A statistically significant enlargement emerged exclusively in pregnant women. The median (Interquartile Range) modification of the diameter of the lesions in cases and controls was +34% (+6%/+65%) and +2% (−6%/+12%), respectively (p<0.001). The median (Interquartile Range) modification of the volume of the lesions was +140% (+23%/+357%) and 0% (−18%/+37%), respectively (p<0.001). In pregnant women, we failed to document any significant correlation between the magnitude of the growth and ovarian responsiveness to hyper-stimulation, suggesting that steroids hormones are not the unique factors involved. In conclusion, fibroids undergo a rapid and remarkable growth during initial pregnancy. Reasons behind this phenomenon remain to be clarified. The early rise in steroids hormones during early pregnancy may not be sufficient to explain the process. Other pregnancy-related hormones and proteins may play also key roles. PMID:24465797

  18. Modulation of growth and differentiation in normal human keratinocytes by transforming growth factor-beta

    SciTech Connect

    Matsumoto, K.; Hashimoto, K.; Hashiro, M.; Yoshimasa, H.; Yoshikawa, K. )

    1990-10-01

    The effect of transforming growth factor-type beta 1(TGF-beta) on the growth and differentiation of normal human skin keratinocytes cultured in serum-free medium was investigated. TGF-beta markedly inhibited the growth of keratinocytes at the concentrations greater than 2 ng/ml under low Ca2+ conditions (0.1 mM). Growth inhibition was accompanied by changes in cell functions related to proliferation. Remarkable inhibition of DNA synthesis was demonstrated by the decrease of (3H)thymidine incorporation. The decrease of (3H)thymidine incorporation was observed as early as 3 hr after addition of TGF-beta. TGF-beta also decreased c-myc messenger RNA (mRNA) expression 30 min after addition of TGF-beta. This rapid reduction of c-myc mRNA expression by TGF-beta treatment is possibly one of the main factors in the process of TGF-beta-induced growth inhibition of human keratinocytes. Since growth inhibition and induction of differentiation are closely related in human keratinocytes, the growth-inhibitory effect of TGF-beta under high Ca2+ conditions was examined. TGF-beta inhibited the growth of keratinocytes under high Ca2+ conditions in the same manner as under low Ca2+ conditions, suggesting that it is a strong growth inhibitor in both low and high Ca2+ environments. The induction of keratinocyte differentiation was evaluated by measuring involucrin expression and cornified envelope formation: TGF-beta at 20 ng/ml increased involucrin expression from 9.3% to 18.8% under high Ca2+ conditions, while it decreased involucrin expression from 7.0% to 3.3% under low Ca2+ conditions. Cornified envelope formation was modulated in a similar way by addition of TGF-beta: TGF-beta at 20 ng/ml decreased cornified envelope formation by 53% under low Ca2+ conditions, while it enhanced cornified envelope formation by 30.7% under high Ca2+ conditions.

  19. 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

  20. Early growth response 1 regulates glucose deprivation-induced necrosis

    PubMed Central

    JEON, HYUN MIN; LEE, SU YEON; JU, MIN KYUNG; KIM, CHO HEE; PARK, HYE GYEONG; KANG, HO SUNG

    2013-01-01

    Necrosis is commonly found in the core region of solid tumours due to metabolic stress such as hypoxia and glucose deprivation (GD) resulting from insufficient vascularization. Necrosis promotes tumour growth and development by releasing the tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the molecular mechanism underlying necrotic cell death remains largely unknown. In this study, we show that early growth response 1 (Egr-1) is induced in a reactive oxygen species (ROS)-dependent manner by GD in several cell lines such as A549, MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1 short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release. Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1 overexpression appeared to make tumour cells more susceptible to GD-induced necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour progression. PMID:23152075

  1. Relationship between early growth and CVD risk factors in adolescents.

    PubMed

    Musa, M G; Kagura, J; Pisa, P T; Norris, S A

    2016-04-01

    Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (n=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0-24 months and 24-48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [β=0.704 (0.40, 1.01)], CW 0-24 [β=1.918 (1.56, 2.28)] and CW24-48 [β=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [β=0.773 (0.54, 1.01)], CW 0-24 [β=1.523 (1.24, 1.80)] and CW24-48 [β=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (P<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population. PMID:26810380

  2. Dimerization of Human Growth Hormone by Zinc

    NASA Astrophysics Data System (ADS)

    Cunningham, Brian C.; Mulkerrin, Michael G.; Wells, James A.

    1991-08-01

    Size-exclusion chromatography and sedimentation equilibrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn2+-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn2+-hGH dimeric complex may be important for storage of hGH in secretory granules.

  3. Postnatal Growth Velocity and Overweight in Early Adolescents: A Comparison of Rural and Urban African Boys and Girls

    PubMed Central

    Chirwa, ED; Griffiths, P; Maleta, K; Ashorn, P; Pettifor, JM; Norris, SA

    2014-01-01

    Objectives To compare growth velocity of two African child cohorts and examine the relationship between postnatal growth velocity in infancy/early childhood and the risk of overweight/stunting in early adolescence. Methods The study used data from two child cohorts from urban (Birth to Twenty Cohort, South Africa) and rural (Lungwena Child Survival Study, Malawi) African settings. Mixed effect modelling was used to derive growth and peak growth velocities. T-tests were used to compare growth parameters and velocities between the two cohorts. Linear and logistic regression models were used to determine the relationship between growth velocity and early adolescent (ages 9–11 years) body mass index and odds of being overweight. Results Children in the BH cohort were significantly taller and heavier than those in the Lungwena cohort, and exhibited faster weight and height growth velocity especially in the first year of life (P < 0.05). No significant association was shown between baseline weight (αw) and overweight in early adolescence (OR = 1.25, CI = 0.67, 2.34). The weight growth velocity parameter βw was highly associated with odds of being overweight. Association between overweight in adolescence and weight velocity was stronger in infancy than in early childhood (OR at 3 months = 4.80, CI = 2.49, 9.26; OR at 5 years = 2.39, CI = 1.65, 3.47). Conclusion High weight and height growth velocity in infancy, independent of size at birth, is highly associated with overweight in early adolescence. However, the long term effects of rapid growth in infancy may be dependent on a particular population's socio-economic status and level of urbanization. Am. J. Hum. Biol. 26:643–651, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID:24948025

  4. Teleoperation support for early human planetary missions.

    PubMed

    Genta, Giancarlo; Perino, Maria Antonietta

    2005-12-01

    A renewed interest in human exploration is flourishing among all the major spacefaring nations. In fact, in the complex scene of planned future space activities, the development of a Moon base and the human exploration of Mars might have the potential to renew the enthusiasm in expanding the human presence beyond the boundaries of Earth. Various initiatives have been undertaken to define scenarios and identify the required infrastructures and related technology innovations. The typical proposed approach follows a multistep strategy, starting with a series of precursor robotic missions to acquire further knowledge of the planet and to select the best potential landing sites, and evolving toward more demanding missions for the development of a surface infrastructure necessary to sustain human presence. The technologies involved in such a demanding enterprise range from typical space technologies, like transportation and propulsion, automation and robotics, rendezvous and docking, entry/reentry, aero-braking, navigation, and deep space communications, to human-specific issues like physiology, psychology, behavioral aspects, and nutritional science for long-duration exposure, that go beyond the traditional boundaries of space activities. Among the required elements to support planetary exploration, both for the precursor robotic missions and to sustain human exploration, rovers and trucks play a key role. A robust level of autonomy will need to be secured to perform preplanned operations, particularly for the surface infrastructure development, and a teleoperated support, either from Earth or from a local base, will enhance the in situ field exploration capability. PMID:16510414

  5. Developmental programming: variations in early growth and adult disease.

    PubMed

    Gallo, Linda A; Tran, Melanie; Moritz, Karen M; Wlodek, Mary E

    2013-11-01

    Suboptimal conditions in utero are associated with the development of adult-onset diseases in offspring. Uteroplacental insufficiency in rats is a well-established animal model used to mimic and study the effects of developmental insults relevant to countries of abundant nutrient supply. However, wide-ranging outcomes for the offspring are apparent between the different investigators that use this model and also between cohorts generated in our laboratory. We aimed to explore the reasons for variability in rat models of uteroplacental insufficiency between different investigators and also between our own animal cohorts. We suggest differences in growth and disease development reflect uniqueness in susceptibility and highlight the complexity of interactions between genetic potential and environmental exposures. The impact of adverse exposures in utero has been described as having far-reaching effects that extend well beyond the first, directly exposed generation. However, the resulting phenotypes are not consistent between generations. This suggests that programmed effects are established de novo in each generation and challenges the prediction of disease. Characterization of growth and disease in the numerous rat models has led to our understanding of the impact of early life experiences on adult health. In order to drive the development of preventative and/or treatment strategies, future studies should focus on identifying the initial cause(s) of uteroplacental insufficiency, including genetic origins and the influence of poor diets. PMID:23581813

  6. Early signaling dynamics of the epidermal growth factor receptor.

    PubMed

    Reddy, Raven J; Gajadhar, Aaron S; Swenson, Eric J; Rothenberg, Daniel A; Curran, Timothy G; White, Forest M

    2016-03-15

    Despite extensive study of the EGF receptor (EGFR) signaling network, the immediate posttranslational changes that occur in response to growth factor stimulation remain poorly characterized; as a result, the biological mechanisms underlying signaling initiation remain obscured. To address this deficiency, we have used a mass spectrometry-based approach to measure system-wide phosphorylation changes throughout the network with 10-s resolution in the 80 s after stimulation in response to a range of eight growth factor concentrations. Significant changes were observed on proteins far downstream in the network as early as 10 s after stimulation, indicating a system capable of transmitting information quickly. Meanwhile, canonical members of the EGFR signaling network fall into clusters with distinct activation patterns. Src homology 2 domain containing transforming protein (Shc) and phosphoinositol 3-kinase (PI3K) phosphorylation levels increase rapidly, but equilibrate within 20 s, whereas proteins such as Grb2-associated binder-1 (Gab1) and SH2-containing tyrosine phosphatase (SHP2) show slower, sustained increases. Proximity ligation assays reveal that Shc and Gab1 phosphorylation patterns are representative of separate timescales for physical association with the receptor. Inhibition of phosphatases with vanadate reveals site-specific regulatory mechanisms and also uncovers primed activating components in the network, including Src family kinases, whose inhibition affects only a subset of proteins within the network. The results presented highlight the complexity of signaling initiation and provide a window into exploring mechanistic hypotheses about receptor tyrosine kinase (RTK) biology. PMID:26929352

  7. Simulations of nucleation and early growth stages of protein crystals.

    PubMed Central

    Kierzek, A M; Wolf, W M; Zielenkiewicz, P

    1997-01-01

    Analysis of known protein crystal structures reveals that interaction energies between monomer pairs alone are not sufficient to overcome entropy loss related to fixing monomers in the crystal lattice. Interactions with several neighbors in the crystal are required for stabilization of monomers in the lattice. A microscopic model of nucleation and early growth stages of protein crystals, based on the above observations, is presented. Anisotropy of protein molecules is taken into account by assigning free energies of association (proportional to the buried surface area) to individual monomer-monomer contacts in the lattice. Lattice simulations of the tetragonal lysozyme crystal based on the model correctly reproduce structural features of the movement of dislocation on the (110) crystal face. The dislocation shifts with the speed equal to the one determined experimentally if the geometric probability of correct orientation is set to 10(-5), in agreement with previously published estimates. At this value of orientational probability, the first nuclei, the critical size of which for lysozyme is four monomers, appear in 1 ml of supersaturated solution on a time scale of microseconds. Formation of the ordered phase proceeds through the growth of nuclei (rather then their association) and requires nucleations on the surface at certain stages. Images FIGURE 2 PMID:9251778

  8. Human Granulocytic Ehrlichiosis Complicating Early Pregnancy

    PubMed Central

    Muffly, Tyler; McCormick, T. Chad; Cook, Christopher; Wall, Jeffrey

    2008-01-01

    Background. The goal of this case is to review the zoonotic infection, human granulocytic ehrlichiosis, presenting with pyrexia. Case. A 22-year-old multigravid female presented to the emergency department with a painful skin rash, high fever, and severe myalgias. The patient underwent a diagnostic evaluation for zoonotic infections due to her geographical and seasonal risk factors. Treatment of human granulocytic ehrlichiosis was successful though the patient spontaneously aborted presumably due to the severity of the acute illness. Conclusion. Treatment of human granulocytic ehrlichiosis in pregnancy presents unique challenges. Management of pyrexia during pregnancy is limited to external cooling in the setting of thrombocytopenia and elevated aminotransferases. Extensive counseling regarding teratogenic potential of medications allows the patient to weigh the pros and cons of treatment. PMID:18509484

  9. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

    PubMed

    Lang, C H; Pollard, V; Fan, J; Traber, L D; Traber, D L; Frost, R A; Gelato, M C; Prough, D S

    1997-07-01

    The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection. PMID:9249574

  10. The Neurobiological Toll of Early Human Deprivation

    PubMed Central

    Nelson, Charles A.; Bos, Karen; Gunnar, Megan R.; Sonuga-Barke, Edmund J. S.

    2013-01-01

    Children raised in institutions frequently suffer from a variety of behavioral, emotional, and neuropsychological sequelae, including deficits in attention, executive functions, disorders of attachment and in some cases a syndrome that mimics autism. The extent and severity of these disorders appears to be mediated, in part, by the age at which the child entered and, in some cases, left the institution. Here we review the neurobiological literature on early institutionalization that may account for the psychological and neurological sequelae discussed in other chapters in this volume. PMID:25018565

  11. 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…

  12. Patterns and rates of enamel growth in the molar teeth of early hominids.

    PubMed

    Beynon, A D; Wood, B A

    A recent study of the surface manifestation of incremental lines associated with enamel formation suggested that the crowns of early hominid incisor teeth were formed more rapidly than those of modern humans. In the absence of comparative data, the authors were forced to assume that enamel increments in fossil teeth were similar to those in modern humans. We have used evidence from the fractured surfaces of molar teeth to deduce estimates for both long- and short-period incremental growth markers within enamel in east African 'robust' australopithecine and early Homo teeth. We conclude that in these early hominids, crown formation times in posterior teeth, particularly in the large thick enamelled molar teeth of the east African 'robust' australopithecines, were shorter than those of modern humans. This evidence, considered together with data on crown and root formation times in modern apes, suggests that the posterior teeth in these hominids both formed and erupted more rapidly than those of modern man. These results have implications for attempts to assess dental and skeletal maturity in hominids. PMID:3104794

  13. Differences between Neandertal and modern human infant and child growth models.

    PubMed

    Martín-González, Jesús A; Mateos, Ana; Goikoetxea, Idoia; Leonard, William R; Rodríguez, Jesús

    2012-07-01

    Studying the emergence of distinctive human growth patterns is essential to understanding the evolution of our species. The large number of Neandertal fossils makes this species the best candidate for a comparative study of growth patterns in archaic and modern humans. Here, Neandertal height growth during infancy and early childhood is described using a mathematical model. Height growth velocities for individuals five years old or younger are modelled as age functions based on different estimates of height and age for a set of ten Neandertal infants and children. The estimated heights of each Neandertal individual are compared with those of two modern human populations based on longitudinal and cross-sectional data. The model highlights differences in growth velocity during infancy (from the age of five months onward). We find that statural growth in Neandertal infants is much slower than that seen in modern humans, Neandertal growth is similar to modern humans at birth, but decreases around the third or fourth month. The markedly slower growth rates of Neandertal infants may be attributable to ontogenetic constraints or to metabolic stress, and contribute to short achieved adult stature relative to modern humans. PMID:22658332

  14. Disentangling direct and growth-mediated influences on early survival: a mechanistic approach.

    PubMed

    Plard, Floriane; Yoccoz, Nigel G; Bonenfant, Christophe; Klein, François; Warnant, Claude; Gaillard, Jean-Michel

    2015-09-01

    1. Early survival is a key life-history trait that often accounts for a large part of the variation in individual fitness and shapes population dynamics. The factors influencing early survival are multiple in large herbivores, including malnutrition, predation, cohort variation or maternal effects. However, the mechanistic pathways connecting these drivers to variation in early survival are much less studied. Indeed, whether these factors influence early survival directly or indirectly through early growth remains to be disentangled. 2. In this study, we used a path analysis to separate the direct and indirect (i.e. mediated by early growth) pathways through which sex, birth date, cohort and family effects influence early survival. We used a large data set of marked roe deer newborns collected from 1985 to 2010 in the intensively monitored population of Trois Fontaines (France). 3. We found that most drivers have indirect influences on early survival through early growth. Indeed, cohort effects influenced early survival through the indirect effect of precipitation around birth on early growth. Precipitation also had direct effects on early survival. Family effects indirectly influenced early survival. Twins from the same litter grew at about the same rate, so they had the same fate. Moreover, some factors, such as birth date, had both direct and indirect effects on roe deer early survival, with fawns born early in the season benefiting from high early survival both because they have more time to grow before the harsh season and because they grow faster during their first days of life than late-born fawns. 4. These findings suggest that most drivers of early survival previously identified in large mammalian herbivores may affect early survival primarily through their influence on early growth. Disentangling the direct and indirect pathways by which different factors influence early survival is of crucial importance to understand the mechanisms shaping this key

  15. Human sexual size dimorphism in early pregnancy.

    PubMed

    Bukowski, Radek; Smith, Gordon C S; Malone, Fergal D; Ball, Robert H; Nyberg, David A; Comstock, Christine H; Hankins, Gary D V; Berkowitz, Richard L; Gross, Susan J; Dugoff, Lorraine; Craigo, Sabrina D; Timor-Tritsch, Ilan E; Carr, Stephen R; Wolfe, Honor M; D'Alton, Mary E

    2007-05-15

    Sexual size dimorphism is thought to contribute to the greater mortality and morbidity of men compared with women. However, the timing of onset of sexual size dimorphism remains uncertain. The authors determined whether human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. Using a prospective cohort study, conducted in 1999-2002 in the United States, they identified 27,655 women who conceived spontaneously and 1,008 whose conception was assisted by in vitro fertilization or intrauterine insemination and for whom a first-trimester measurement of fetal crown-rump length was available. First-trimester size was expressed as the difference between the observed and expected size of the fetus, expressed as equivalence to days of gestational age. The authors evaluated the association between fetal sex, first-trimester size, and birth weight. Eight to 12 weeks after conception, males were larger than females (mean difference: assisted conception = 0.4 days, 95% confidence interval (CI): 0.1, 0.7, p = 0.008; spontaneous conception = 0.3 days, 95% CI: 0.2, 0.4, p < 0.00001). The size discrepancy remained significant at birth (mean birth weight difference: assisted conception = 90 g, 95% CI: 22, 159, p = 0.009; spontaneous conception = 120 g, 95% CI: 107, 132, p < 0.00001). These data demonstrate that human fetuses exhibit sexual size dimorphism in the first trimester of pregnancy. PMID:17344203

  16. Palmitic Acid in Early Human Development.

    PubMed

    Innis, Sheila M

    2016-09-01

    Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental. PMID:25764297

  17. Taste development: differential growth rates of tongue regions in humans.

    PubMed

    Temple, Elizabeth C; Hutchinson, Ian; Laing, David G; Jinks, Anthony L

    2002-04-30

    There is a paucity of information about the anatomical and functional development of the human gustatory system. Although the anatomical development of the taste-sensitive fungiform, circumvallate and foliate papillae in the respective anterior, posterior and latero-posterior regions of the dorsal surface of the tongue has been well documented in the fetus, there is limited information about how these regions grow and when they exhibit adult function. The present study is concerned with determining when the growth of one of these taste-sensitive regions becomes adult in size, namely, the anterior region, and how this growth compares with that of the remaining posterior region. Two-hundred and thirty-two living subjects aged between 4 and 32 years participated. Following the identification and marking of a series of landmarks on the dorsal surface of the tongue with blue food dye, five measurements of the width and length of various parts of the tongue allowed calculation of the growth of the anterior and posterior regions. The results indicate that the fungiform papillae-rich anterior region attains adult-size by 8-10 years of age whilst the posterior region continues to grow until 15-16 years. Interestingly, this early development is not matched by achievement of adult function [Dev. Brain Res. 82 (1994) 286] or adult size papillae or taste pores [Dev. Brain Res., submitted]. Finally, the findings of the present study will allow studies of the development of taste function in humans to be conducted using equivalent tongue areas in subjects of different ages. PMID:11978394

  18. Human Population: Fundamentals of Growth and Change.

    ERIC Educational Resources Information Center

    Stauffer, Cheryl Lynn, Ed.

    This booklet focuses on eight elements of population dynamics: "Population Growth and Distribution"; "Natural Increase and Future Growth"; "Effect of Migration on Population Growth"; "Three Patterns of Population Change"; "Patterns of World Urbanization"; "The Status of Women"; "World Health"; and "Environmental Relationships." Charts and graphs…

  19. Early NACA human computers at work

    NASA Technical Reports Server (NTRS)

    1949-01-01

    The women of the Computer Department at NACA High-Speed Flight Research Station are shown busy with test flight calculations. The computers under the direction of Roxanah Yancey were responsible for accurate calculations on the research test flights made at the Station. There were no mechanical computers at the station in 1949, but data was reduced by human computers. Shown in this photograph starting at the left are: Geraldine Mayer and Mary (Tut) Hedgepeth with Friden calculators on the their desks; Emily Stephens conferring with engineer John Mayer; Gertrude (Trudy) Valentine is working on an oscillograph recording reducing the data from a flight. Across the desk is Dorothy Clift Hughes using a slide rule to complete data calculations. Roxanah Yancey completes the picture as she fills out engineering requests for further data.

  20. Index selection in terminal sires improves early lamb growth.

    PubMed

    Márquez, G C; Haresign, W; Davies, M H; Emmans, G C; Roehe, R; Bünger, L; Simm, G; Lewis, R M

    2012-01-01

    The use of terminal sires (TS) for crossbreeding is integral to the UK sheep industry where approximately 71% of market lambs are sired by TS rams. Early growth of these crossbred lambs affects profitability. The objectives of this study were i) to evaluate the effectiveness of index selection among TS on BW and ADG of their crossbred offspring; and ii) to compare the efficacy of that selection within TS breeds. The most widely used TS breeds in the United Kingdom are Charollais, Suffolk, and Texel. These participated in sire referencing schemes in which they were evaluated on a lean growth index designed to increase carcass lean weight at a given age. From 1999 to 2002, approximately 15 high and 15 low lean growth index rams per breed (93 in total, differing in index on average by 4.6 SD) were selected from within their sire referencing schemes and mated to Welsh and Scottish Mule ewes. Their crossbred offspring were reared commercially on 3 experimental farms in England, Scotland, and Wales. A total of 6,515 lambs were born between 2000 and 2003. Lambs were weighed at birth (BWT), 5 wk (5WT), and 10 wk (10WT), and their ADG from birth to 10 wk was calculated. Lambs sired by high index rams were on average, across breeds, heavier at all ages (P < 0.01) with 0.07 ± 0.03, 0.3 ± 0.1, and 0.4 ± 0.1 kg greater BWT, 5WT, and 10WT, respectively. Their ADG was 5.1 ± 1.9 g/d greater than low-index-sired lambs (P < 0.01). Suffolk-sired lambs were on average heavier at all ages, with greater ADG, whereas Charollais-sired lambs were lightest with smallest ADG. Overall, there was no significant interaction between sire index and sire breed (P > 0.10). Within Suffolk-sired lambs, there was little difference between high and low index sires for the traits studied (P > 0.3). High and low index Charollais-sired lambs differed in BWT (0.09 ± 0.04 kg) and 5WT (0.3 ± 0.1 kg), and Texel-sired lambs differed in 5WT (0.5 ± 0.1 kg), 10WT (0.9 ± 0.2 kg), and ADG (10.2 ± 3.3 g

  1. PHYSIOLOGICAL CONSEQUENCES OF EARLY NEONATAL GROWTH RETARDATION: EFFECTS OF A-DIFLUOROMETHYLORNITHINE ON RENAL GROWTH AND FUNCTION IN THE RAT

    EPA Science Inventory

    The physiological consequences of early neonatal growth retardation in the kidney are investigated using DFMO (a-difluoromethylornithine), a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines. e administered 500 eg/kg/...

  2. 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

    2014-10-01

    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

  3. 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

  4. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease.

    PubMed

    Nagy, Eniko; Rodriguiz, Ramona M; Wetsel, William C; MacIver, Nancie J; Hale, Laura P

    2016-01-01

    Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC), using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 ("T/I" mice). Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 ("T/I-het" dams) that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type (WT) pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and for development

  5. Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease

    PubMed Central

    Nagy, Eniko; Rodriguiz, Ramona M.; Wetsel, William C.; MacIver, Nancie J.; Hale, Laura P.

    2016-01-01

    Studies in transgenic murine models have provided insight into the complexity underlying inflammatory bowel disease (IBD), a disease hypothesized to result from an injurious immune response against intestinal microbiota. We recently developed a mouse model of IBD that phenotypically and histologically resembles human childhood-onset ulcerative colitis (UC), using mice that are genetically modified to be deficient in the cytokines TNF and IL-10 (“T/I” mice). Here we report the effects of early life onset of colon inflammation on growth and reproductive performance of T/I mice. T/I dams with colitis often failed to get pregnant or had small litters with pups that failed to thrive. Production was optimized by breeding double homozygous mutant T/I males to females homozygous mutant for TNF deficiency and heterozygous for deficiency of IL-10 (“T/I-het” dams) that were not susceptible to spontaneous colon inflammation. When born to healthy (T/I-het) dams, T/I pups initially gained weight similarly to wild type (WT) pups and to their non-colitis-susceptible T/I-het littermates. However, their growth curves diverged between 8 and 13 weeks, when most T/I mice had developed moderate to severe colitis. The observed growth failure in T/I mice occurred despite a significant increase in their food consumption and in the absence of protein loss in the stool. This was not due to TNF-induced anorexia or altered food consumption due to elevated leptin levels. Metabolic studies demonstrated increased consumption of oxygen and water and increased production of heat and CO2 in T/I mice compared to their T/I-het littermates, without differences in motor activity. Based on the clinical similarities of this early life onset model of IBD in T/I mice to human IBD, these results suggest that mechanisms previously hypothesized to explain growth failure in children with IBD require re-evaluation. The T/I mouse model may be useful for further investigation of such mechanisms and for

  6. Direct dating of Early Upper Palaeolithic human remains from Mladec.

    PubMed

    Wild, Eva M; Teschler-Nicola, Maria; Kutschera, Walter; Steier, Peter; Trinkaus, Erik; Wanek, Wolfgang

    2005-05-19

    The human fossil assemblage from the Mladec Caves in Moravia (Czech Republic) has been considered to derive from a middle or later phase of the Central European Aurignacian period on the basis of archaeological remains (a few stone artefacts and organic items such as bone points, awls, perforated teeth), despite questions of association between the human fossils and the archaeological materials and concerning the chronological implications of the limited archaeological remains. The morphological variability in the human assemblage, the presence of apparently archaic features in some specimens, and the assumed early date of the remains have made this fossil assemblage pivotal in assessments of modern human emergence within Europe. We present here the first successful direct accelerator mass spectrometry radiocarbon dating of five representative human fossils from the site. We selected sample materials from teeth and from one bone for 14C dating. The four tooth samples yielded uncalibrated ages of approximately 31,000 14C years before present, and the bone sample (an ulna) provided an uncertain more-recent age. These data are sufficient to confirm that the Mladec human assemblage is the oldest cranial, dental and postcranial assemblage of early modern humans in Europe and is therefore central to discussions of modern human emergence in the northwestern Old World and the fate of the Neanderthals. PMID:15902255

  7. Early Acceleration of Students in Mathematics: Does It Promote Growth and Stability of Growth in Achievement across Mathematical Areas?

    ERIC Educational Resources Information Center

    Ma, Xin

    2005-01-01

    Using data from the Longitudinal Study of American Youth (LSAY), the present study examined whether early acceleration of students into formal algebra at the beginning of middle school promoted evident growth in different mathematical areas (basic skills, algebra, geometry, and quantitative literacy) and stable growth across these mathematical…

  8. 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.

  9. Factors associated with early growth in Egyptian infants: implications for addressing the dual burden of malnutrition.

    PubMed

    Kavle, Justine A; Flax, Valerie L; Abdelmegeid, Ali; Salah, Farouk; Hafez, Seham; Ramzy, Magda; Hamed, Doaa; Saleh, Gulsen; Galloway, Rae

    2016-01-01

    Optimal nutrition is critical to the attainment of healthy growth, human capital and sustainable development. In Egypt, infants and young children face overlapping forms of malnutrition, including micronutrient deficiencies, stunting and overweight. Yet, in this setting, little is known about the factors associated with growth during the first year of life. A rise in stunting in Lower Egypt from 2005 to 2008 prompted this implementation research study, which followed a longitudinal cohort of infants from birth to 1 year of age within the context of a USAID-funded maternal and child health integrated programme. We sought to determine if growth patterns and factors related to early growth differed in Lower and Upper Egypt, and examined the relationship between weight loss and subsequent stunting at 12 months of age. Growth patterns revealed that length-for-age z-score (LAZ) decreased and weight-for-length z-score (WLZ) increased from 6 to 12 months of age in both regions. One-quarter of infants were stunted and nearly one-third were overweight by 12 months of age in lower Egypt. Minimum dietary diversity was significantly associated with WLZ in Lower Egypt (β = 0.22, P < 0.05), but not in Upper Egypt. Diarrhoea, fever and programme exposure were not associated with any growth outcome. Weight loss during any period was associated with a twofold likelihood of stunting at 12 months in Lower Egypt, but not Upper Egypt. In countries, like Egypt, facing the nutrition transition, infant and young child nutrition programmes need to address both stunting and overweight through improving dietary quality and reducing reliance on energy-dense foods. PMID:26373408

  10. Human oocytes and preimplantation embryos express mRNA for growth hormone receptor.

    PubMed

    Ménézo, Y J; el Mouatassim, S; Chavrier, M; Servy, E J; Nicolet, B

    2003-11-01

    Human genetic expression of growth hormone receptor (GHR) gene was qualitatively analysed using reverse transcription polymerase chain reaction (RT-PCR) in cumulus cells, immature germinal vesicle (GV) and mature metaphase II (MII) stage oocytes and preimplantation human embryos. The transcripts encoding GHR were detected in cumulus cells and also in naked oocytes, either mature or not. In this case, a nested PCR is needed, as for early embryo preimplantation stages, before genomic activation. The GHR gene is highly expressed from the 4-day morula onwards. This suggests that GHR transcription follows a classical scheme associated with genomic activation. It is probable that, in human, growth hormone plays a role in the final stages of oocyte maturation and early embryogenesis as it does for several other mammalian species. PMID:15085728

  11. 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. PMID:26886800

  12. 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

  13. Human milk feeding supports adequate growth in infants ≤ 1250 grams birth weight

    PubMed Central

    2013-01-01

    Background 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 objective of this study was to evaluate growth velocities and incidence of extrauterine growth restriction in infants ≤ 1250 grams (g) birth weight (BW) receiving an exclusive human milk-based diet with early and rapid advancement of fortification using a donor human milk derived fortifier. Methods In a single center, prospective observational cohort study, preterm infants weighing ≤ 1250 g BW were fed an exclusive human milk-based diet until 34 weeks postmenstrual age. Human milk fortification with donor human milk derived fortifier was started at 60 mL/kg/d and advanced to provide 6 to 8 additional kilocalories per ounce (or 0.21 to 0.28 kilocalories per gram). Data for growth were compared to historical growth standards and previous human milk-fed cohorts. Results We consecutively evaluated 104 infants with mean gestational age of 27.6 ± 2.0 weeks and BW of 913 ± 181 g (mean ± standard deviation). Weight gain was 24.8 ± 5.4 g/kg/day with length 0.99 ± 0.23 cm/week and head circumference 0.72 ± 0.14 cm/week. There were 3 medical NEC cases and 1 surgical NEC case. 22 infants (21%) were small for gestational age at birth. Overall, 45 infants (43%) had extrauterine growth restriction. Weight velocity was affected by day of fortification (p = 0.005) and day of full feeds (p = 0.02). Our cohort had significantly greater growth in weight and length compared to previous entirely human milk-fed cohorts. Conclusions A feeding protocol for infants ≤ 1250 g BW providing an exclusive human milk-based diet with early and rapid advancement of fortification leads to growth meeting targeted standards with a low rate of extrauterine growth restriction. Consistent

  14. Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation.

    PubMed Central

    Pertovaara, L; Sistonen, L; Bos, T J; Vogt, P K; Keski-Oja, J; Alitalo, K

    1989-01-01

    Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta. Images PMID:2725496

  15. Early diagnosis and testing for human immunodeficiency virus.

    PubMed

    Hesman, Amanda

    2016-06-01

    Human immunodeficiency virus (HIV) is now considered a long-term condition. However, HIV can only become a long-term condition if it is diagnosed early and antiretroviral therapy is commenced immediately. Individuals with HIV who are diagnosed late have an increased risk of death in the year after diagnosis compared to those diagnosed promptly. This article outlines HIV testing policy in the UK, the importance of the early diagnosis of HIV, the barriers to HIV testing, and how to offer testing in a range of settings. PMID:27286626

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    In the current study, we examined latent growth in 731 young children's inhibitory control from the ages of two to four years, 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, children's inhibitory…

  17. Telomerase Activity is Downregulated Early During Human Brain Development.

    PubMed

    Ishaq, Abbas; Hanson, Peter S; Morris, Christopher M; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6-19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  18. Telomerase Activity is Downregulated Early During Human Brain Development

    PubMed Central

    Ishaq, Abbas; Hanson, Peter S.; Morris, Christopher M.; Saretzki, Gabriele

    2016-01-01

    Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. PMID:27322326

  19. 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

  20. Intracellular processing of epidermal growth factor by early wound healing cells

    SciTech Connect

    Seyfer, A.E.; Nassaux, P.; Emory, R.; Wray, H.L.; Schaudies, R.P. )

    1990-01-01

    Epidermal growth factor (EGF) is a potent 53-amino-acid residue polypeptide that has been implicated in normal wound healing. Although past studies have shown that locally applied EGF accelerates wound healing, these studies have not examined intracellular events related to the processing of the growth factor. The objective of this study was to characterize both initial and later postbinding intracellular processing of EGF by a responsive cell line (osteoblasts) that is important in the healing of wounds. Cloned mouse calvarial osteoblasts (MC-3TC-E1) were incubated with radiolabeled EGF, with and without preincubation with nonlabeled EGF, for specific time intervals. Cell-associated radioactivity was characterized by nondenaturing polyacrylamide gel electrophoresis. Results showed that EGF is processed as three distinct species and that the relative proportions of these species are altered at later time periods when compared with initial processing. The patterns, similar to those reported for human fibroblasts, indicate a possible common pathway for the mitogenic signal in cells associated with the early events of wound healing. In addition, these data represent the first direct evidence that preexposure of cells to nonlabeled EGF alters the processing of radiolabeled EGF. This is significant, because cells must be exposed to EGF for 5 to 8 hours to elicit a growth response. Such data may help to explain the lag phase of wound healing.

  1. 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…

  2. Developmental atlas of the early first trimester human embryo.

    PubMed

    Yamada, Shigehito; Samtani, Rajeev R; Lee, Elaine S; Lockett, Elizabeth; Uwabe, Chigako; Shiota, Kohei; Anderson, Stasia A; Lo, Cecilia W

    2010-06-01

    Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies. PMID:20503356

  3. Autophagy in Normal and Abnormal Early Human Pregnancies.

    PubMed

    Avagliano, Laura; Terraneo, Laura; Virgili, Eleonora; Martinelli, Carla; Doi, Patrizia; Samaja, Michele; Bulfamante, Gaetano Pietro; Marconi, Anna Maria

    2015-07-01

    Autophagy is an inducible catabolic process by which cells degrade and recycle materials to survive stress, starvation, and hypoxia. The aim of this study was to evaluate autophagy at the fetal-maternal interface, to assess autophagy involvement during the early phase of human gestation, and to explore autophagic modification in case of early abnormal pregnancy outcome. Specimens were collected from first-trimester normal gestations undergoing legal termination of pregnancy and first-trimester sporadic spontaneous miscarriages. Autophagy was studied in villous and decidual samples by transmission electron microscopy, immunohistochemistry, immunofluorescence, and Western blotting. Autophagy markers were found in cytotrophoblast, syncytiotrophoblast, extravillous trophoblast, and decidual stromal cells. Autophagy is physiologically involved in early normal gestation. Compared with normal pregnancy, spontaneous miscarriage presents an increase in autophagy expression in villous specimens due to an increment in concentration of autophagic vacuole in syncytiotrophoblast, suggesting a cytoprotective mechanism of the cells to respond to microenvironmental challenge. PMID:25544676

  4. Variations in growth of roseate tern (Sterna dougallii) chicks: II. Early growth as an index of parental quality

    USGS Publications Warehouse

    Nisbet, I.C.T.; Spendelow, J.A.; Hatfield, J.S.; Zingo, J.M.; Gough, G.A.

    1998-01-01

    We measured growth of Roseate Tern (Sterna dougallii) chicks at a colony in Connecticut in 10 successive years. Data on body mass during the first three to four days of life were fitted to a quadratic regression model, yielding three parameters of early growth for each of 1,551 chicks: mass at hatching (Mo), linear growth (a) and quadratic growth (b). First chicks in each brood (A-chicks) exceeded second chicks (B-chicks) in each of the three growth parameters; A-chicks from broods of two grew faster than single chicks during the first three days. Mo depended on egg mass, hatch order, hatch date, and year. The linear coefficient (a) depended on hatch date, hatch order, and year, but not on egg mass or Mo. The quadratic coefficient (b) depended on a, hatch date, Mo, and hatch order. Subsequent growth and survival of chicks were predicted well by these parameters of early growth, with b contributing more to these predictions than Mo or a. After controlling for effects of early growth, none of the other variables measured (hatch date, egg mass, parental age, hatch interval between chicks, mass difference between chicks, female-female pairing, or trapping) contributed significantly to explaining later growth and survival. Year effects were substantial in only two of the 10 years of study. Individual pairs were consistent in performance (as indexed by chick growth) in successive years. These results suggest that growth and survival of Roseate Tern chicks are determined primarily by parental quality; much of the information about parental quality is expressed by the time the eggs are laid, and most of it is expressed by the time the chicks are three days old.

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

    PubMed

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

    2013-11-01

    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

  6. 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...

  7. The Human Health, Growth, and Development Curriculum.

    ERIC Educational Resources Information Center

    Boyles, Linda R.; And Others

    This health and human development curriculum for grades 1-6 contains tips for teachers and overviews of the philosophy behind teaching these topics to elementary school students. The section on health education is structured around ten content strands: (1) health knowledge, attitudes, decisions, and behavior; (2) emotional and social health; (3)…

  8. Ozone selectively inhibits growth of human cancer cells

    SciTech Connect

    Sweet, F.; Kao, M.S.; Lee, S.C.; Hagar, W.L.; Sweet, W.E.

    1980-08-01

    The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as noncancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The noncancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.

  9. Expression of immediate early genes after treatment of human astrocytoma cells with radiation and taxol

    SciTech Connect

    Gubits, R.M.; Geard, C.R.; Schiff, P.B.

    1993-10-20

    The promising chemotherapeutic agent, taxol, has been shown to sensitize the G18 line of human astrocytoma cells to ionizing radiation. The present studies were performed to identify specific changes in gene expression associated with this altered sensitivity. The products of immediate early genes, which are induced transiently in cells in response to a variety of treatments, including growth factors, neurotransmitters, and irradiation with UV light or X rays, are thought to initiate a cascade of genetic responses to alterations in cellular environment. The present results demonstrate a dramatic attenuation in one immediate early gene response in association with a treatment that enhances radiosensitivity in a refractory human brain tumor line. 22 refs., 5 figs., 1 tab.

  10. 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.

  11. 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.

  12. 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

  13. Zika virus impairs growth in human neurospheres and brain organoids.

    PubMed

    Garcez, Patricia P; Loiola, Erick Correia; Madeiro da Costa, Rodrigo; Higa, Luiza M; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana Minardi; Brindeiro, Rodrigo; Tanuri, Amilcar; Rehen, Stevens K

    2016-05-13

    Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. PMID:27064148

  14. Gestational weight gain and offspring longitudinal growth in early life

    PubMed Central

    Diesel, Jill C.; Eckhardt, Cara L.; Day, Nancy L.; Brooks, Maria M.; Arslanian, Silva A.; Bodnar, Lisa M.

    2015-01-01

    Background Excessive gestational weight gain (GWG) increases the risk of childhood obesity, but little is known about its association with infant growth patterns. Aim To examine the GWG-infant growth association. Methods Pregnant women (n=743) self-reported GWG at delivery, which we classified as inadequate, adequate, or excessive based on current guidelines. Offspring weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ (with height-for-age (HAZ) in place of length at 36 months)), and body mass index z-scores (BMIZ) were calculated at birth, 8, 18, and 36 months using the 2006 WHO growth standards. Linear mixed models estimated the change in z-scores from birth to 36 months by GWG. Results The mean (SD) WAZ was −0.22 (1.20) at birth. Overall, WAZ and BMIZ increased from birth to approximately 24 months and decreased from 24 to 36 months, while LAZ/HAZ decreased from birth through 36 months. Excessive GWG was associated with higher offspring WAZ and BMIZ at birth, 8, and 36 months, and higher HAZ at 36 months, compared with adequate GWG. Compared with the same referent, inadequate GWG was associated with smaller WAZ and BMIZ at birth and 8 months. Conclusion Excessive GWG may predispose infants to obesogenic growth patterns while inadequate GWG may not have a lasting impact on infant growth. PMID:26279171

  15. Estrogen Receptor β Isoform-Specific Induction of Transforming Growth Factor β-Inducible Early Gene-1 in Human Osteoblast Cells: An Essential Role for the Activation Function 1 Domain

    PubMed Central

    Hawse, John R.; Subramaniam, Malayannan; Monroe, David G.; Hemmingsen, Amanda H.; Ingle, James N.; Khosla, Sundeep; Oursler, Merry Jo; Spelsberg, Thomas C.

    2008-01-01

    The estrogen receptors (ER) α and β are important ligand-mediated transcription factors known to play significant biological roles in numerous tissues including bone. Despite the high homology shared by these receptors, recent studies have suggested that their function is largely unique. Although these receptors have been studied in detail for more than a decade, little data exist concerning the mechanisms by which these two proteins regulate distinct sets of genes. Using the TGFβ-inducible early gene-1 (TIEG) as a model, we demonstrate that TIEG is rapidly induced in response to estrogen in osteoblasts by ERβ, but not ERα. We have identified the regulatory elements utilized by ERβ and have demonstrated that ERβ recruits steroid receptor coactivator (SRC)1 and SRC2 to this regulatory region. Additionally, deletion of the ERβ-activation function 1 (AF1) domain drastically decreases the estrogen induction of TIEG. Through the use of chimeric receptors, we have demonstrated that the AF1 domain of ERβ is responsible for recruiting SRC1 and SRC2 and inducing the expression of TIEG in osteoblasts. Finally, SRC1, but not SRC2, is essential for TIEG induction by ERβ. Overall, these data demonstrate that the estrogen induction of TIEG is ERβ specific and that the AF1 domain of ERβ confers this specificity. Finally, a novel and important role for ERβ’s AF1 is implicated in the recruitment of specific coactivators, suggesting that the AF1 may play a significant role in conferring the differences in regulation of gene expression by these two receptors. PMID:18483178

  16. Growth factors in the treatment of early osteoarthritis

    PubMed Central

    Civinini, Roberto; Nistri, Lorenzo; Martini, Caterina; Redl, Birgit; Ristori, Gabriele; Innocenti, Massimo

    2013-01-01

    Summary Regenerative medicine is the science that studies the regeneration of biological tissues obtained through use of cells, with the aid of support structures and with biomolecules such as growth factors. As regards the growth factors the PRP, or the platelet-rich plasma, obtained from a withdrawal of autologous blood, concentrating the platelets, represents a safe, economical, easy to prepare and easy to apply source of growth factors. Numerous growth factors are in fact within the platelets and in particular a large number of them have a specific activity on neo-proliferation, on cartilage regeneration and in particular also an antiapoptotic effect on chondroblasts: - The PDGF which regulates the secretion and synthesis of collagen;- The EGF that causes cellular proliferation, endothelial chemotaxis and angiogenesis;- The VEGF that increases angiogenesis and vascular permeability;- The TGF-beta that stimulates the proliferation of undifferentiated MSC, stimulates chemotaxis of endothelial cells and angiogenesis;- The bFGF that promotes the growth and differentiation of chondrocytes and osteoblasts stimulates mitogenesis of mesenchymal cells, chondrocytes and osteoblasts. These properties have led to the development of studies that evaluated the efficacy of treatment of infiltrations in the knee and hip with platelet-derived growth factors. Regarding the knee it was demonstrated that in patients with moderate degree of gonarthrosis, the PRP is able to significantly reduce the pain and improve joint function, both on placebo and towards infiltrations with hyaluronic acid. The success of the treatment was proportional to the age of and inversely proportional to the severity of osteoarthritis according to Kellgren and Lawrence classification. The possibility of infiltrations guided with ultrasound into the hip led us to extend the indications also to hip arthrosis, as already showed by Sanchez. Even in coxarthrosis preliminary results at 6 and 12 months show that

  17. 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

  18. Mental development and growth in children with chronic liver disease of early and late onset.

    PubMed

    Stewart, S M; Uauy, R; Kennard, B D; Waller, D A; Benser, M; Andrews, W S

    1988-08-01

    Comparison was made of the mental function and physical growth of 21 children in whom liver disease occurred in the first year of life with 15 patients with late (17 months of age to 12 years of age) manifestation of liver disease. Ages (mean +/- SD) at testing for the two groups was 8 +/- 3 years for the early group and 11 +/- 5 years for the late group. Wechsler verbal, performance, and full-scale IQ scores were lower for the early group (range of mean scores: early, 85 to 86 v late, 96 to 103). Growth measures were significantly different in the two groups. Means +/- SD (percentage of standard) were: length for early group, 92 +/- 9; for late, 99 +/- 7; and head circumference for early, 98 +/- 4; for late, 101 +/- 2. The groups were similar in severity of liver disease and acute nutritional status, however. Patients with intellectual impairment had a longer duration of illness, poor nutritional status, and vitamin E deficiency; 82% of impaired patients were in the early group. The data suggest that liver disease during early life has pernicious effects on intellectual function and linear growth. Careful monitoring of nutritional status of children with early-onset liver disease and aggressive nutritional support beginning at the time of diagnosis may help reduce delays in growth and mental development. PMID:3399290

  19. Reciprocal regulation of expression of the human adenosine 5′-triphosphate binding cassette, sub-family A, transporter 2 (ABCA2) promoter by the early growth response-1 (EGR-1) and Sp-family transcription factors

    PubMed Central

    Davis, Warren; Chen, Zhijian J.; Ile, Kristina E.; Tew, Kenneth D.

    2003-01-01

    The human ABCA2 transporter gene encodes a member of a large family of ATP-binding proteins that transport a variety of macromolecules across biological membranes. We have performed luciferase reporter gene assays with promoter constructs comprising the 5′-flanking region to identify cis-regulatory DNA elements and have mapped the minimal promoter region to 321 bp upstream of the translation start site. We have discovered a functional role for two GC-boxes located in the proximal promoter of the ABCA2 gene that contain overlapping sites for the EGR-1 and Sp1 transcription factors. We observed that oligonucleotides containing overlapping EGR-1/Sp1 sites bind the Sp1, Sp3 and Sp4 transcription factors. When BE(2)-M17 cells were treated with phorbol 12-myristate 13-acetate, we observed inducible expression and binding of the EGR-1 transcription factor to the two GC-boxes. Transfection of Sp1, Sp3 or Sp4 expression constructs into Drosophila S2 induced a dose-dependent increase in transcriptional activation of the ABCA2 promoter, but transfection of EGR-1 alone failed to activate transcription. When increasing amounts of EGR-1 were transfected into the BE(2)-M17 neuroblastoma cells we observed a dose-dependent decrease in expression of the ABCA2 promoter, although expression of the endogenous ABCA2 gene increased following transfection of EGR-1. PMID:12560508

  20. 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.

  1. The Early Communication Indicator for Infants and Toddlers: Early Head Start Growth Norms from Two States

    ERIC Educational Resources Information Center

    Greenwood, Charles R.; Walker, Dale; Buzhardt, Jay

    2010-01-01

    The Early Communication Indicator (ECI) is a measure relevant to intervention decision making and progress monitoring for infants and toddlers. With increasing recognition of the importance of quality early childhood education and intervention for all children, measurement plays an important role in documenting children's progress and outcomes of…

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

    PubMed

    Hellström, Ann; Ley, David; Hansen-Pupp, Ingrid; Hallberg, Boubou; Ramenghi, Luca A; Löfqvist, Chatarina; Smith, Lois E H; Hård, Anna-Lena

    2016-09-01

    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

  3. Bee venom inhibits growth of human cervical tumors in mice.

    PubMed

    Lee, Hye Lim; Park, Sang Ho; Kim, Tae Myoung; Jung, Yu Yeon; Park, Mi Hee; Oh, Sang Hyun; Yun, Hye Seok; Jun, Hyung Ok; Yoo, Hwan Soo; Han, Sang-Bae; Lee, Ung Soo; Yoon, Joo Hee; Song, Min Jong; Hong, Jin Tae

    2015-03-30

    We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway. PMID:25730901

  4. Early growth and devlopment response to corn to canola competition and shade stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Corn-weed competition studies indicate that resource limitation slows normal corn growth and development and often results in lower yields. However there is minimal information on the physiological basis of crop competition, especially at the early growth stages when resources would be expected to b...

  5. Early corn growth and development in response to weed, nitrogen, and shade stresses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early season crop-weed interactions during a critical weed-free period (CWFP) influence corn growth that commonly results in reduced yield. Yield loss is not mitigated by weed removal after the CWFP, hence, weeds cause an irreversible negative impact on growth and development during the CWFP. Howeve...

  6. Diversity of the Human Skin Microbiome Early in Life

    PubMed Central

    Capone, Kimberly A; Dowd, Scot E; Stamatas, Georgios N; Nikolovski, Janeta

    2011-01-01

    Within days after birth, rapid surface colonization of infant skin coincides with significant functional changes. Gradual maturation of skin function, structure, and composition continues throughout the first years of life. Recent reports have revealed topographical and temporal variations in the adult skin microbiome. Here we address the question of how the human skin microbiome develops early in life. We show that the composition of cutaneous microbial communities evolves over the first year of life, showing increasing diversity with age. Although early colonization is dominated by Staphylococci, their significant decline contributes to increased population evenness by the end of the first year. Similar to what has been shown in adults, the composition of infant skin microflora appears to be site specific. In contrast to adults, we find that Firmicutes predominate on infant skin. Timely and proper establishment of healthy skin microbiome during this early period might have a pivotal role in denying access to potentially infectious microbes and could affect microbiome composition and stability extending into adulthood. Bacterial communities contribute to the establishment of cutaneous homeostasis and modulate inflammatory responses. Early microbial colonization is therefore expected to critically affect the development of the skin immune function. PMID:21697884

  7. 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…

  8. The Human Microbiome. Early Life Determinant of Health Outcomes

    PubMed Central

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  9. The human microbiome. Early life determinant of health outcomes.

    PubMed

    Martinez, Fernando D

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  10. 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. PMID:23267092

  11. 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

  12. Early gait development in human infants: Plasticity and clinical applications.

    PubMed

    Teulier, Caroline; Lee, Do Kyeong; Ulrich, Beverly D

    2015-05-01

    In this paper we focus on how a developmental perspective on plasticity in the control of human movement can promote early therapy and improve gait acquisition in infants with developmental disabilities. Current knowledge about stepping development in healthy infants across the first year of life highlights strong plasticity, both in behavioral outcome and in underlying neuro-muscular activation. These data show that stepping, like other motor skills, emerges from the interaction between infant's maturation and the environment. This view is reinforced by showing that infants with different internal resources (like genetic disorder or neural tube defect) show unique developmental trajectories when supported on a treadmill, yet do respond. Moreover, we will show that their behavior can be improved by context manipulations (mostly sensory stimulation) or practice. Overall, plasticity in the neural, skeletal, and muscle tissues create new opportunities for optimizing early intervention by creatively tapping into the same developmental processes experienced by healthy infants. PMID:25782975

  13. An early history of human breast cancer: West meets East

    PubMed Central

    Yan, Shou-He

    2013-01-01

    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. PMID:23958056

  14. In vitro follicle growth supports human oocyte meiotic maturation

    PubMed Central

    Xiao, Shuo; Zhang, Jiyang; Romero, Megan M.; Smith, Kristin N.; Shea, Lonnie D.; Woodruff, Teresa K.

    2015-01-01

    In vitro follicle growth is a potential approach to preserve fertility for young women who are facing a risk of premature ovarian failure (POF) caused by radiation or chemotherapy. Our two-step follicle culture strategy recapitulated the dynamic human follicle growth environment in vitro. Follicles developed from the preantral to antral stage, and, for the first time, produced meiotically competent metaphase II (MII) oocytes after in vitro maturation (IVM). PMID:26612176

  15. In vitro follicle growth supports human oocyte meiotic maturation.

    PubMed

    Xiao, Shuo; Zhang, Jiyang; Romero, Megan M; Smith, Kristin N; Shea, Lonnie D; Woodruff, Teresa K

    2015-01-01

    In vitro follicle growth is a potential approach to preserve fertility for young women who are facing a risk of premature ovarian failure (POF) caused by radiation or chemotherapy. Our two-step follicle culture strategy recapitulated the dynamic human follicle growth environment in vitro. Follicles developed from the preantral to antral stage, and, for the first time, produced meiotically competent metaphase II (MII) oocytes after in vitro maturation (IVM). PMID:26612176

  16. An early modern human from Tianyuan Cave, Zhoukoudian, China

    PubMed Central

    Shang, Hong; Tong, Haowen; Zhang, Shuangquan; Chen, Fuyou; Trinkaus, Erik

    2007-01-01

    Thirty-four elements of an early modern human (EMH) were found in Tianyuan Cave, Zhoukoudian, China in 2003. Dated to 42,000–39,000 calendrical years before present by using direct accelerator mass spectrometry radiocarbon, the Tianyuan 1 skeleton is among the oldest directly dated EMHs in eastern Eurasia. Morphological comparison shows Tianyuan 1 to have a series of derived modern human characteristics, including a projecting tuber symphyseos, a high anterior symphyseal angle, a broad scapular glenoid fossa, a reduced hamulus, a gluteal buttress, and a pilaster on the femora. Other features of Tianyuan 1 that are more common among EMHs are its modest humeral pectoralis major tuberosities, anteriorly rotated radial tuberosity, reduced radial curvature, and modest talar trochlea. It also lacks several mandibular features common among western Eurasian late archaic humans, including mandibular foramen bridging, mandibular notch asymmetry, and a large superior medial pterygoid tubercle. However, Tianyuan 1 exhibits several late archaic human features, such as its anterior to posterior dental proportions, a large hamulus length, and a broad and rounded distal phalangeal tuberosity. This morphological pattern implies that a simple spread of modern humans from Africa is unlikely. PMID:17416672

  17. 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. PMID:23267102

  18. 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

  19. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

    PubMed Central

    Vetter, U; Zapf, J; Heit, W; Helbing, G; Heinze, E; Froesch, E R; Teller, W M

    1986-01-01

    Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life. Images PMID:3519682

  20. Debatable questions of Siberia settlement by early humans

    NASA Astrophysics Data System (ADS)

    Kuzmin, Ya. V.; Kazanskii, A. Yu.

    2015-01-01

    Data on the age and natural environment of earliest archaeological sites in Siberia are critically analyzed. Particular attention is paid to the Karama site in the Altai Mountains, whose age was earlier estimated at about 1.77-1.95 Ma. The combination of geological, geomorphological, sedimentological, palynological, and paleomagnetic data makes it possible to determine the lower limit of the age of this object at only about 800 ka. Judging by the results of a preliminary study of the Zasukhino site in Trans-Baikal, early humans could have appeared in Siberia about 1 million years ago, but additional research is required in order to obtain reliable information.

  1. Growth and hemodynamics after early embryonic aortic arch occlusion*

    PubMed Central

    Lindsey, Stephanie E.; Menon, Prahlad G.; Kowalski, William J.; Shekhar, Akshay; Yalcin, Huseyin C.; Nishimura, Nozomi; Schaffer, Chris B.; Butcher, Jonathan T.; Pekkan, Kerem

    2015-01-01

    The majority of severe clinically significant forms of congenital heart disease (CHD) is associated with great artery lesions, including hypoplastic, double, right or interrupted aortic arch morphologies. While fetal and neonatal interventions are advancing, their potential ability to restore cardiac function, optimal timing, location, and intensity required for intervention remain largely unknown. We here combine computational fluid dynamics (CFD) simulations with in vivo experiments to test how individual pharyngeal arch artery hemodynamics alters as a result of local interventions to obstruct individual arch artery flow. Simulated isolated occlusions within each pharyngeal arch artery were created with image derived three-dimensional (3D) reconstructions of normal chick pharyngeal arch anatomy at Hamburger-Hamilton (HH) developmental stages HH18 and HH24. Acute flow redistributions were then computed using in vivo measured subject-specific aortic sinus inflow velocity profiles. A kinematic vascular growth-rendering algorithm was then developed and implemented to test the role of changing local wall shear stress patterns in downstream 3D morphogenesis of arch arteries. CFD simulations predicted that altered pressure gradients and flow redistributions were most sensitive to occlusion of the IVth arches. To evaluate these simulations experimentally, a novel in vivo experimental model of pharyngeal arch occlusion was developed and implemented using two-photon microscopy guided femtosecond laser based photodisruption surgery. The right IVth arch was occluded at HH18, and resulting diameter changes were followed for up to 24 hours. Pharyngeal arch diameter responses to acute hemodynamic changes were predicted qualitatively but poorly quantitatively. Chronic growth and adaptation to hemodynamic changes however were predicted in a subset of arches. Our findings suggest that this complex biodynamic process is governed through more complex forms of mechanobiological

  2. Induction of nerve growth factor receptors on cultured human melanocytes

    SciTech Connect

    Peacocke, M.; Yaar, M.; Mansur, C.P.; Chao, M.V.; Gilchrest, B.A. )

    1988-07-01

    Normal differentiation and malignant transformation of human melanocytes involve a complex series of interactions during which both genetic and environmental factors play roles. At present, the regulation of these processes is poorly understood. The authors have induced the expression of nerve growth factor (NGF) receptors on cultured human melanocytes with phorbol 12-tetradecanoate 13-acetate and have correlated this event with the appearance of a more differentiated, dendritic morphology. Criteria for NGF receptor expression included protein accumulation and cell-surface immunofluorescent staining with a monoclonal antibody directed against the human receptor and induction of the messenger RNA species as determined by blot-hybridization studies. The presence of the receptor could also be induced by UV irradiation or growth factor deprivation. The NGF receptor is inducible in cultured human melanocytes, and they suggest that NGF may modulate the behavior of this neural crest-derived cell in the skin.

  3. 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. PMID:25960070

  4. Enhanced jun gene expression is an early genomic response to transforming growth factor. beta. stimulation

    SciTech Connect

    Pertovaara, L.; Sistonen, L.; Keski-Oja, J.; Alitalo, K. ); Bos, T.J.; Vogt, P.K. . Dept. of Microbiology)

    1989-03-01

    Transforming growth factor {beta} (TGF{beta}) is a multifunctional polypeptide4 that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF{beta} signal transduction in cells is unknown. The authors report here that an early effect of TGF{beta} is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF{beta}, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF{beta}, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TFG{beta}. The increase in jun mRNA occurred with picomolar TGF{beta} concentrations within 1 h of TGF{beta} stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-fine levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF{beta}, evidently in a protein synthesis-independent fashion. The junB response to TGF{beta} was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF{beta} may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF{beta}.

  5. 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.

  6. Perinatal programming of childhood asthma: early fetal size, growth trajectory during infancy, and childhood asthma outcomes.

    PubMed

    Turner, Steve

    2012-01-01

    The "fetal origins hypothesis" or concept of "developmental programming" suggests that faltering fetal growth and subsequent catch-up growth are implicated in the aetiology of cardiovascular disease. Associations between reduced birth weight, rapid postnatal weight gain, and asthma suggest that there are fetal origins to respiratory disease. The present paper first summarises the literature relating birth weight and post natal growth trajectories to asthma outcomes. Second, issues regarding the interpretation of antenatal fetal ultrasound measurements are discussed. Finally, recent reports linking antenatal measurement and growth trajectory to early childhood asthma outcomes are discussed. Understanding the nature and timing of factors which influence antenatal growth may give important insight into the antecedents of early-onset asthma with implications for interventions. PMID:22400043

  7. Enhancement of Human Hair Growth Using Ecklonia cava Polyphenols

    PubMed Central

    Shin, Hyoseung; Cho, A-Ri; Kim, Dong Young; Munkhbayer, Semchin; Choi, Soon-Jin; Jang, Sunhyae; Kim, Seong Ho; Shin, Hyeon-Cheol

    2016-01-01

    Background Ecklonia cava is a brown alga that contains various compounds, including carotenoids, fucoidans, and phlorotannins. E. cava polyphenols (ECPs) are known to increase fibroblast survival. The human dermal papilla cell (hDPC) has the properties of mesenchymal-origin fibroblasts. Objective This study aims to investigate the effect of ECPs on human hair growth promotion in vitro and ex vivo. Methods MTT assays were conducted to examine the effect of ECPs on hDPC proliferation. Hair growth was measured using ex-vivo hair follicle cultures. Real-time polymerase chain reaction was performed to evaluate the mRNA expression of various growth factors in ECP-treated hDPCs. Results Treatment with 10 µg/ml purified polyphenols from E. cava (PPE) enhanced the proliferation of hDPCs 30.3% more than in the negative control (p<0.001). Furthermore, 0.1 µg/ml PPE extended the human hair shaft 30.8% longer than the negative control over 9 days (p<0.05). Insulin-like growth factor-1 (IGF-1) mRNA expression increased 3.2-fold in hDPCs following treatment with 6 µg/ml PPE (p<0.05). Vascular endothelial growth factor (VEGF) mRNA expression was also increased 2.0-fold by 3 µg/ml PPE (p<0.05). Treatment with 10 µg/ml PPE reduced oxidative stress in hDPCs (p<0.05). Conclusion These results suggest that PPE could enhance human hair growth. This can be explained by hDPC proliferation coupled with increases in growth factors such as IGF-1 and VEGF. Reducing oxidative stress is also thought to help increase hDPCs. These favorable results suggest that PPE is a promising therapeutic candidate for hair loss. PMID:26848214

  8. Growth-regulated synthesis and secretion of biologically active nerve growth factor by human keratinocytes.

    PubMed

    Di Marco, E; Marchisio, P C; Bondanza, S; Franzi, A T; Cancedda, R; De Luca, M

    1991-11-15

    Nerve growth factor (NGF) transcripts were identified in normal human keratinocytes in primary and secondary culture. The expression of the NGF mRNA was strongly down-regulated by corticosteroids and was maximal when keratinocytes were in the exponential phase of growth. Immunofluorescence studies on growing keratinocytes colonies and on elutriated keratinocytes obtained from growing colonies and mature stratified epithelium showed specific staining of the Golgi apparatus only in basal keratinocytes in the exponential phase of growth. The keratinocyte-derived NGF was secreted in a biologically active form as assessed by neurite induction in sensory neurons obtained from chick embryo dorsal root ganglia. Based on these data we suggest that the basal keratinocyte is the cell synthesizing and secreting NGF in the human adult epidermis. The paracrine secretion of NGF by keratinocytes might have a major role in regulating innervation, lymphocyte function, and melanocyte growth and differentiation in epidermal morphogenesis as well as during wound healing. PMID:1718982

  9. 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. PMID:25592941

  10. Early enteral feeding with human milk for VLBW infants.

    PubMed

    De Nisi, G; Berti, M; De Nisi, M; Bertino, E

    2012-01-01

    In a NICU early enteral feeding is usually possible only when the newborn clinical conditions permit it. Because of the frequent need of umbilical/central catheters, they usually start with parenteral feeding and/or with minimal enteral feeding (trophic feeding). This kind of management is even more frequent in VLBWIs, in which the risk of NEC is very high. In this work we describe a model of early enteral exclusive feeding (EEEF) based on the use of banking human milk followed by mother milk. In the Centre of Neonatology of Trento, as in other Centers, the newborns weighing less than 750g or with a GE< 27 weeks, are treated with parenteral nutrition and minimal enteral feeding. The newborn weighing 750-1249g and with GE > 26 weeks define a group in which we find critical neonates, who can not be treated with enteral feeding, and neonates whose clinical conditions permit EEEF. In particular, in a period of 16 years (1994-2009) in Trento, 308 newborns weighing 750-1249 g and GE > than 26 weeks were admitted. The 90,9 % has been treated with prenatal steroids, the 91,9 % was inborn, the 96,1% survived. In the 59,1 % of the cases (175) we gave EEEF. We could continue with a complete EEEF in the 40,2 % of the total (119 cases). The characteristics of these neonates and our centre management, based mainly on early use of banking human milk and mother milk, are detailed described. PMID:23158518

  11. 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

  12. Spiritual Reading and Its Effects on Human Growth.

    ERIC Educational Resources Information Center

    Duncan, James C.

    This research study sought to explore the relationship between spiritual reading and its effects on human growth. The emphasis of the study was how participants felt they had grown in their relationship with God through reading. Participants were clergypersons in the Tidewater, Virginia area. The 30 pastors interviewed for this study indicated…

  13. Growth of early continental crust by partial melting of eclogite.

    PubMed

    Rapp, Robert P; Shimizu, Nobumichi; Norman, Marc D

    2003-10-01

    The tectonic setting in which the first continental crust formed, and the extent to which modern processes of arc magmatism at convergent plate margins were operative on the early Earth, are matters of debate. Geochemical studies have shown that felsic rocks in both Archaean high-grade metamorphic ('grey gneiss') and low-grade granite-greenstone terranes are comprised dominantly of sodium-rich granitoids of the tonalite-trondhjemite-granodiorite (TTG) suite of rocks. Here we present direct experimental evidence showing that partial melting of hydrous basalt in the eclogite facies produces granitoid liquids with major- and trace-element compositions equivalent to Archaean TTG, including the low Nb/Ta and high Zr/Sm ratios of 'average' Archaean TTG, but from a source with initially subchondritic Nb/Ta. In modern environments, basalts with low Nb/Ta form by partial melting of subduction-modified depleted mantle, notably in intraoceanic arc settings in the forearc and back-arc regimes. These observations suggest that TTG magmatism may have taken place beneath granite-greenstone complexes developing along Archaean intraoceanic island arcs by imbricate thrust-stacking and tectonic accretion of a diversity of subduction-related terranes. Partial melting accompanying dehydration of these generally basaltic source materials at the base of thickened, 'arc-like' crust would produce compositionally appropriate TTG granitoids in equilibrium with eclogite residues. PMID:14534583

  14. Modulation of epidermal growth factor receptors by human alpha interferon.

    PubMed Central

    Zoon, K C; Karasaki, Y; zur Nedden, D L; Hu, R Q; Arnheiter, H

    1986-01-01

    Treatment of Madin-Darby bovine kidney (MDBK) cells with human interferon (IFN)-alpha 2 at 37 degrees C results in a dose-dependent inhibition of cell growth and a reduction of the subsequent binding of 125I-labeled epidermal growth factor (EGF) at 4 degrees C. Human IFN-beta and -gamma, which exhibit little antiviral and antiproliferative activities on MDBK cells, have little effect on cell growth or the binding of 125I-labeled EGF to these cells. The binding of EGF is decreased after exposure to IFN-alpha for greater than 8 hr. Scatchard analyses of the EGF binding data indicate that a 20-hr exposure period results in a decrease in the apparent number of cell-surface EGF receptors and a reduction in the affinity of EGF for its receptor. The rate of internalization of EGF by MDBK cells does not appear to be affected by IFN treatment. PMID:3095830

  15. Modulation of epidermal growth factor receptors by human alpha interferon.

    PubMed

    Zoon, K C; Karasaki, Y; zur Nedden, D L; Hu, R Q; Arnheiter, H

    1986-11-01

    Treatment of Madin-Darby bovine kidney (MDBK) cells with human interferon (IFN)-alpha 2 at 37 degrees C results in a dose-dependent inhibition of cell growth and a reduction of the subsequent binding of 125I-labeled epidermal growth factor (EGF) at 4 degrees C. Human IFN-beta and -gamma, which exhibit little antiviral and antiproliferative activities on MDBK cells, have little effect on cell growth or the binding of 125I-labeled EGF to these cells. The binding of EGF is decreased after exposure to IFN-alpha for greater than 8 hr. Scatchard analyses of the EGF binding data indicate that a 20-hr exposure period results in a decrease in the apparent number of cell-surface EGF receptors and a reduction in the affinity of EGF for its receptor. The rate of internalization of EGF by MDBK cells does not appear to be affected by IFN treatment. PMID:3095830

  16. Overview: early history of crop growth and photosynthesis modeling.

    PubMed

    El-Sharkawy, Mabrouk A

    2011-02-01

    As in industrial and engineering systems, there is a need to quantitatively study and analyze the many constituents of complex natural biological systems as well as agro-ecosystems via research-based mechanistic modeling. This objective is normally addressed by developing mathematically built descriptions of multilevel biological processes to provide biologists a means to integrate quantitatively experimental research findings that might lead to a better understanding of the whole systems and their interactions with surrounding environments. Aided with the power of computational capacities associated with computer technology then available, pioneering cropping systems simulations took place in the second half of the 20th century by several research groups across continents. This overview summarizes that initial pioneering effort made to simulate plant growth and photosynthesis of crop canopies, focusing on the discovery of gaps that exist in the current scientific knowledge. Examples are given for those gaps where experimental research was needed to improve the validity and application of the constructed models, so that their benefit to mankind was enhanced. Such research necessitates close collaboration among experimentalists and model builders while adopting a multidisciplinary/inter-institutional approach. PMID:20826195

  17. A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion.

    PubMed

    Hill, David S; Robinson, Neil D P; Caley, Matthew P; Chen, Mei; O'Toole, Edel A; Armstrong, Jane L; Przyborski, Stefan; Lovat, Penny E

    2015-11-01

    Metastatic melanoma remains incurable, emphasizing the acute need for improved research models to investigate the underlying biologic mechanisms mediating tumor invasion and metastasis, and to develop more effective targeted therapies to improve clinical outcome. Available animal models of melanoma do not accurately reflect human disease and current in vitro human skin equivalent models incorporating melanoma cells are not fully representative of the human skin microenvironment. We have developed a robust and reproducible, fully humanized three-dimensional (3D) skin equivalent comprising a stratified, terminally differentiated epidermis and a dermal compartment consisting of fibroblast-generated extracellular matrix. Melanoma cells incorporated into the epidermis were able to invade through the basement membrane and into the dermis, mirroring early tumor invasion in vivo. Comparison of our novel 3D melanoma skin equivalent with melanoma in situ and metastatic melanoma indicates that this model accurately recreates features of disease pathology, making it a physiologically representative model of early radial and vertical growth-phase melanoma invasion. PMID:26330548

  18. Krüppel-Like Factor 12 Promotes Colorectal Cancer Growth through Early Growth Response Protein 1

    PubMed Central

    Kim, Sun-Hee; Park, Yun-Yong; Cho, Sung-Nam; Margalit, Ofer; Wang, Dingzhi; DuBois, Raymond N.

    2016-01-01

    Krüppel-like factor 12 (KLF12) is a transcription factor that plays a role in normal kidney development and repression of decidualization. KLF12 is frequently elevated in esophageal adenocarcinoma and has been reported to promote gastric cancer progression. Here, we examined the role of KLF12 in colorectal cancer (CRC). Indeed, KLF12 promotes tumor growth by directly activating early growth response protein 1 (EGR1). The levels of KLF12 and EGR1 correlate synergistically with a poor prognosis. These results indicate that KLF12 likely plays an important role in CRC and could serve as a potential prognostic marker and therapeutic target. PMID:27442508

  19. The biology of human epidermal growth factor receptor 2.

    PubMed

    Sundaresan, S; Penuel, E; Sliwkowski, M X

    1999-09-01

    Our understanding of the normal signaling mechanisms and functions of human epidermal growth factor receptor 2 (HER2) and other members of the HER family, namely epidermal growth factor receptor, HER3, and HER4, is growing rapidly. Activation of these receptors results in a diverse array of signals through the formation of homodimeric and heterodimeric receptor complexes; HER2 is the preferred dimerization partner for the other HERs. These oligomeric receptor complexes activate distinct signaling pathways, such as the Ras-MAPK and PI3-kinase pathways. These, in turn, affect various cellular processes. Recent gene deletion experiments in mice point to an important role for HER2 in cardiac and neural development, and evidence from other studies indicates that HER2 is involved in normal breast growth and development. Thus, HER2 is a key component of a complex signaling network that plays a critical role in the regulation of tissue development, growth, and differentiation. PMID:11122793

  20. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi

    PubMed Central

    Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N.; Lima, Maria F.; Pratap, Siddharth; Nde, Pius N.

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  1. Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

    PubMed

    Udoko, Aniekanabassi N; Johnson, Candice A; Dykan, Andrey; Rachakonda, Girish; Villalta, Fernando; Mandape, Sammed N; Lima, Maria F; Pratap, Siddharth; Nde, Pius N

    2016-01-01

    The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF-β dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy

  2. UVA Phototransduction Drives Early Melanin Synthesis in Human Melanocytes

    PubMed Central

    Wicks, Nadine L.; Chan, Jason W.; Najera, Julia A.; Ciriello, Jonathan M.; Oancea, Elena

    2013-01-01

    Summary Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% UVA and ~5% UVB at the Earth’s surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or PLC inhibitors, or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to five-fold after 24 hours. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis, and may underlie the mechanism of IPD in human skin. PMID:22055294

  3. Early Human Prostate Adenocarcinomas Harbor Androgen-Independent Cancer Cells

    PubMed Central

    Fiñones, Rita R.; Yeargin, Jo; Lee, Melissa; Kaur, Aman Preet; Cheng, Clari; Sun, Paulina; Wu, Christopher; Nguyen, Catherine; Wang-Rodriguez, Jessica; Meyer, April N.; Baird, Stephen M.; Donoghue, Daniel J.; Haas, Martin

    2013-01-01

    Although blockade of androgen receptor (AR) signaling represents the main treatment for advanced prostate cancer (PrCa), many patients progress to a lethal phenotype of “Castration-Resistant” prostate cancer (CR-PrCa). With the hypothesis that early PrCa may harbor a population of androgen-unresponsive cancer cells as precursors to CR-recurrent disease, we undertook the propagation of androgen-independent cells from PrCa-prostatectomy samples of early, localized (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases was established, among which 54 were adenocarcinomas. Hormone-free cell culture conditions were developed allowing routine propagation of cells expressing prostate basal cell markers and stem/progenitor cell markers, and which proliferated as spheres/spheroids in suspension cultures. Colonies of androgen-independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma cases studied in detail. Fluorescence microscopy and flow cytometry showed that CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin α2β1, SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of 22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in intact and castrated SCID mice, generating histologically typical locally-invasive human PrCa or undifferentiated cancers, respectively, in 6–8 weeks. Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA expression. We report here the propagation of Cancer Initiating Cells (CIC) directly from Stage I human PrCa tissue without selection or genetic manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from early human prostate carcinomas suggests the existence of a subpopulation of cells resistant to androgen-deprivation therapy and which may drive the subsequent emergence of disseminated CR-PrCa. PMID:24086346

  4. Transforming growth factor (TGF)-. alpha. in human milk

    SciTech Connect

    Okada, Masaki; Wakai, Kae; Shizume, Kazuo ); Iwashita, Mitsutoshi ); Ohmura, Eiji; Kamiya, Yoshinobu; Murakami, Hitomi; Onoda, Noritaka; Tsushima, Toshio

    1991-01-01

    Transforming growth factor (TGF)-{alpha} and epidermal growth factor (EGF) were measured in human milk by means of homologous radioimmunoassay. As previously reported, EGF concentration in the colostrum was approximately 200 ng/ml and decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF-{alpha} was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the concentration of IR-TGF-{alpha} was fairly stable during the 7 postpartum days. There was no relationship between the concentrations of IR-TGF-{alpha} and IR-EGF, suggesting that the regulatory mechanism in the release of the two growth factors is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared in the fraction corresponding to that of authentic human EGF, while 70%-80% of the IR-TGF-{alpha} was eluted as a species with a molecular weight greater than that of authentic human TGF-{alpha}. Although the physiological role of TGF-{alpha} in milk is not known, it is possible that it is involved in the development of the mammary gland and/or the growth of newborn infants.

  5. Early canine pregnancy--a battle for successful growth and angiogenesis.

    PubMed

    Schäfer-Somi, S

    2012-12-01

    Currently, no early pregnancy marker has been identified in the bitch. However, significantly decreased concentrations of heat-shock protein (HSP) 70 and increased activity of matrix metalloproteinases (MMP) 2,9 were detected in serum from bitches during the pre-implantation period between days 5 and 13 after mating, that is, 2-3 days after ovulation as determined by the measurement of progesterone and vaginal cytology. Especially during the implantation period and thereafter (days 15-55), high serum concentrations of antibodies against desmin are present, which is believed to indicate or regulate decidualization. Pre-implantation embryos express mRNA for enzymes and cytokines, known to promote and regulate trophoblast growth, and some intrauterine changings like the increased activity of MMP 2,9 in maternal endometrium are dependant on the presence of embryos. Some mechanisms that protect canine embryos from attack by the maternal immune system can also be identified. The embryos express CD4, a receptor known to interact with immune cells. They, furthermore, do not express MHC I and II, which might prevent them from being recognized as foreign antigen. Pre-implantation embryos express FasL, which probably renders them able to destroy Fas-bearing cytotoxic T cells. Furthermore, the uterus during pre-implantation and implantation expresses cytokines that modulate the intrauterine milieu towards a predominance of Th2 cells. During pre-implantation and implantation, an increased uterine expression of platelet activating factor (PAF) and PAFR, vascular endothelial growth factor (VEGF) and EGFR2 as well as epithelial growth factor (EGF) is characteristic. Towards placentation, the upregulation of leukaemia inhibiting factor (LIF) and at placentation the expression of insulin-like growth factor(IGF)2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are striking. Progesterone receptor (PR) appears to be downregulated inside the uterus except at placentation

  6. 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

  7. Does nutrition support stimulate tumor growth in humans?

    PubMed

    Bossola, Maurizio; Pacelli, Fabio; Rosa, Fausto; Tortorelli, Antonio; Doglietto, Giovan Battista

    2011-04-01

    Many studies have been conducted to ascertain if nutrition support (NS), either as parenteral nutrition (PN) or enteral nutrition (EN), stimulates tumor growth and causes cancer progression, but after almost 30 years, the question remains at least in part unresolved. In this study, previous studies were reviewed to evaluate the effect of NS on tumor growth, tumor proliferation, tumor apoptosis, and cancer-related survival in humans. MEDLINE and PubMed were searched using combinations of the following keywords: PN, EN, tumor growth, tumor proliferation, tumor apoptosis, arginine, ω-3 fatty acids, and glutamine. Unfortunately, the effect of nutrition support on tumor growth has been assessed only in terms of tumor proliferation, whereas the interferences on tumor apoptosis have never been determined. Overall, the results seem conflicting and inconclusive. Similarly, it remains unknown if PN or EN enriched with specific nutrients such as arginine, ω-3 fatty acids, and glutamine can affect tumor growth in humans. It is hoped that further studies will elucidate if NS with conventional or specific nutrients stimulates tumor proliferation, interferes with tumor apoptosis, and causes cancer progression. PMID:21447771

  8. 3-D Volumetric Evaluation of Human Mandibular Growth

    PubMed Central

    Reynolds, Mathew; Reynolds, Michael; Adeeb, Samer; El-Bialy, Tarek

    2011-01-01

    Bone growth is a complex process that is controlled by a multitude of mechanisms that are not fully understood.Most of the current methods employed to measure the growth of bones focus on either studying cadaveric bones from different individuals of different ages, or successive two-dimensional (2D) radiographs. Both techniques have their known limitations. The purpose of this study was to explore a technique for quantifying the three dimensional (3D) growth of an adolescent human mandible over the period of one year utilizing cone beam computed tomography (CBCT) scans taken for regular orthodontic records. Three -dimensional virtual models were created from the CBCT data using mainstream medical imaging software. A comparison between computer-generated surface meshes of successive 3-D virtual models illustrates the magnitude of relative mandible growth. The results of this work are in agreement with previously reported data from human cadaveric studies and implantable marker studies. The presented method provides a new relatively simple basis (utilizing commercially available software) to visualize and evaluate individualized 3D (mandibular) growth in vivo. PMID:22046201

  9. STAT5B deficiency: Impacts on human growth and immunity.

    PubMed

    Hwa, Vivian

    2016-06-01

    Growth hormone (GH) promotes postnatal human growth primarily by regulating insulin-like growth factor (IGF)-I production through activation of the GH receptor (GHR)-signal transducer and activator of transcription (STAT)-5B signaling cascade. The critical importance of STAT5B in human IGF-I production was confirmed with the identification of the first homozygous, autosomal recessive, STAT5B mutation in a young female patient who phenotypically resembled patients with classical growth hormone insensitivity (GHI) syndrome (Laron syndrome) due to mutations in the GHR gene, presenting with severe postnatal growth failure and marked IGF-I deficiency. Of note, the closely related STAT5A, which shares >95% amino acid identity with STAT5B, could not compensate for loss of functional STAT5B. To date, 7 homozygous, inactivating, STAT5B mutations in 10 patients have been reported. STAT5B deficient patients, unlike patients deficient in GHR, can also present with a novel, potentially fatal, primary immunodeficiency, which can manifest as chronic pulmonary disease. STAT5B deficiency may be underestimated in endocrine, immunology and pulmonary clinics. PMID:26703237

  10. Functional activation of the egr-1 (early growth response-1) gene by hydrogen peroxide.

    PubMed

    Nose, K; Ohba, M

    1996-06-01

    The redox-based regulation of gene expression is one of the fundamental mechanisms of cellular functions, and hydrogen peroxide seems to act as an intracellular second messenger of signal transduction of cytokines. Hydrogen peroxide at non-toxic doses induced the accumulation of mRNA for the early growth response-1 (egr-1) gene in mouse osteoblastic cells. The Egr-1 protein is a transcription factor that binds the GCGGGGGCG sequence and contains a zinc-finger structure that is essential for DNA binding. Egr-1 protein is sensitive to oxidative stress and loses specific DNA-binding activity when exposed to high levels of oxidative stress. Incubating cells with hydrogen peroxide at about 50 microM, however, increased the accumulation of Egr-1 protein, and the Egr-1 product seemed to be functional, judging by its binding activity to the GCGGGGGCG sequence and its ability to activate the chloramphenicol acetyltransferase reporter gene under the control of the human thymidine kinase enhancer containing the Egr-1 binding sequence. It was reported that the activity of Egr-1 protein as a transcription factor was negatively regulated by active oxygens. However, with appropriate concentrations of active oxygen, its capacity to bind a specific DNA sequence and to enhance the transcriptional activity of target genes is thought to be elevated. PMID:8687376

  11. Triparanol suppresses human tumor growth in vitro and in vivo

    SciTech Connect

    Bi, Xinyu; Han, Xingpeng; Zhang, Fang; He, Miao; Zhang, Yi; Zhi, Xiu-Yi; Zhao, Hong

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  12. Oral iron acutely elevates bacterial growth in human serum

    PubMed Central

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

    2015-01-01

    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. PMID:26593732

  13. Early Trypanosoma cruzi Infection Reprograms Human Epithelial Cells

    PubMed Central

    Chiribao, María Laura; Libisch, Gabriela; Parodi-Talice, Adriana; Robello, Carlos

    2014-01-01

    Trypanosoma cruzi, the causative agent of Chagas disease, has the peculiarity, when compared with other intracellular parasites, that it is able to invade almost any type of cell. This property makes Chagas a complex parasitic disease in terms of prophylaxis and therapeutics. The identification of key host cellular factors that play a role in the T. cruzi invasion is important for the understanding of disease pathogenesis. In Chagas disease, most of the focus is on the response of macrophages and cardiomyocytes, since they are responsible for host defenses and cardiac lesions, respectively. In the present work, we studied the early response to infection of T. cruzi in human epithelial cells, which constitute the first barrier for establishment of infection. These studies identified up to 1700 significantly altered genes regulated by the immediate infection. The global analysis indicates that cells are literally reprogrammed by T. cruzi, which affects cellular stress responses (neutrophil chemotaxis, DNA damage response), a great number of transcription factors (including the majority of NFκB family members), and host metabolism (cholesterol, fatty acids, and phospholipids). These results raise the possibility that early host cell reprogramming is exploited by the parasite to establish the initial infection and posterior systemic dissemination. PMID:24812617

  14. mRNAs from human adenovirus 2 early region 4.

    PubMed Central

    Virtanen, A; Gilardi, P; Näslund, A; LeMoullec, J M; Pettersson, U; Perricaudet, M

    1984-01-01

    The molecular structure of the mRNAs from early region 4 of human adenovirus 2 has been studied by Northern blot analysis, S1 nuclease analysis, and sequence analysis of cDNA clones. The results make it possible to identify four different splice donor sites and six different splice acceptor sites. The structure of 12 different mRNAs can be deduced from the analysis. The mRNAs have identical 5' and 3' ends and are thus likely to be processed from a common mRNA precursor by differential splicing. The different mRNA species are formed by the removal of one to three introns, and they all carry a short 5' leader segment. The introns appear to serve two functions; they either place a 5' leader segment in juxtaposition with an open reading frame or fuse two open translational reading frames. The early region 4 mRNAs can encode at least seven unique polypeptides. Images PMID:6088804

  15. Inhibition of Human Colon Cancer Growth by Antibody-Directed Human LAK Cells in SCID Mice

    NASA Astrophysics Data System (ADS)

    Takahashi, Hiroshi; Nakada, Tetsuya; Puisieux, Isabelle

    1993-03-01

    Advanced human colon cancer does not respond to lymphokine-activated killer (LAK) cells. In order to direct cytotoxic cells to the tumor, human LAK cells linked with antibodies to a tumor cell surface antigen were tested with established hepatic metastases in severe combined immunodeficient (SCID) mice. These cells had increased uptake into the tumor and suppression of tumor growth as compared with LAK cells alone, thereby improving the survival of tumor-bearing mice. Thus, tumor growth can be inhibited by targeted LAK cells, and SCID mice can be used to test the antitumor properties of human effector cells.

  16. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    SciTech Connect

    Ramasharma, K.; Li, C.H.

    1987-05-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and ..cap alpha..-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin.

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

    PubMed Central

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

    2014-01-01

    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. PMID:25342868

  18. Defining human insulin-like growth factor I gene regulation.

    PubMed

    Mukherjee, Aditi; Alzhanov, Damir; Rotwein, Peter

    2016-08-01

    Growth hormone (GH) plays an essential role in controlling somatic growth and in regulating multiple physiological processes in humans and other species. Insulin-like growth factor I (IGF-I), a conserved, secreted 70-amino acid peptide, is a critical mediator of many of the biological effects of GH. Previous studies have demonstrated that GH rapidly and potently promotes IGF-I gene expression in rodents and in some other mammals through the transcription factor STAT5b, leading to accumulation of IGF-I mRNAs and production of IGF-I. Despite this progress, very little is known about how GH or other trophic factors control human IGF1 gene expression, in large part because of the absence of any cellular model systems that robustly express IGF-I. Here, we have addressed mechanisms of regulation of human IGF-I by GH after generating cells in which the IGF1 chromosomal locus has been incorporated into a mouse cell line. Using this model, we found that physiological levels of GH rapidly stimulate human IGF1 gene transcription and identify several potential transcriptional enhancers in chromatin that bind STAT5b in a GH-regulated way. Each of the putative enhancers also activates a human IGF1 gene promoter in reconstitution experiments in the presence of the GH receptor, STAT5b, and GH. Thus we have developed a novel experimental platform that now may be used to determine how human IGF1 gene expression is controlled under different physiological and pathological conditions. PMID:27406741

  19. Matriptase regulates proliferation and early, but not terminal, differentiation of human keratinocytes

    PubMed Central

    Chen, Ya-Wen; Wang, Jehng-Kang; Chou, Fen-Pai; Wu, Bai-Yao; Hsiao, Hui-Chung; Chiu, Han; Xu, Zhonghong; Baksh, Adrienne NH; Shi, Galen; Kaul, Malvika; Barndt, Robert; Shanmugam, Victoria K.; Johnson, Michael D.; Lin, Chen-Yong

    2013-01-01

    Genetic defects in matriptase are linked to two congenital ichthyosis, autosomal recessive ichthyosis with hypotrichosis (ARIH, OMIM 610765) and, ichthyosis, follicular atrophoderma, hypotrichosis, and hypohidrosis (IFAH, OMIM602400). Mouse models with matriptase deficiency indicate an involvement of matriptase in suprabasal keratinocytes in the maintenance of the epidermal barrier. In contrast to what has been reported for mouse skin, we show that in human skin, matriptase is primarily expressed in the basal and spinous keratinocytes, but not in the more differentiated keratinocytes of the granular layer. In addition, matriptase zymogen activation was predominantly detected in the basal cells. Furthermore, using skin organotypic cultures as a model system to monitor the course of human epidermal differentiation, we found elevated matriptase zymogen activation during early stages of epidermal differentiation, coupled with a loss of matriptase expression in the late stages of this process. We also show here that matriptase deficiency in HaCaT cells modestly reduces cell proliferation and temporally affects calcium-induced expression of differentiation markers. These collective data suggests that, unlike mouse matriptase, human matriptase may be involved in regulation of keratinocyte growth and early differentiation, rather than terminal differentiation, providing mechanistic insights for the pathology of the two congenital ichthyoses, ARIH and IFAH. PMID:23900022

  20. The Evolution of Brains from Early Mammals to Humans

    PubMed Central

    Kaas, Jon H.

    2012-01-01

    The large size and complex organization of the human brain makes it unique among primate brains. In particular, the neocortex constitutes about 80% of the brain, and this cortex is subdivided into a large number of functionally specialized regions, the cortical areas. Such a brain mediates accomplishments and abilities unmatched by any other species. How did such a brain evolve? Answers come from comparative studies of the brains of present-day mammals and other vertebrates in conjunction with information about brain sizes and shapes from the fossil record, studies of brain development, and principles derived from studies of scaling and optimal design. Early mammals were small, with small brains, an emphasis on olfaction, and little neocortex. Neocortex was transformed from the single layer of output pyramidal neurons of the dorsal cortex of earlier ancestors to the six layers of all present-day mammals. This small cap of neocortex was divided into 20–25 cortical areas, including primary and some of the secondary sensory areas that characterize neocortex in nearly all mammals today. Early placental mammals had a corpus callosum connecting the neocortex of the two hemispheres, a primary motor area, M1, and perhaps one or more premotor areas. One line of evolution, Euarchontoglires, led to present-day primates, tree shrews, flying lemurs, rodents and rabbits. Early primates evolved from small-brained, nocturnal, insect-eating mammals with an expanded region of temporal visual cortex. These early nocturnal primates were adapted to the fine branch niche of the tropical rainforest by having an even more expanded visual system that mediated visually guided reaching and grasping of insects, small vertebrates, and fruits. Neocortex was greatly expanded, and included an array of cortical areas that characterize neocortex of all living primates. Specializations of the visual system included new visual areas that contributed to a dorsal stream of visuomotor processing in a

  1. The early fetal development of human neocortical GABAergic interneurons.

    PubMed

    Al-Jaberi, Nahidh; Lindsay, Susan; Sarma, Subrot; Bayatti, Nadhim; Clowry, Gavin J

    2015-03-01

    GABAergic interneurons are crucial to controlling the excitability and responsiveness of cortical circuitry. Their developmental origin may differ between rodents and human. We have demonstrated the expression of 12 GABAergic interneuron-associated genes in samples from human neocortex by quantitative rtPCR from 8 to 12 postconceptional weeks (PCW) and shown a significant anterior to posterior expression gradient, confirmed by in situ hybridization or immunohistochemistry for GAD1 and 2, DLX1, 2, and 5, ASCL1, OLIG2, and CALB2. Following cortical plate (CP) formation from 8 to 9 PCW, a proportion of cells were strongly stained for all these markers in the CP and presubplate. ASCL1 and DLX2 maintained high expression in the proliferative zones and showed extensive immunofluorescent double-labeling with the cell division marker Ki-67. CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67. Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium. It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex. PMID:24047602

  2. Motogenic substrata and chemokinetic growth factors for human skin cells

    PubMed Central

    Sutherland, Jennifer; Denyer, Morgan; Britland, Stephen

    2005-01-01

    Extracellular matrix remodelling and accurate spatio-temporal coordination of growth factor expression are two factors that are believed to regulate mitoses and cell migration in developing and regenerating tissues. The present quantitative videomicroscopical study examined the influence of some of the principal components of extracellular matrix and several growth factors that are known to be expressed in dermal wounds on three important facets of human skin cell behaviour in culture. Keratinocytes, melanocytes and dermal fibroblasts (and myofibroblast controls) exhibited varying degrees of substrate adhesion, division and migration depending on the composition of the culture substrate. Substrates that are recognized components of transitional matrices generally accentuated cell adhesion and proliferation, and were motogenic, when compared with serum-treated control surfaces, whereas components of more stable structures such as basement membrane had less influence. Platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and α fibroblastic growth factor (αFGF) all promoted cell proliferation and were chemokinetic to dermal fibroblasts, but not keratinocyte growth factor (KGF) or transforming growth factor β (TGFβ). PDGF, EGF and KGF, but not TGFβ or αFGF, all enhanced proliferation of dermal keratinocytes. The same growth factors, and in addition KGF, all stimulated motility in keratinocytes, but TGFβ and αFGF again had no effect. Developing a better understanding of the interdependency of factors that control crucial cell behaviour may assist those who are interested in the regulation of histogenesis and also inform the development of rational therapeutic strategies for the management of chronic and poorly healed wounds. PMID:16011545

  3. Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects.

    PubMed

    Luo, Xiaoji; Chen, Jin; Song, Wen-Xin; Tang, Ni; Luo, Jinyong; Deng, Zhong-Liang; Sharff, Katie A; He, Gary; Bi, Yang; He, Bai-Cheng; Bennett, Erwin; Huang, Jiayi; Kang, Quan; Jiang, Wei; Su, Yuxi; Zhu, Gao-Hui; Yin, Hong; He, Yun; Wang, Yi; Souris, Jeffrey S; Chen, Liang; Zuo, Guo-Wei; Montag, Anthony G; Reid, Russell R; Haydon, Rex C; Luu, Hue H; He, Tong-Chuan

    2008-12-01

    Osteosarcoma (OS) is the most common primary malignancy of bone. Here, we investigated a possible role of defective osteoblast differentiation in OS tumorigenesis. We found that basal levels of the early osteogenic marker alkaline phosphatase (ALP) activity were low in OS lines. Osteogenic regulators Runx2 and OSX, and the late marker osteopontin (OPN) expressed at low levels in most OS lines, indicating that most OS cells fail to undergo terminal differentiation. Furthermore, OS cells were refractory to osteogenic BMP-induced increases in ALP activity. Osteogenic BMPs were shown to upregulate early target genes, but not late osteogenic markers OPN and osteocalcin (OC). Furthermore, osteogenic BMPs failed to induce bone formation from human OS cells, rather effectively promoted OS tumor growth in an orthotopic OS model. Exogenous expression of early target genes enhanced BMP-stimulated OS tumor growth, whereas osteogenic BMP-promoted OS tumor growth was inhibited by exogenous Runx2 expression. These results suggest that alterations in osteoprogenitors may disrupt osteogenic differentiation pathway. Thus, identifying potential differentiation defects in OS tumors would allow us to reconstruct the tumorigenic events in osteoprogenitors and to develop rational differentiation therapies for clinical OS management. PMID:18838962

  4. Effects of Foliar Fertilizer and Mepiquat Penteborate on Early Planted Cotton Growth and Lint Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multiple growth regulators and foliar fertilizers are currently marketed for use in cotton (Gossypium hirsutum L.) with varying effectiveness in promoting yield improvement. This research addressed the effectiveness of these products in a cotton early planting production system with its higher yiel...

  5. 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…

  6. Ultrastructure of Pseudomonas saccharophila at early and late log phase of growth.

    NASA Technical Reports Server (NTRS)

    Young, H. L.; Chao, F.-C.; Turnbill, C.; Philpott, D. E.

    1972-01-01

    Description of the fine structure of Pseudomonas saccarophila at the early log phase and the late log phase of growth, such as shown by electron microscopy with the aid of various techniques of preparation. The observations reported suggested that, under the experimental conditions applied, P. saccharophila multiplies by the method of constrictive division.

  7. 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…

  8. Growth hormone releasing factor-like immunoreactivity in human milk.

    PubMed

    Werner, H; Amarant, T; Fridkin, M; Koch, Y

    1986-03-28

    The presence of immunoreactive growth hormone-releasing factor (GRF) in human milk has been demonstrated. By using sequential high performance liquid chromatography, it has been shown that most of the immunoreactivity co-elutes with the synthetic, hypothalamic-like, GRF (1-40). The concentrations of GRF detected (between 152 and 432 pg GRF/ml milk) exceed several fold its values in plasma. PMID:3083812

  9. Network effects in a human capital based economic growth model

    NASA Astrophysics Data System (ADS)

    Vaz Martins, Teresa; Araújo, Tanya; Augusta Santos, Maria; St Aubyn, Miguel

    2009-06-01

    We revisit a recently introduced agent model [ACS, 11, 99 (2008)], where economic growth is a consequence of education (human capital formation) and innovation, and investigate the influence of the agents’ social network, both on an agent’s decision to pursue education and on the output of new ideas. Regular and random networks are considered. The results are compared with the predictions of a mean field (representative agent) model.

  10. Nerve growth factor levels and localisation in human asthmatic bronchi.

    PubMed

    Olgart Höglund, C; de Blay, F; Oster, J P; Duvernelle, C; Kassel, O; Pauli, G; Frossard, N

    2002-11-01

    Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo, and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from

  11. Growth and differentiation in cultured human thyroid cells: effects of epidermal growth factor and thyrotropin.

    PubMed

    Errick, J E; Ing, K W; Eggo, M C; Burrow, G N

    1986-01-01

    Human thyroid cells were grown and subcultured in vitro to examine their responses to known hormones and growth factors, and to serum. The cells were obtained from surgical specimens and were either neoplastic or nonneoplastic. The effects of culture conditions on cell growth were measured by changes in cell numbers and by stimulation of [3H]thymidine incorporation. The results showed that serum (0.5%) was essential for cell proliferation, and that a mixture of insulin (10 micrograms/ml), transferrin (5 micrograms/ml), hydrocortisone (10 micrograms/ml), somatostatin (10 ng/ml), and glycyl-histidyl-lysine (10 ng/ml) enhanced the effect of serum. Maximum growth of the cells was obtained when epidermal growth factor was present at 10(-9) M. Differentiation was measured by production of thyroglobulin, which was found to be stimulated by thyrotropin. This system provides a means to study the hormonal control of growth and differentiation in human thyroid cells. PMID:3511027

  12. Immunolocalisation of vascular endothelial growth factor (VEGF) in human neonatal growth plate cartilage

    PubMed Central

    HORNER, A.; BISHOP, N. J.; BORD, S.; BEETON, C.; KELSALL, A. W.; COLEMAN, N.; COMPSTON, J. E.

    1999-01-01

    Angiogenesis is essential for the replacement of cartilage by bone during growth and repair. In order to obtain a better understanding of the mechanisms regulating vascular invasion at sites of endochondral ossification we have investigated the expression of the endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), by chondrocytes in human neonatal growth plates. VEGF was absent from chondrocytes in the resting zone and only weakly expressed by occasional chondrocytes in the proliferating region. In the hypertrophic zone the number of chondrocytes stained and the intensity of staining for VEGF increased with chondrocyte hypertrophy, maximum expression of VEGF being observed in chondrocytes in the lower hypertrophic and mineralised regions of the cartilage. These observations provide the first demonstration of the presence of VEGF in situ in developing human bone and are consistent with in vitro observations demonstrating the upregulation of proangiogenic growth factor production with increasing chondrocyte hypertrophy. The presence of numerous small blood vessels and vascular structures in the subchondral region where VEGF expression was maximal indicates that VEGF produced by hypertrophic chondrocytes may play a key role in the regulation of vascular invasion of the growth plate. PMID:10445820

  13. 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

  14. Prolonged cyclic strain inhibits human endothelial cell growth.

    PubMed

    Peyton, Kelly J; Liu, Xiao-ming; Durante, William

    2016-01-01

    The vascular endothelium is continuously exposed to cyclic mechanical strain due to the periodic change in vessel diameter as a result of pulsatile blood flow. Since emerging evidence indicates the cyclic strain plays an integral role in regulating endothelial cell function, the present study determined whether application of a physiologic regimen of cyclic strain (6% at 1 hertz) influences the proliferation of human arterial endothelial cells. Prolonged exposure of human dermal microvascular or human aortic endothelial cells to cyclic strain for up to 7 days resulted in a marked decrease in cell growth. The strain-mediated anti-proliferative effect was associated with the arrest of endothelial cells in the G2/M phase of the cell cycle, did not involve cell detachment or cytotoxicity, and was due to the induction of p21. Interestingly, the inhibition in endothelial cell growth was independent of the strain regimen since prolonged application of constant or intermittent 6% strain was also able to block endothelial cell proliferation. The ability of chronic physiologic cyclic strain to inhibit endothelial cell growth represents a previously unrecognized mechanism by which hemodynamic forces maintain these cells in a quiescent, non-proliferative state. PMID:26709656

  15. Newborn human skin fibroblasts senesce in vitro without acquiring adult growth factor requirements

    SciTech Connect

    Wharton, W.

    1984-01-01

    Cultures of human fibroblasts were prepared from chest skin obtained either from newborns (less than 3 months old) or adults (more than 35 years old) and maintained in vitro until they senesced. Adult cells grew logarithmically in medium supplemented with whole blood serum but not with platelet-poor plasma. Early passage cells obtained from newborns grew equally well in either plasma- or serum-supplemented medium. The difference in growth factor requirements between adult and newborn cells persisted through the lifespan of the cells; i.e., newborn cells did not develop adult hormonal requirements when maintained in culture. Thus, in vitro cellular aging can be distinguished from some types of differentiation.

  16. 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

  17. The relationship between early growth and survival of hatchling saltwater crocodiles (Crocodylus porosus) in captivity.

    PubMed

    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

  18. Ultrastructural study on human placenta from intrauterine growth retardation cases.

    PubMed

    Battistelli, Michela; Burattini, Sabrina; Pomini, Francesco; Scavo, Maria; Caruso, Alessandro; Falcieri, Elisabetta

    2004-10-01

    A morphological study was performed on 27 human placentas from normal gestations (Group 1) and compared with those from eight cases of intrauterine growth restriction (IUGR) (Group 2). Semithin section light microscopy, transmission, and scanning electron microscopy were carried out on trophoblastic terminal villi, carefully identified under the stereomicroscope. In growth retardation cases, villi appear longer, thinner, and less vascularized, compared to the normal condition. Fibrinoid, an extracellular material of hematic origin, frequently fills villar stroma. The density of apical microvilli appears considerably reduced and occasional microvilli-free areas are observed in growth retardation cases. Moreover, the underlying basal membrane appears significantly thicker than that of normal syncytiotrophoblast. Recently, particular attention has been paid to apoptosis as a possible cell deletion mechanism in growth restriction. In our study, a majority of typical apoptotic features appear indifferently in both IUGR and normal pregnancy. Our data hints that growth retardation might be correlated with a complex of structural changes, suggestive of maternofetal traffic downregulation, but further studies are required to understand the underlying functional mechanisms. PMID:15605416

  19. 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 (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. PMID:26270988

  20. 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. PMID:26270988

  1. The Human Early-Life Exposome (HELIX): Project Rationale and Design

    PubMed Central

    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; Gražulevicˇiene˙, 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.

    2014-01-01

    Background: 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. Objectives: 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. Methods: 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. Conclusions: 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. Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P

  2. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF)

    PubMed Central

    He, Yonghua; Schmidt, Monica A.; Erwin, Christopher; Guo, Jun; Sun, Raphael; Pendarvis, Ken; Warner, Brad W.; Herman, Eliot M.

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. PMID:27314851

  3. Effects of Selenium Yeast on Oxidative Stress, Growth Inhibition, and Apoptosis in Human Breast Cancer Cells.

    PubMed

    Guo, Chih-Hung; Hsia, Simon; Shih, Min-Yi; Hsieh, Fang-Chin; Chen, Pei-Chung

    2015-01-01

    Recent evidence suggests that selenium (Se) yeast may exhibit potential anti-cancer properties; whereas the precise mechanisms remain unknown. The present study was aimed at evaluating the effects of Se yeast on oxidative stress, growth inhibition, and apoptosis in human breast cancer cells. Treatments of ER-positive MCF-7 and triple-negative MDA-MB-231 cells with Se yeast (100, 750, and 1500 ng Se/mL), methylseleninic acid (MSA, 1500 ng Se/mL), or methylselenocysteine (MSC, 1500 ng Se/mL) at a time course experiment (at 24, 48, 72, and 96 h) were analyzed. Se yeast inhibited the growth of these cancer cells in a dose- and time-dependent manner. Compared with the same level of MSA, cancer cells exposure to Se yeast exhibited a lower growth-inhibitory response. The latter has also lower superoxide production and reduced antioxidant enzyme activities. Furthermore, MSA (1500 ng Se/mL)-exposed non-tumorigenic human mammary epithelial cells (HMEC) have a significant growth inhibitory effect, but not Se yeast and MSC. Compared with MSA, Se yeast resulted in a greater increase in the early apoptosis in MCF-7 cells as well as a lower proportion of early and late apoptosis in MDA-MB-231 cells. In addition, nuclear morphological changes and loss of mitochondrial membrane potential were observed. In conclusion, a dose of 100 to 1500 ng Se/mL of Se yeast can increase oxidative stress, and stimulate growth inhibitory effects and apoptosis induction in breast cancer cell lines, but does not affect non-tumorigenic cells. PMID:26392813

  4. 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

  5. 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

  6. Composite growth model applied to human oral and pharyngeal structures and identifying the contribution of growth types.

    PubMed

    Wang, Yuan; Chung, Moo K; Vorperian, Houri K

    2013-11-13

    The growth patterns of different anatomic structures in the human body vary in terms of growth amount over time, growth rate and growth periods. The oral and pharyngeal structures, also known as vocal tract structures, are housed in the craniofacial complex where the cranium/brain follows a distinct neural growth pattern, and the face follows a distinct somatic or skeletal growth pattern. Thus, it is reasonable to expect the oral and pharyngeal structures to follow a combined or mixed growth pattern. Existing parametric growth models are limited in that they are mainly focused on modeling one particular type of growth pattern. In this paper, we propose a novel composite growth model using neural and somatic baseline curves to fit the combined growth pattern of select vocal tract structures. The method can also determine the overall percent contribution of each of the growth types. PMID:24226094

  7. Composite Growth Model Applied to Human Oral and Pharyngeal Structures and Identifying the Contribution of Growth Types

    PubMed Central

    Wang, Yuan; Chung, Moo K.; Vorperian, Houri K.

    2014-01-01

    The growth patterns of different anatomic structures in the human body vary in terms of growth amount over time, growth rate and growth periods. The oral and pharyngeal structures, also known as vocal tract structures, are housed in the craniofacial complex where the cranium/brain follows a distinct neural growth pattern, and the face follows a distinct somatic or skeletal growth pattern. Thus, it is reasonable to expect the oral and pharyngeal structures to follow a combined or mixed growth pattern. Existing parametric growth models are limited in that they are mainly focused on modeling one particular type of growth pattern. In this paper, we propose a novel composite growth model using neural and somatic baseline curves to fit the combined growth pattern of select vocal tract structures. The method can also determine the overall percent contribution of each of the growth types. PMID:24226094

  8. Early Zinc Supplementation and Enhanced Growth of the Low-Birth Weight Neonate

    PubMed Central

    El-Farghali, Ola; El-Wahed, Mohamed Abd; Hassan, Nayera E.; Imam, Safaa; Alian, Khadija

    2014-01-01

    BACKGROUND: Nutritional deficits are almost universal in Low-Birth Weight babies. Zinc is essential for normal infant growth and its supplementation assists growth probably through insulin-like growth factor-1. AIM: This double-blind randomized-controlled trial aimed at evaluating the role of zinc in catch-up growth of low-birth-weight infants and investigating its proposed mediator. MATERIAL AND METHODS: The study was conducted in Ain Shams University Maternity Hospital. Two hundred low-birth-weight neonates were simply randomized to either oral zinc therapy or placebo. Anthropometric measurements were recorded at birth, 3, 6, and 12 months; including weight, recumbent length, head, waist, chest, and mid-upper arm circumferences, and triceps and sub-scapular skin fold thickness. RESULTS: We found that initial and 3-months measurements, except weight, were comparable in the 2 groups. All measurements at 6- and 12-months, except sub-scapular skin-fold-thickness, were significantly higher in zinc group than placebo. Catch-up growth, at 12-months, was significant in zinc group and was significantly higher in appropriate-for-gestational-age vs. small-for-gestational-age, in preterm vs. term, and in male vs. female infants. The median 6-months insulin-like growth factor-1 levels were significantly higher in zinc group. CONCLUSION: We conclude that early start of oral zinc supplementation in low-birth-weight neonates assists catch-up growth, probably through rise of insulin-like growth factor-1.

  9. Net Photosynthesis and Early Growth Trends of a Dominant White Oak (Quercus alba L.) 1

    PubMed Central

    Dougherty, Phillip M.; Teskey, Robert O.; Phelps, John E.; Hinckley, Thomas M.

    1979-01-01

    Examination of the relationship between photosynthesis and growth of a dominant white oak (Quercus alba L.) tree has shown that most growth processes were either completed or well underway before the establishment of significant positive rates of net photosynthesis. Growth was initiated first in the root system (March 3), followed by stem cambial growth (March 26) and later by flower, leaf, and branch growth (April 10). During the period of rapid leaf and branch growth, root and cambial growth ceased and then resumed as the leaves approached maturity. The rapid rate of leaf maturation, the early appearance of positive rates of net photosynthesis in leaves (15% of final size) and the CO2-refixing capability of elongating branch tissue reduced the period of time that this white oak tree was dependent on stored reserves. Lower temperature optima and compensation points in developing leaves and stems indicated that the growth-temperature response was optimized for the lower seasonal temperatures observed during the spring. This temperature adaptation further reduced the time that this tree was dependent on stored reserves. Images PMID:16661108

  10. Early literacy individual growth and development indicators (EL-IGDIs): growth trajectories using a large, internet-based sample.

    PubMed

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

    2012-08-01

    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 achievement delays. There were three major findings. First, results identified sensitivity to longitudinal change for all three EL-IGDIs (i.e., Picture naming, Rhyming, and Alliteration). Second, results demonstrated age-related differences in growth rates between 3- and 4-year-olds, especially for Rhyming and Alliteration. Third, preliminary national norms were reported. Discussion highlights the need for research examining the sensitivity of EL-IGDIs for younger preschoolers. PMID:22710017

  11. Rat embryo fibroblast cells expressing human papillomavirus 1a genes exhibit altered growth properties and tumorigenicity.

    PubMed Central

    Green, M; Brackmann, K H; Loewenstein, P M

    1986-01-01

    Human papillomavirus 1a (HPV1a) induces benign tumors (papillomas or warts) in humans under natural conditions of infection but has not been found to replicate significantly in cell culture or in experimental animals. To establish model systems to study the oncogenic properties and expression of HPV genes, we established cell lines by cotransfecting the 3Y1 rat fibroblast cell line with HPV1a DNA constructs containing an intact early gene region and the Tn5 neomycin resistance gene. Most cell lines selected for expression of the neomycin resistance gene by treatment with the antibiotic G-418 contained viral DNA in a high-molecular-weight form. The growth characteristics of several cell lines containing high copy numbers of HPV1a DNA were studied further. They were shown to differ from the parental cell line and from G-418-resistant cell lines that did not incorporate viral DNA in the following properties: morphological alteration, increased cell density at confluence, growth in 0.5% serum, efficient anchorage-independent growth in soft agar, and rapid formation of tumors in nude mice. Those cell lines that possessed altered growth properties and tumorigenicity were found to express abundant quantities of polyadenylated virus-specific RNA species in the cytoplasm. Images PMID:3023676

  12. Early Detection, Referral, Investigation, and Diagnosis of Children with Growth Disorders.

    PubMed

    Savage, Martin O; Backeljauw, Philippe F; Calzada, Raúl; Cianfarani, Stefano; Dunkel, Leo; Koledova, Ekaterina; Wit, Jan M; Yoo, Han-Wook

    2016-01-01

    Early diagnosis is a key objective in clinical medicine, and early detection of pathological short stature has tangible benefits for growth prognosis and the well-being of the child. Despite late diagnosis being common in growth disorders, programmes of height screening in primary care are not universal in developed countries and may be random or non-existent. A notable exception is automated growth monitoring in Finland, where an algorithm to detect abnormal growth is integrated into children's electronic health records, resulting in increased diagnoses of pathological short stature. Evidence-based anthropometric criteria for referral of short stature to secondary or tertiary care are now published, due largely to excellent studies in the Netherlands. Following referral of the short child, the protocol for laboratory investigations remains somewhat controversial because in healthy children their diagnostic yield can be too low for cost-effectiveness. However, outside of tertiary academic paediatric endocrinology centres, baseline screening tests are considered worthwhile and may speed up diagnosis and treatment. Finally, auxological cut-offs cannot replace good clinical practice, and the understanding that early and effective management depends on commitment to a diagnosis and individualisation of therapy in the short child cannot be overemphasised. PMID:27055026

  13. Resting state functional connectivity in early blind humans

    PubMed Central

    Burton, Harold; Snyder, Abraham Z.; Raichle, Marcus E.

    2014-01-01

    Task-based neuroimaging studies in early blind humans (EB) have demonstrated heightened visual cortex responses to non-visual paradigms. Several prior functional connectivity studies in EB have shown altered connections consistent with these task-based results. But these studies generally did not consider behavioral adaptations to lifelong blindness typically observed in EB. Enhanced cognitive abilities shown in EB include greater serial recall and attention to memory. Here, we address the question of the extent to which brain intrinsic activity in EB reflects such adaptations. We performed a resting-state functional magnetic resonance imaging study contrasting 14 EB with 14 age/gender matched normally sighted controls (NS). A principal finding was markedly greater functional connectivity in EB between visual cortex and regions typically associated with memory and cognitive control of attention. In contrast, correlations between visual cortex and non-deprived sensory cortices were significantly lower in EB. Thus, the available data, including that obtained in prior task-based and resting state fMRI studies, as well as the present results, indicate that visual cortex in EB becomes more heavily incorporated into functional systems instantiating episodic recall and attention to non-visual events. Moreover, EB appear to show a reduction in interactions between visual and non-deprived sensory cortices, possibly reflecting suppression of inter-sensory distracting activity. PMID:24778608

  14. Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells

    PubMed Central

    Pook, Martin; Teino, Indrek; Kallas, Ade; Maimets, Toivo; Ingerpuu, Sulev; Jaks, Viljar

    2015-01-01

    Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain—145 kDa—accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation. PMID:26378917

  15. Production of human epidermal growth factor using adenoviral based system

    PubMed Central

    Negahdari, Babak; Shahosseini, Zahra; Baniasadi, Vahid

    2016-01-01

    Epidermal growth factor (EGF), a growth factor involved in cell growth and differentiation, is a small polypeptide with molecular weight of approximately 6 kDa known to be present in a number of different mammalian species. Experimental studies in animals and humans have demonstrated that the topical application of EGF accelerates the rate of epidermal regeneration of partial-thickness wounds and second-degree burns. Due to its commercial applications, Human EGF (hEGF) has been cloned in several forms. In the present study, adenoviral based expression system was used to produce biologically active recombinant hEGF. The presence of secreted recombinant hEGF was confirmed by a dot blot and its expression level was determined by enzyme-linked immuno-sorbent assay. Moreover, biological activity of secreted hEGF was evaluated by a proliferation assay performed on A549 cells. For production of hEGF in a secretory form, a chimeric gene coding for the hEGF fused to the signal peptide was expressed using adenoviral based method. This method enables the production of hEGF at the site of interest and moreover it could be used for cell proliferation and differentiation assays in tissue engineering research experiments instead of using commercially available EGF. PMID:27051431

  16. 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

  17. Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

    SciTech Connect

    Tao, Jun; Xiang, Jun-Jian; Li, Dan; Deng, Ning; Wang, Hong; Gong, Yi-Ping

    2010-04-09

    Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10{sup -9} M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

  18. Calcium oxalate crystal growth in human urinary stones

    SciTech Connect

    Kim, K.M.; Johnson, F.B.

    1981-01-01

    Calcium oxalate stones are very common and increasing. Crystal growth is no less important than the crystal nucleation in the pathogenesis of stone formation. The crystal growth was studied in human calcium oxalate stones by a combined electron microscopy and x-ray diffraction. The main mode of weddellite growth was interpenetration twinning of tetrahedral bipyramids. Bipyramids may form as initial crystal seeds, develop from anhedral crystals (crystals which lack flat symmetric faces) of spherular or mulberry shape, develop on the surface of preformed bipyramids by spiral dislocation mechanisms, or develop on whewellite crystal by heterogeneous nucleation and epitaxy. Heterogeneous nucleations of whewellite on weddellite, and calcium apatite on whewellite were also observed. Whewellite grew mainly by parallel twinning. Interpenetration twinning was exceptional. Transformation of anhedral to euhedral (completely bounded by flat faces that are set ar fixed angles to one another) whewellite occurred by parallel fissurations followed by brick wall like stacking of the crystals, while euhedral transformation of weddellite occurred by protrusion of bipyramids frm anhedral crystal surface. Occasionally, an evidence of crystal dissolution was noted. Although an aggregation of crystals is believed to play a pivotal role in stone nidus formation, growth in size of the formed crystals, and twinning and epitactic crystal intergrowth apparently play a significant role in the obstructive urinary stone formation.

  19. Early growth response protein 1 acts as an activator of SOX18 promoter

    PubMed Central

    Petrovic, Isidora; Kovacevic-Grujicic, Natasa

    2010-01-01

    Sex-determining region Y box 18 (Sox18/SOX18) gene is an important regulator of vascular development playing a role in endothelial cell specification or differentiation, angiogenesis and atherogenesis. The aim of this study was to perform comprehensive functional characterization of the human SOX18 promoter, including determination of transcription start point (tsp) and identification of control elements involved in the regulation of SOX18 gene expression, with an emphasis on angiogenesis-related transcription factors. Analyses were performed in HeLa cells, representing a tumor cell line, and in EA.hy926 cells used as an endothelial model system. We have determined unique tsp of SOX18 gene, located 172 nucleotides upstream from ATG codon. Further, we have shown that SOX18 promoter region, -726 to -89 bp relative to tsp, contains positive cis-regulatory element(s) that stimulates SOX18 promoter activity, while region -89 to + 166 represents the minimal promoter. Within this region we have recognized the presence of essential element(s), positioned from -89 to +29, which harbors cluster of three putative early growth response 1 (EGR1) binding sites. By in vitro binding assays and functional analyses we have shown that these three putative binding sites are functionally relevant and sufficient for EGR1-induced SOX18 transcription. Mutations of these binding sites significantly impaired activity of the SOX18 promoter, particularly in EA.hy926 cells, indicating the importance of these regulatory elements for SOX18 promoter activity in endothelial setting. By data presented in this study, we have established SOX18 as a novel target gene regulated by EGR1 transcription factor, thus providing the first functional link between two transcription factors previously shown to be involved in the control of angiogenesis. PMID:20054233

  20. Nordihydroguaiaretic Acid Inhibits Insulin-Like Growth Factor Signaling, Growth, and Survival in Human Neuroblastoma Cells

    PubMed Central

    Meyer, Gary E.; Chesler, Louis; Liu, Dandan; Gable, Karissa; Maddux, Betty A.; Goldenberg, David D.; Youngren, Jack F.; Goldfine, Ira D.; Weiss, William A.; Matthay, Katherine K.; Rosenthal, Stephen M.

    2010-01-01

    Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin-like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP-AEW541, a specific inhibitor of the IGF-I receptor (IGF-IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti-tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF-IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling. PMID:17486636

  1. Early development and allometric growth patterns of the grumatã (Prochilodus vimboides Kner, 1859).

    PubMed

    Souza, Guilherme; Melo, Edésio J T; Caramaschi, Erica P; Andrade, Dalcio R; Monteiro, Leandro R

    2016-06-01

    The objective of this study was to characterize the early development and allometric growth of the grumatã (Prochilodus vimboides). We describe a sample of 266 eggs and larvae obtained through induced spawning. The eggs were spherical (mean 3.7 mm diameter), exhibited a yellow yolk and were non-adhesive and pelagic after fertilization and hydration. The time elapsed between the early cleavage and post-flexion stages was considered short (328 hours, 8054 hour-degrees) in regard to the development times of other Neotropical rheophilic species, but time to hatching was considerably longer than in other Prochilodus species. The most notable anatomical changes were observed between the end of the yolk larval stage and the beginning of the pre-flexion stage, when the larvae displayed directed swimming and the digestive system became functional, enabling the transition from endogenous to exogenous feeding. After hatching, the larvae grew from 6.04 to 15.15 mm in total length average. Two growth phases were observed at this stage: a non-linear asymptotic curve in yolk-sac larvae, and a linear constant-rate growth phase after exogenous feeding started. Allometric growth related to standard length was positive for head length, negative for eye diameter, and switched between phases from negative to positive in body depth and head height. Morphological development and allometric growth in different larval phases impose drastic anatomical and physiological changes that are synchronic with habitat changes and the flood cycles during the reproductive period. PMID:26199146

  2. A global search reveals epistatic interaction between QTL for early growth in the chicken.

    PubMed

    Carlborg, Orjan; Kerje, Susanne; Schütz, Karin; Jacobsson, Lina; Jensen, Per; Andersson, Leif

    2003-03-01

    We have identified quantitative trait loci (QTL) explaining a large proportion of the variation in body weights at different ages and growth between chronological ages in an F(2) intercross between red junglefowl and White Leghorn chickens. QTL were mapped using forward selection for loci with significant marginal genetic effects and with a simultaneous search for epistatic QTL pairs. We found 22 significant loci contributing to these traits, nine of these were only found by the simultaneous two-dimensional search, which demonstrates the power of this approach for detecting loci affecting complex traits. We have also estimated the relative contribution of additive, dominance, and epistasis effects to growth and the contribution of epistasis was more pronounced prior to 46 days of age, whereas additive genetic effects explained the major portion of the genetic variance later in life. Several of the detected loci affected either early or late growth but not both. Very few loci affected the entire growth process, which points out that early and late growth, at least to some extent, have different genetic regulation. PMID:12618372

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

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.

    1984-01-01

    A multiphase study was conducted to examine the properties of growth hormone cells. Topics investigated included: (1) to determine if growth hormone (GH) cells contained within the rat pituitary gland can be separated from the other hormone producing cell types by continuous flow electrophoresis (CFE); (2) to determine what role, if any, gravity plays in the electrophoretic separation of GH cells; (3) to compare in vitro GH release from rat pituitary cells previously exposed to microgravity conditions vs release from cells not exposed to microgravity; (4) to determine if the frequency of different hormone producing pituitary cell types contained in cell suspensions can be quantitated by flow cytometry; and (5) to determine if GH contained within the human post mortem pituitary gland can be purified by CFE. Specific experimental procedures and results are included.

  4. 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

  5. Predictors of early growth in academic achievement: the head-toes-knees-shoulders task.

    PubMed

    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

  6. 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. PMID:19845874

  7. AMPK regulation of the growth of cultured human keratinocytes

    SciTech Connect

    Saha, Asish K. . E-mail: aksaha@bu.edu; Persons, Kelly; Safer, Joshua D.; Luo Zhijun; Holick, Michael F.; Ruderman, Neil B.

    2006-10-20

    AMP kinase (AMPK) is a fuel sensing enzyme that responds to cellular energy depletion by increasing processes that generate ATP and inhibiting others that require ATP but are not acutely necessary for survival. In the present study, we examined the relationship between AMPK activation and the growth (proliferation) of cultured human keratinocytes and assessed whether the inhibition of keratinocyte growth by vitamin D involves AMPK activation. In addition, we explored whether the inhibition of keratinocyte proliferation as they approach confluence could be AMPK-related. Keratinocytes were incubated for 12 h with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-{beta}-D-ribofuranoside (AICAR). At concentrations of 10{sup -4} and 10{sup -3} M, AICAR inhibited keratinocyte growth by 50% and 95%, respectively, based on measurements of thymidine incorporation into DNA. It also increased AMPK and acetyl CoA carboxylase phosphorylation (P-AMPK and P-ACC) and decreased the concentration of malonyl CoA confirming that AMPK activation had occurred. Incubation with the thiazolidinedione, troglitazone (10{sup -6} M) caused similar alterations in P-AMPK, P-ACC, and cell growth. In contrast, the well known inhibition of keratinocyte growth by 1,25-dihydroxyvitamin D{sub 3} (10{sup -7} and 10{sup -6} M) was not associated with changes in P-AMPK or P-ACC. Like most cells, the growth of keratinocytes diminished as they approached confluence. Thus, it was of note that we found a progressive increase in P-AMPK (1.5- to 2-fold, p < 0.05) as keratinocytes grown in control medium went from 25% to 100% confluence. In conclusion, the data are consistent with the hypothesis that activation of AMPK acts as a signal to diminish the proliferation of cultured keratinocytes as they approach confluence. They also suggest that AMPK activators, such as AICAR and troglitazone, inhibit keratinocyte growth and that the inhibition of cell growth by 1,25-dihydroxyvitamin D{sub 3} is AMPK-independent.

  8. Perspective: Proteomic approach to detect biomarkers of human growth hormone

    PubMed Central

    Ding, Juan; List, Edward O.; Okada, Shigeru; Kopchick, John J.

    2009-01-01

    Several serum biomarkers for recombinant human growth hormone (rhGH) have been established, however, none alone or in combination have generate a specific, sensitive, and reproducible ‘kit’ for the detection of rhGH abuse. Thus, the search for additional GH specific biomarkers continues. In this review, we focus on the use of proteomics in general and 2-dimensional electrophoresis (2-DE) in particular for the discovery of new GH induced serum biomarkers. Also, we review some of the protocols involved in 2DE. Finally, the possibility of tissues other than blood for biomarker discovery is discussed. PMID:19501004

  9. On the growth and internal structure of the human lens

    PubMed Central

    Augusteyn, Robert C

    2010-01-01

    Growth of the human lens and the development of its internal features are examined using in vivo and in vitro observations on dimensions, weights, cell sizes, protein gradients and other properties. In vitro studies have shown that human lens growth is biphasic, asymptotic until just after birth and linear for most of postnatal life. This generates two distinct compartments, the prenatal and the postnatal. The prenatal growth mode leads to the formation of an adult nuclear core of fixed dimensions and the postnatal, to an ever-expanding cortex. The nuclear core and the cortex have different properties and can readily be physically separated. Communication and adhesion between the compartments is poor in older lenses. In vivo slit lamp examination reveals several zones of optical discontinuity in the lens. Different nomenclatures have been used to describe these, with the most common recognizing the embryonic, foetal, juvenile and adult nuclei as well as the cortex and outer cortex. Implicit in this nomenclature is the idea that the nuclear zones were generated at defined periods of development and growth. This review examines the relationship between the two compartments observed in vitro and the internal structures revealed by slit lamp photography. Defining the relationship is not as simple as it might seem because of remodeling and cell compaction which take place, mostly in the first 20 years of postnatal life. In addition, different investigators use different nomenclatures when describing the same regions of the lens. From a consideration of the dimensions, the dry mass contents and the protein distributions in the lens and in the various zones, it can be concluded that the juvenile nucleus and the layers contained within it, as well as most of the adult nucleus, were actually produced during prenatal life and the adult nucleus was completed within 3 months after birth, in the final stages of the prenatal growth mode. Further postnatal growth takes place

  10. Growth performance of early-weaned pigs is enhanced by feeding epidermal growth factor-expressing Lactococcus lactis fermentation product.

    PubMed

    Bedford, Andrea; Huynh, Evanna; Fu, Molei; Zhu, Cuilan; Wey, Doug; de Lange, Cornelis; Li, Julang

    2014-03-10

    We have previously generated epidermal growth factor expressing Lactococcus lactis (EGF-LL) using bioengineering approach, and shown that feeding newly-weaned piglets EGF-LL improves digestive function. To address concerns over the use of genetically modified organisms (GMO), the objective of the current study was to investigate the effect of feeding the EGF-LL fermentation product, after removal of the genetically modified EGF-LL, on growth performance and intestine development of newly-weaned piglets. One hundred and twenty newly-weaned piglets were fed ad libitum according to a 2-phase feeding program. Four pens were assigned to each of three treatments: (1) complete EGF-LL fermentation product (Ferm), (2) supernatant of EGF-LL fermentation product, after removal of EGF-LL (Supern), or (3) blank M17GE media (Control). EGF-LL or its fermented supernatant was administrated to piglets in the first 3 weeks post-weaning; their growth performance was monitored throughout treatment, and for the following week. Daily body weight gain (254.8g vs. 200.5g) and Gain:Feed (0.541kg/kg vs. 0.454kg/kg) of pigs on the Supern group were significantly improved compared to that of Control, although no difference was observed between the Ferm and Control pigs. Intestinal sucrase activity was increased in Supern- compared to Control group (166.3±62.1 vs. 81.4±56.5nmol glucose released/mg protein; P<0.05). The lack of growth response with Ferm pigs may be attributed to an overload of bacteria (daily dose included 4.56×10(10)CFU/kg BW/day EGF-LL). These results suggest that GMO-free EGF-LL fermentation product is effective in increasing growth performance of early-weaned piglets. PMID:24445174

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  12. 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…

  13. 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…

  14. Early Human Occupation on the Northeast Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Rhode, D.; Madsen, D.; Brantingham, P.; Perrault, C.

    2010-12-01

    The Tibetan Plateau presents great challenges for human occupation: low oxygen, high ultraviolet radiation, harsh seasonal climate, low overall biological productivity. How and when early humans were able to cope physiologically, genetically, and behaviorally with these extremes is important for understanding the history of human adaptive flexibility. Our investigations of prehistoric human settlement on the northeast Tibetan Plateau focus on (a) establishing well-dated evidence for occupation of altitudes >3000 m, (b) the environmental context of high altitude adaptation, and (c) relations of hunting and pastoralism to lower-altitude agrarian systems. We observe two major prehistoric settlement patterns in the Qinghai Lake area. The earliest, ~15,000-7500 yr old, consists of small isolated firehearths with sparse associated stone tools and wild mammal remains (1). Numerous hearths often occur in the same localities, indicating repeated short-duration occupations by small hunting parties. A second pattern, ~9000-4000 yr old, was established during the Holocene climatic optimum. These sites represent prolonged seasonal residential occupation, containing dark anthropogenic midden, hearth and pit constructions, abundant stone tools, occasional ceramics, and abundant diverse faunal remains (including medium-large mammals but lacking domestic sheep/yak)(2). These Plateau-margin base camps allowed greater intensity of use of the high Plateau. Residential occupation was strongly influenced by nearby lower-altitude farming communities; development of the socioeconomic landscape along the Yellow River likely played at least as great a role in Plateau occupation patterns as did Holocene environmental changes. Holocene vegetation changes in the NE Tibetan Plateau have been attributed to climate (3) or anthropogenic modification (4). Our results document changes in shrub/tree presence from ~12,000-4000 BP, similar to pollen records, that likely reflect climate rather than

  15. Autophagy in human keratinocytes: an early step of the differentiation?

    PubMed

    Aymard, Elodie; Barruche, Vincent; Naves, Thomas; Bordes, Sylvie; Closs, Brigitte; Verdier, Mireille; Ratinaud, Marie-Hélène

    2011-03-01

    Studies have established that autophagy constitutes an efficient process to recycle cellular components and certain proteins. The phenomenon was demonstrated primarily in response to nutrient starvation, and there are increasing evidences that it is implied in differentiation. Keratinocyte differentiation was going along an activation of lysosomal enzymes and organelle clearance, and terminal steps are sometimes described as a specialized form of cell death leading to corneocytes. We examined whether initiation of the process in human keratinocyte HaCaT involves autophagy. The KSFM™ culture medium was substituted by M199, which contains a low glucose concentration but a high calcium level (known to induce differentiation). Metabolic stress reduced enhanced cell number in G(1) phase, without apoptotic features (ΔΨmt and membrane integrity are unchanged). Morphological changes were associated with a lower integrin ß1 expression and modifications of protein levels involved in keratinocyte differentiation (involucrin, keratin K10 and ΔNp63α). Whereas autophagic signalling was supported by SIRT1 and pAMPK (T172) increase according to time kinetic, which led to the disappearance of mTOR phosphorylated on S2448 residue. The significant Bcl-X(L) level reduction with stress promoted autophagy, by the release of Beclin-1, whereas ATG5-ATG12 and LC3-II that are involved in autophagosome formation were enhanced significantly. Then, the level of lysosomal protein cathepsin B rose to execute autophagy. Kinetic studies established that autophagy would constitute an early signalling process required for keratinocyte commitment in differentiation pathway. PMID:21166723

  16. 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…

  17. 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.…

  18. 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

  19. Spermidine Promotes Human Hair Growth and Is a Novel Modulator of Human Epithelial Stem Cell Functions

    PubMed Central

    Bíró, Tamás; Abu Bakar, Mohd Hilmi; Sugawara, Koji; Philpott, Michael P.; Harrison, Wesley; Pietilä, Marko; Paus, Ralf

    2011-01-01

    Background Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF) is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown. Methods and Findings We have studied the effects of the prototypic polyamine, spermidine (0.1–1 µM), on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth (anagen). Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase (ODC), downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S/G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration (POP3), or endoplasmic reticulum and mitochondrial functions (SYVN1, NACA and SLC25A3). Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF's companion layer in situ. Conclusions These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology. PMID:21818338

  20. Angiogenin expression during early human placental development; association with blood vessel formation.

    PubMed

    Pavlov, Nadine; Frendo, Jean-Louis; Guibourdenche, Jean; Degrelle, Séverine A; Evain-Brion, Danièle; Badet, Josette

    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

  1. Targeting the opioid growth factor: opioid growth factor receptor axis for treatment of human ovarian cancer.

    PubMed

    Zagon, Ian S; Donahue, Renee; McLaughlin, Patricia J

    2013-05-01

    The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a biological pathway that is present in human ovarian cancer cells and tissues. OGF, chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interfaces with OGFr to delay cells moving through the cell cycle by upregulation of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose dependent, receptor mediated, reversible, protein and RNA dependent, but not related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an opioid antagonist, which stimulates production of OGF and OGFr for subsequent interaction following blockade of the receptor. The OGF-OGFr axis may be a feasible target for treatment of cancer of the ovary (i) in a prophylactic fashion, (ii) following cytoreduction or (iii) in conjunction with standard chemotherapy for additive effectiveness. In summary, preclinical data support the transition of these novel therapies for treatment of human ovarian cancer from the bench to bedside to provide additional targets for treatment of this devastating disease. PMID:23856908

  2. 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.

  3. 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

  4. Iron, Human Growth, and the Global Epidemic of Obesity

    PubMed Central

    Sangani, Rahul G.; Ghio, Andrew J.

    2013-01-01

    Iron is an essential nutrient utilized in almost every aspect of cell function and its availability has previously limited life. Those same properties which allow iron to function as a catalyst in the reactions of life also present a threat via generation of oxygen-based free radicals. Accordingly; life exists at the interface of iron-deficiency and iron-sufficiency. We propose that: (1) human life is no longer positioned at the limits of iron availability following several decades of fortification and supplementation and there is now an overabundance of the metal among individuals of many societies; (2) this increased iron availability exerts a positive effect on growth by targeting molecules critical in regulating the progression of the cell cycle; there is increased growth in humans provided greater amounts of this metal; and indices of obesity can positively correlate with body stores of iron; and (3) diseases of obesity reflect this over-abundance of iron. Testing potential associations between iron availability and both obesity and obesity-related diseases in populations will be difficult since fortification and supplementation is so extensively practiced. PMID:24152754

  5. Adaptation to statins restricts human tumour growth in Nude mice

    PubMed Central

    2011-01-01

    Background Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. Methods HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. Results L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Conclusions Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years. PMID:22107808

  6. The effects of early time laser drive on hydrodynamic instability growth in National Ignition Facility implosions

    SciTech Connect

    Peterson, J. L.; Clark, D. S.; Suter, L. J.; Masse, L. P.

    2014-09-15

    Defects on inertial confinement fusion capsule surfaces can seed hydrodynamic instability growth and adversely affect capsule performance. The dynamics of shocks launched during the early period of x-ray driven National Ignition Facility (NIF) implosions determine whether perturbations will grow inward or outward at peak implosion velocity and final compression. In particular, the strength of the first shock, launched at the beginning of the laser pulse, plays an important role in determining Richtmyer-Meshkov (RM) oscillations on the ablation front. These surface oscillations can couple to the capsule interior through subsequent shocks before experiencing Rayleigh-Taylor (RT) growth. We compare radiation hydrodynamic simulations of NIF implosions to analytic theories of the ablative RM and RT instabilities to illustrate how early time laser strength can alter peak velocity growth. We develop a model that couples the RM and RT implosion phases and captures key features of full simulations. We also show how three key parameters can control the modal demarcation between outward and inward growth.

  7. Propagule size and predispersal damage by insects affect establishment and early growth of mangrove seedlings.

    PubMed

    Sousa, Wayne P; Kennedy, Peter G; Mitchell, Betsy J

    2003-05-01

    Variation in rates of seedling recruitment, growth, and survival can strongly influence the rate and course of forest regeneration following disturbance. Using a combination of field sampling and shadehouse experiments, we investigated the influence of propagule size and predispersal insect damage on the establishment and early growth of the three common mangrove species on the Caribbean coast of Panama: Avicennia germinans, Laguncularia racemosa, and Rhizophora mangle. In our field samples, all three species exhibited considerable intraspecific variation in mature propagule size, and suffered moderate to high levels of predispersal attack by larval insects. Rates of insect attack were largely independent of propagule size both within and among trees. Our experimental studies using undamaged mature propagules showed that, for all three species, seedlings established at high rates regardless of propagule size. However, propagule size did have a marked effect on early seedling growth: seedlings that developed from larger propagules grew more rapidly. Predispersal insect infestations that had destroyed or removed a substantial amount of tissue, particularly if that tissue was meristematic or conductive, reduced the establishment of propagules of all three species. The effect of sublethal tissue damage or loss on the subsequent growth of established seedlings varied among the three mangrove species. For Avicennia, the growth response was graded: for a propagule of a given size, the more tissue lost, the slower the growth of the seedling. For Laguncularia, the response to insect attack appeared to be all-or-none. If the boring insect penetrated the outer spongy seed coat and reached the developing embryo, it usually caused sufficient damage to prevent a seedling from developing. On the other hand, if the insect damaged but did not penetrate the seed coat, a completely healthy seedling developed and its growth rate was indistinguishable from a seedling developing from an

  8. Early Holocene human remains from the Argentinean Pampas: additional evidence for distinctive cranial morphology of early South Americans.

    PubMed

    Pucciarelli, Héctor M; Perez, S Ivan; Politis, Gustavo G

    2010-10-01

    The cranial morphology of Early Holocene American human samples is characterized by a long and narrow cranial vault, whereas more recent samples exhibit a shorter and wider cranial vault. Two hypotheses have been proposed to account for the morphological differences between early and late-American samples: (a) the migratory hypothesis that suggests that the morphological variation between early and late American samples was the result of a variable number of migratory waves; and (b) the local diversification hypothesis, that is, the morphological differences between early and late American samples were mainly generated by local, random (genetic drift), and nonrandom factors (selection and phenotypic plasticity). We present the first craniometric study of three early skulls from the Argentinean Pampas, dated ∼8,000 cal. years BP (Arroyo Seco 2, Chocorí, and La Tigra), and one associated with mega-faunal remains (Fontezuelas skull). In addition, we studied several Late Holocene samples. We show that the skulls from the Argentinean Pampas are morphologically similar to other Early Holocene American skulls (i.e., Lagoa Santa from Brazil, Tequendama, Checua, and Aguazuque from Colombia, Lauricocha from Peru, and early Mexicans) that exhibit long and narrow cranial vaults. These samples differ from the Late Holocene American samples that exhibit a shorter and wider cranial vault. Our results underscore the important differences in cranial morphology between early and late-American samples. However, we emphasize the need for further studies to discuss alternative hypotheses regarding such differences. PMID:20623674

  9. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  10. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  11. Spaceflight hardware for conducting plant growth experiments in space: the early years 1960-2000

    NASA Technical Reports Server (NTRS)

    Porterfield, D. M.; Neichitailo, G. S.; Mashinski, A. L.; Musgrave, M. E.

    2003-01-01

    The best strategy for supporting long-duration space missions is believed to be bioregenerative life support systems (BLSS). An integral part of a BLSS is a chamber supporting the growth of higher plants that would provide food, water, and atmosphere regeneration for the human crew. Such a chamber will have to be a complete plant growth system, capable of providing lighting, water, and nutrients to plants in microgravity. Other capabilities include temperature, humidity, and atmospheric gas composition controls. Many spaceflight experiments to date have utilized incomplete growth systems (typically having a hydration system but lacking lighting) to study tropic and metabolic changes in germinating seedlings and young plants. American, European, and Russian scientists have also developed a number of small complete plant growth systems for use in spaceflight research. Currently we are entering a new era of experimentation and hardware development as a result of long-term spaceflight opportunities available on the International Space Station. This is already impacting development of plant growth hardware. To take full advantage of these new opportunities and construct innovative systems, we must understand the results of past spaceflight experiments and the basic capabilities of the diverse plant growth systems that were used to conduct these experiments. The objective of this paper is to describe the most influential pieces of plant growth hardware that have been used for the purpose of conducting scientific experiments during the first 40 years of research. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

  12. Plasma epidermal growth factor decreased in the early stage of Parkinson's disease.

    PubMed

    Jiang, Qian-Wen; Wang, Cheng; Zhou, Yi; Hou, Miao-Miao; Wang, Xi; Tang, Hui-Dong; Wu, Yi-Wen; Ma, Jian-Fang; Chen, Sheng-Di

    2015-06-01

    Epidermal growth factor (EGF) is a neurotrophic factor that plays an important role in Parkinson's disease (PD). We measured plasma EGF level in PD, essential tremor (ET) and normal controls to investigate whether it changes in PD and whether it is associated with motor and non-motor symptoms of PD. 100 patients with PD, 40 patients with ET as disease control and 76 healthy persons were enrolled in the present study. Motor and non-motor symptoms were assessed by different scales. Plasma EGF levels of three groups were measured by enzyme-linked immunosorbent assay kit. Spearman test and linear logistics regression model were used to test the correlation of EGF with motor and non-motor symptoms of PD. Plasma EGF level was significantly decreased in early PD patients compared with normal control, but not in advanced PD patients. Interestingly, plasma EGF level was significantly increased in advanced PD and total PD patients compared with ET patients, but not in early PD patients. In addition, plasma EGF level was correlated with UPDRS-III scores in PD. Also plasma EGF level was correlated with UPDRS-III scores and NMS scores in early PD. Our results suggested that plasma EGF decreased in the early stage of PD and increased later on in the PD disease course. Also, plasma EGF level was increased significantly in PD compared with ET patients and correlated with motor and non-motor symptoms in early PD. PMID:26029474

  13. Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis

    PubMed Central

    Olson, J. Casey; Takahashi, Ayuko; Glotzbecker, Michael P.; Snyder, Brian D.

    2015-01-01

    Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have

  14. 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

  15. Effect of Comprehensive Dental Rehabilitation on Growth Parameters in Pediatric Patients with Severe Early Childhood Caries

    PubMed Central

    Bansal, Kalpana; Chopra, Radhika

    2016-01-01

    ABSTRACT Background: Children who have severe early childhood caries (S-ECC) weigh significantly less than caries-free children. The association between S-ECC and weight suggests that its timely treatment at early stages may preserve general health, in addition to preventing pain and infection. Objective: This study was conducted to evaluate whether children with untreated S-ECC had lower weight and height as compared with children with low caries and to evaluate whether full mouth rehabilitation of children with S-ECC resulted in the phenomenon of catch-up growth. Materials and methods: The weight and height of children with noncontributory medical histories and S-ECC (3-6 years) were compared with caries-free children, before and 6 months after full mouth dental rehabilitation. Results: Prior to dental rehabilitation, children with S-ECC had significantly less weight and height than their comparison counterparts (p < 0.001). Following therapeutic intervention, the test group children exhibited catch-up growth in relation to weight, as there was no significant difference in the body weight of the test and control groups (p = 0.171). Conclusion: Comprehensive full mouth rehabilitation of children with S-ECC results in catch-up growth, thus improving the overall health of the child. How to cite this article: Sachdev J, Bansal K, Chopra R. Effect of Comprehensive Dental Rehabilitation on Growth Parameters in Pediatric Patients with Severe Early Childhood Caries. Int J Clin Pediatr Dent 2016;9(1):15-20. PMID:27274149

  16. East African climate pulses and early human evolution

    NASA Astrophysics Data System (ADS)

    Maslin, Mark A.; Brierley, Chris M.; Milner, Alice M.; Shultz, Susanne; Trauth, Martin H.; Wilson, Katy E.

    2014-10-01

    Current evidence suggests that all of the major events in hominin evolution have occurred in East Africa. Over the last two decades, there has been intensive work undertaken to understand African palaeoclimate and tectonics in order to put together a coherent picture of how the environment of East Africa has varied in the past. The landscape of East Africa has altered dramatically over the last 10 million years. It has changed from a relatively flat, homogenous region covered with mixed tropical forest, to a varied and heterogeneous environment, with mountains over 4 km high and vegetation ranging from desert to cloud forest. The progressive rifting of East Africa has also generated numerous lake basins, which are highly sensitive to changes in the local precipitation-evaporation regime. There is now evidence that the presence of precession-driven, ephemeral deep-water lakes in East Africa were concurrent with major events in hominin evolution. It seems the unusual geology and climate of East Africa created periods of highly variable local climate, which, it has been suggested could have driven hominin speciation, encephalisation and dispersal out of Africa. One example is the significant hominin speciation and brain expansion event at ˜1.8 Ma that seems to have been coeval with the occurrence of highly variable, extensive, deep-water lakes. This complex, climatically very variable setting inspired first the variability selection hypothesis, which was then the basis for the pulsed climate variability hypothesis. The newer of the two suggests that the long-term drying trend in East Africa was punctuated by episodes of short, alternating periods of extreme humidity and aridity. Both hypotheses, together with other key theories of climate-evolution linkages, are discussed in this paper. Though useful the actual evolution mechanisms, which led to early hominins are still unclear and continue to be debated. However, it is clear that an understanding of East African

  17. Sulfolipid-1 biosynthesis restricts Mycobacterium tuberculosis growth in human macrophages.

    PubMed

    Gilmore, Sarah A; Schelle, Michael W; Holsclaw, Cynthia M; Leigh, Clifton D; Jain, Madhulika; Cox, Jeffery S; Leary, Julie A; Bertozzi, Carolyn R

    2012-05-18

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is a highly evolved human pathogen characterized by its formidable cell wall. Many unique lipids and glycolipids from the Mtb cell wall are thought to be virulence factors that mediate host-pathogen interactions. An intriguing example is Sulfolipid-1 (SL-1), a sulfated glycolipid that has been implicated in Mtb pathogenesis, although no direct role for SL-1 in virulence has been established. Previously, we described the biochemical activity of the sulfotransferase Stf0 that initiates SL-1 biosynthesis. Here we show that a stf0-deletion mutant exhibits augmented survival in human but not murine macrophages, suggesting that SL-1 negatively regulates the intracellular growth of Mtb in a species-specific manner. Furthermore, we demonstrate that SL-1 plays a role in mediating the susceptibility of Mtb to a human cationic antimicrobial peptide in vitro, despite being dispensable for maintaining overall cell envelope integrity. Thus, we hypothesize that the species-specific phenotype of the stf0 mutant is reflective of differences in antimycobacterial effector mechanisms of macrophages. PMID:22360425

  18. Maillard reaction products modulating the growth of human tumor cells in vitro.

    PubMed

    Marko, Doris; Habermeyer, Michael; Kemény, Monika; Weyand, Ulrike; Niederberger, Ellen; Frank, Oliver; Hofmann, Thomas

    2003-01-01

    We investigated the effect of a series of Maillard reaction products formed from carbohydrates under household heating conditions on the growth of human tumor cells in vitro. 4-Hydroxy-5-methyl-3-(2H)-furanone (1) was found to potently enhance the proliferation of human tumor cells. In contrast, the Maillard-type chromophores 2-(2-furyl)methylidene-4-hydroxy-5-methyl-2H-furan-3-one (2), 4-(2-furyl)-7-[(2-furyl)methylidene]-2-hydroxy-2H,7H,8aH-pyrano[2,3-b]- pyran-3-one (6), and 3-hydroxy-4[(E)-(2-furyl)methylidene]methyl-3-cyclopentene-1,2 dione (13) inhibited the growth of human tumor cells in vitro in the low micromolar range. GXF251L cells (gastric carcinoma), synchronized by serum deprivation, were retained in the G1-phase of the cell cycle after treatment with 2, 6, or 13 for 24 h. Concomitantly, a distinct sub-G1 peak was observed, indicative for apoptosis induction. DNA fragmentation was further investigated by ELISA using antibodies raised against histones and DNA. 2 induced a significant increase of fragmented DNA at concentrations > or = 30 microM. After treatment with compound 6, DNA fragmentation was observed at a higher concentration range (> or = 50 microM), whereas incubation with 13 resulted in a marked DNA fragmentation already at 20 microM. On the protein level, the activation of caspase 3, as an early marker for apoptosis induction, was determined. The results were almost identical to those obtained in the DNA fragmentation ELISA. In summary, Maillard reaction products potently modulating the growth of human tumor cells were identified. The Maillard-type chromophores 2, 6, and 13 were found to interfere with the proliferation of gastric carcinoma cells, causing cell cycle arrest and apoptosis induction. PMID:12693030

  19. Smad-Independent Transforming Growth Factor-β Regulation of Early Growth Response-1 and Sustained Expression in Fibrosis

    PubMed Central

    Bhattacharyya, Swati; Chen, Shu-Jen; Wu, Minghua; Warner-Blankenship, Matthew; Ning, Hongyan; Lakos, Gabriella; Mori, Yasuji; Chang, Eric; Nihijima, Chihiro; Takehara, Kazuhiro; Feghali-Bostwick, Carol; Varga, John

    2008-01-01

    Transforming growth factor-β (TGF-β) plays a key role in scleroderma pathogenesis. The transcription factor early growth response-1 (Egr-1) mediates the stimulation of collagen transcription elicited by TGF-β and is necessary for the development of pulmonary fibrosis in mice. Here, we report that TGF-β causes a time- and dose-dependent increase in Egr-1 protein and mRNA levels and enhanced transcription of the Egr-1 gene via serum response elements in normal fibroblasts. The ability of TGF-β to stimulate Egr-1 was preserved in Smad3-null mice and in explanted Smad3-null fibroblasts. The response was blocked by a specific mitogen-activated protein kinase kinase 1 (MEK1) inhibitor but not by an ALK5 kinase inhibitor. Furthermore, MEK1 was phosphorylated by TGF-β, which was sufficient to drive Egr-1 transactivation. Stimulation by TGF-β enhanced the transcriptional activity of Elk-1 via the MEK-extracellular signal-regulated kinase 1/2 pathway. Bleomycin-induced scleroderma in the mouse was accompanied by increased Egr-1 accumulation in lesional fibroblasts. Furthermore, biopsies of lesional skin and lung from patients with scleroderma showed increased Egr-1 levels, which were highest in early diffuse disease. Moreover, both Egr-1 mRNA and protein were elevated in explanted scleroderma skin fibroblasts in vitro. Together, these findings define a Smad-independent TGF-β signal transduction mechanism that underlies the stimulation of Egr-1, demonstrate for the first time sustained Egr-1 up-regulation in fibrotic lesions and suggests that Egr-1 has a role in the induction and progression of fibrosis. PMID:18772333

  20. An assay to probe Plasmodium falciparum growth, transmission stage formation and early gametocyte development

    PubMed Central

    Brancucci, Nicolas M B; Goldowitz, Ilana; Buchholz, Kathrin; Werling, Kristine; Marti, Matthias

    2015-01-01

    Conversion from asexual proliferation to sexual differentiation initiates the production of the gametocyte, which is the malaria parasite stage required for human-to-mosquito transmission. This protocol describes an assay designed to probe the effect of drugs or other perturbations on asexual replication, sexual conversion and early gametocyte development in the major human malaria parasite Plasmodium falciparum. Synchronized asexually replicating parasites are induced for gametocyte production by the addition of conditioned medium, and they are then exposed to the treatment of interest during sexual commitment or at any subsequent stage of early gametocyte development. Flow cytometry is used to measure asexual proliferation and gametocyte production via DNA dye staining and the gametocyte-specific expression of a fluorescent protein, respectively. This screening approach may be used to identify and evaluate potential transmission-blocking compounds and to further investigate the mechanism of sexual conversion in malaria parasites. The full protocol can be completed in 11 d. PMID:26134953

  1. Early stages of growth and crystal structure evolution of boron nitride thin films

    NASA Astrophysics Data System (ADS)

    Henry, Anne; Chubarov, Mikhail; Czigány, Zsolt; Garbrecht, Magnus; Högberg, Hans

    2016-05-01

    A study of the nucleation and crystal structure evolution at the early stages of the growth of sp2-BN thin films on 6H-SiC and α-Al2O3 substrates is presented. The growth is performed at low pressure and high temperature in a hot wall CVD reactor, using ammonia and triethylboron as precursors, and H2 as carrier gas. From high-resolution transmission electron microscopy and X-ray thin film diffraction measurements we observe that polytype pure rhombohedral BN (r-BN) is obtained on 6H-SiC substrates. On α-Al2O3 an AlN buffer obtained by nitridation is needed to promote the growth of hexagonal BN (h-BN) to a thickness of around 4 nm followed by a transition to r-BN growth. In addition, when r-BN is obtained, triangular features show up in plan-view scanning electron microscopy which are not seen on thin h-BN layers. The formation of BN after already one minute of growth is confirmed by X-ray photoelectron spectroscopy.

  2. Investing in early human development: timing and economic efficiency.

    PubMed

    Doyle, Orla; Harmon, Colm P; Heckman, James J; Tremblay, Richard E

    2009-03-01

    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the "antenatal investment hypothesis". We conclude by discussing a suite of new European interventions that will inform this optimal timing debate. PMID:19213617

  3. Investing in Early Human Development: Timing and Economic Efficiency

    PubMed Central

    Doyle, Orla; Harmon, Colm P.; Heckman, James J.; Tremblay, Richard E.

    2010-01-01

    Policy discussions to ameliorate socioeconomic (SES) inequalities are increasingly focused on investments in early childhood. Yet such interventions are costly to implement, and clear evidence on the optimal time to intervene to yield a high economic and social return in the future is meagre. The majority of successful early childhood interventions start in the preschool years. However socioeconomic gradients in cognitive skills, socio-emotional functioning and health can be observed by age three, suggesting that preventative programmes starting earlier in childhood may be even more effective. We discuss the optimal timing of early childhood intervention with reference to recent research in developmental neuroscience. We motivate the need for early intervention by providing an overview of the impact of adverse risk factors during the antenatal and early childhood periods on outcomes later in life. We provide a brief review of the economic rationale for investing early in life and propose the “antenatal investment hypothesis”. We conclude by discussing a suite of new European interventions that will inform this optimal timing debate. PMID:19213617

  4. Adaptive Use of Information during Growth Can Explain Long-Term Effects of Early Life Experiences.

    PubMed

    English, Sinead; Fawcett, Tim W; Higginson, Andrew D; Trimmer, Pete C; Uller, Tobias

    2016-05-01

    Development is a continuous process during which individuals gain information about their environment and adjust their phenotype accordingly. In many natural systems, individuals are particularly sensitive to early life experiences, even in the absence of later constraints on plasticity. Recent models have highlighted how the adaptive use of information can explain age-dependent plasticity. These models assume that information gain and phenotypic adjustments either cannot occur simultaneously or are completely independent. This assumption is not valid in the context of growth, where finding food results both in a size increase and learning about food availability. Here, we describe a simple model of growth to provide proof of principle that long-term effects of early life experiences can arise through the coupled dynamics of information acquisition and phenotypic change in the absence of direct constraints on plasticity. The increase in reproductive value from gaining information and sensitivity of behavior to experiences declines across development. Early life experiences have long-term impacts on age of maturity, yet-due to compensatory changes in behavior-our model predicts no substantial effects on reproductive success. We discuss how the evolution of sensitive windows can be explained by experiences having short-term effects on informational and phenotypic states, which generate long-term effects on life-history decisions. PMID:27104994

  5. Expression of cyr61, a growth factor-inducible immediate-early gene.

    PubMed Central

    O'Brien, T P; Yang, G P; Sanders, L; Lau, L F

    1990-01-01

    A set of immediate-early genes that are rapidly activated by serum or purified platelet-derived growth factor in mouse 3T3 fibroblasts has been previously identified. Among these genes, several are related to known or putative transcription factors and growth factors, supporting the notion that some of these genes encode regulatory molecules important to cell growth. We show here that a member of this set of genes, cyr61 (originally identified by its cDNA 3CH61), encodes a 379-amino-acid polypeptide rich in cysteine residues. cyr61 can be induced through protein kinase C-dependent and -independent pathways. Unlike many immediate-early genes that are transiently expressed, the cyr61 mRNA is accumulated from the G0/G1 transition through mid-G1. This expression pattern is due to persistent transcription, while the mRNA is rapidly turned over during the G0/G1 transition and in mid-G1 at the same rate. In logarithmically growing cells, the cyr61 mRNA level is constant throughout the cell cycle. Cyr61 contains an N-terminal secretory signal sequence; however, it is not detected in the culture medium by immunoprecipitation. Cyr61 is synthesized maximally at 1 to 2 h after serum stimulation and has a short half-life within the cell. Images PMID:2355916

  6. 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

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

    SciTech Connect

    Thomas, S.C.; Jasienski, M.; Bazzaz, F.A. . Dept. of Organismic and Evolutionary Biology)

    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 Panicum 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.

  8. Growth retardation at early life and metabolic adaptation among North Korean children.

    PubMed

    Lee, S-K; Nam, S-Y; Hoffman, D J

    2015-08-01

    The high prevalence of obesity is a major public health issue and contributes to the 'double burden' of disease in developing countries. Early exposure to poor nutrition may cause metabolic adaptations that, when accompanied by exposure to 'affluent' nutrition, may increase the risk for obesity and other metabolic disorders. The aim of this study was to determine differences in energy metabolism and nutritional status between normal-height and growth-retarded North Korean children living in South Korea. A total of 29 children were recruited and underwent measurements of resting energy expenditure (REE), respiratory quotient (RQ), anthropometrics and dietary intake. There was no difference in REE or any assessment of obesity between the growth-retarded and normal-height children. Children who were classified as growth retarded (HAZ<-1.0) or stunted (HAZ<-2.0) had a significantly higher RQ (β=0.036 or 0.060, respectively, P=0.018 or 0.016), independent of sex, age, fat-free mass, fat mass and food quotient, compared with children with normal height. The results from this study, the first from an Asian population, add to the growing body of literature suggesting that undernutrition early in life results in adaptations in energy metabolism that favor fat deposition, increasing the risk of stunted children becoming overweight or obese later in life. Continued research on this topic is warranted, given the continued rise in the prevalence of the double burden in transitional countries. PMID:25997456

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

    PubMed

    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

  10. Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development.

    PubMed

    Goktas, Selda; Uslu, Fazil E; Kowalski, William J; Ermek, Erhan; Keller, Bradley B; Pekkan, Kerem

    2016-01-01

    The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis. PMID:27552150

  11. Time-Series Interactions of Gene Expression, Vascular Growth and Hemodynamics during Early Embryonic Arterial Development

    PubMed Central

    Goktas, Selda; Uslu, Fazil E.; Kowalski, William J.; Ermek, Erhan; Keller, Bradley B.

    2016-01-01

    The role of hemodynamic forces within the embryo as biomechanical regulators for cardiovascular morphogenesis, growth, and remodeling is well supported through the experimental studies. Furthermore, clinical experience suggests that perturbed flow disrupts the normal vascular growth process as one etiology for congenital heart diseases (CHD) and for fetal adaptation to CHD. However, the relationships between hemodynamics, gene expression and embryonic vascular growth are poorly defined due to the lack of concurrent, sequential in vivo data. In this study, a long-term, time-lapse optical coherence tomography (OCT) imaging campaign was conducted to acquire simultaneous blood velocity, pulsatile micro-pressure and morphometric data for 3 consecutive early embryonic stages in the chick embryo. In conjunction with the in vivo growth and hemodynamics data, in vitro reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to track changes in transcript expression relevant to histogenesis and remodeling of the embryonic arterial wall. Our non-invasive extended OCT imaging technique for the microstructural data showed continuous vessel growth. OCT data coupled with the PIV technique revealed significant but intermitted increases in wall shear stress (WSS) between first and second assigned stages and a noticeable decrease afterwards. Growth rate, however, did not vary significantly throughout the embryonic period. Among all the genes studied, only the MMP-2 and CASP-3 expression levels remained unchanged during the time course. Concurrent relationships were obtained among the transcriptional modulation of the genes, vascular growth and hemodynamics-related changes. Further studies are indicated to determine cause and effect relationships and reversibility between mechanical and molecular regulation of vasculogenesis. PMID:27552150

  12. 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

  13. Brg1 Enables Rapid Growth of the Early Embryo by Suppressing Genes That Regulate Apoptosis and Cell Growth Arrest.

    PubMed

    Singh, Ajeet P; Foley, Julie F; Rubino, Mark; Boyle, Michael C; Tandon, Arpit; Shah, Ruchir; Archer, Trevor K

    2016-08-01

    SWI/SNF (switching/sucrose nonfermenting)-dependent chromatin remodeling establishes coordinated gene expression programs during development, yet important functional details remain to be elucidated. We show that the Brg1 (Brahma-related gene 1; Smarca4) ATPase is globally expressed at high levels during postimplantation development and its conditional ablation, beginning at gastrulation, results in increased apoptosis, growth retardation, and, ultimately, embryonic death. Global gene expression analysis revealed that genes upregulated in Rosa26CreERT2; Brg1(flox/flox) embryos (here referred to as Brg1(d/d) embryos to describe embryos with deletion of the Brg1(flox/flox) alleles) negatively regulate cell cycle progression and cell growth. In addition, the p53 (Trp53) protein, which is virtually undetectable in early wild-type embryos, accumulated in the Brg1(d/d) embryos and activated the p53-dependent pathways. Using P19 cells, we show that Brg1 and CHD4 (chromodomain helicase DNA binding protein 4) coordinate to control target gene expression. Both proteins physically interact and show a substantial overlap of binding sites at chromatin-accessible regions adjacent to genes differentially expressed in the Brg1(d/d) embryos. Specifically, Brg1 deficiency results in reduced levels of the repressive histone H3 lysine K27 trimethylation (H3K27me3) histone mark and an increase in the amount of open chromatin at the regulatory region of the p53 and p21 (Cdkn1a) genes. These results provide insights into the mechanisms by which Brg1 functions, which is in part via the p53 program, to constrain gene expression and facilitate rapid embryonic growth. PMID:27185875

  14. 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.

  15. THE ROLE OF MERGERS IN EARLY-TYPE GALAXY EVOLUTION AND BLACK HOLE GROWTH

    SciTech Connect

    Schawinski, Kevin; Dowlin, Nathan; Urry, C. Megan; Thomas, Daniel; Edmondson, Edward

    2010-05-01

    Models of galaxy formation invoke the major merger of gas-rich progenitor galaxies as the trigger for significant phases of black hole growth and the associated feedback that suppresses star formation to create red spheroidal remnants. However, the observational evidence for the connection between mergers and active galactic nucleus (AGN) phases is not clear. We analyze a sample of low-mass early-type galaxies known to be in the process of migrating from the blue cloud to the red sequence via an AGN phase in the green valley. Using deeper imaging from Sloan Digital Sky Survey Stripe 82, we show that the fraction of objects with major morphological disturbances is high during the early starburst phase, but declines rapidly to the background level seen in quiescent early-type galaxies by the time of substantial AGN radiation several hundred Myr after the starburst. This observation empirically links the AGN activity in low-redshift early-type galaxies to a significant merger event in the recent past. The large time delay between the merger-driven starburst and the peak of AGN activity allows for the merger features to decay to the background and hence may explain the weak link between merger features and AGN activity in the literature.

  16. Stable isotope dietary analysis of the Tianyuan 1 early modern human

    PubMed Central

    Hu, Yaowu; Shang, Hong; Tong, Haowen; Nehlich, Olaf; Liu, Wu; Zhao, Chaohong; Yu, Jincheng; Wang, Changsui; Trinkaus, Erik; Richards, Michael P.

    2009-01-01

    We report here on the isotopic analysis of the diet of one of the oldest modern humans found in Eurasia, the Tianyuan 1 early modern human dating to ≈40,000 calendar years ago from Tianyuan Cave (Tianyuandong) in the Zhoukoudian region of China. Carbon and nitrogen isotope analysis of the human and associated faunal remains indicate a diet high in animal protein, and the high nitrogen isotope values suggest the consumption of freshwater fish. To confirm this inference, we measured the sulfur isotope values of terrestrial and freshwater animals around the Zhoukoudian area and of the Tianyuan 1 human, which also support the interpretation of a substantial portion of the diet from freshwater fish. This analysis provides the direct evidence for the consumption of aquatic resources by early modern humans in China and has implications for early modern human subsistence and demography. PMID:19581579

  17. U.S. Human Immunodeficiency Virus Type 1 Epidemic: Date of Origin, Population History, and Characterization of Early Strains

    PubMed Central

    Robbins, Kenneth E.; Lemey, Philippe; Pybus, Oliver G.; Jaffe, Harold W.; Youngpairoj, Ae S.; Brown, Teresa M.; Salemi, Marco; Vandamme, Anne-Mieke; Kalish, Marcia L.

    2003-01-01

    Human immunodeficiency virus (HIV) type 1 subtype B sequences (whole envelope and the p17 region of gag) were obtained from peripheral blood mononuclear cell samples collected in 1981 from seven HIV-infected U.S. individuals and in 1982 from one infected Canadian resident. Phylogenetic and nucleotide distance analyses were performed by using database sequences representing North American strains collected from 1978 to 1995. The estimated phylogeny was starlike, with early strains represented on different lineages. When sequences were grouped by years of collection, nucleotide distance comparisons demonstrated an increase in diversity over time and indicated that contemporary strains are more closely related to early epidemic strains than to each other. Using a recently developed likelihood ratio reduction procedure, the date of origin of the U.S. epidemic was estimated to be 1968 ± 1.4 years. A coalescent approach was also used to estimate the population history of the U.S. subtype B epidemic. Our analyses provide new information that implies an exponential growth rate from the beginning of the U.S. HIV epidemic. The dating results suggest a U.S. introduction date (or date of divergence from the most recent common ancestor) that precedes the date of the earliest known AIDS cases in the late 1970s. Furthermore, the estimated epidemic growth curve shows a period of exponential growth that preceded most of the early documented cases and also indicates a leveling of prevalence rates in the recent past. PMID:12743293

  18. Molecular basis of human growth hormone gene deletions.

    PubMed Central

    Vnencak-Jones, C L; Phillips, J A; Chen, E Y; Seeburg, P H

    1988-01-01

    Crossover sites resulting from unequal recombination within the human growth hormone (GH) gene cluster that cause GH1 gene deletions and isolated GH deficiency type 1A were localized in nine patients. In eight unrelated subjects homozygous for 6.7-kilobase (kb) deletions, the breakpoints are within two blocks of highly homologous DNA sequences that lie 5' and 3' to the GH1 gene. In seven of these eight cases, the breakpoints map within a 1250-base-pair (bp) region composed of 300-bp Alu sequences of 86% homology and flanking non-Alu sequences that are 600 and 300 bp in length and are of 96% and 88% homology, respectively. In the eighth patient, the breakpoints are 5' to these Alu repeats and are most likely within a 700-bp region of 96% homologous DNA sequences. In the ninth patient homozygous for a 7.6-kb deletion, the breakpoints are contained within a 29-bp perfect repeat lying 5' to GH1 and the human chorionic somatomammotropin pseudogene (CSHP1). Together, these results indicate that the presence of highly homologous DNA sequences flanking GH1 predispose to recurrent unequal recombinational events presumably through chromosomal misalignment. Images PMID:2840669

  19. Rapid growth of seed black holes in the early universe by supra-exponential accretion.

    PubMed

    Alexander, Tal; Natarajan, Priyamvada

    2014-09-12

    Mass accretion by black holes (BHs) is typically capped at the Eddington rate, when radiation's push balances gravity's pull. However, even exponential growth at the Eddington-limited e-folding time t(E) ~ few × 0.01 billion years is too slow to grow stellar-mass BH seeds into the supermassive luminous quasars that are observed when the universe is 1 billion years old. We propose a dynamical mechanism that can trigger supra-exponential accretion in the early universe, when a BH seed is bound in a star cluster fed by the ubiquitous dense cold gas flows. The high gas opacity traps the accretion radiation, while the low-mass BH's random motions suppress the formation of a slowly draining accretion disk. Supra-exponential growth can thus explain the puzzling emergence of supermassive BHs that power luminous quasars so soon after the Big Bang. PMID:25103410

  20. Rapid growth of seed black holes in the early universe by supra-exponential accretion

    NASA Astrophysics Data System (ADS)

    Alexander, Tal; Natarajan, Priyamvada

    2014-09-01

    Mass accretion by black holes (BHs) is typically capped at the Eddington rate, when radiation's push balances gravity's pull. However, even exponential growth at the Eddington-limited e-folding time tE ~ few × 0.01 billion years is too slow to grow stellar-mass BH seeds into the supermassive luminous quasars that are observed when the universe is 1 billion years old. We propose a dynamical mechanism that can trigger supra-exponential accretion in the early universe, when a BH seed is bound in a star cluster fed by the ubiquitous dense cold gas flows. The high gas opacity traps the accretion radiation, while the low-mass BH's random motions suppress the formation of a slowly draining accretion disk. Supra-exponential growth can thus explain the puzzling emergence of supermassive BHs that power luminous quasars so soon after the Big Bang.

  1. Early Differentiation within the Animate Domain: Are Humans Something Special?

    ERIC Educational Resources Information Center

    Pauen, Sabina

    2000-01-01

    Two experiments investigated whether preverbal infants distinguish between humans and mammals. Study 1 found that 7-, 9-, and 11-month-olds distinguished humans from mammals in an object-examination task. Study 2 found that 7-month-olds but not 5-month-olds showed evidence for category discrimination with the 2-dimensional color photos of toy…

  2. Mecasermin (recombinant human insulin-like growth factor I).

    PubMed

    Rosenbloom, Arlan L

    2009-01-01

    Growth hormone (GH) exercises its growth effects by stimulating insulin-like growth factor I (IGF-I) synthesis in the liver (endocrine IGF-I) and by inducing chondrocyte differentiation/replication and local production of IGF-I (paracrine/autocrine IGF-I). Injectable recombinant human (rh)IGF-I (mecasermin) has been available for nearly 20 years for treatment of the rare instances of GH insensitivity caused by GH receptor defects or GH-inhibiting antibodies. Full restoration of normal growth, as occurs with rhGH replacement of GH deficiency, is not seen, presumably because only the endocrine deficiency is addressed. RhIGF-I has also been effective as an insulin-sensitizing agent in severe insulin-resistant conditions. Although the insulin-sensitizing effect may benefit both type 1 and type 2 diabetes, there are no ongoing clinical trials because of concern about risk of retinopathy and other complications. Promotion of rhIGF-I for treatment of idiopathic short stature has been intensive, with neither data nor rationale suggesting that there might be a better response than has been documented with rhGH. Other applications that have either been considered or are undergoing clinical trial are based on the ubiquitous tissue-building properties of IGF-I and include chronic liver disease, cystic fibrosis, wound healing, AIDS muscle wasting, burns, osteoporosis, Crohn's disease, anorexia nervosa, Werner syndrome, X-linked severe combined immunodeficiency, Alzheimer's disease, muscular dystrophy, amyotrophic lateral sclerosis, hearing loss prevention, spinal cord injury, cardiovascular protection, and prevention of retinopathy of prematurity. The most frequent side effect is hypoglycemia, which is readily controlled by administration with meals. Other common adverse effects involve hyperplasia of lymphoid tissue, which may require tonsillectomy/adenoidectomy, accumulation of body fat, and coarsening of facies. The anti-apoptotic properties of IGF-I are implicated in cancer

  3. Growth-stimulatory monoclonal antibodies against human insulin-like growth factor I receptor.

    PubMed

    Xiong, L; Kasuya, J; Li, S L; Kato, J; Fujita-Yamaguchi, Y

    1992-06-15

    Monoclonal antibodies (mAbs) against purified human placental insulin-like growth factor I (IGF-I) receptors were prepared and characterized. Three IgG mAbs were specific for the human IGF-I receptor and displayed negligible crossreactivity with the human insulin receptor. They stimulated 125I-labeled IGF-I (125I-IGF-I) or 125I-IGF-II binding to purified human placental IGF-I receptors and to IGF-I receptors expressed in NIH 3T3 cells in contrast to the well-studied mAb alpha IR-3, which inhibits 125I-IGF-I or 125I-IGF-II binding to both forms of IGF-I receptors. The mAbs introduced in this study stimulated DNA synthesis in NIH 3T3 cells expressing human IGF-I receptors approximately 1.5-fold above the basal level and the IGF-I- or IGF-II-stimulated level. In contrast, alpha IR-3 inhibited both basal and IGF-I or IGF-II-stimulated DNA synthesis by approximately 30%. Inhibition of IGF-II-stimulated DNA synthesis by alpha IR-3 was as potent as its inhibition of IGF-I-stimulated DNA synthesis, although IGF-II binding to the IGF-I receptors was not inhibited by IGF-II as potently as was IGF-I. With the purified IGF-I receptors, both inhibitory and stimulatory mAbs were shown to activate autophosphorylation of the IGF-I receptor beta subunit and to induce microaggregation of the receptors. These results suggest that conformational changes resulting from receptor dimerization in the presence of either type of mAb may affect the signal-transducing function of the IGF-I receptor differently. These additional mAbs and alpha IR-3 immunoprecipitated nearly 90% of IGF-I binding activity from Triton X-100-solubilized human placental membranes, indicating that IGF-I receptor reactive with these mAbs is the major form of the IGF-I receptor in human placenta. PMID:1319060

  4. Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements

    SciTech Connect

    Band, V.; Zajchowski, D.; Kulesa, V.; Sager, R. )

    1990-01-01

    Human papilloma virus (HPV) types 16 and 18 are most commonly associated with cervical carcinoma in patients and induce immortalization of human keratinocytes in culture. HPV has not been associated with breast cancer. This report describes the immortalization of normal human mammary epithelial cells (76N) by plasmid pHPV18 or pHPV16, each containing the linearized viral genome. Transfectants were grown continuously for more than 60 passages, whereas 76N cells senesce after 18-20 passages. The transfectants also differ from 76N cells in cloning in a completely defined medium called D2 and growing a minimally supplemented defined medium (D3) containing epidermal growth factor. All transfectant tested contain integrated HPV DNA, express HPV RNA, and produce HPV E7 protein. HPV transfectants do not form tumors in a nude mouse assay. It is concluded that products of the HPV genome induce immortalization of human breast epithelial cells and reduce their growth factor requirements. This result raises the possibility that HPV might be involved in breast cancer. Furthermore, other tissue-specific primary epithelial cells that are presently difficult to grown and investigate may also be immortalized by HPV.

  5. Early environmental effects on epigenetic regulation in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We all know our environment affects our risk of disease. But importantly, the health consequences of environmental exposures depend not only on their severity, but also on their timing relative to developmental milestones. The developmental origins hypothesis is based on the fact that certain early ...

  6. Expression of the human growth hormone variant gene in cultured fibroblasts and transgenic mice

    SciTech Connect

    Selden, R.F.; Wagner, T.E.; Blethen, S.; Yun, J.S.; Rowe, M.E.; Goodman, H.M. )

    1988-11-01

    The nucleotide sequence of the human growth hormone variant gene, one of the five members of the growth hormone gene family, predicts that it encodes a growth hormone-like protein. As a first step in determining whether this gene is functional in humans, the authors have expressed a mouse methallothionein I/human growth hormone variant fusion gene in mouse L cells and in transgenic mice. The growth hormone variant protein expressed in transiently transfected L cells is distinct from growth hormone itself with respect to reactivity with anti-growth hormone monoclonal antibodies, behavior during column chromatography, and isoelectric point. Transgenic mice expressing the growth hormone variant protein are 1.4- to 1.9-fold larger than nontransgenic controls, suggesting that the protein has growth-promoting properties.

  7. 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…

  8. The superantigen-homologous viral immediate-early gene ie14/vsag in herpesvirus saimiri-transformed human T cells.

    PubMed Central

    Knappe, A; Hiller, C; Thurau, M; Wittmann, S; Hofmann, H; Fleckenstein, B; Fickenscher, H

    1997-01-01

    Herpesvirus saimiri C488 transforms human T lymphocytes to stable growth in culture. The growth-transformed human T cells harbor the viral genome in a nonintegrated episomal form without production of virus particles. In these cells, virus gene expression was previously found to be confined to the transforming genes stpC and tip. In order to analyze virus gene expression in more detail, we applied a subtractive hybridization technique and compared stimulated virus-transformed cells with uninfected parental T cells of the same donor. A number of known T-cell activation genes were isolated. Viral stpC/tip cDNAs were enriched after subtraction. In addition, the viral immediate-early, superantigen-homologous gene ie14/vsag was represented by numerous cDNA clones that comprised the entire spliced transcript. Whereas a weak basal expression of ie14/vsag was detected by reverse transcription-PCR only, the phorbol ester-induced transcripts were readily shown by Northern blotting. ie14/vsag, which before had been classified as a major immediate-early gene of herpesvirus saimiri, is localized within a highly conserved region with extensive homologies to the cellular genome. Mutant viruses without the ie14/vsag gene are replication competent and fully capable of transforming human and marmoset T cells. Since ie14/vsag is transiently expressed after stimulation, it may increase T-cell proliferation in an activation-dependent and superantigen-like but apparently Vbeta-independent way. PMID:9371569

  9. Friend or Foe? Early Social Evaluation of Human Interactions

    PubMed Central

    Buon, Marine; Jacob, Pierre; Margules, Sylvie; Brunet, Isabelle; Dutat, Michel; Cabrol, Dominique; Dupoux, Emmanuel

    2014-01-01

    We report evidence that 29-month-old toddlers and 10-month-old preverbal infants discriminate between two agents: a pro-social agent, who performs a positive (comforting) action on a human patient and a negative (harmful) action on an inanimate object, and an anti-social agent, who does the converse. The evidence shows that they prefer the former to the latter even though the agents perform the same bodily movements. Given that humans can cause physical harm to their conspecifics, we discuss this finding in light of the likely adaptive value of the ability to detect harmful human agents. PMID:24586355

  10. Fine specificity of cellular immune responses in humans to human cytomegalovirus immediate-early 1 protein.

    PubMed Central

    Alp, N J; Allport, T D; Van Zanten, J; Rodgers, B; Sissons, J G; Borysiewicz, L K

    1991-01-01

    Cell-mediated immunity is important in maintaining the virus-host equilibrium in persistent human cytomegalovirus (HCMV) infection. The HCMV 72-kDa major immediate early 1 protein (IE1) is a target for CD8+ cytotoxic T cells in humans, as is the equivalent 89-kDa protein in mouse. Less is known about responses against this protein by CD4+ T cells, which may be important as direct effector cells or helper cells for antibody and CD8+ responses. Proliferative-T-cell responses to HCMV IE1 were studied in normal seropositive subjects. Peripheral blood mononuclear cells from 85% of seropositive subjects proliferated in response to HCMV from infected fibroblasts, and of these, 73% responded to recombinant baculovirus IE1. Responding cells were predominantly CD3+ CD4+. IE1 antigen preparations, including baculovirus recombinant protein, transfected rat cell nuclei, and synthetic peptides, induced IE1-specific T-cell lines which cross-reacted between the preparations. The fine specificity of these IE1-specific T-cell lines was studied by using overlapping synthetic peptides encompassing the entire sequence of the IE1 protein. The regions of the IE1 molecule recognized were identified and these varied between individuals, possibly reflecting differences in major histocompatibility complex (MHC) class II haplotype. In one subject, the peptide specificities of proliferative and MHC class I-restricted cytotoxic determinants on IE1 were spatially distinct. Thus, no single immunodominant T-cell determinant within HCMV IE1 was identified, suggesting that multiple peptides or a region of the 72-kDa IE1 protein would be required to induce specific T-cell responses in humans. PMID:1714519

  11. 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.

  12. Bone morphogenetic protein 2 inhibits the proliferation and growth of human colorectal cancer cells

    PubMed Central

    ZHANG, YUNYUAN; CHEN, XIAN; QIAO, MIN; ZHANG, BING-QIANG; WANG, NING; ZHANG, ZHONGLIN; LIAO, ZHAN; ZENG, LIYI; DENG, YOULIN; DENG, FANG; ZHANG, JUNHUI; YIN, LIANGJUN; LIU, WEI; ZHANG, QIAN; YAN, ZHENGJIAN; YE, JIXING; WANG, ZHONGLIANG; ZHOU, LAN; LUU, HUE H.; HAYDON, REX C.; HE, TONG-CHUAN; ZHANG, HONGYU

    2014-01-01

    Colorectal cancer (CRC) is one of the most deadly cancers worldwide. Significant progress has been made in understanding the molecular pathogenesis of CRC, which has led to successful early diagnosis, surgical intervention and combination chemotherapy. However, limited therapeutic options are available for metastatic and/or drug-resistant CRC. While the aberrantly activated Wnt/β-catenin pathway plays a critical initiating role in CRC development, disruption of the bone morphogenetic protein (BMP) pathway causes juvenile polyposis syndrome, suggesting that BMP signaling may play a role in CRC development. However, conflicting results have been reported concerning the possible roles of BMP signaling in sporadic colon cancer. Here, we investigated the effect of BMP2 on the proliferation, migration, invasiveness and tumor growth capability of human CRC cells. Using an adenovirus vector that overexpresses BMP2 and the piggyBac transposon-mediated stable BMP2 overexpression CRC line, we found that exogenous BMP2 effectively inhibited HCT116 cell proliferation and colony formation. BMP2 was shown to suppress colon cancer cell migration and invasiveness. Under a low serum culture condition, forced expression of BMP2 induced a significantly increased level of apoptosis in HCT116 cells. Using a xenograft tumor model, we found that forced expression of BMP2 in HCT116 cells suppressed tumor growth, accompanied by decreased cell proliferation activity. Taken together, our results strongly suggest that BMP2 plays an important inhibitory role in governing the proliferation and aggressive features of human CRC cells. PMID:24993644

  13. Noninvasive Index of Cryorecovery and Growth Potential for Human Follicles In Vitro1

    PubMed Central

    Barrett, Susan L.; Shea, Lonnie D.; Woodruff, Teresa K.

    2010-01-01

    Cryopreservation of oocytes and embryos is commonly used to preserve fertility. However, women undergoing cancer treatment may not have the time or may not be good candidates for these options. Ovarian cortical tissue cryopreservation and subsequent tissue transplant has been proven successful yet inefficient in preserving larger secondary follicles, and is not recommended as a fertility preservation option for women with certain cancers. We evaluated cryopreservation of individual follicles as an alternative option in rodents, nonhuman primates, and human primates. Under optimal conditions, cryopreserved mouse secondary follicles were able to reestablish granulosa cell-oocyte interactions, which are essential for subsequent follicle growth. Individual secondary follicles survived cryopreservation, were able to be cultured in a three-dimensional alginate hydrogel matrix to the antral stage, and the enclosed oocytes were competent for fertilization. Using a vital imaging technique (pol-scope) employed in many fertility centers, we were able to bioassay the thawed, cultured follicles for the presence of transzonal connections between the somatic and germ cells. Perturbations in these linkages were shown to be reversed when follicles were cryopreserved under optimal freezing conditions. We applied the optimized cryopreservation protocol to isolated rhesus monkey and human secondary follicles, and using the birefringent bioassay, we were able to show good correlation between early follicle growth and healthy somatic cell-oocyte connections. Our results suggest that ovarian follicles can be cryopreserved, thawed, and analyzed noninvasively, making follicle preservation an additional option for young cancer patients. PMID:20200211

  14. Recombinant porcine epidermal growth factor-secreting Lactococcus lactis promotes the growth performance of early-weaned piglets

    PubMed Central

    2014-01-01

    Background Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets’ production. Results A recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the

  15. The transcription factor early growth response factor-1 (EGR-1) promotes apoptosis of neuroblastoma cells.

    PubMed Central

    Pignatelli, Miguel; Luna-Medina, Rosario; Pérez-Rendón, Arturo; Santos, Angel; Perez-Castillo, Ana

    2003-01-01

    Early growth response factor-1 (EGR-1) is an immediate early gene, which is rapidly activated in quiescent cells by mitogens or in postmitotic neurons after depolarization. EGR-1 has been involved in diverse biological functions such as cell growth, differentiation and apoptosis. Here we report that enforced expression of the EGR-1 gene induces apoptosis, as determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labelling (TUNEL) analysis, in murine Neuro2A cells. In accordance with this role of EGR-1 in cell death, antisense oligonucleotides increase cell viability in cells cultured in the absence of serum. This apoptotic activity of the EGR-1 appears to be mediated by p73, a member of the p53 family of proteins, since an increase in the amount of p73 is observed in clones stably expressing the EGR-1 protein. We also observed an increase in the transcriptional activity of the mdm2 promoter in cells overexpressing EGR-1, which is paralleled by a marked decrease in the levels of p53 protein, therefore excluding a role of this protein in mediating EGR-1-induced apoptosis. Our results suggest that EGR-1 is an important factor involved in neuronal apoptosis. PMID:12755686

  16. Transcriptome Analysis of Early Surface-Associated Growth of Shewanella oneidensis MR-1

    PubMed Central

    Gödeke, Julia; Binnenkade, Lucas; Thormann, Kai M.

    2012-01-01

    Bacterial biofilm formation starts with single cells attaching to a surface, however, little is known about the initial attachment steps and the adaptation to the surface-associated life style. Here, we describe a hydrodynamic system that allows easy harvest of cells at very early biofilm stages. Using the metal ion-reducing gammaproteobacterium Shewanella oneidensis MR-1 as a model organism, we analyzed the transcriptional changes occurring during surface-associated growth between 15 and 60 minutes after attachment. 230 genes were significantly upregulated and 333 were downregulated by a factor of ≥2. Main functional categories of the corresponding gene products comprise metabolism, uptake and transport, regulation, and hypothetical proteins. Among the genes highly upregulated those implicated in iron uptake are highly overrepresented, strongly indicating that S. oneidensis MR-1 has a high demand for iron during surface attachment and initial biofilm stages. Subsequent microscopic analysis of biofilm formation under hydrodynamic conditions revealed that addition of Fe(II) significantly stimulated biofilm formation of S. oneidensis MR-1 while planktonic growth was not affected. Our approach to harvest cells for transcriptional analysis of early biofilm stages is expected to be easily adapted to other bacterial species. PMID:22860070

  17. 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. PMID:24504211

  18. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

    PubMed Central

    An, Chansik; Choi, Youn Ah; Choi, Dongil; Paik, Yong Han; Ahn, Sang Hoon; Kim, Myeong-Jin; Paik, Seung Woon; Han, Kwang-Hyub

    2015-01-01

    Background/Aims The goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate. Methods Patients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients. Results The median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234). Conclusions The etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC. PMID:26523271

  19. Technology, conflict early warning systems, public health, and human rights.

    PubMed

    Pham, Phuong N; Vinck, Patrick

    2012-01-01

    Public health and conflict early warning are evolving rapidly in response to technology changes for the gathering, management, analysis and communication of data. It is expected that these changes will provide an unprecedented ability to monitor, detect, and respond to crises. One of the potentially most profound and lasting expected change affects the roles of the various actors in providing and sharing information and in responding to early warning. Communities and civil society actors have the opportunity to be empowered as a source of information, analysis, and response, while the role of traditional actors shifts toward supporting those communities and building resilience. However, by creating new roles, relationships, and responsibilities, technology changes raise major concerns and ethical challenges for practitioners, pressing the need for practical guidelines and actionable recommendations in line with existing ethical principles. PMID:23568944

  20. Human evolution. Evolution of early Homo: an integrated biological perspective.

    PubMed

    Antón, Susan C; Potts, Richard; Aiello, Leslie C

    2014-07-01

    Integration of evidence over the past decade has revised understandings about the major adaptations underlying the origin and early evolution of the genus Homo. Many features associated with Homo sapiens, including our large linear bodies, elongated hind limbs, large energy-expensive brains, reduced sexual dimorphism, increased carnivory, and unique life history traits, were once thought to have evolved near the origin of the genus in response to heightened aridity and open habitats in Africa. However, recent analyses of fossil, archaeological, and environmental data indicate that such traits did not arise as a single package. Instead, some arose substantially earlier and some later than previously thought. From ~2.5 to 1.5 million years ago, three lineages of early Homo evolved in a context of habitat instability and fragmentation on seasonal, intergenerational, and evolutionary time scales. These contexts gave a selective advantage to traits, such as dietary flexibility and larger body size, that facilitated survival in shifting environments. PMID:24994657

  1. Growth Performance of Early Finishing Gilts as Affected by Different Net Energy Concentrations in Diets

    PubMed Central

    Lee, Gang Il; Kim, Kwang-Sik; Kim, Jong Hyuk; Kil, Dong Yong

    2015-01-01

    The objectives of the current experiment were to study the response of the growth performance of early finishing gilts to different net energy (NE) concentrations in diets, and to compare the NE values of diets between calculated NE values and measured NE values using French and Dutch CVB (Centraal Veevoederbureau; Central Bureau for Livestock Feeding) NE systems. In a metabolism trail, the NE concentrations in five diets used for the growth trial were determined based on digestible nutrient concentrations, digestible energy, and metabolizable energy using a replicated 5×5 Latin square design with 10 barrows (initial body weight [BW], 39.2±2.2 kg). In a growth trial, a total of 60 early finishing gilts (Landrace×Yorkshire; initial BW, 47.7±3.5 kg) were allotted to five dietary treatments of 8.0, 9.0, 10.0, 11.0, and 12.0 MJ NE/kg (calculated, as-is basis) with 12 replicate pens and one pig per pen in a 42-d feeding experiment. The NE and amino acid (AA) concentrations in all diets were calculated based on the values from NRC (2012). Ratios between standardized ileal digestible AA and NE concentrations in all diets were closely maintained. Pigs were allowed ad libitum access to feed and water. Results indicated that calculated NE concentrations in diets (i.e., five dietary treatments) were close to measured NE concentrations using French NE system in diets. The final BW was increased (linear and quadratic, p<0.05) with increasing NE concentrations in diets. Furthermore, average daily gain (ADG) was increased (linear and quadratic, p<0.01) with increasing NE concentrations in diets. There was a quadratic relationship (p<0.01) between average daily feed intake and NE concentrations in diets. Feed efficiency (G:F) was also increased (linear, p<0.01) as NE concentrations in diets were increased. The NE intake per BW gain (kcal NE/kg of BWG) was increased (linear, p<0.01) with increasing NE concentrations in diets that were predicted from both French and Dutch CVB NE

  2. 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

  3. Glypican-1 controls brain size through regulation of fibroblast growth factor signaling in early neurogenesis

    PubMed Central

    Jen, Yi-Huei Linda; Musacchio, Michele; Lander, Arthur D

    2009-01-01

    Background Cell surface heparan sulfate proteoglycans (HSPGs) act as co-receptors for multiple families of growth factors that regulate animal cell proliferation, differentiation and patterning. Elimination of heparan sulfate during brain development is known to produce severe structural abnormalities. Here we investigate the developmental role played by one particular HSPG, glypican-1 (Gpc1), which is especially abundant on neuronal cell membranes, and is the major HSPG of the adult rodent brain. Results Mice with a null mutation in Gpc1 were generated and found to be viable and fertile. The major phenotype associated with Gpc1 loss is a highly significant reduction in brain size, with only subtle effects on brain patterning (confined to the anterior cerebellum). The brain size difference emerges very early during neurogenesis (between embryonic days 8.5 and 9.5), and remains roughly constant throughout development and adulthood. By examining markers of different signaling pathways, and the differentiation behaviors of cells in the early embryonic brain, we infer that Gpc1-/- phenotypes most likely result from a transient reduction in fibroblast growth factor (FGF) signaling. Through the analysis of compound mutants, we provide strong evidence that Fgf17 is the FGF family member through which Gpc1 controls brain size. Conclusion These data add to a growing literature that implicates the glypican family of HSPGs in organ size control. They also argue that, among heparan sulfate-dependent signaling molecules, FGFs are disproportionately sensitive to loss of HSPGs. Finally, because heterozygous Gpc1 mutant mice were found to have brain sizes half-way between homozygous and wild type, the data imply that endogenous HSPG levels quantitatively control growth factor signaling, a finding that is both novel and relevant to the general question of how the activities of co-receptors are exploited during development. PMID:19732411

  4. Self-regulating the early growth of black holes through global warming

    NASA Astrophysics Data System (ADS)

    Haiman, Zoltán; Tanaka, Takamitsu; Perna, Rosalba

    2012-09-01

    A decade after their first discovery, the origin of giant supermassive black holes (SMBHs), with masses in excess of 109 Msolar, at redshifts as early as z > 6, remains a puzzle. One possibility is that stellar-mass ``seed'' BHs, left behind by the first stars, accrete gas at close to the Eddington limit during a large fraction (>~ 50%) of the time. While maintaining such a high accretion rate may itself be difficult, here we focus on another, less commonly discussed problem in this scenario: unless BH seed formation and growth are preferentially suppressed in less massive protogalaxies, the mass density in M~106Msolar SMBHs at z ~ 6 already exceeds the locally observed SMBH mass density by several orders of magnitude. We show that the X-rays from the earliest accreting BHs themselves can cause a self-regulation, by partially ionizing and heating the intergalactic medium (IGM). This ``global warming'' suppresses the formation and growth of subsequent generations of BHs in low-mass halos, and can produce excellent agreement with recent estimates of the z = 6 SMBH mass function, without impeding the growth of the largest (M>~109Msolar) holes, which reside in the most massive galaxies that formed first. The proposed gravitational-wave observatory eLISA could detect several tens of major mergers between SMBHs at z > 6.

  5. Comparative pharmacokinetics and pharmacodynamics of a PEGylated recombinant human growth hormone and daily recombinant human growth hormone in growth hormone-deficient children

    PubMed Central

    Hou, Ling; Chen, Zhi-hang; Liu, Dong; Cheng, Yuan-guo; Luo, Xiao-ping

    2016-01-01

    Objective Recombinant human growth hormone (rhGH) replacement therapy in children generally requires daily subcutaneous (sc) injections, which may be inconvenient for patients. Jintrolong® is a PEGylated rhGH with the purpose of weekly sc injections. The aim of the current study was to examine the pharmacokinetics, pharmacodynamics, safety, and tolerability of multiple sc doses of Jintrolong® vs daily doses of rhGH. Design and methods Twelve children with growth hormone deficiency participated in this single-center, open-label, crossover Phase I trial. All subjects received daily sc injections of rhGH at 0.0286 mg/kg/d for 7 days, followed by a 4-week washout period and six weekly doses of Jintrolong® at 0.2 mg/kg/w. Results In comparison with rhGH, sc injection of Jintrolong® produced a noticeably higher Cmax, significantly longer half-life (t1/2), and slower plasma clearance, signifying a profile suitable for long-term treatment. The ratio of the area under the concentration vs time curve (AUC) after the seventh and first injections (AUC(0–∞)7th/AUC(0–∞)1st) of rhGH was 1.02, while the AUC(0–∞)6th/AUC(0–∞)1st of Jintrolong ® was 1.03, indicating no accumulation of circulating growth hormone. There was no significant difference in the change in insulin-like growth factor-1 expression produced by 7 days of sc rhGH and weekly Jintrolong® injections. There were no severe adverse events during the trial. Conclusion The elimination rate of Jintrolong® was slower than that of sc rhGH. No progressive serum accumulation of Jintrolong® was found. The changes in insulin-like growth factor-1 expression produced by rhGH and Jintrolong® were comparable, indicating similar pharmacodynamics. Our results demonstrate that Jintrolong® is suitable for long-term growth hormone treatment in children with growth hormone deficiency. PMID:26719670

  6. Algorithmic complexity of growth hormone release in humans

    SciTech Connect

    Prank, K.; Wagner, M.; Brabant, G.

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  7. Purification and Cultivation of Human Pituitary Growth Hormones Secreting Cells

    NASA Technical Reports Server (NTRS)

    Hymer, W. C.; Todd, P.; Grindeland, R.; Lanham, W.; Morrison, D.

    1985-01-01

    The rat and human pituitary gland contains a mixture of hormone producing cell types. The separation of cells which make growth hormone (GH) is attempted for the purpose of understanding how the hormone molecule is made within the pituitary cell; what form(s) it takes within the cell; and what form(s) GH assumes as it leaves the cell. Since GH has a number of biological targets (e.g., muscle, liver, bone), the assessment of the activities of the intracellular/extracellular GH by new and sensitive bioassays. GH cells contained in the mixture was separated by free flow electrophoresis. These experiments show that GH cells have different electrophoretic mobilities. This is relevant to NASA since a lack of GH could be a prime causative factor in muscle atrophy. Further, GH has recently been implicated in the etiology of motion sickness in space. Continous flow electrophoresis experiment on STS-8 showed that GH cells could be partially separated in microgravity. However, definitive cell culture studies could not be done due to insufficient cell recoveries.

  8. Human Ecology and Television in Early Childhood Education.

    ERIC Educational Resources Information Center

    Schleicher, Klaus

    A human ecological approach to the study of children's television viewing raises questions that researchers have largely neglected. Does television influence the interaction patterns of socializing agents with children and with one another? Are there long-term, psychological consequences of unintegrated and competing influences from television and…

  9. No Evidence of Neandertal mtDNA Contribution to Early Modern Humans

    PubMed Central

    2004-01-01

    The retrieval of mitochondrial DNA (mtDNA) sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution. PMID:15024415

  10. A Life-Span Human Development Model of Learning for Early Education.

    ERIC Educational Resources Information Center

    Languis, Marlin; Wilcox, Jean

    1981-01-01

    A life-span human development model of learning in early childhood is presented. Learning is viewed as a human enterprise which spans the entire lifetime and involves interaction among people. The bounds of interaction are derived from philosophy and from the biological and social behavioral sciences. (JN)

  11. Early East Antarctic Ice Sheet growth recorded in the landscape of the Gamburtsev Subglacial Mountains

    NASA Astrophysics Data System (ADS)

    Rose, Kathryn C.; Ferraccioli, Fausto; Jamieson, Stewart S. R.; Bell, Robin E.; Corr, Hugh; Creyts, Timothy T.; Braaten, David; Jordan, Tom A.; Fretwell, Peter T.; Damaske, Detlef

    2013-08-01

    The Gamburtsev Subglacial Mountains are regarded as a key nucleation site for the Antarctic Ice Sheet and they retain a unique long-term record of pre-glacial and early glacial landscape evolution. Here, we use a range of morphometric analyses to constrain the nature of early glaciation and subsequent ice sheet evolution in the interior of East Antarctica, using a new digital elevation model of the Gamburtsev Subglacial Mountains, derived from an extensive airborne radar survey. We find that an inherited fluvial landscape confirms the existence of the Gamburtsev Subglacial Mountains prior to the onset of glaciation at the Eocene-Oligocene climate boundary (ca. 34 Ma). Features characteristic of glaciation, at a range of scales, are evident across the mountains. High elevation alpine valley heads, akin to cirques, identified throughout the mountains, are interpreted as evidence for early phases of glaciation in East Antarctica. The equilibrium line altitudes associated with these features, combined with information from fossil plant assemblages, suggest that they formed at, or prior to, 34 Ma. It cannot be ruled out that they may have been eroded by ephemeral ice between the Late Cretaceous and the Eocene (100-34 Ma). Hanging valleys, overdeepenings, truncated spurs and steep-sided, linear valley networks are indicative of a more widespread alpine glaciation in this region. These features represent ice growth at, or before, 33.7 Ma and provide a minimum estimate for the scale of the East Antarctic Ice Sheet between ca. 34 and 14 Ma, when dynamic fluctuations in ice extent are recorded at the coast of Antarctica. The implications are that the early East Antarctic Ice Sheet grew rapidly and developed a cold-based core that preserved the alpine landscape. The patterns of landscape evolution identified provide the earliest evidence for the development of the East Antarctic Ice Sheet and can be used to test coupled ice-climate evolution models.

  12. Extension rates and growth in tooth height of modern human and fossil hominin canines and molars.

    PubMed

    Dean, M Christopher

    2009-01-01

    The aim of this study was to describe similarities and differences in the way modern and fossil hominin teeth grow in height. Measurements from longitudinal ground sections of 7 modern human canines and 19 first permanent molars were used to calculate extension rates in the crowns and roots and to plot distance curves for growth in tooth height. These were compared with identical data for 3 fossil hominin teeth attributed respectively to Paranthropus robustus, Homo erectus and Homo neanderthalensis. Enamel extension rates in each of the three fossil taxa fell within the range of modern humans. Root extension rates in the fossil taxa also fell within modern human ranges but differed in their pattern with either an early or late marked increase in root length. Extension rates in the canine crowns were higher in cuspal enamel than in lateral enamel. Combinations of high or low cuspal enamel extension rates, with either longer or shorter times taken to form lateral enamel, explain how crown formation times may vary independently of completed crown heights. PMID:19828973

  13. Theoretical Foundations of the Early Childhood Research Institute on Measuring Growth and Development: An Early Childhood Problem-Solving Model. Technical Report #6.

    ERIC Educational Resources Information Center

    McConnell, Scott; McEvoy, Mary; Carta, Judith J.; Greenwood, Charles R.; Kaminski, Ruth; Good, Roland H., III; Shinn, Mark

    This report describes the decision-making model that provides the theoretical framework being developed by the Early Childhood Research Institute on Measuring Growth and Development (ECRI-MGD) in a 5-year project to generate a set of common child and family indicators that can be used within a comprehensive system of service delivery for young…

  14. 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. PMID:25054305

  15. 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

  16. Early detection of intentional harm in the human amygdala.

    PubMed

    Hesse, Eugenia; Mikulan, Ezequiel; Decety, Jean; Sigman, Mariano; Garcia, María del Carmen; Silva, Walter; Ciraolo, Carlos; Vaucheret, Esteban; Baglivo, Fabricio; Huepe, David; Lopez, Vladimir; Manes, Facundo; Bekinschtein, Tristan A; Ibanez, Agustin

    2016-01-01

    A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These networks rely on the amygdala as a critical hub, likely through frontotemporal connections indexing stimulus salience. We assessed inferences about perceived harm using a paradigm validated through functional magnetic resonance imaging, eye-tracking and electroencephalogram recordings. During the task, we measured local field potentials in three patients with depth electrodes (n = 115) placed in the amygdala and in several frontal, temporal, and parietal locations. Direct electrophysiological recordings demonstrate that intentional harm induces early activity in the amygdala (<200 ms), which--in turn--predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classification of events as intentional. Moreover, connectivity analysis showed that intentional harm induced stronger frontotemporal information sharing at early stages. Results support the 'many roads' view of the amygdala and highlight its role in the rapid encoding of intention and salience--critical components of mentalizing and moral evaluation. PMID:26608745

  17. Early electrophysiological markers of visual awareness in the human brain.

    PubMed

    Ohla, Kathrin; Busch, Niko A; Herrmann, Christoph S

    2007-10-01

    The present study investigated neuronal correlates of stimulus processing leading to conscious perception of a task irrelevant global structure in a visual display. To study the underlying neuronal processes, participants were presented different types of dot patterns (Glass patterns) either forming a global structure or forming no global structure while EEG was recorded. Participants were naive about the pattern types and performed a demanding colour discrimination task. Following the experiment, the degree to which participants acquired awareness of the global visual structure was assessed. Early gamma-frequency band responses (gamma, 25-100 Hz) over occipital, parietal, and central areas were enhanced to circular Glass patterns as compared to random dot patterns at 90 ms post-stimulus. This effect was observed exclusively in participants who were subjectively aware of the global pattern structure. In this group of observers, the pattern effect built up gradually during the course of the experiment. The significance of enhanced early gamma responses to global patterns for the production of awareness of the pattern might lie in the increased impact of information conveyed by well synchronised neuronal assemblies to upstream cortical areas. PMID:17656113

  18. Human memory development and its dysfunction after early hippocampal injury.

    PubMed

    de Haan, Michelle; Mishkin, Mortimer; Baldeweg, Torsten; Vargha-Khadem, Faraneh

    2006-07-01

    Cognitive memory involves long-term memories for facts (semantic memory) and personal experiences (episodic memory) that can be brought to mind. There is consensus that the hippocampus and related medial temporal lobe (MTL) structures are crucial for adult cognitive memory, but much less is known about their contribution to memory during infancy and childhood. We argue that the MTL is involved in memory from early in life, supporting recognition memory within the first postnatal months and recall memory within the first year. We propose that normal development involves a sequence in which a form of semantic-like memory emerges first, whereas the characteristics of episodic memory develop only later with progressive development of the hippocampus. Early bilateral injury to the hippocampus disrupts this normal pattern such that memory skills cannot develop beyond the stage of semantic memories. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/). PMID:16750273

  19. Rate of language growth in children with hearing loss in an auditory-verbal early intervention program.

    PubMed

    Jackson, Carla Wood; Schatschneider, Christopher

    2014-01-01

    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. (PLS-4; Zimmerman, Steiner, & Pond, 2002) for 24 children with hearing loss in a convenience sample. A statistically significant change in raw scores was observed across 6-month intervals. However, growth in standard scores did not show statistically significant predictable change across the 6-month intervals. Scores on the language measure were closer to expectations for younger peers with normal hearing when compared to data reported for the PLS-4 normative sample. Language outcomes varied significantly for individual children based on time spent in early intervention, suggesting that intervention was contributing to growth. PMID:24745108

  20. Early Life Growth Predicts Pubertal Development in South African Adolescents123

    PubMed Central

    Norris, Shane A; Martorell, Reynaldo; Mehta, Neil K; Richter, Linda M

    2016-01-01

    Background: 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. Objective: We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa. Methods: 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. Results: 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). Conclusion: 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

  1. Do early growth dynamics explain recruitment success in Japanese flounder Paralichthys olivaceus off the Pacific coast of northern Japan?

    NASA Astrophysics Data System (ADS)

    Oshima, Masakane; Robert, Dominique; Kurita, Yutaka; Yoneda, Michio; Tominaga, Osamu; Tomiyama, Takeshi; Yamashita, Yoh; Uehara, Shinji

    2010-07-01

    We examined the relative importance of growth-related processes operating during the larval and early juvenile stage in explaining variability in year class success of Japanese flounder off the Pacific coast of northern Japan. Early growth trajectory of larvae and juveniles sampled in 2005 (strong year class) and in 2006 (weak year class) was estimated from the analysis of the lapillar otolith. The larval pelagic stage was characterized by lower growth and developmental rates, as well as high selection for fast growth in the metamorphosis/settlement period, during the strong recruitment event of 2005 relative to 2006. Growth appeared higher in 2005 only after settlement despite high density in the nursery, which likely reflected superior productivity during that year combined with an increased probability of cannibalism from early settlers on late settlers. This implies that larval growth dynamics did not play an important role in determining recruitment strength in the two years considered. The decreasing distance from the nursery areas of pelagic larvae through ontogeny in 2005, combined with low age at settlement, suggest that larvae benefited from positive transport conditions during the dominant year class. To the contrary, unfavorable hydrographic conditions likely prevailed in 2006 as distance from the nurseries increased with ontogeny and settlement occurred later than in 2005 despite faster growth potential and developmental rate. We conclude that transport conditions to the nursery grounds, rather than larval growth potential, represented the most important determinant of year class success in the two years considered.

  2. New developments in the treatment of early-onset spinal deformity: role of the Shilla growth guidance system

    PubMed Central

    Morell, Sean M; McCarthy, Richard E

    2016-01-01

    Early-onset scoliosis is a complex condition with multiple facets. The goal of treating any spinal deformity is to improve the condition of the patient with the least intervention necessary. A system that allows for continuation of natural spinal growth while correcting the deformity should be the goal of treating this complex condition. The SHILLA growth guidance system allows for continued growth of the pediatric spine while correcting and guiding the apex and guiding the future growth of the curvature. The system involves selective fusion across the apex of the curvature, and minimally invasive instrumentation is then used above and below the apex to allow for continued growth of the spine. A review of recent literature on the SHILLA growth guidance system shows promising results. Early animal models showed continued growth across unfused levels with minimal facet articular damage. Comparative studies to traditional growing rods showed significantly less total surgeries along with comparable correction and longitudinal growth. The SHILLA growth guidance system is a good option for this complex patient group. Results are comparable with other growing constructs with significantly less operative interventions. The SHILLA system allows for natural growth of the pediatric spine while correcting the scoliotic deformity in a minimally invasive method. The goal of this article is to present a comprehensive review of the SHILLA system surgical technique and the associated literature concerning this topic. PMID:27499651

  3. 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…

  4. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study

    PubMed Central

    Matijasevich, Alicia; Howe, Laura D; Tilling, Kate; Santos, Iná S; Barros, Aluísio J D; Lawlor, Debbie A

    2012-01-01

    Summary Matijasevich A, Howe LD, Tilling K, Santos IS, Barros AJD, Lawlor DA. Maternal education inequalities in height growth rates in early childhood: 2004 Pelotas birth cohort study. Paediatric and Perinatal Epidemiology 2012; 26: 236–249. Socio-economic inequalities in attained height have been reported in many countries. The aim of this study was to explore the age at which maternal education inequalities in child height emerge among children from a middle-income country. Using data from the 2004 Pelotas cohort study from Brazil we modelled individual height growth trajectories in 2106 boys and 1947 girls from birth to 4 years using a linear spline mixed-effects model. We examined the associations of maternal education with birth length and trajectories of growth in length/height, and explored the effect of adjusting for a number of potential confounder or mediator factors. We showed linear and positive associations of maternal education with birth length and length/height growth rates at 0–3 months and 12–29/32 months with very little association at 3–12 months, particularly in boys. By age 4 years the mean height of boys was 101.06 cm (SE = 0.28) in the lowest and 104.20 cm (SE = 0.15) in the highest education category (mean difference 3.14 cm, SE = 0.32, P < 0.001). Among girls the mean height was 100.02 cm (SE = 0.27) and 103.03 cm (SE = 0.15) in the lowest and highest education categories, respectively (mean difference 3.01 cm, SE = 0.31, P < 0.001). For both boys and girls there was on average a 3-cm difference between the extreme education categories. Adjusting for maternal height reduced the observed birth length differences across maternal education categories, but differences in postnatal growth rates persisted. Our data demonstrate an increase in the absolute and relative inequality in height after birth; inequality increases from approximately 0.2 standard deviations of birth length to approximately 0.7 standard deviations of height at age

  5. 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

  6. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    PubMed Central

    Li, Yue; Xie, Changchun; Murphy, Susan K.; Skaar, David; Nye, Monica; Vidal, Adriana C.; Cecil, Kim M.; Dietrich, Kim N.; Puga, Alvaro; Jirtle, Randy L.; Hoyo, Cathrine

    2015-01-01

    Background: 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. Objectives: 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. Methods: Questionnaire data and serial blood lead levels were obtained from 105 participants (64 females, 41 males) of the Cincinnati Lead Study from 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. Results: 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

  7. Early growth of Kohala volcano and formation of long Hawaiian rift zones

    USGS Publications Warehouse

    Lipman, P.W.; Calvert, A.T.

    2011-01-01

    Transitional-composition pillow basalts from the toe of the Hilo Ridge, collected from outcrop by submersible, have yielded the oldest ages known from the Island of Hawaii: 1138 ?? 34 to 1159 ?? 33 ka. Hilo Ridge has long been interpreted as a submarine rift zone of Mauna Kea, but the new ages validate proposals that it is the distal east rift zone of Kohala, the oldest subaerial volcano on the island. These ages constrain the inception of tholeiitic volcanism at Kohala, provide the first measured duration of tholeiitic shield building (???870 k.y.) for any Hawaiian volcano, and show that this 125-km-long rift zone developed to near-total length during early growth of Kohala. Long eastern-trending rift zones of Hawaiian volcanoes may follow fractures in oceanic crust activated by arching of the Hawaiian Swell in front of the propagating hotspot. ?? 2011 Geological Society of America.

  8. Thermodynamic characterization of an intermediate state of human growth hormone.

    PubMed Central

    Gomez-Orellana, I.; Variano, B.; Miura-Fraboni, J.; Milstein, S.; Paton, D. R.

    1998-01-01

    The thermal denaturation of recombinant human growth hormone (rhGH) was studied by differential scanning calorimetry and circular dichroism spectroscopy (CD). The thermal unfolding is reversible only below pH 3.5, and under these conditions a single two-state transition was observed between 0 and 100 degrees C. The magnitudes of the deltaH and deltaCp of this transition indicate that it corresponds to a partial unfolding of rhGH. This is also supported by CD data, which show that significant secondary structure remains after the unfolding. Above pH 3.5 the thermal denaturation is irreversible due to the aggregation of rhGH upon unfolding. This aggregation is prevented in aqueous solutions of alcohols such as n-propanol, 2-propanol, or 1,2-propanediol (propylene glycol), which suggests that the self-association of rhGH is caused by hydrophobic interactions. In addition, it was found that the native state of rhGH is stable in relatively high concentrations of propylene glycol (up to 45% v/v at pH 7-8 or 30% at pH 3) and that under these conditions the thermal unfolding is cooperative and corresponds to a transition from the native state to a partially folded state, as observed at acidic pH in the absence of alcohols. In higher concentrations of propylene glycol, the tertiary structure of rhGH is disrupted and the cooperativity of the unfolding decreases. Moreover, the CD and DSC data indicate that a partially folded intermediate with essentially native secondary structure and disordered tertiary structure becomes significantly populated in 70-80% propylene glycol. PMID:9655339

  9. CytoregR inhibits growth and proliferation of human adenocarcinoma cells via induction of apoptosis

    PubMed Central

    Kumi-Diaka, J; Hassanhi, M; Brown, J; Merchant, K; Garcia, C; Jimenez, W

    2006-01-01

    Background Cancer is one of the devastating neovascular diseases that incapacitate so many people the world over. Recent reports from the National Cancer Institute indicate some significant gain therapy and cancer management as seen in the increase in the 5-year survival rate over the past two decades. Although near-perfect cure rate have been reported in the early-stage disease, these data reveal high recurrence rate and serious side effects including second malignancies and fatalities. Most of the currently used anticancer agents are only effective against proliferating cancer cells. Thus attention has been focused on potential anti-cancer agents capable of killing cancer cells independent of the cell cycle state, to ensure effective elimination of most cancer cells. The objective of this study was to test the chemosensitivity and potential mechanism of action of a novel cancer drug, CytoregR, in a panel of human cancer cells. Methods the study was performed using a series of bioassays including Trypan blue exclusion, MTS Growth inhibition, LDH-cytotoxicity, TUNEL-Terminal DNA fragmentation Apoptosis Assay, and the Caspase protease CPP32 activity assays. Results CytoregR induced significant dose- and time-dependent inhibition of growth in all the cells; with significant differences in chemosensitivity (P < 0.05) between the target cells becoming more apparent at 48 hr exposure. CytoregR showed no significant effect on normal cells relative to the tumor cells. Growth inhibition in all the cells was due to induction of apoptosis at lower concentrations of cytoregR (> 1:300). CytoregR-induced caspase protease-3 (CPP32) activation significantly and positively correlated with apoptosis induction and growth inhibition; thus implicating CPP32 as the principal death pathway in cytoregR-induced apoptosis. Conclusion CytoregR exerted a dose-and time-dependent growth inhibitory effect in all the target cells through induction of apoptosis via the CPP32 death pathway

  10. Pertuzumab in human epidermal growth-factor receptor 2-positive breast cancer: clinical and economic considerations

    PubMed Central

    Lamond, Nathan WD; Younis, Tallal

    2014-01-01

    In the absence of specific therapy, the 15%–20% of breast cancers demonstrating human epidermal growth-factor receptor 2 (HER2) protein overexpression and/or gene amplification are characterized by a more aggressive phenotype and poorer prognosis compared to their HER2-negative counterparts. Trastuzumab (Herceptin), the first anti-HER2-targeted therapy, has been associated with improved survival outcomes in HER2-positive breast cancer. However, many patients with early stage disease continue to relapse, and metastatic disease remains incurable. In order to further improve these outcomes, several novel HER2-targeted agents have recently been developed. Pertuzumab (Perjeta), a monoclonal antibody against the HER2 dimerization domain, has also been associated with improved patient outcomes in clinical trials, and has recently been approved in combination with chemotherapy and trastuzumab for neoadjuvant therapy of early stage, HER2-positive breast cancer and first-line treatment of metastatic disease. This review briefly summarizes pertuzumab’s clinical development as well as the published evidence supporting its use, and highlights some of the currently unanswered questions that will influence pertuzumab’s incorporation into clinical practice. PMID:24876795

  11. Attenuating Growth: A More Humane Alternative--A Response to Gunther and Diekema

    ERIC Educational Resources Information Center

    Romer, Lyle T; Crocker, Allen C.

    2006-01-01

    An astonishing tract has been published that involves a plan for the modification of the growth of children with severe developmental disabilities by administering hormonal treatments designed to arrest growth at an early age (Gunther & Diekema, 2006). The schema put forth is based upon the concern of the authors for the burdensome effect families…

  12. Brightness–Color Interactions in Human Early Visual Cortex

    PubMed Central

    Ouni, Ahmed; Chen, Stephanie; Sahmoud, Hinde; Gordon, James; Shapley, Robert

    2015-01-01

    The interaction between brightness and color causes there to be different color appearance when one and the same object is viewed against surroundings of different brightness. Brightness contrast causes color to be desaturated, as has been found in perceptual experiments on color induction and color-gamut expansion in human vision. However, it is not clear yet where in the cerebral cortex the brightness–color interaction that causes these major perceptual effects is located. One hypothesis is that brightness and color signals are processed separately and in parallel within the primary visual cortex V1 and only interact in extrastriate cortex. Another hypothesis is that color and brightness contrast interact strongly already within V1. We localized the brightness–color interaction in human V1 by means of recording the chromatic visual-evoked potential. The chromatic visual-evoked potential measurements decisively support the idea that brightness–color interaction arises in a recurrent inhibitory network in V1. Furthermore, our results show that the inhibitory signal for brightness–color interaction is generated by local brightness contrast at the boundary between target and surround, instead of by the luminance difference between the interior of the color target and its large background. PMID:25653377

  13. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2015-06-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  14. Edwin Grant Dexter: an early researcher in human behavioral biometeorology

    NASA Astrophysics Data System (ADS)

    Stewart, Alan E.

    2014-09-01

    Edwin Grant Dexter (1868-1938) was one of the first researchers to study empirically the effects of specific weather conditions on human behavior. Dexter (1904) published his findings in a book, Weather influences. The author's purposes in this article were to (1) describe briefly Dexter's professional life and examine the historical contexts and motivations that led Dexter to conduct some of the first empirical behavioral biometeorological studies of the time, (2) describe the methods Dexter used to examine weather-behavior relationships and briefly characterize the results that he reported in Weather influences, and (3) provide a historical analysis of Dexter's work and assess its significance for human behavioral biometeorology. Dexter's Weather influences, while demonstrating an exemplary approach to weather, health, and behavior relationships, came at the end of a long era of such studies, as health, social, and meteorological sciences were turning to different paradigms to advance their fields. For these reasons, Dexter's approach and contributions may not have been fully recognized at the time and are, consequently, worthy of consideration by contemporary biometeorologists.

  15. Differential regulation of human Eag1 channel expression by serum and epidermal growth factor in lung and breast cancer cells

    PubMed Central

    Acuña-Macías, Isabel; Vera, Eunice; Vázquez-Sánchez, Alma Yolanda; Mendoza-Garrido, María Eugenia; Camacho, Javier

    2015-01-01

    Oncogenic ether à-go-go-1 (Eag1) potassium channels are overexpressed in most primary human solid tumors. Low oxygen and nutrient/growth factor concentrations play critical roles in tumorigenesis. However, the mechanisms by which tumor cells survive and proliferate under growth factor-depleted conditions remain elusive. Here, we investigated whether serum-deprived conditions and epidermal growth factor (EGF) regulate Eag1 expression in human lung and breast cancer cells. The human cancer cell lines A549 and MCF-7 (from the lungs and breast, respectively) were obtained from the American Type Culture Collection and cultured following the manufacturer’s recommendations. Eag1 gene and protein expression were studied by real-time PCR and immunocytochemistry, respectively. Cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and ERK1/2 phosphorylation was investigated by Western blot. Serum-deprived conditions increased Eag1 mRNA and protein expression in both cell lines. This Eag1 upregulation was prevented by EGF and the ERK1/2 inhibitor U0126 in only lung cancer cells; vascular endothelial growth factor did not prevent Eag1 upregulation. Our results suggest that Eag1 may act as a survival and mitogenic factor under low-serum and nutrient conditions and may be a clinical target during the early stages of tumor development. PMID:26527881

  16. [Use of translational medicine in the early diagnosis of xenobiotic-induced intrauterine growth retardation].

    PubMed

    Liu, Yan-Song; Wang, Hui

    2011-01-01

    Translational medicine is an emerging idea in current medical research area. Typically, for the purpose of bridging the gap between basic and clinical research, it not only emphasizes the urgency and necessity to break the traditional working formats, including single subject centered research team and limited cooperation among different scientific groups, but also highlights a more close and frequent interaction between basic scientist and clinician. In order to reach this goal, the theory and method of systems biology should be employed. This paper mainly focused on a central issue that how to carry out an investigation on early clinical diagnosis of xenobiotic-induced intrauterine growth retardation (IUGR) by using research concept of translational medicine and method of systems biology. Briefly, a hypothesis of common mechanism of IUGR was first proposed and subsequent validation was performed via integrating--omics (e.g. genomics, proteomics, cytomics, metabonomics/metabolomics) and molecular biology techniques. Metabonomics was further utilized to explore IUGR biomarker and establish preliminary forecasting model by bioinformatics and computational biology, which is available for early diagnosis of IUGR and make a complement to current evaluation criteria. PMID:21465805

  17. Delayed Phenotypic Expression of Growth Hormone Transgenesis during Early Ontogeny in Atlantic Salmon (Salmo salar)?

    PubMed Central

    Moreau, Darek T. R.; Gamperl, A. Kurt; Fletcher, Garth L.; Fleming, Ian A.

    2014-01-01

    Should growth hormone (GH) transgenic Atlantic salmon escape, there may be the potential for ecological and genetic impacts on wild populations. This study compared the developmental rate and respiratory metabolism of GH transgenic and non-transgenic full sibling Atlantic salmon during early ontogeny; a life history period of intense selection that may provide critical insight into the fitness consequences of escaped transgenics. Transgenesis did not affect the routine oxygen consumption of eyed embryos, newly hatched larvae or first-feeding juveniles. Moreover, the timing of early life history events was similar, with transgenic fish hatching less than one day earlier, on average, than their non-transgenic siblings. As the start of exogenous feeding neared, however, transgenic fish were somewhat developmentally behind, having more unused yolk and being slightly smaller than their non-transgenic siblings. Although such differences were found between transgenic and non-transgenic siblings, family differences were more important in explaining phenotypic variation. These findings suggest that biologically significant differences in fitness-related traits between GH transgenic and non-transgenic Atlantic salmon were less than family differences during the earliest life stages. The implications of these results are discussed in light of the ecological risk assessment of genetically modified animals. PMID:24763675

  18. Growth trajectories of alcohol information processing and associations with escalation of drinking in early adolescence

    PubMed Central

    Colder, Craig R.; O’Connor, Roisin M.; Read, Jennifer P.; Eiden, Rina D.; Lengua, Liliana J.; Hawk, Larry W.; Wieczorek, William F.

    2014-01-01

    This longitudinal study provided a comprehensive examination of age-related changes in alcohol outcome expectancies, subjective evaluation of alcohol outcomes, and automatic alcohol associations in early adolescence. A community sample (52% female, 75% White/Non-Hispanic) was assessed annually for three years (mean age at the first assessment = 11.6 years). Results from growth modeling suggested that perceived likelihood of positive outcomes increased and that subjective evaluations of these outcomes were more positive with age. Perceived likelihood of negative outcomes declined with age. Automatic alcohol associations were assessed with an Implicit Association Task (IAT), and were predominantly negative, but these negative associations weakened with age. High initial levels of perceived likelihood of positive outcomes at age 11 were associated with escalation of drinking. Perceived likelihood of negative outcomes was associated with low risk for drinking at age 11, but not with changes in drinking. Increases in positive evaluations of positive outcomes were associated with increases in alcohol use. Overall, findings suggest that at age 11, youth maintain largely negative attitudes and perceptions about alcohol, but with the transition into adolescence, there is a shift toward a more neutral or ambivalent view of alcohol. Some features of this shift are associated with escalation of drinking. Our findings point to the importance of delineating multiple aspects of alcohol information processing for extending cognitive models of alcohol use to the early stages of drinking. PMID:24841180

  19. Growth trajectories of alcohol information processing and associations with escalation of drinking in early adolescence.

    PubMed

    Colder, Craig R; O'Connor, Roisin M; Read, Jennifer P; Eiden, Rina D; Lengua, Liliana J; Hawk, Larry W; Wieczorek, William F

    2014-09-01

    This longitudinal study provided a comprehensive examination of age-related changes in alcohol outcome expectancies, subjective evaluation of alcohol outcomes, and automatic alcohol associations in early adolescence. A community sample (52% female, 75% White/non-Hispanic) was assessed annually for 3 years (mean age at the first assessment = 11.6 years). Results from growth modeling suggested that perceived likelihood of positive outcomes increased and that subjective evaluations of these outcomes were more positive with age. Perceived likelihood of negative outcomes declined with age. Automatic alcohol associations were assessed with an Implicit Association Task (IAT), and were predominantly negative, but these negative associations weakened with age. High initial levels of perceived likelihood of positive outcomes at age 11 were associated with escalation of drinking. Perceived likelihood of negative outcomes was associated with low risk for drinking at age 11, but not with changes in drinking. Increases in positive evaluations of positive outcomes were associated with increases in alcohol use. Overall, findings suggest that at age 11, youth maintain largely negative attitudes and perceptions about alcohol, but with the transition into adolescence, there is a shift toward a more neutral or ambivalent view of alcohol. Some features of this shift are associated with escalation of drinking. Our findings point to the importance of delineating multiple aspects of alcohol information processing for extending cognitive models of alcohol use to the early stages of drinking. PMID:24841180

  20. Clinical implications of insulin-like growth factor 1 system in early-stage cervical cancer

    PubMed Central

    Huang, Y-F; Shen, M-R; Hsu, K-F; Cheng, Y-M; Chou, C-Y

    2008-01-01

    This study was aimed to identify the expression and the correlation of insulin-like growth factor-1 (IGF-1) system and their prognostic impacts in cervical cancer. Seventy-two patients with early-stage cervical cancer were eligible. We obtained the serum levels of total IGF-1 and IGF binding protein-3 (IGFBP-3) by enzyme-linked immunosorbent assay and the expression of IGF-1 receptor (IGF-1R) in cancerous tissue by immuno-fluorescent (IF) stains. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.003 and P=0.01, respectively) among patients with high-grade expression of tissue IGF-1R, compared with those with low-grade expression. After adjustment for other factors, preoperative serum total IGF-1 or IGFBP-3 levels failed to predict cancer death and recurrence. High-grade expression of IGF-1R and elevated preoperative squamous cell carcinoma antigen level were independent predictors of both death and recurrence, and combination of both factors could further help identify the subgroup of patients at higher death risk. The IF staining indicates the colocalisation of IGF-1 and IGF-1R in the cancerous tissues, whereas the IGF-1R expression is not correlated with circulating levels of IGF-1 or IGFBP-3. In early-stage cervical cancer, IGF-1 system may have a paracrine or autocrine function and the adverse impacts on prognosis by IGF-1R overexpression are implicated. PMID:18781172

  1. Impact of starter fertilizer on cotton growth, development, lint yield, and fiber quality production for an early planted no-till system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Improved yield potentials occur when planting cotton (Gossypium hirsutum L.) early, but cool conditions often associated with early planting can hamper early seedling growth. Starter fertilizers could be good source of P for seedling growth under cool conditions due to reduced soil P mineralizatio...

  2. mga genosensor for early detection of human rheumatic heart disease.

    PubMed

    Singh, Swati; Kaushal, Ankur; Khare, Shashi; Kumar, Ashok

    2014-05-01

    The 5' amino-labeled DNA probe complementary to mga gene of Streptococcus pyogenes was immobilized on carboxylated multiwall carbon nanotubes electrode and hybridized with 0.1-100 ng/6 μl single-stranded genomic DNA (ssG-DNA) of S. pyogenes from throat swab of suspected rheumatic heart disease (RHD) patients. Electrochemical response was measured by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance (EI). The sensitivity of the sensor was 106.03 (μA/cm(2))/ng and limit of detection (LOD) was found 0.014 ng/6 μl with regression coefficient (R(2)) of 0.921 using DPV. The genosensor was characterized by FTIR and SEM, and electrode was found stable for 6 months on storage at 4 °C with 5-6 % loss in initial DPV current. mga genosensor is the first report on RHD sensor which can save life of several suspected patients by early diagnosis in 30 min. PMID:24639090

  3. Vascular endothelial growth factor (VEGF) isoform regulation of early forebrain development

    PubMed Central

    Darland, Diane C.; Cain, Jacob T.; Berosik, Matthew A.; Saint-Geniez, Magali; Odens, Patrick W.; Schaubhut, Geoffrey J.; Frisch, Sarah; Stemmer-Rachamimov, Anat; Darland, Tristan; D’Amore, Patricia A.

    2011-01-01

    This work was designed to determine the role of the vascular endothelial growth factor A (VEGF) isoforms during early neuroepithelial development in the mammalian central nervous system (CNS), specifically in the forebrain. An emerging model of interdependence between neural and vascular systems includes VEGF, with its dual roles as a potent angiogenesis factor and neural regulator. Although a number of studies have implicated VEGF in CNS development, little is known about the role that the different VEGF isoforms play in early neurogenesis. We used a mouse model of disrupted VEGF isoform expression that eliminates the predominant brain isoform, VEGF164, and expresses only the diffusible form, VEGF120. We tested the hypothesis that VEGF164 plays a key role in controlling neural precursor populations in developing cortex. We used microarray analysis to compare gene expression differences between wild type and VEGF120 mice at E9.5, the primitive stem cell stage of the neuroepithelium. We quantified changes in PHH3-positive nuclei, neural stem cell markers (Pax6 and nestin) and the Tbr2-positive intermediate progenitors at E11.5 when the neural precursor population is expanding rapidly. Absence of VEGF164 (and VEGF188) leads to reduced proliferation without an apparent effect on the number of Tbr2-positive cells. There is a corresponding reduction in the number of mitotic spindles that are oriented parallel to the ventricular surface relative to those with a vertical or oblique angle. These results support a role for the VEGF isoforms in supporting the neural precursor population of the early neuroepithelium. PMID:21803034

  4. The effects of recessive white and dominant white genotypes on early growth rate.

    PubMed

    Fox, W; Smyth, J R

    1985-03-01

    The purpose of the studies reported herein was to determine whether the depressing effects on growth rate of dominant white (I) and recessive white (c/c) are additive or possibly interact with each other. A synthetic stock was used that was segregating for both dominant white and recessive white. Using phenotypic observations of down color and juvenile plumage color; it was possible to identify the genotypes at the I and C+ loci and to utilize a factorial experiment that provided for an evaluation of interaction effects between the loci. Five replications of this design were conducted with the following results: 1) the main effect of dominant white on 6 and 8 week body weight was not statistically significant; 2) recessive white consistently depresses early growth rate and the difference (congruent to 4%) between C+/- vs. c/c was highly significant (P less than .01); 3) there was a significant interaction (P less than .05) between I and c indicating that depressing effects of these loci are not additive. It does not appear to be necessary to eliminate (I) from recessive white broiler stocks, but it would be economically advantageous to remove hypostatic (c) from dominant white lines. PMID:3991420

  5. Black hole growth in the early Universe is self-regulated and largely hidden from view.

    PubMed

    Treister, Ezequiel; Schawinski, Kevin; Volonteri, Marta; Natarajan, Priyamvada; Gawiser, Eric

    2011-06-16

    The formation of the first massive objects in the infant Universe remains impossible to observe directly and yet it sets the stage for the subsequent evolution of galaxies. Although some black holes with masses more than 10(9) times that of the Sun have been detected in luminous quasars less than one billion years after the Big Bang, these individual extreme objects have limited utility in constraining the channels of formation of the earliest black holes; this is because the initial conditions of black hole seed properties are quickly erased during the growth process. Here we report a measurement of the amount of black hole growth in galaxies at redshift z = 6-8 (0.95-0.7 billion years after the Big Bang), based on optimally stacked, archival X-ray observations. Our results imply that black holes grow in tandem with their host galaxies throughout cosmic history, starting from the earliest times. We find that most copiously accreting black holes at these epochs are buried in significant amounts of gas and dust that absorb most radiation except for the highest-energy X-rays. This suggests that black holes grew significantly more during these early bursts than was previously thought, but because of the obscuration of their ultraviolet emission they did not contribute to the re-ionization of the Universe. PMID:21677753

  6. Subcompartmentalization by cross-membranes during early growth of Streptomyces hyphae.

    PubMed

    Yagüe, Paula; Willemse, Joost; Koning, Roman I; Rioseras, Beatriz; López-García, María T; Gonzalez-Quiñonez, Nathaly; Lopez-Iglesias, Carmen; Shliaha, Pavel V; Rogowska-Wrzesinska, Adelina; Koster, Abraham J; Jensen, Ole N; van Wezel, Gilles P; Manteca, Ángel

    2016-01-01

    Bacteria of the genus Streptomyces are a model system for bacterial multicellularity. Their mycelial life style involves the formation of long multinucleated hyphae during vegetative growth, with occasional cross-walls separating long compartments. Reproduction occurs by specialized aerial hyphae, which differentiate into chains of uninucleoid spores. While the tubulin-like FtsZ protein is required for the formation of all peptidoglycan-based septa in Streptomyces, canonical divisome-dependent cell division only occurs during sporulation. Here we report extensive subcompartmentalization in young vegetative hyphae of Streptomyces coelicolor, whereby 1 μm compartments are formed by nucleic acid stain-impermeable barriers. These barriers possess the permeability properties of membranes and at least some of them are cross-membranes without detectable peptidoglycan. Z-ladders form during the early growth, but cross-membrane formation does not depend on FtsZ. Thus, a new level of hyphal organization is presented involving unprecedented high-frequency compartmentalization, which changes the old dogma that Streptomyces vegetative hyphae have scarce compartmentalization. PMID:27514833

  7. Low Dose Nicotine Attenuates Aβ Neurotoxicity through Activation Early Growth Response Gene 1 Pathway

    PubMed Central

    Zhang, Jie; Qiu, Jinhua; Du, Guicheng; Qiao, Zhiliang; Jin, Guanghui; Gao, Fengguang; Zhang, Qiqing

    2015-01-01

    Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ25–35) -induced neurotoxicity. Although nicotine and Aβ25–35 can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ25–35. This study demonstrates that low dose nicotine attenuates Aβ25–35-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway. PMID:25815723

  8. Microstructural mechanisms of cyclic deformation, fatigue crack initiation and early crack growth.

    PubMed

    Mughrabi, Haël

    2015-03-28

    In this survey, the origin of fatigue crack initiation and damage evolution in different metallic materials is discussed with emphasis on the responsible microstructural mechanisms. After a historical introduction, the stages of cyclic deformation which precede the onset of fatigue damage are reviewed. Different types of cyclic slip irreversibilities in the bulk that eventually lead to the initiation of fatigue cracks are discussed. Examples of trans- and intercrystalline fatigue damage evolution in the low cycle, high cycle and ultrahigh cycle fatigue regimes in mono- and polycrystalline face-centred cubic and body-centred cubic metals and alloys and in different engineering materials are presented, and some microstructural models of fatigue crack initiation and early crack growth are discussed. The basic difficulties in defining the transition from the initiation to the growth of fatigue cracks are emphasized. In ultrahigh cycle fatigue at very low loading amplitudes, the initiation of fatigue cracks generally occupies a major fraction of fatigue life and is hence life controlling. PMID:25713457

  9. Subcompartmentalization by cross-membranes during early growth of Streptomyces hyphae

    PubMed Central

    Yagüe, Paula; Willemse, Joost; Koning, Roman I.; Rioseras, Beatriz; López-García, María T.; Gonzalez-Quiñonez, Nathaly; Lopez-Iglesias, Carmen; Shliaha, Pavel V.; Rogowska-Wrzesinska, Adelina; Koster, Abraham J.; Jensen, Ole N.; van Wezel, Gilles P.; Manteca, Ángel

    2016-01-01

    Bacteria of the genus Streptomyces are a model system for bacterial multicellularity. Their mycelial life style involves the formation of long multinucleated hyphae during vegetative growth, with occasional cross-walls separating long compartments. Reproduction occurs by specialized aerial hyphae, which differentiate into chains of uninucleoid spores. While the tubulin-like FtsZ protein is required for the formation of all peptidoglycan-based septa in Streptomyces, canonical divisome-dependent cell division only occurs during sporulation. Here we report extensive subcompartmentalization in young vegetative hyphae of Streptomyces coelicolor, whereby 1 μm compartments are formed by nucleic acid stain-impermeable barriers. These barriers possess the permeability properties of membranes and at least some of them are cross-membranes without detectable peptidoglycan. Z-ladders form during the early growth, but cross-membrane formation does not depend on FtsZ. Thus, a new level of hyphal organization is presented involving unprecedented high-frequency compartmentalization, which changes the old dogma that Streptomyces vegetative hyphae have scarce compartmentalization. PMID:27514833

  10. 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

  11. Early modern humans and morphological variation in Southeast Asia: fossil evidence from Tam Pa Ling, Laos.

    PubMed

    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

  12. Mammalian Herbivores Alter the Population Growth and Spatial Establishment of an Early-Establishing Grassland Species.

    PubMed

    Sullivan, Lauren L; Danielson, Brent J; Harpole, W Stanley

    2016-01-01

    Plant-herbivore interactions influence the establishment context of plant species, as herbivores alter the community context in which individual species establish, and the spatial relationship between individuals and their source population as plants invade. This relationship can be described using an establishment kernel, which takes into account movement through seed dispersal, and subsequent establishment of adults. Mammalian herbivores are hypothesized to influence plant population growth and establishment through a combination of consumption of seeds and seedlings, and movement of seeds. While the movement abilities of plants are well known, we have very few empirical mechanistic tests of how biotic factors like mammalian herbivores influence this spread potential. As herbivores of all sizes are abundant on the landscape, we asked the question, how do mammalian herbivores influence the population growth, spatial establishment, and the community establishment context of an early-recruiting native prairie legume, Chamaecrista fasciculata? We planted C. fasciculata in source populations within a four-acre tallgrass prairie restoration in plots with and without herbivores, and monitored its establishment with respect to distance from the source populations. We found that herbivores decreased population growth, and decreased the mean and range establishment distance. Additionally, C. fasciculata established more often without herbivores, and when surrounded by weedy, annual species. Our results provide insight into how the interactions between plants and herbivores can alter the spatial dynamics of developing plant communities, which is vital for colonization and range spread with fragmentation and climate change. Mammalian herbivores have the potential to both slow rates of establishment, but also determine the types of plant communities that surround invading species. Therefore, it is essential to consider the herbivore community when attempting to restore

  13. Cultural variation in early feeding pattern and maternal perceptions of infant growth.

    PubMed

    van Eijsden, Manon; Meijers, Claire M C; Jansen, Jessica E; de Kroon, Marlou L A; Vrijkotte, Tanja G M

    2015-08-14

    The perception of healthy growth and weight may differ between cultures, which could influence feeding practises and consequently affect the development of overweight. The present study examined ethnic variation in maternal perceptions of growth and their influence on feeding practises among Turkish and Dutch infants aged 0-6 months. Data were obtained from the mothers of 143 Turkish and 143 Dutch healthy, singleton, term infants with birth weights appropriate for gestational age, using structured interviews at 1, 4 and 6 months after birth. Compared with Dutch mothers, mothers of Turkish descent perceived a chubby infant more often as pretty (43 v. 22%), and were more often worried about their infant's growth (13 v. 4%). Turkish mothers were more likely to give full breast-feeding (BF) until at least 6 months (adjusted OR (aOR) 2.1, 95% CI 1.0, 4.3) and to start introducing complementary feeding, including rice flour porridge, at the age of 6 months (aOR 2.4, 95% CI 1.1, 4.9). Infants of Turkish descent were fed on average one milk feeding more during the day and, if introduced to complementary foods before 6 months, were more often given uncommon types of foods (e.g., yogurt and cookies) (aOR 2.1, 95% CI 1.1, 4.3). The differences in perceptions affected differences in feeding practises only to a small extent. Preventive advice offered to Turkish mothers in Child Health Care should include discussing choices of complementary foods and frequency of feeding from an early age onwards. In Dutch mothers, support for the continuation of BF remains an important issue. PMID:26166487

  14. Mammalian Herbivores Alter the Population Growth and Spatial Establishment of an Early-Establishing Grassland Species

    PubMed Central

    Sullivan, Lauren L.; Danielson, Brent J.; Harpole, W. Stanley

    2016-01-01

    Plant-herbivore interactions influence the establishment context of plant species, as herbivores alter the community context in which individual species establish, and the spatial relationship between individuals and their source population as plants invade. This relationship can be described using an establishment kernel, which takes into account movement through seed dispersal, and subsequent establishment of adults. Mammalian herbivores are hypothesized to influence plant population growth and establishment through a combination of consumption of seeds and seedlings, and movement of seeds. While the movement abilities of plants are well known, we have very few empirical mechanistic tests of how biotic factors like mammalian herbivores influence this spread potential. As herbivores of all sizes are abundant on the landscape, we asked the question, how do mammalian herbivores influence the population growth, spatial establishment, and the community establishment context of an early-recruiting native prairie legume, Chamaecrista fasciculata? We planted C. fasciculata in source populations within a four-acre tallgrass prairie restoration in plots with and without herbivores, and monitored its establishment with respect to distance from the source populations. We found that herbivores decreased population growth, and decreased the mean and range establishment distance. Additionally, C. fasciculata established more often without herbivores, and when surrounded by weedy, annual species. Our results provide insight into how the interactions between plants and herbivores can alter the spatial dynamics of developing plant communities, which is vital for colonization and range spread with fragmentation and climate change. Mammalian herbivores have the potential to both slow rates of establishment, but also determine the types of plant communities that surround invading species. Therefore, it is essential to consider the herbivore community when attempting to restore

  15. Early spring leaf out enhances growth and survival of saplings in a temperate deciduous forest.

    PubMed

    Augspurger, Carol K

    2008-05-01

    Saplings of many canopy tree species in winter deciduous forests receive the major portion of their light budget for their growing season prior to canopy closure in the spring. This period of high light may be critical for achieving a positive carbon (C) gain, thus contributing strongly to their growth and survival. This study of saplings of Aesculus glabra and Acer saccharum in Trelease Woods, Illinois, USA, tested this hypothesis experimentally by placing tents of shade cloth over saplings during their spring period of high light prior to canopy closure in three consecutive years. Leaf senescence began 16 days (year 0) and 60 days (year 1) earlier for shaded A. glabra saplings than control saplings. No change in senescence occurred for A. saccharum. The annual absolute growth in stem diameter of both species was negligible or negative for shaded saplings, but positive for control saplings. Only 7% of the shaded A. glabra saplings were alive after 2 years, while all control saplings survived for 3 years; only 20% of the shaded A. saccharum saplings survived for 3 years, while 73% of control saplings were alive after the same period. Early spring leaf out is a critical mechanism that allows the long-term persistence of saplings of these species in this winter deciduous forest. Studies and models of C gain, growth, and survival of saplings in deciduous forests may need to take into account their spring phenology because saplings of many species are actually "sun" individuals in the spring prior to their longer period in the summer shade. PMID:18347817

  16. Observations of Nucleation and Early Stage Growth of Amorphous Silica on Carboxyl-Terminated Model Biosubstrates

    NASA Astrophysics Data System (ADS)

    Wallace, A. F.; Dove, P. M.

    2005-12-01

    surface. While controlling solution chemistry, we can make in situ measurements of nucleation and early stage growth at these interfaces with Atomic Force Microscopy (AFM). Preliminary experiments show that at pH 4 to 7, and supersaturations of 0.76 to 1.45 (σ = ln([H4SiO4]/Ksp)), silica nucleates on carboxyl-terminated areas of the surface, that are less than 30 nm in diameter. The nuclei evolve during early stages of growth to spread over the surface into a sheet like form.

  17. Growth failure starts from early infancy in children with short stature at age 6

    PubMed Central

    Noda, Masahiro; Sato, Naoko; Tanaka, Toshiaki

    2015-01-01

    Abstract We compared the growth of 183 children with short stature (≤ 2SD) and 73 children of normal height at age six who were visiting the Tanaka Growth Clinic. We classified these short children as suffering from either idiopathic short stature (ISS, n = 119), GH deficiency (GHD, n = 33) or small-for-gestational-age short stature (SGASS, n = 31) on the basis of subsequent test results and other factors. We also conducted a retrospective study of changes in their height, wt and nutritional intake over time. The mean changes in height SD score from birth to 6 yr were –0.24 SD in normal height children with a normal birth length and +2.27 SD in normal height children with a low birth length. In short children, these changes were –1.93 SD for children with ISS, –2.41 SD for those with GHD and +0.58 for those with SGASS. The mean changes from birth to 6 mo were –0.84 SD, −1.03 SD and +0.38 SD in children with ISS, GHD and SGASS, respectively. The mean change in height SD score from birth to age 1 yr was –1.07 SD, –1.44 SD and +0.35 SD, respectively. The decrease in height SD score from birth to 6 mo accounted for 43.5% of the decrease in height SD score from birth to 6 yr in children with ISS and it accounted for 42.6% of the decrease in children with GHD. Only 19% of short children bottle-fed well, and 53% fed poorly, as opposed to 56% and 16% of normal height children who fed well and poorly, respectively. Post weaning, only 22% of short children ate well, and 56% fed poorly, as opposed to 53% and 17% of normal height children who fed well and poorly, respectively. These findings demonstrated that growth failure started from early infancy in ISS and GHD children. It was suggested that poor nutritional intake in infancy and early childhood was a partial cause of short stature at age 6. PMID:25678754

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

    SciTech Connect

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

    1987-04-01

    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 2 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.

  19. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study

    PubMed Central

    Meeren, Hanneke K. M.; Hadjikhani, Nouchine; Ahlfors, Seppo P.; Hämäläinen, Matti S.; de Gelder, Beatrice

    2016-01-01

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream. PMID:27095660

  20. Early Preferential Responses to Fear Stimuli in Human Right Dorsal Visual Stream - A Meg Study.

    PubMed

    Meeren, Hanneke K M; Hadjikhani, Nouchine; Ahlfors, Seppo P; Hämäläinen, Matti S; de Gelder, Beatrice

    2016-01-01

    Emotional expressions of others are salient biological stimuli that automatically capture attention and prepare us for action. We investigated the early cortical dynamics of automatic visual discrimination of fearful body expressions by monitoring cortical activity using magnetoencephalography. We show that right parietal cortex distinguishes between fearful and neutral bodies as early as 80-ms after stimulus onset, providing the first evidence for a fast emotion-attention-action link through human dorsal visual stream. PMID:27095660

  1. Position stand on androgen and human growth hormone use.

    PubMed

    Hoffman, Jay R; Kraemer, William J; Bhasin, Shalender; Storer, Thomas; Ratamess, Nicholas A; Haff, G Gregory; Willoughby, Darryn S; Rogol, Alan D

    2009-08-01

    Hoffman, JR, Kraemer, WJ, Bhasin, S, Storer, T, Ratamess, NA, Haff, GG, Willoughby, DS, and Rogol, AD. Position stand on Androgen and human growth hormone use. J Strength Cond Res 23(5): S1-S59, 2009-Perceived yet often misunderstood demands of a sport, overt benefits of anabolic drugs, and the inability to be offered any effective alternatives has fueled anabolic drug abuse despite any consequences. Motivational interactions with many situational demands including the desire for improved body image, sport performance, physical function, and body size influence and fuel such negative decisions. Positive countermeasures to deter the abuse of anabolic drugs are complex and yet unclear. Furthermore, anabolic drugs work and the optimized training and nutritional programs needed to cut into the magnitude of improvement mediated by drug abuse require more work, dedication, and preparation on the part of both athletes and coaches alike. Few shortcuts are available to the athlete who desires to train naturally. Historically, the NSCA has placed an emphasis on education to help athletes, coaches, and strength and conditioning professionals become more knowledgeable, highly skilled, and technically trained in their approach to exercise program design and implementation. Optimizing nutritional strategies are a vital interface to help cope with exercise and sport demands (). In addition, research-based supplements will also have to be acknowledged as a strategic set of tools (e.g., protein supplements before and after resistance exercise workout) that can be used in conjunction with optimized nutrition to allow more effective adaptation and recovery from exercise. Resistance exercise is the most effective anabolic form of exercise, and over the past 20 years, the research base for resistance exercise has just started to develop to a significant volume of work to help in the decision-making process in program design (). The interface with nutritional strategies has been less

  2. ATP-competitive mTOR kinase inhibitors delay plant growth by triggering early differentiation of meristematic cells but no developmental patterning change

    PubMed Central

    Menand, Benoît

    2013-01-01

    The TOR (target of rapamycin) protein, a large phosphatidylinositol 3-kinase-like protein kinase (PIKK) that is conserved in eukaryotes and is a central regulator of growth and metabolism. The analysis of function of TOR in plant growth and development has been limited by the fact that plants are very poorly sensitive to rapamycin. As the kinase domain of TOR is highly conserved, this study analysed the dose-dependent effect of three sets of first- and second-generation ATP-competitive inhibitors (called asTORis for active-site TOR inhibitors) recently developed for the human TOR kinase on Arabidopsis thaliana growth. All six asTORis inhibited plant root growth in a dose-dependent manner, with 50% growth inhibitory doses (GI50) of <10 μM and <1 μM for the first- and second-generation inhibitors, respectively, similarly to the values in mammalian cells. A genetic approach further demonstrated that only asTORis inhibited root growth in an AtTOR gene-dosage-dependent manner. AsTORis decreased the length of: (i) the meristematic zone (MZ); (ii) the division zone in the MZ; (iii) epidermal cells in the elongation zone; and (iv) root hair cells. Whereas meristematic cells committed to early differentiation, the pattern of cell differentiation was not affected per se. AsTORis-induced root hair growth phenotype was shown to be specific by using other growth inhibitors blocking the cell cycle or translation. AsTORis dose-dependent inhibition of growth and root hairs was also observed in diverse groups of flowering plants, indicating that asTORis can be used to study the TOR pathway in other angiosperms, including crop plants. PMID:23963679

  3. 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

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

    PubMed

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

    2013-12-01

    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

  5. [Early life stressful experiences and neuropsychiatric vulnerability: evidences from human and animal models].

    PubMed

    Rincel, Marion; Lépinay, Amandine; Gabory, Anne; Théodorou, Vassilia; Koehl, Muriel; Daugé, Valérie; Maccari, Stefania; Darnaudéry, Muriel

    2016-01-01

    The human newborn is highly dependent on parental care for its survival but also for the healthy development of its brain. A large body of literature demonstrates the impact of early life adversity, even during the prenatal period, on the adult's health. The susceptibility to neuropsychiatric diseases is often potentiated by early stress. If there is an agreement that a critical developmental period exists, the mechanisms underlying the long term effects of early life adversity are still poorly understood. Recent studies in animals highlight the involvement of epigenetic processes in the transmission of such vulnerabilities, notably via modifications in germ cells, which can be transmitted in the next generations. PMID:26850613

  6. 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

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

    PubMed

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

    2016-01-15

    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

  8. Recombinant human nerve growth factor for clinical trials: protein expression, purification, stability and characterisation of binding to infusion pumps.

    PubMed

    Allen, S J; Robertson, A G; Tyler, S J; Wilcock, G K; Dawbarn, D

    2001-02-26

    Nerve growth factor (NGF) has been suggested to be of therapeutic benefit to patients with Alzheimer's disease. One of the early changes in this disease is a loss of cholinergic function within the brain, and NGF is able to rescue cholinergic neurons both in vitro and in vivo. We describe the production of recombinant human beta-NGF (rhNGF), using baculovirus infection of insect cells; its purification, formulation and subsequent stability for use in clinical trials. Tests were also carried out to monitor release of protein from infusion pumps and catheters for intracerebroventricular administration (icv). Initial problems with non-specific binding were overcome using a blocking formula. PMID:11245895

  9. Macrophages modulate the viability and growth of human mesenchymal stem cells.

    PubMed

    Freytes, Donald O; Kang, Jung W; Marcos-Campos, Ivan; Vunjak-Novakovic, Gordana

    2013-01-01

    Following myocardial infarction, tissue repair is mediated by the recruitment of monocytes and their subsequent differentiation into macrophages. Recent findings have revealed the dynamic changes in the presence of polarized macrophages with pro-inflammatory (M1) and anti-inflammatory (M2) properties during the early (acute) and late (chronic) stages of cardiac ischemia. Mesenchymal stem cells (MSCs) delivered into the injured myocardium as reparative cells are subjected to the effects of polarized macrophages and the inflammatory milieu. The present study investigated how cytokines and polarized macrophages associated with pro-inflammatory (M1) and anti-inflammatory (M2) responses affect the survival of MSCs. Human MSCs were studied using an in vitro platform with individual and combined M1 and M2 cytokines: IL-1β, IL-6, TNF-α, and IFN-γ (for M1), and IL-10, TGF-β1, TGF-β3, and VEGF (for M2). In addition, polarization molecules (M1: LPS and IFN-γ; M2: IL-4 and IL-13) and common chemokines (SDF-1 and MCP-1) found during inflammation were also studied. Indirect and direct co-cultures were conducted using M1 and M2 polarized human THP-1 monocytes. M2 macrophages and their associated cytokines supported the growth of hMSCs, while M1 macrophages and their associated cytokines inhibited the growth of hMSCs in vitro under certain conditions. These data imply that an anti-inflammatory (M2) environment is more accommodating to the therapeutic hMSCs than a pro-inflammatory (M1) environment at specific concentrations. PMID:22903635

  10. Growth of HIV-Infected Children in the Early Stage of Antiretroviral Treatment: A Retrospective Cohort Study in China.

    PubMed

    Hu, Ran; Mu, Weiwei; Sun, Xin; Wu, Hao; Pang, Lin; Wang, Liming; Zhao, Qingxia; Wu, Yasong; Zhao, Decai; Chen, Meiling; Ma, Ye; Zhang, Fujie

    2016-08-01

    Malnutrition and human immunodeficiency virus (HIV)-related complications are commonly seen in HIV-infected children, and these have been shown in high-prevalent areas such as Africa. Antiviral therapy (ART) has notably controlled disease progression, whereas it effectively reverses underweight and growth retardation in HIV-infected children. This study was conducted to evaluate the growth status after initiation of ART in HIV-infected children in China. A retrospective cohort study was conducted based on the National Science and Technology Major Project. HIV-infected children who initiated antiretroviral treatment between January 1st, 2012 and December 31st, 2012 were followed up to December 31st, 2014. Z-scores of height and weight were calculated by WHO Anthro (plus). Linear mixed-effects models were used to model trajectories of weight- and height-for-age Z-scores. Seven hundred forty-four participants enrolled in the study, with 585 participants and 712 participants who had WAZ (weight-for-age Z-score) and HAZ (height-for-age Z-score), respectively, before initiation of ART. Among them, 125 (21.4%) were underweight and 301 (42.3%) were stunted. After treatment, among the 125 underweight children, WAZ improved in 69 patients, regained more than -2 on average. Among the 301 stunted children, HAZ improved in 123 patients, regained more than -2 on average. WAZ improved for the first 6 months by 0.052 units each month and then stabilized, whereas HAZ consistently improved by 0.014 units each month over time. Antiretroviral treatment reversed the adverse effects of HIV to some degree. Early diagnosis and treatment, with an effective nutrition program, is necessary to improve malnutrition further. PMID:27509236

  11. A Candida albicans Strain Expressing Mammalian Interleukin-17A Results in Early Control of Fungal Growth during Disseminated Infection

    PubMed Central

    Huppler, Anna R.; Whibley, Natasha; Woolford, Carol A.; Childs, Erin E.; He, Jie; Biswas, Partha S.; McGeachy, Mandy J.; Mitchell, Aaron P.

    2015-01-01

    Candida albicans is normally a commensal fungus of the human mucosae and skin, but it causes life-threatening systemic infections in hospital settings in the face of predisposing conditions, such as indwelling catheters, abdominal surgery, or antibiotic use. Immunity to C. albicans involves various immune parameters, but the cytokine interleukin-17A (IL-17A) (also known as IL-17) has emerged as a centrally important mediator of immune defense against both mucosal and systemic candidiasis. Conversely, IL-17A has been suggested to enhance the virulence of C. albicans, indicating that it may exert detrimental effects on pathogenesis. In this study, we hypothesized that a C. albicans strain expressing IL-17A would exhibit reduced virulence in vivo. To that end, we created a Candida-optimized expression cassette encoding murine IL-17A, which was transformed into the DAY286 strain of C. albicans. Candida-derived IL-17A was indistinguishable from murine IL-17A in terms of biological activity and detection in standard enzyme-linked immunosorbent assays (ELISAs). Expression of IL-17A did not negatively impact the growth of these strains in vitro. Moreover, the IL-17A-expressing C. albicans strains showed significantly reduced pathogenicity in a systemic model of Candida infection, mainly evident during the early stages of disease. Collectively, these findings suggest that IL-17A mitigates the virulence of C. albicans. PMID:26150537

  12. Genetic organization, size, and complete sequence of early region 3 genes of human adenovirus type 41.

    PubMed Central

    Yeh, H Y; Pieniazek, N; Pieniazek, D; Luftig, R B

    1996-01-01

    The complete nucleotide and predicted amino acid sequences for open reading frames (ORFs) of the human adenovirus type 41 (Ad41) early region 3 (E3) gene have been determined. The sequence of the Ad41 E3 gene (map units 74 to 83.9) consists of 3,373 nucleotides and has one TATA box and two polyadenylation signals (AATAAA). Analysis of the nucleotide sequence reveals that the E3 gene can encode six ORFs, designated RL1 to RL6. These are all expressed at the mRNA level, as determined by reverse transcription-PCR analysis of AD41-infected cell RNA. When compared with known E3 sequences of most other human adenoviruses deposited in GenBank, the sequences of RL1 to RL3 were found to be unique to subgroup F adenoviruses (Ad40 and Ad41). They encode putative proteins of 173 amino acids (19.4 kDa) and 276 amino acids (31.6 kDa) in one reading frame as well as a 59- amino-acid (6.7 kDa) protein in an overlapping reading frame. RL4 encodes a 90-amino-acid protein (10.1 kDa) with 40% homology to the Ad2 E3 10.4-kDa protein, which induces degradation of the epidermal growth factor receptor and functions together with the Ad2 E3 14.5-kDa protein to protect mouse cell lines against lysis. RL5 encodes a protein of 107 amino acid residues (12.3 kDa) and is analogous to the Ad E3 14.5-kDa protein. RL6 codes for a protein of 122 amino acids (14.7 kDa) that is analogous to the Ad2 14.7-kDa protein, which functions to protect Ad-infected cells from tumor necrosis factor-induced cytolysis. This finding of three unique (RL1 to RL3) E3 gene ORFs may explain why subgroup F adenoviruses differ substantially from other human adenoviruses in their host range; i.e., they replicate predominantly in the host's gastrointestinal rather than respiratory tract. A recent phylogenetic study that compared subgroup F Ad40 DNA sequences with representatives of subgroups B (Ad3), C (Ad2), and E (Ad4) reached a similar conclusion about the uniqueness of RL1 and RL2. PMID:8642703

  13. Localization of transforming growth factor-beta at the human fetal-maternal interface: role in trophoblast growth and differentiation.

    PubMed

    Graham, C H; Lysiak, J J; McCrae, K R; Lala, P K

    1992-04-01

    We examined the localization of transforming growth factor (TGF)-beta in first-trimester and term human decidua and chorionic villi and explored the role of this factor on the proliferation and differentiation of cultured trophoblast cells. Two antibodies, 1D11.16.8, a mouse monoclonal neutralizing antibody capable of recognizing both TGF-beta 1 and TGF-beta 2 and CL-B1/29, a rabbit polyclonal antibody capable of recognizing TGF-beta 2, were used to immunolocalize TGF-beta in fixed, paraffin-embedded, or fixed, frozen sections of placenta and decidua, providing similar results. Intense labeling was observed in the extracellular matrix (ECM) of the first-trimester decidua and cytoplasm of term decidual cells. Syncytiotrophoblast cell cytoplasm as well as the ECM in the core of the chorionic villi of both first-trimester and term placentas exhibited a moderate degree of labeling. Strong cytoplasmic labeling was observed in the cytotrophoblastic shell of the term placenta. To examine the role of TGF-beta on trophoblast proliferation and differentiation, early passage cultures of first-trimester and primary cultures of term trophoblast cells were established and characterized on the basis of numerous immunocytochemical and functional markers. These cells expressed cytokeratin, placental alkaline phosphatase, urokinase-type plasminogen activator, and pregnancy-specific beta glycoprotein, but not factor VIII or 63D3; they also produced hCG and collagenase type IV. Exposure of first-trimester trophoblast cultures to TGF-beta 1 significantly inhibited proliferation in a dose-dependent manner. An antiproliferative effect was also noted in the presence of TGF-beta 2. These effects were abrogated in the presence of the neutralizing anti-TGF-beta antibody (1D11.16.8) in a concentration-dependent manner. In a 3-day culture, exogenous TGF-beta 1 stimulated formation of multinucleated cells by the first trimester as well as term trophoblast cells. Addition of neutralizing anti

  14. 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.

  15. Examining Breast Cancer Growth and Lifestyle Risk Factors: Early Life, Childhood, and Adolescence

    PubMed Central

    Ruder, Elizabeth H.; Dorgan, Joanne F.; Kranz, Sibylle; Kris-Etherton, Penny M.; Hartman, Terryl J.

    2009-01-01

    The perinatal period, childhood, and adolescence are important intervals for breast cancer risk development. Endogenous estrogen exposure is thought to be highest in utero, and exposure to estrogens throughout life plays an important role in increasing breast cancer risk. Some evidence suggests that breast tissue is not fully differentiated until after the first full-term pregnancy; thus, breast tissue might be more susceptible to carcinogenic influences during early life and adolescence. Birth characteristics of the daughter, including gestational age, birth weight, and birth length are associated with maternal hormone levels during the index pregnancy, and birth size has been related to daughter's timing of puberty and adult breast cancer incidence. Furthermore, early life and adolescence are critical times for maturation of the hypothalamic pituitary ovarian axis, which regulates production of ovarian hormones including estrogen and progesterone. Childhood height, growth, diet, and body mass index (BMI) have also been associated with breast cancer risk later in life. Of the examined characteristics, we conclude that the available evidence is suggestive of a positive relationship of breast cancer risk with birth weight, birth length, and adolescent height, and an inverse relationship with gestational age and childhood BMI, although several inconsistencies exist in the literature. The best evidence for a relationship of adolescent diet and adult breast cancer risk is indirect, and the relationship of diet, weight status, and weight gain in childhood deserves further attention. The interaction of birth characteristics with established risk factors over the life course, such as age at menarche, in addition to gene-environment interactions, require more research. Further study is also needed to clarify the biologic mechanisms influencing the observed associations. PMID:18757260

  16. Examining breast cancer growth and lifestyle risk factors: early life, childhood, and adolescence.

    PubMed

    Ruder, Elizabeth H; Dorgan, Joanne F; Kranz, Sibylle; Kris-Etherton, Penny M; Hartman, Terryl J

    2008-08-01

    The perinatal period, childhood, and adolescence are important intervals for breast cancer risk development. Endogenous estrogen exposure is thought to be highest in utero, and exposure to estrogens throughout life plays an important role in increasing breast cancer risk. Some evidence suggests that breast tissue is not fully differentiated until after the first full-term pregnancy; thus, breast tissue might be more susceptible to carcinogenic influences during early life and adolescence. Birth characteristics of the daughter, including gestational age, birth weight, and birth length are associated with maternal hormone levels during the index pregnancy, and birth size has been related to daughter's timing of puberty and adult breast cancer incidence. Furthermore, early life and adolescence are critical times for maturation of the hypothalamic pituitary ovarian axis, which regulates production of ovarian hormones including estrogen and progesterone. Childhood height, growth, diet, and body mass index (BMI) have also been associated with breast cancer risk later in life. Of the examined characteristics, we conclude that the available evidence is suggestive of a positive relationship of breast cancer risk with birth weight, birth length, and adolescent height, and an inverse relationship with gestational age and childhood BMI, although several inconsistencies exist in the literature. The best evidence for a relationship of adolescent diet and adult breast cancer risk is indirect, and the relationship of diet, weight status, and weight gain in childhood deserves further attention. The interaction of birth characteristics with established risk factors over the life course, such as age at menarche, in addition to gene-environment interactions, require more research. Further study is also needed to clarify the biologic mechanisms influencing the observed associations. PMID:18757260

  17. Transgenerational Effects of Early Life Starvation on Growth, Reproduction, and Stress Resistance in Caenorhabditis elegans.

    PubMed

    Jobson, Meghan A; Jordan, James M; Sandrof, Moses A; Hibshman, Jonathan D; Lennox, Ashley L; Baugh, L Ryan

    2015-09-01

    Starvation during early development can have lasting effects that influence organismal fitness and disease risk. We characterized the long-term phenotypic consequences of starvation during early larval development in Caenorhabditis elegans to determine potential fitness effects and develop it as a model for mechanistic studies. We varied the amount of time that larvae were developmentally arrested by starvation after hatching ("L1 arrest"). Worms recovering from extended starvation grew slowly, taking longer to become reproductive, and were smaller as adults. Fecundity was also reduced, with the smallest individuals most severely affected. Feeding behavior was impaired, possibly contributing to deficits in growth and reproduction. Previously starved larvae were more sensitive to subsequent starvation, suggesting decreased fitness even in poor conditions. We discovered that smaller larvae are more resistant to heat, but this correlation does not require passage through L1 arrest. The progeny of starved animals were also adversely affected: Embryo quality was diminished, incidence of males was increased, progeny were smaller, and their brood size was reduced. However, the progeny and grandprogeny of starved larvae were more resistant to starvation. In addition, the progeny, grandprogeny, and great-grandprogeny were more resistant to heat, suggesting epigenetic inheritance of acquired resistance to starvation and heat. Notably, such resistance was inherited exclusively from individuals most severely affected by starvation in the first generation, suggesting an evolutionary bet-hedging strategy. In summary, our results demonstrate that starvation affects a variety of life-history traits in the exposed animals and their descendants, some presumably reflecting fitness costs but others potentially adaptive. PMID:26187123

  18. Cultured human foreskin fibroblasts produce a factor that stimulates their growth with properties similar to basic fibroblast growth factor

    SciTech Connect

    Story, M.T. )

    1989-05-01

    To determine if fibroblasts could be a source of fibroblast growth factor (FGF) in tissue, cells were initiated in culture from newborn human foreskin. Fibroblast cell lysates promoted radiolabeled thymidine uptake by cultured quiescent fibroblasts. Seventy-nine percent of the growth-promoting activity of lysates was recovered from heparin-Sepharose. The heparin-binding growth factor reacted on immunoblots with antiserum to human placenta-derived basic FGF and competed with iodinated basic FGF for binding to antiserum to (1-24)bFGF synthetic peptide. To confirm that fibroblasts were the source of the growth factor, cell lysates were prepared from cells incubated with radiolabeled methionine. Heparin affinity purified material was immunoprecipitated with basic FGF antiserum and electrophoresed. Radiolabeled material was detected on gel autoradiographs in the same molecular weight region as authentic iodinated basic FGF. The findings are consistant with the notion that cultured fibroblasts express basic FGF. As these cells also respond to the mitogen, it is possible that the regulation of their growth is under autocrine control. Fibroblasts may be an important source of the growth factor in tissue.

  19. Association of myostatin on early calf mortality, growth, and carcass composition traits in crossbred cattle.

    PubMed

    Casas, E; Bennett, G L; Smith, T P L; Cundiff, L V

    2004-10-01

    The objective of this study was to investigate a potential association of an inactive myostatin allele with early calf mortality, and evaluate its effect on growth and carcass traits in a crossbred population. Animals were obtained by mating F1 cows to F1 (Belgian Blue x British Breed) or Charolais sires. Cows were obtained from mating Hereford, Angus, and MARC III (1/4 Hereford, 1/4 Angus, 1/4 Pinzgauer, and 1/4 Red Poll) dams to Hereford, Angus, Tuli, Boran, Brahman, or Belgian Blue sires. Belgian Blue was the source of the inactive myostatin allele. Myostatin genotypes were determined for all animals including those that died before weaning. Early calf mortality was examined in the F2 subpopulation (n = 154), derived from the F1 sires mated to F1 cows from Belgian Blue sires, to evaluate animals with zero, one, or two copies of inactive myostatin allele. An overall 1:2:1 ratio (homozygous active myostatin allele:heterozygous:homozygous inactive myostatin allele) was observed in the population; however, a comparison between calves dying before weaning and those alive at slaughter showed an unequal distribution across genotypes (P < 0.01). Calves with two copies of the inactive allele were more likely (P < 0.01) to die before weaning. Postweaning growth traits were evaluated in the surviving animals (n = 1,370), including birth, weaning, and live weight at slaughter, and postweaning ADG. Carcass composition traits analyzed were hot carcass weight, fat thickness, LM area, marbling score, USDA yield grade, estimated kidney, pelvic, and heart fat, retail product yield and weight, fat yield and weight, bone yield and weight, and percentage of carcasses classified as Choice. Charolais lack the inactive myostatin allele segregating in Belgian Blue; thus, in the population sired by Charolais (n = 645), only animals with zero or one copy of the inactive myostatin allele were evaluated. Animals carrying one copy were heavier at birth and at weaning, and their carcasses

  20. Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy

    PubMed Central

    Bhattacharyya, Swati; Wu, Minghua; Fang, Feng; Tourtellotte, Warren; Feghali-Bostwick, Carol; Varga, John

    2011-01-01

    Fibrosis is a deregulated and ultimately defective form of tissue repair that underlies a large number of chronic human diseases, as well as obesity and aging. The pathogenesis of fibrosis involves multiple cell types and extracellular signals, of which transforming growth factor- β (TGF-β) is pre-eminent. The prevalence of fibrosis is rising worldwide, and to date no agents has shown clinical efficacy in the attenuating or reversing the process. Recent studies implicate the immediate-early response transcription factor Egr-1 in the pathogenesis of fibrosis. Egr-1 couples acute changes in the cellular environment to sustained alterations in gene expression, and mediates a broad spectrum of biological responses to injury and stress. In contrast to other ligand-activated transcription factors such as NF-κB, c-jun and Smad2/3 that undergo post-translational modification such as phosphorylation and nuclear translocation, Egr-1 activity is regulated via its biosynthesis. Aberrant Egr-1 expression or activity is implicated in cancer, inflammation, atherosclerosis, and ischemic injury and recent studies now indicate an important role for Egr-1 in TGF-β-dependent profibrotic responses. Fibrosis in various animal models and human diseases such as scleroderma (SSc) and idiopathic pulmonary fibrosis (IPF) is accompanied by aberrant Egr-1 expression. Moreover Egr-1 appears to be required for physiologic and pathological connective tissue remodeling, and Egr-1-null mice are protected from fibrosis. As a novel profibrotic mediator, Egr-1 thus appears to be a promising potential target for the development of anti-fibrotic therapies. PMID:21511034

  1. Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells

    SciTech Connect

    Miyazaki, Takamichi; Futaki, Sugiko; Hasegawa, Kouichi; Kawasaki, Miwa; Sanzen, Noriko; Hayashi, Maria; Kawase, Eihachiro; Sekiguchi, Kiyotoshi Nakatsuji, Norio; Suemori, Hirofumi

    2008-10-10

    Human embryonic stem cells (hESCs) are thought to be a promising cell source for cell transplantation therapy. For such a clinical application, the hESCs should be manipulated using appropriate and qualified materials. In this study, we examined the efficacy of recombinant human laminin (rhLM) isoforms on the undifferentiated growth of hESCs. We first determined the major integrins expressed on the hESCs to reveal the preference of the hESCs for rhLMs, and found that the hESCs mainly expressed integrin {alpha}6{beta}1, which binds predominantly to laminin-111, -332 and -511/-521. When the hESCs were seeded onto rhLMs, the cells indeed adhered markedly to rhLM-332, and to rhLM-511 and rhLM-111 to a lesser extent. The hESCs proliferated on these three rhLMs for several passages while preserving their pluripotency. These results show that rhLM-111, -332, and -511 are good substrates to expand undifferentiated hESCs due to their high affinity to integrin {alpha}6{beta}1 expressed on hESCs.

  2. Effect of saline water on seed germination and early seedling growth of the halophyte quinoa.

    PubMed

    Panuccio, M R; Jacobsen, S E; Akhtar, S S; Muscolo, A

    2014-01-01

    Salinization is increasing on a global scale, decreasing average yields for most major crop plants. Investigations into salt resistance have, unfortunately, mainly been focused on conventional crops, with few studies screening the potential of available halophytes as new crops. This study has been carried out to investigate the mechanisms used by quinoa, a facultative halophytic species, in order to cope with high salt levels at various stages of its development. Quinoa is regarded as one of the crops that might sustain food security in this century, grown primarily for its edible seeds with their high protein content and unique amino acid composition. Although the species has been described as a facultative halophyte, and its tolerance to salt stress has been investigated, its physiological and molecular responses to seawater (SW) and other salts have not been studied. We evaluated the effects of SW and different salts on seed germination, seedling emergence and the antioxidative pathway of quinoa. Seeds were germinated in Petri dishes and seedlings grown in pots with SW solutions (25, 50, 75 and 100 %) and NaCl, CaCl2, KCl and MgCl2 individually, at the concentrations in which they are present in SW. Our results demonstrated that all salts, at lower concentrations, increased the germination rate but not the germination percentages, compared with control (pure water). Conversely, seedlings were differently affected by treatments in respect to salt type and concentration. Growth parameters affected were root and shoot length, root morphology, fresh and dry weight, and water content. An efficient antioxidant mechanism was present in quinoa, activated by salts during germination and early seedling growth, as shown by the activities of antioxidant enzymes. Total antioxidant capacity was always higher under salt stress than in water. Moreover, osmotic and ionic stress factors had different degrees of influence on germination and development. PMID:25139769

  3. Impact of hydrocarbons from a diesel fuel on the germination and early growth of subantarctic plants.

    PubMed

    Macoustra, Gabriella K; King, Catherine K; Wasley, Jane; Robinson, Sharon A; Jolley, Dianne F

    2015-07-01

    Special Antarctic Blend (SAB) is a diesel fuel dominated by aliphatic hydrocarbons that is commonly used in Antarctic and subantarctic regions. The past and present use of SAB fuel at Australia's scientific research stations has resulted in multiple spills, contaminating soils in these pristine areas. Despite this, no soil quality guidelines or remediation targets have been developed for the region, primarily due to the lack of established indigenous test species and subsequent biological effects data. In this study, twelve plant species native to subantarctic regions were collected from Macquarie Island and evaluated to determine their suitably for use in laboratory-based toxicity testing, using germination success and seedling growth (shoot and root length) as endpoints. Two soil types (low and high organic carbon (OC)) were investigated to reflect the variable OC content found in soils on Macquarie Island. These soils were spiked with SAB fuel and aged for 14 days to generate a concentration series of SAB-contaminated soils. Exposure doses were quantified as the concentration of total petroleum hydrocarbons (TPH, nC9-nC18) on a soil dry mass basis. Seven species successfully germinated on control soils under laboratory conditions, and four of these species (Colobanthus muscoides Hook.f., Deschampsia chapmanii Petrie, Epilobium pendunculare A.Cunn. and Luzula crinita Hook.f.) showed a dose-dependent inhibition of germination when exposed to SAB-contaminated soils. Contaminated soils with low OC were generally more toxic to plants than high organic carbon soils. Increasing soil-TPH concentrations significantly inhibited shoot and root growth, and root length was identified as the most sensitive endpoint. Although the test species were tolerant to SAB-contaminated soils in germination assays, development of early life stages (up to 28 days) were generally more sensitive indicator of exposure effects, and may be more useful endpoints for future testing. PMID

  4. Effect of saline water on seed germination and early seedling growth of the halophyte quinoa

    PubMed Central

    Panuccio, M. R.; Jacobsen, S. E.; Akhtar, S. S.; Muscolo, A.

    2014-01-01

    Salinization is increasing on a global scale, decreasing average yields for most major crop plants. Investigations into salt resistance have, unfortunately, mainly been focused on conventional crops, with few studies screening the potential of available halophytes as new crops. This study has been carried out to investigate the mechanisms used by quinoa, a facultative halophytic species, in order to cope with high salt levels at various stages of its development. Quinoa is regarded as one of the crops that might sustain food security in this century, grown primarily for its edible seeds with their high protein content and unique amino acid composition. Although the species has been described as a facultative halophyte, and its tolerance to salt stress has been investigated, its physiological and molecular responses to seawater (SW) and other salts have not been studied. We evaluated the effects of SW and different salts on seed germination, seedling emergence and the antioxidative pathway of quinoa. Seeds were germinated in Petri dishes and seedlings grown in pots with SW solutions (25, 50, 75 and 100 %) and NaCl, CaCl2, KCl and MgCl2 individually, at the concentrations in which they are present in SW. Our results demonstrated that all salts, at lower concentrations, increased the germination rate but not the germination percentages, compared with control (pure water). Conversely, seedlings were differently affected by treatments in respect to salt type and concentration. Growth parameters affected were root and shoot length, root morphology, fresh and dry weight, and water content. An efficient antioxidant mechanism was present in quinoa, activated by salts during germination and early seedling growth, as shown by the activities of antioxidant enzymes. Total antioxidant capacity was always higher under salt stress than in water. Moreover, osmotic and ionic stress factors had different degrees of influence on germination and development. PMID:25139769

  5. An Examination of Growth in Vocabulary and Phonological Awareness in Early Childhood: An Individual Growth Model Approach

    ERIC Educational Resources Information Center

    Cassano, Christina Marie

    2013-01-01

    The present study used individual growth modeling to examine the role of specific forms (i.e., receptive, expressive, and definitional vocabulary and grammatical skill) and levels of oral vocabulary skill (i.e., 25th, 50th, or 75th percentile) in phonological awareness growth during the preschool and kindergarten years. Sixty-one,…

  6. Impact of Witnessing Violence on Growth Curves for Problem Behaviors among Early Adolescents in Urban and Rural Settings

    ERIC Educational Resources Information Center

    Farrell, Albert D.; Sullivan, Terri N.

    2004-01-01

    Two studies used latent growth-curve analysis to examine the relation between witnessing violence and changes in problem behaviors (drug use, aggression, and delinquency) and attitudes during early adolescence. In Study 1, six waves of data covering 6th to 8th grades were collected from 731 students in urban schools serving mostly African-American…

  7. Kindergarten Predictors of Mathematical Growth in the Primary Grades: An Investigation Using the Early Childhood Longitudinal Study--Kindergarten Cohort

    ERIC Educational Resources Information Center

    DiPerna, James Clyde; Lei, Pui-Wa; Reid, Erin E.

    2007-01-01

    This study examined longitudinal predictive relationships between young children's classroom behaviors and their growth in mathematics skills during the primary grades. Using the Early Childhood Longitudinal Study--Kindergarten cohort, the authors tested a longitudinal model featuring positive (interpersonal skills and approaches to learning) and…

  8. Tracing Student Responsiveness to Intervention with Early Literacy Skills Indicators: Do They Reflect Growth toward Text Reading Outcomes?

    ERIC Educational Resources Information Center

    Clemens, Nathan H.; Hilt-Panahon, Alexandra; Shapiro, Edward S.; Yoon, Myeongsun

    2012-01-01

    This study investigated four widely-used early literacy skills indicators in reflecting growth toward first-grade text reading skills. Examining the progress of 101 students across kindergarten and first grade, Letter Naming Fluency (LNF) and Nonsense Word Fluency (NWF) were more accurate than Initial Sounds Fluency and Phoneme Segmentation…

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

    PubMed

    Sebastián, 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. PMID:27131621

  10. Sonographic monitoring of early follicle growth induced by melatonin implants in camels and the subsequent fertility

    PubMed Central

    Dholpuria, S.; Vyas, S.; Purohit, G.N.; Pathak, K.M.L.

    2012-01-01

    The present study examined the effect of melatonin implants on follicle growth in dromedary camels two months ahead of their natural breeding season (December to March). Female camels (n = 6) were treated with melatonin implants at the dose rate of 1 implant per 28 kg body weight sc. Control camels (n = 6) were administered an SC placebo implant of 8 ml vitamin A. Ovarian ultrasonography was performed at weekly interval upto 7 weeks. Camels were mated with virile stud when a follicle (≥10 mm) was visible on either of the ovaries. Blood was collected on day 7, 9, 15, 20, 25 and 30 for assay of plasma progesterone and sonography performed at the same time. Small follicles (2-3 mm) appeared around the periphery of ovaries in 83.3% of camels by day 7 and in 100% camels by day 14. By the end of 7th week an ovulatory size follicle (≥1.0 cm) could be observed in 83.3% of treated camels, and these camels were mated with virile studs. In control group, small follicles appeared at the periphery of ovaries only in 66.6% camels but did not progress in growth except in one camel (16.6%) however, ovulating size (≥10 mm) follicle was not observed in any camel by the end of 7th week. All treated camels ovulated and one treated camel became pregnant while early embryonic death occurred in one camel. Non–pregnant camels of both groups were mated during the breeding season. All camels of treatment group and 33.33% camels of control group became pregnant by the end of breeding season (April 2010). It was concluded that melatonin implants can augment the follicle growth in lactating camels ahead of the breeding season and pregnancy can occur on mating. Fertility of treated camels during the breeding season is improved. PMID:23396356

  11. Early Motherhood and Harsh Parenting: The Role of Human, Social, and Cultural Capital

    ERIC Educational Resources Information Center

    Lee, Yookyong

    2009-01-01

    Objective: This study examined the role of maternal human, social, and cultural capital in the relationship between early motherhood and harsh parenting behavior. Methods: This study used data from the Fragile Families and Child Wellbeing (FFCW) Study. Harsh parenting behaviors by mothers who were 19 years or younger at birth of the focal child (n…

  12. Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

    ERIC Educational Resources Information Center

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

    2008-01-01

    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…

  13. Early loss of oligodendrocytes in human and experimental neuromyelitis optica lesions

    PubMed Central

    Wrzos, Claudia; Winkler, Anne; Metz, Imke; Kayser, Dieter M.; Thal, Dietmar R.; Wegner, Christiane; Brück, Wolfgang; Nessler, Stefan; Bennett, Jeffrey L.

    2014-01-01

    Neuromyelitis optica (NMO) is a chronic, mostly relapsing inflammatory demyelinating disease of the CNS characterized by serum anti-aquaporin 4 (AQP4) antibodies in the majority of patients. Anti-AQP4 antibodies derived from NMO patients target and deplete astrocytes in experimental models when co-injected with complement. However, the time course and mechanisms of oligodendrocyte loss and demyelination and the fate of oligodendrocyte precursor cells (OPC) have not been examined in detail. Also, no studies regarding astrocyte repopulation of experimental NMO lesions have been reported. We utilized two rat models using either systemic transfer or focal intracerebral injection of recombinant human anti-AQP4 antibodies to generate NMO-like lesions. Time-course experiments were performed to examine oligodendroglial and astroglial damage and repair. In addition, oligodendrocyte pathology was studied in early human NMO lesions. Apart from early complement-mediated astrocyte destruction, we observed a prominent, very early loss of oligodendrocytes and oligodendrocyte precursor cells (OPCs) as well as a delayed loss of myelin. Astrocyte repopulation of focal NMO lesions was already substantial after 1 week. Olig2-positive OPCs reappeared before NogoA-positive, mature oligodendrocytes. Thus, using two experimental models that closely mimic the human disease, our study demonstrates that oligodendrocyte and OPC loss is an extremely early feature in the formation of human and experimental NMO lesions and leads to subsequent, delayed demyelination, highlighting an important difference in the pathogenesis of MS and NMO. PMID:24292009

  14. The Influence of Theoretical Conceptions of Human Development on the Practice of Early Childhood Education.

    ERIC Educational Resources Information Center

    Gardner, D. Bruce

    Communication is urged between theorists of human development and practitioners in early childhood education. Major psychological theories on maturation, child development, child behavior, personality formation, and affective and intellectual development are summarized and their effects on nursery school practices from the 1920's to the present…

  15. STATIONARY PATTERN ADAPTATION AND THE EARLY COMPONENTS IN HUMAN VISUAL EVOKED POTENTIALS

    EPA Science Inventory

    Pattern-onset visual evoked potentials were elicited from humans by sinusoidal gratings of 0.5., 1, 2 and 4 cpd (cycles/degree) following adaptation to a blank field or one of the gratings. The wave forms recorded after blank field adaptation showed an early positive component, P...

  16. NT-3 attenuates the growth of human neuron cells through the ERK pathway.

    PubMed

    Li, Ruifeng; Wu, Yimin; Jiang, Dianming

    2016-08-01

    Spinal cord injury is a devastating health problem that affects thousands of individuals each year. The neurons were destroyed. NT-3 is a recently discovered neurotrophin. This study sought to understand the potential involvement of MAPKs in NT-3-mediated growth inhibition of human neurons. We applied different concentrations of NT-3 and observed the growth rate of the cells and the changes in the phosphorylation state of the MAPKs ERK1/2, JNK and p38. This study discovered that NT-3-induced HNC growth was promoted primarily by phosphorylated ERK1/2, and that this phosphorylation, as well p90(rsk)phosphorylation, was mediated by TrkC. The ERK1/2 pathway is known to play an essential role in the NT-3-mediated growth of human neurons. In conclusion, our study suggests that NT-3 promotes the growth of human neurons cells primarily through the TrkC/ERK pathway. PMID:25501303

  17. Increased induction in FeCo-based nanocomposite materials with reduced early transition metal growth inhibitors

    NASA Astrophysics Data System (ADS)

    Miller, K. J.; Leary, A.; Kernion, S. J.; Wise, A.; Laughlin, D. E.; McHenry, M. E.; Keylin, Vladimir; Huth, Joe

    2010-05-01

    We report on new high-saturation induction, high-temperature nanocomposite alloys with reduced glass formers. The amounts of the magnetic transition metals and early transition metal growth inhibitors were systematically varied to determine trade-offs between higher inductions and fine microstructures with consequently lower magnetic losses. Alloys of nominal composition (Fe65Co35)79.5+xNb4-xB13Si2Cu1.5 (x=0-4) were cast into a 28 mm wide, 20 μm thick ribbon from which toroidal cores were wound. Inductions and magnetic losses were measured after nanocrystallization and stress relief. We report technical magnetic properties: permeability, maximum induction, remanence ratio, coercive field, and high frequency magnetic losses as a function of composition and annealing temperature for these alloys. Of note is the development of maximum inductions in excess of 1.76 T in cores made of alloys with the x=4 composition and maximum inductions in excess of 1.67 T in alloys with the x=3 composition, which also exhibit power losses smaller than 10 W/kg at 0.2 T induction levels in 20 kHz fields. We discuss optimization of induction with chemistry and correlate the microstructures with losses.

  18. Reduction of early-time perturbation growth in ablatively driven laser targets using tailored density profiles

    NASA Astrophysics Data System (ADS)

    Metzler, Nathan; Velikovich, Alexander L.; Gardner, John H.

    1999-08-01

    The effects of tailoring the density profile in a laser target in order to decrease imprinting of mass perturbations due to the long-wavelength modes are investigated analytically and numerically. Inverting the acceleration of the ablation front during the shock transit time could reduce the early-time mass perturbation amplitudes developed in the target after the shock transit. This principle was first suggested for mitigating the Rayleigh-Taylor (RT) instability of imploding Z-pinches [Velikovich et al., Phys. Rev. Lett. 77, 853 (1996); Phys. Plasmas 5, 3377 (1998)]. As the shock wave slows down propagating into higher density layers, the effective gravity near the ablation front has the same direction as the density gradient. This makes the mass perturbations near it oscillate at a higher frequency and at a lower amplitude than they normally would due to the "rocket effect" caused by mass ablation [Sanz, Phys. Rev. Lett. 73, 2700 (1994); Piriz et al., Phys. Plasmas 4, 1117 (1997)]. So, tailoring density profiles instead of using flat densities is demonstrated to reduce the "seed" mass perturbation amplitude at the onset of the exponential RT growth.

  19. Regulation of low affinity neurotrophin receptor (p75NTR) by early growth response (Egr) transcriptional regulators

    PubMed Central

    Gao, Xiaoguang; Daugherty, Rebecca L.; Tourtellotte, Warren G.

    2007-01-01

    The low affinity neurotrophin receptor p75NTR is a multifunctional receptor with important roles in neurotrophin signaling, axon outgrowth, and oligodendroglia and neuron survival. It is transcriptionally regulated with spatial and temporal precision during nervous system development, injury and regeneration. Very little is known about how p75NTR expression is dynamically regulated but it is likely to influence how p75NTR signals in particular cellular contexts. Here, we identify the early growth response (Egr) transcriptional regulators, Egr1 and Egr3, as direct modulators of p75NTR gene expression. Egr1 and Egr3 bind and transactivate the p75NTR promoter in vitro and in vivo, using distinct response elements on the p75NTR promoter. Consistent with these results, p75NTR expression is greatly diminished in muscle spindle stretch receptors and in peripheral nerve Schwann cells in Egr gene deficient mice. Taken together, the results elucidate a novel mechanism whereby Egr proteins can directly modulate p75NTR expression and signaling in vivo. PMID:17916431

  20. Impaired extinction of learned contextual fear memory in early growth response 1 knockout mice.

    PubMed

    Han, Seungrie; Hong, Soontaek; Mo, Jiwon; Lee, Dongmin; Choi, Eunju; Choi, June-seek; Sun, Woong; Lee, Hyun Woo; Kim, Hyun

    2014-01-01

    Inductive expression of early growth response 1 (Egr-1) in neurons is associated with many forms of neuronal activity. However, only a few Egr-1 target genes are known in the brain. The results of this study demonstrate that Egr-1 knockout (KO) mice display impaired contextual extinction learning and normal fear acquisition relative to wild-type (WT) control animals. Genome-wide microarray experiments revealed 368 differentially expressed genes in the hippocampus of Egr-1 WT exposed to different phases of a fear conditioning paradigm compared to gene expression profiles in the hippocampus of KO mice. Some of genes, such as serotonin receptor 2C (Htr2c), neuropeptide B (Npb), neuronal PAS domain protein 4 (Npas4), NPY receptor Y1 (Npy1r), fatty acid binding protein 7 (Fabp7), and neuropeptide Y (Npy) are known to regulate processing of fearful memories, and promoter analyses demonstrated that several of these genes contained Egr-1 binding sites. This study provides a useful list of potential Egr-1 target genes which may be regulated during fear memory processing. PMID:24552706

  1. MASSIVE NEUTRINOS PROMOTE THE SIZE GROWTH OF EARLY-TYPE GALAXIES

    SciTech Connect

    Song, Hyunmi; Lee, Jounghun E-mail: jounghun@astro.snu.ac.kr

    2013-05-10

    The effect of massive neutrinos on the evolution of early-type galaxies in size and stellar mass is explored by tracing the merging history of galaxy progenitors with the help of robust semi-analytic prescriptions. We show that as the presence of massive neutrinos plays a role in enhancing the mean merger rate per halo as well as the merger-driven increment in halo mass, the high-z progenitors of a massive descendant galactic halo evolve more rapidly in mass-normalized size for a {Lambda}MDM ({Lambda} cold dark matter + massive neutrinos) model than for the {Lambda}CDM ({Lambda} cold dark matter) case. We provide a physical reason for why the halo mass growth rate and the merger rate are higher in a {Lambda}MDM cosmology and conclude that if the presence and the role of massive neutrinos are properly taken into account, then it may explain the anomalous compactness of the high-z massive ETGs compared with local giant ellipticals with similar stellar masses.

  2. Growth factors with heparin binding affinity in human synovial fluid

    SciTech Connect

    Hamerman, D.; Taylor, S.; Kirschenbaum, I.; Klagsbrun, M.; Raines, E.W.; Ross, R.; Thomas, K.A.

    1987-12-01

    Synovial effusions were obtained from the knees of 15 subjects with joint trauma, menisceal or ligamentous injury, or osteoarthritis. Heparin-Sepharose affinity chromatography of these synovial fluids revealed, in general, three major peaks of mitogenic activity as measured by incorporation of /sup 3/H-thymidine into 3T3 cells. Gradient elution patterns showed activities at 0.5M NaCl, which is characteristic of platelet derived growth factor, and at 1.1 M NaCl and 1.6M NaCl, indicative of acidic and basic fibroblast growth factors, respectively. The identities of these mitogenic fractions were confirmed by specific immunologic and receptor-binding assays. The presence of platelet derived, acidic and basic fibroblast growth factors in the synovial fluid may contribute to wound healing in the arthritic joint.

  3. 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)

  4. Early life-stage test in zebrafish versus a growth test in rainbow trout to evaluate toxic effects

    SciTech Connect

    Bresch, H. )

    1991-05-01

    The aim of the work presented in this paper was to compare toxic threshold concentrations of three substances obtained from growth test in rainbow trout (Salmo gairdneri) with data from early life-stages in zebrafish. The growth test was conducted over a period of 7 wk in case of 4-chloroaniline and 4 wk in case of 3,4-dichloroaniline and diazinon. The data from the experiment in zebrafish originate from life-cycle studies; here, only the results obtained within the first 6 wk of development after fertilization are considered. These time limits have been set, as in the FRG a growth test in rainbow trout extending over 4 wk and an early life-stage test in zebrafish extending over 6 wk are being discussed for the Chemical Act.

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

    PubMed

    Peng, Y; Lu, Z; Li, G; Piechowicz, M; Anderson, M; Uddin, Y; Wu, J; Qiu, S

    2016-07-01

    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 has 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

  6. Controlled fire use in early humans might have triggered the evolutionary emergence of tuberculosis.

    PubMed

    Chisholm, Rebecca H; Trauer, James M; Curnoe, Darren; Tanaka, Mark M

    2016-08-01

    Tuberculosis (TB) is caused by the Mycobacterium tuberculosis complex (MTBC), a wildly successful group of organisms and the leading cause of death resulting from a single bacterial pathogen worldwide. It is generally accepted that MTBC established itself in human populations in Africa and that animal-infecting strains diverged from human strains. However, the precise causal factors of TB emergence remain unknown. Here, we propose that the advent of controlled fire use in early humans created the ideal conditions for the emergence of TB as a transmissible disease. This hypothesis is supported by mathematical modeling together with a synthesis of evidence from epidemiology, evolutionary genetics, and paleoanthropology. PMID:27457933

  7. Early pregnancy factor is an immunosuppressive contaminant of commercial preparations of human chorionic gonadotrophin.

    PubMed Central

    Rolfe, B E; Morton, H; Clarke, F M

    1983-01-01

    Early pregnancy factor (EPF) is a pregnancy associated substance detected in human serum and urine throughout the first and second trimesters of pregnancy. It has also been detected in several commercial preparations of human chorionic gonadotrophin (hCG). The various molecular weight forms of EPF which occur in human pregnancy serum, urine and commercial hCG preparations have been partially characterized and found to be similar to each other but distinct from hCG. Further evidence is presented which suggests that it is EPF rather than hCG which is responsible for the immunosuppressive activity of some crude hCG preparations. PMID:6831771

  8. Synthesis of human adenovirus early RNA species is similar in productive and abortive infections of monkey and human cells.

    PubMed Central

    Anderson, K P; Klessig, D F

    1982-01-01

    Northern (RNA) blot analysis has been used to show that synthesis of early mRNA species is similar in monkey cells productively or abortively infected with human adenovirus. mRNA species from all five major early regions (1A, 1B, 2, 3, 4) are identical in size and comparable in abundance whether isolated from monkey cells infected with adenovirus type 2 or with the host range mutant Ad2hr400 or coinfected with adenovirus type 2 plus simian virus 40. The mRNA species isolated from monkey cells are identical in size to those isolated from human cells. Production of virus-associated RNA is also identical in productive and abortive infections of monkey cells. Synthesis of virus-associated RNA is, however, significantly greater in HeLa cells than in CV1 cells at late times after infection regardless of which virus is used in the infection. Images PMID:6283181

  9. Growth in early childhood in a cohort of children born to HIV-1-infected women from Durban, South Africa.

    PubMed

    Bobat, R; Coovadia, H; Moodley, D; Coutsoudis, A; Gouws, E

    2001-09-01

    This study describes growth in a cohort of black South African children born to HIV-1-infected women in Durban. Children born to HIV-1-seropositive women were followed up from birth to early childhood. At birth and at each visit, growth parameters were measured. Mean Z-scores were calculated for weight-for-length, weight-for-age and length-for-age and, if they were low, the children were regarded as wasted, malnourished or stunted, respectively. At the end of the study, there were 48 infected and 93 uninfected children. There were no significant differences between the two groups at birth. Thereafter, the infected group was found to have early and sustained low mean Z-scores for length-for-age and weight-for-age but not for weight-for-length. The means reached significance at ages 3, 6 and 12 months for length and at 3, 6 and 9 months for weight. Infected children who died early had more severe stunting, wasting and malnutrition than infected children who survived. Infected children born to HIV-positive women have early and sustained stunting and are malnourished but not wasted. Children with rapidly progressive disease have both stunting and wasting and are more severely affected. Early nutritional intervention might help prevent early progression or death in HIV-infected children, particularly in developing countries without access to anti-retroviral therapy in state hospitals. PMID:11579858

  10. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma.

    PubMed

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  11. Uptake of Plasmin-PN-1 Complexes in Early Human Atheroma

    PubMed Central

    Boukais, Kamel; Bayles, Richard; Borges, Luciano de Figueiredo; Louedec, Liliane; Boulaftali, Yacine; Ho-Tin-Noé, Benoit; Arocas, Véronique; Bouton, Marie-Christine; Michel, Jean-Baptiste

    2016-01-01

    Zymogens are delivered to the arterial wall by radial transmural convection. Plasminogen can be activated within the arterial wall to produce plasmin, which is involved in evolution of the atherosclerotic plaque. Vascular smooth muscle cells (vSMCs) protect the vessels from proteolytic injury due to atherosclerosis development by highly expressing endocytic LDL receptor-related protein-1 (LRP-1), and by producing anti-proteases, such as Protease Nexin-1 (PN-1). PN-1 is able to form covalent complexes with plasmin. We hypothesized that plasmin-PN-1 complexes could be internalized via LRP-1 by vSMCs during the early stages of human atheroma. LRP-1 is also responsible for the capture of aggregated LDL in human atheroma. Plasmin activity and immunohistochemical analyses of early human atheroma showed that the plasminergic system is activated within the arterial wall, where intimal foam cells, including vSMCs and platelets, are the major sites of PN-1 accumulation. Both PN-1 and LRP-1 are overexpressed in early atheroma at both messenger and protein levels. Cell biology studies demonstrated an increased expression of PN-1 and tissue plasminogen activator by vSMCs in response to LDL. Plasmin-PN-1 complexes are internalized via LRP-1 in vSMCs, whereas plasmin alone is not. Tissue PN-1 interacts with plasmin in early human atheroma via two complementary mechanisms: plasmin inhibition and tissue uptake of plasmin-PN-1 complexes via LRP-1 in vSMCs. Despite this potential protective effect, plasminogen activation by vSMCs remains abnormally elevated in the intima in early stages of human atheroma. PMID:27445860

  12. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    SciTech Connect

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-12-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection.

  13. 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

  14. Early Pleistocene third metacarpal from Kenya and the evolution of modern human-like hand morphology.

    PubMed

    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

  15. Epidermal growth factor-expressing Lactococcus lactis enhances growth performance of early-weaned pigs fed diets devoid of blood plasma.

    PubMed

    Bedford, A; Li, Z; Li, M; Ji, S; Liu, W; Huai, Y; de Lange, C F M; Li, J

    2012-12-01

    The effect of supplementing Lactococcus lactis (L. lactis) that was engineered to express epidermal growth factor (EGF-LL) to early-weaned pigs fed diets with typical levels of blood plasma (5%) or diets without blood plasma [blood plasma was substituted with soybean (Glycine max) meal and fish meal, based on amino acid supply] was examined. A total of 108 weaned piglets (19-26 d of age; mean initial BW 6.58 kg; 9 pigs per pen) were fed ad libitum according to a 2-phase feeding program without growth promoters. Three pens were assigned to each of 4 treatments: i) blood plasma-containing diet with blank bacterial growth medium (BP-Con), ii) blood plasma-containing diet with fermented EGF-LL (BP-EGF), iii) blood plasma-free diet with blank bacterial growth medium (BPF-Con), and iv) blood plasma-free diet with fermented EGF-LL (BPF-EGF). The amount of epidermal growth factor (EGF) was determined in the fermentation product and pigs were allotted 60 μg EGF/kg BW/d for 3 wk postweaning. There were no differences in overall growth performance between BP-Con and BP-EGF pigs and no differences in overall growth performance between LoCon and BPF-EGF pigs. Pigs fed BPF-EGF showed increased daily BW gain (410 vs. 260 g/d; P < 0.01) and gain:feed (0.67 vs. 0.58; P < 0.05) compared to BPF-Con pigs in wk 3 postweaning; this was comparable to values for the BP-Con group (400 g/d and 0.64). These results indicate that supplementation with EGF-LL can be effective in enhancing the performance of early-weaned piglets fed a low complexity diet and reduces the need for feeding high-quality animal proteins and antibiotics. PMID:23365266

  16. Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease.

    PubMed

    Rodriguez, Santiago; Gaunt, Tom R; Day, Ian N M

    2007-08-01

    The human growth hormone gene (GH1) and the insulin-like growth factor 1 and 2 genes (IGF1 and IGF2) encode the central elements of a key pathway influencing growth in humans. This "growth pathway" also includes transcription factors, agonists, antagonists, receptors, binding proteins, and endocrine factors that constitute an intrincate network of feedback loops. GH1 is evolutionarily coupled with other genes in linkage disequilibrium in 17q24.2, and the same applies to IGF2 in 11p15.5. In contrast, IGF1 in 12q22-24.1 is not in strong linkage disequilibrium with neighbouring genes. Knowledge of the functional architecture of these regions is important for the understanding of the combined evolution and function of GH1, IGF2 and IGF1 in relation to complex diseases. A number of mutations accounting for rare Mendelian disorders have been described in GH-IGF elements. The constellation of genes in this key pathway contains potential candidates in a number of complex diseases, including growth disorders, metabolic syndrome, diabetes (notably IGF2BP2) cardiovascular disease, and central nervous system diseases, and in longevity, aging and cancer. We review these genes and their associations with disease phenotypes, with special attention to metabolic risk traits. PMID:17534663

  17. Information for People Treated with Human Growth Hormone (Comprehensive Report)

    MedlinePlus

    ... org ) is a nonprofit organization concerned with children's growth disorders and adult GH deficiency. The HGF has information available online and through its toll-free number, 1–800–451–6434. The HGF also supports an Internet mailing list to help the exchange of information ...

  18. Human milk feeding supports adequate growth in infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  19. Human disturbance influences reproductive success and growth rate in California sea lions (Zalophus californianus).

    PubMed

    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

  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. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells

    PubMed Central

    Lee, Jieun; Taylor, Sarah E. B.; Smeriglio, Piera; Lai, Janice; Maloney, William J.; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    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)9low cluster of differentiation (CD)44lowCD140low prechondrogenic population during hiPSC differentiation. In addition, 2 distinct Sox9-regulated gene networks were identified in the Sox9low and Sox9high 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.—Lee, J., Taylor, S. E. B., Smeriglio, P., Lai, J., Maloney, W. J., Yang, F., Bhutani, N. Early induction of a prechondrogenic population allows efficient generation of stable chondrocytes from human induced pluripotent stem cells. PMID:25911615

  2. 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

  3. Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

    PubMed Central

    Kim, Youngsook; Hong, Jae Won; Chung, Yoon-Sok; Kim, Sung-Woon; Cho, Yong-Wook; Kim, Jin Hwa; Kim, Byung-Joon

    2014-01-01

    Purpose The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage™) supplement in patients with growth hormone deficiency were evaluated. Materials and Methods This trial is 12-week prospective, single-arm, open-label trial. Men and women aged ≥20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. Results The IGF-1 level of 108.67±74.03 ng/mL was increased to 129.01±68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80±6.51 to 7.55±5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. Conclusion Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events. PMID:24954335

  4. Neonatal and fetal exposure to trans-fatty acid retards early growth and adiposity while adversely affecting glucose in mice

    PubMed Central

    Kavanagh, Kylie; Sajadian, Soraya; Jenkins, Kurt A.; Wilson, Martha D.; Carr, J. Jeffery; Wagner, Janice D.; Rudel, Lawrence L.

    2010-01-01

    Industrially produced trans fatty acids (TFAs) consumed in western diets are incorporated into maternal and fetal tissues, and are passed linearly to offspring via breast milk. We hypothesized that TFA exposure in utero and during lactation in infants would promote obesity and poor glycemic control as compared to unmodified fatty acids. We further hypothesized that in utero exposure alone may program for these outcomes in adulthood. To test this hypothesis we fed female C57/BL6 mice identical western diets that differed only in cis- or trans-isomers of C18:1 and then aimed to determine whether maternal transfer of TFAs through pregnancy and lactation alters growth, body composition and glucose metabolism. Mice were unexposed, exposed during pregnancy, during lactation, or throughout pregnancy and lactation to TFA. Body weight and composition (by computed tomography), and glucose metabolism we assessed at weaning and adulthood. TFA exposure through breast milk caused significant early growth retardation (p<0.001) and higher fasting glucose (p=0.01) but insulin sensitivity was not different. Elevated plasma insulin-like growth factor-1 in mice consuming TFA-enriched milk (p=0.02) may contribute to later catch-up growth, leanness and preserved peripheral insulin sensitivity observed in these mice. Mice exposed to TFA in utero underwent rapid early neonatal growth with TFA-free breast milk and had significantly impaired insulin sensitivity (p<0.05) and greater abdominal fat (p=0.01). We conclude that very early catch-up growth resulted in impaired peripheral insulin sensitivity in this model of diet-related fetal and neonatal programming. TFA surprisingly retarded growth and adiposity while still adversely affecting glucose metabolism. PMID:20650350

  5. Digital Literacy Practices and Pedagogical Moments: Human and Non-Human Intertwining in Early Childhood Education

    ERIC Educational Resources Information Center

    Lafton, Tove

    2015-01-01

    Various forms of digital devices have established themselves as resources within constructions of professional practices in early childhood education. This article is centred on the question of how we might rethink an example of digital practice based on a Foucauldian understanding of discourse and a rhizomatic understanding of digital practice…

  6. Growth inhibition of human prostate cells in vitro by novel inhibitors of androgen synthesis.

    PubMed

    Klus, G T; Nakamura, J; Li, J S; Ling, Y Z; Son, C; Kemppainen, J A; Wilson, E M; Brodie, A M

    1996-11-01

    The long-standing strategy for the treatment of metastatic prostate cancer has been to reduce androgenic stimulation of tumor growth by removal of the testes, the primary site of testosterone synthesis. However, a low level of androgenic stimulation may continue, even after castration, by the conversion of adrenal androgens to 5alpha-dihydrotestosterone (DHT) in the prostate tumor cells. Two important enzymes of the androgen biosynthetic pathway are 17alpha-hydroxylase/C17,20-lyase, which regulates an early step in the synthesis of testosterone and other androgens in both the testes and adrenal glands, and 5alpha-reductase, which converts testosterone to the more potent androgen, DHT, in the prostate. We have identified new inhibitors of these enzymes that may be of use in achieving a more complete ablation of androgens in the treatment of metastatic prostate cancer. Three derivatives of androstene were shown to inhibit 17alpha-hydroxylase/C17,20-lyase with potencies 2-20-fold greater than that of ketoconazole, a previously established inhibitor of this enzyme. Derivatives of pregnane and pregnene displayed activities against 5alpha-reductase that were comparable to that of N-(1,1-dimethyl-ethyl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-car boxamide. All of the 5alpha-reductase inhibitors were able to at least partially inhibit the mitogenic effect of testosterone in either histocultures of human benign prostatic hypertrophic tissue or in cultures of the LNCaP human prostatic tumor cell line. For these compounds, it appears that this inhibition can be attributed to a reduction of DHT synthesis in these cultures, because no inhibitory effect was observed in DHT-treated cultures, and none of the compounds had a cytotoxic effect. Surprisingly, one of the inhibitors of 17alpha-hydroxylase/C17,20-lyase, 17beta-(4-imidazolyl)-5-pregnen-3beta-ol, was also able to inhibit the mitogenic effect of testosterone in both the histoculture and cell culture assays and had an effect

  7. Human precision-cut liver slices as a model to test antifibrotic drugs in the early onset of liver fibrosis.

    PubMed

    Westra, Inge M; Mutsaers, Henricus A M; Luangmonkong, Theerut; Hadi, Mackenzie; Oosterhuis, Dorenda; de Jong, Koert P; Groothuis, Geny M M; Olinga, Peter

    2016-09-01

    Liver fibrosis is the progressive accumulation of connective tissue ultimately resulting in loss of organ function. Currently, no effective antifibrotics are available due to a lack of reliable human models. Here we investigated the fibrotic process in human precision-cut liver slices (PCLS) and studied the efficacy of multiple putative antifibrotic compounds. Our results demonstrated that human PCLS remained viable for 48h and the early onset of fibrosis was observed during culture, as demonstrated by an increased gene expression of Heat Shock Protein 47 (HSP47) and Pro-Collagen 1A1 (PCOL1A1) as well as increased collagen 1 protein levels. SB203580, a specific inhibitor of p38 mitogen-activated protein kinase (MAPK) showed a marked decrease in HSP47 and PCOL1A1 gene expression, whereas specific inhibitors of Smad 3 and Rac-1 showed no or only minor effects. Regarding the studied antifibrotics, gene levels of HSP47 and PCOL1A1 could be down-regulated with sunitinib and valproic acid, while PCOL1A1 expression was reduced following treatment with rosmarinic acid, tetrandrine and pirfenidone. These results are in contrast with prior data obtained in rat PCLS, indicating that antifibrotic drug efficacy is clearly species-specific. Thus, human PCLS is a promising model for liver fibrosis. Moreover, MAPK signaling plays an important role in the onset of fibrosis in this model and transforming growth factor beta pathway inhibitors appear to be more effective than platelet-derived growth factor pathway inhibitors in halting fibrogenesis in PCLS. PMID:27235791

  8. 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

  9. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.

    PubMed

    Millar, Neal L; Akbar, Moeed; Campbell, Abigail L; Reilly, James H; Kerr, Shauna C; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G; Leach, William J; Rooney, Brian P; Crowe, Lindsay A N; Murrell, George A C; McInnes, Iain B

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing 'early pathology') along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in 'early tendinopathy' compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  10. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy

    PubMed Central

    Millar, Neal L.; Akbar, Moeed; Campbell, Abigail L.; Reilly, James H.; Kerr, Shauna C.; McLean, Michael; Frleta-Gilchrist, Marina; Fazzi, Umberto G.; Leach, William J.; Rooney, Brian P.; Crowe, Lindsay A. N.; Murrell, George A. C.; McInnes, Iain B.

    2016-01-01

    Increasingly, inflammatory mediators are considered crucial to the onset and perpetuation of tendinopathy. We sought evidence of interleukin 17A (IL-17A) expression in early human tendinopathy and thereafter, explored mechanisms whereby IL-17A mediated inflammation and tissue remodeling in human tenocytes. Torn supraspinatus tendon (established pathology) and matched intact subscapularis tendon (representing ‘early pathology’) along with control biopsies were collected from patients undergoing shoulder surgery. Markers of inflammation and IL-17A were quantified by RT-PCR and immunohistochemistry. Human tendon cells were derived from hamstring tendon obtained during ACL reconstruction. In vitro effects of IL-17A upon tenocytes were measured using RT-PCR, multiplex cytokine assays, apoptotic proteomic profiling, immunohistochemistry and annexin V FACS staining. Increased expression of IL-17A was detected in ‘early tendinopathy’ compared to both matched samples and non-matched control samples (p < 0.01) by RT-PCR and immunostaining. Double immunofluoresence staining revealed IL-17A expression in leukocyte subsets including mast cells, macrophages and T cells. IL-17A treated tenocytes exhibited increased production of proinflammatory cytokines (p < 0.001), altered matrix regulation (p < 0.01) with increased Collagen type III and increased expression of several apoptosis related factors. We propose IL-17A as an inflammatory mediator within the early tendinopathy processes thus providing novel therapeutic approaches in the management of tendon disorders. PMID:27263531

  11. Starch grains on human teeth reveal early broad crop diet in northern Peru.

    PubMed

    Piperno, Dolores R; Dillehay, Tom D

    2008-12-16

    Previous research indicates that the Nanchoc Valley in northern Peru was an important locus of early and middle Holocene human settlement, and that between 9200 and 5500 (14)C 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 (14)C 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 Nanchoc region by 8000 (14)C 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

  12. General pharmacology of recombinant human basic fibroblast growth factor.

    PubMed

    Okumura, M; Yajima, M; Nishimura, T; Ikeda, H; Nishimori, T

    1996-07-01

    General pharmacological effects of recombinant human basic fibroblast growth factor (bFGF) were investigated. 1. Central nervous system: Basic FGF produced almost no effect on the general symptoms and behaviors of mice. Basic FGF did not influence the spontaneous motor activity, hexobarbital-induced anesthesia, electroshock seizure threshold, pentylenetetrazole-induced seizure in mice and normal body temperature and spinal reflex in rats up to a dose of 1 mg/kg (s.c., i.v.). As regards pain sensation, it inhibited the acetic acid-induced writhing at 1 mg/kg (s.c.). No abnormal waves were observed in spontaneous EEG of the rabbit up to 1 mg/kg (i.v.) of bFGF, but at 0.1 mg/kg it had a slight effect on the ratio of EEG levels and at 1 mg/kg induced an increase in rest period, disappearance in the period of fast wave sleep and a decrease in the period of deep sleep. 2. Somatic nervous system: Basic FGF did not influence the corneal reflex, twitch response of the skin and diaphragm-phrenic nerve preparations. 3. Autonomic nervous system and smooth muscle: Basic FGF showed little effects on the spontaneous movement of the isolated ileum, contraction induced by various agonists in isolated ileum, resting tension and noradrenaline(NA)-induced contraction of the aorta, resting tension and histamine-induced contraction of isolated trachea, spontaneous movement and 5-HT-induced contraction of isolated strips of stomach fundus, NA-induced contraction of isolated vas deferens of the rat up to the concentration of 10(-4) g/ml. Basic FGF augmented the tone of the isolated non-pregnant uterus at the concentrations of 10(-5) g/ml and above and inhibited or tended to inhibit the contractile tension of non-pregnant or pregnant uterus at 10(-4) g/ml, but it did not influence the spontaneous movement of the uterus, either the non-pregnant or pregnant, under in situ conditions even at a dose of 1 mg/kg (i.v.). Basic FGF did not influence the pupil size. 4. Respiratory and circulatory

  13. Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

    SciTech Connect

    Romshe, C.A.; Zipf, W.B.; Miser, A.; Miser, J.; Sotos, J.F.; Newton, W.A.

    1984-02-01

    We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significant differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.

  14. Monitoring Children's Growth in Early Literacy Skills: Effects of Feedback on Performance and Classroom Environments

    ERIC Educational Resources Information Center

    Ball, Carrie; Gettinger, Maribeth

    2009-01-01

    The study examined the benefits of providing kindergarten teachers with feedback about students' performance on early literacy progress-monitoring probes. Students were administered the "Dynamic Indicators of Basic Early Literacy Skills (DIBELS)" in fall, winter, and spring; classroom environment was evaluated using the "Early Language and…

  15. Novel human growth hormone like protein HGH-V encoded in the human genome

    SciTech Connect

    Seeburg, P.H.

    1987-05-12

    This patent describes the human growth hormone protein, HGH-V, having the amino acid sequence: phe pro thr ile pro leu ser arg leu phe asp asn ala met leu arg ala arg arg leu tyr gln leu ala tyr asp thr tyr gln glu phe glu glu ala tyr ile leu lys glu gln lys tyr ser phe leu gln asn pro gln thr ser leu cys phe ser glu ser ile pro thr pro ser asn arg val lys thr gln gln lys ser asn leu glu leu leu arg ile ser leu leu leu ile gln ser trp leu glu pro val gln leu leu arg ser val phe ala asn ser leu val tyr gly ala ser asp ser asn val tyr arg his leu lys asp leu glu glu gly ile gln thr leu met trp arg leu glu asp gly ser pro arg thr gly gln ile phe asn-glycosylation site gln ser tyr ser lys phe asp thr lys ser his asn asp asp ala leu leu lys asn tyr gly leu leu tyr cys Phe arg lys asp met asp lys val glu thr phe leu arg ile val gln cys arg ser val glu gly ser cys gly phe.

  16. Ammonia volatilization from urea-application influenced germination and early seedling growth of dry direct-seeded rice.

    PubMed

    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

  17. 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

  18. Impact of growth patterns and early diet on obesity and cardiovascular risk factors in young children from developing countries.

    PubMed

    Corvalán, Camila; Kain, Juliana; Weisstaub, Gerardo; Uauy, Ricardo

    2009-08-01

    Non-communicable chronic diseases are now a worldwide epidemic. Diet and physical activity throughout life are among its main determinants. In countries undergoing the early stages of the nutrition transition weight gain from birth to 2 years of life is related to lean mass gain, while ponderal gain after age 2 years is related to adiposity and later diabetes and CVD risk. Evidence from developing countries undergoing the more advanced stages of the nutrition transition is limited. The early growth patterns of a cohort of Chilean children born in 2002 with normal birth weight who at 4 years had a high prevalence of obesity and CVD risk factors have been assessed. Results indicate that BMI gain in early life, particularly from 6 months to 24 months, is positively associated with adiposity and CVD risk status at 4 years. These results together with existing evidence suggest that actions to prevent obesity and nutrition-related chronic diseases in developing countries should start early in life, possibly after 6 months of age. This approach should consider assessing the effect of mode of feeding and the amount and type of energy fed, as well as the resulting growth patterns. The challenge for researchers addressing the nutrition transition is to define the optimal nutrition in early life, considering not only the short- and long-term health consequences but also taking into account the stage of the nutritional transition for the given population of interest. The latter will probably require redefining optimal postnatal growth based on the context of maternal size and fetal growth. PMID:19400973

  19. DNA analysis of an early modern human from Tianyuan Cave, China.

    PubMed

    Fu, Qiaomei; Meyer, Matthias; Gao, Xing; Stenzel, Udo; Burbano, Hernán A; Kelso, Janet; Pääbo, Svante

    2013-02-01

    Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia. PMID:23341637

  20. DNA analysis of an early modern human from Tianyuan Cave, China

    PubMed Central

    Fu, Qiaomei; Meyer, Matthias; Gao, Xing; Stenzel, Udo; Burbano, Hernán A.; Kelso, Janet; Pääbo, Svante

    2013-01-01

    Hominins with morphology similar to present-day humans appear in the fossil record across Eurasia between 40,000 and 50,000 y ago. The genetic relationships between these early modern humans and present-day human populations have not been established. We have extracted DNA from a 40,000-y-old anatomically modern human from Tianyuan Cave outside Beijing, China. Using a highly scalable hybridization enrichment strategy, we determined the DNA sequences of the mitochondrial genome, the entire nonrepetitive portion of chromosome 21 (∼30 Mbp), and over 3,000 polymorphic sites across the nuclear genome of this individual. The nuclear DNA sequences determined from this early modern human reveal that the Tianyuan individual derived from a population that was ancestral to many present-day Asians and Native Americans but postdated the divergence of Asians from Europeans. They also show that this individual carried proportions of DNA variants derived from archaic humans similar to present-day people in mainland Asia. PMID:23341637

  1. Genetic parameters for litter size, piglet growth and sow's early growth and body composition in the Chinese-European line Tai Zumu.

    PubMed

    Banville, M; Riquet, J; Bahon, D; Sourdioux, M; Canario, L

    2015-08-01

    Genetics of piglet growth in association with sow's early growth and body composition were estimated in the Tai Zumu line. Piglet and sow's litter growth traits were calculated from individual weights collected at birth and at 3 weeks of age. Sow's litter traits included the number of piglets born alive (NBA), the mean piglet weight (MW) and the standard deviation of weights within the litter (SDW). Sow's early growth was measured by the age at 100 kg (A100), and body composition included backfat thickness (BF100). A main objective of this study was to estimate separately the direct genetic effect (d) and the maternal genetic effect (m) on piglet weight and daily weight gain during lactation. Variance components were estimated using the restricted maximum likelihood methodology based on animal models. The heritability estimates were 0.19 for NBA, 0.15 and 0.26 for SDW and MW at 3 weeks and 0.42 and 0.70 for A100 and BF100. The NBA was almost independent from SDW. Conversely, the A100 and BF100 were correlated unfavourably with SDW (rg <-0.24, SE<0.12). A stronger selection for litter size should have little effect on litter homogeneity in weights. Selection for lean growth rate tends to favour heterogeneity in weights. The direct effect on piglet weight at birth and daily weight gain accounted for 12% (h(²) (d) = 0.02) and 50% (h(²) (d) = 0.11) of the genetic variance, respectively. The association between d and m for piglet weight was not different from zero at birth (rg = 0.19, SE = 0.27), but a strong antagonism between d and m for daily weight gain from birth to 3 weeks was found (rg = -0.41, SE = 0.17). Substantial direct and maternal genetic effects influenced piglet growth until weaning in opposite way. PMID:25424416

  2. Loss of transcription factor early growth response gene 1 results in impaired endochondral bone repair

    PubMed Central

    Reumann, Marie K.; Strachna, Olga; Yagerman, Sarah; Torrecilla, Daniel; Kim, Jihye; Doty, Steven B.; Lukashova, Lyudmila; Boskey, Adele L.; Mayer-Kuckuk, Philipp

    2011-01-01

    Transcription factors that play a role in ossification during development are expected to participate in postnatal fracture repair since the endochondral bone formation that occurs in embryos is recapitulated during fracture repair. However, inherent differences exist between bone development and fracture repair, including a sudden disruption of tissue integrity followed by an inflammatory response. This raises the possibility that repair-specific transcription factors participate in bone healing. Here, we assessed the consequence of loss of early growth response gene 1 (EGR-1) on endochondral bone healing because this transcription factor has been shown to modulate repair in vascularized tissues. Model fractures were created in ribs of wild type (wt) and EGR-1−/− mice. Differences in tissue morphology and composition between these two animal groups were followed over 28 post fracture days (PFDs). In wt mice, bone healing occurred in healing phases characteristic of endochondral bone repair. A similar healing sequence was observed in EGR-1−/− mice but was impaired by alterations. A persistent accumulation of fibrin between the disconnected bones was observed on PFD7 and remained pronounced in the callus on PFD14. Additionally, the PFD14 callus was abnormally enlarged and showed increased deposition of mineralized tissue. Cartilage ossification in the callus was associated with hyper-vascularity and -proliferation. Moreover, cell deposits located in proximity to the callus within skeletal muscle were detected on PFD14. Despite these impairments, repair in EGR-1−/− callus advanced on PFD28, suggesting EGR-1 is not essential for healing. Together, this study provides genetic evidence that EGR-1 is a pleiotropic regulator of endochondral fracture repair. PMID:21726677

  3. Microbial Communities: Tracing Growth Processes from Antarctic Lakes to Early Earth to Other Planets

    NASA Astrophysics Data System (ADS)

    Sumner, D. Y.

    2014-12-01

    Life in the Universe is dominated by microbes: they are numerically the most abundant cells in our bodies and in Earth's biosphere, and they are the only life that might be present elsewhere in our solar system. Life beyond our solar system could include macroscopic organisms, but everything we understand about the origin of life suggests it must start with microbes. Thus, understanding microbial ecosystems, in the absence of macroscopic organisms, is critical to understanding early life on Earth and life elsewhere in the Universe - if it exists. But what are the general principles of microbial ecology in the absence of predation? What happens when each cell is a chemical factory that can swap among metabolic processes in response to environmental and emergent cues? Geobiologists and astrobiologists are addressing these questions in diverse ways using both Earth's modern biosphere and its fossil record. Modern microbial communities in shallow, ice-covered lakes, Antarctica (Fig.), provide a model for high productivity microbial ecosystems with no to low predation. In these lakes, photosynthetic communities create macroscopic pinnacles and domes, sometime lithified into stromatolites. They provide an ecological, geochemical and morphological model for Precambrian microbial communities in low sedimentation, low current environments. Insights from these communities include new growth processes for ancient mats, especially some that grew prior to the oxidation of Earth's atmosphere. The diversity of biosignatures created in these communities also provides context for models of life under ice elsewhere in our solar system such as paleolakes on Mars and on icy moons. Results from the Mars Science Laboratory (MSL) team document formerly habitable fluvial and lacustrine environments. Lacustrine environments, in particular, are favorable for preserving biosignatures, and continued investigations by MSL will provide a deeper understanding of the duration of habitable

  4. Anti-Vascular Endothelial Growth Factor Treatment Suppresses Early Brain Injury After Subarachnoid Hemorrhage in Mice.

    PubMed

    Liu, Lei; Fujimoto, Masashi; Kawakita, Fumihiro; Nakano, Fumi; Imanaka-Yoshida, Kyoko; Yoshida, Toshimichi; Suzuki, Hidenori

    2016-09-01

    The role of vascular endothelial growth factor (VEGF) in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. The aim of this study was to investigate effects of anti-VEGF therapy on EBI after SAH. C57BL/6 male mice underwent sham or filament perforation SAH modeling, and vehicle or two dosages (0.2 and 1 μg) of anti-VEGF antibody were randomly administrated by an intracerebroventricular injection. Neuroscore, brain water content, immunoglobulin G staining, and Western blotting were performed to evaluate EBI at 24-48 h. To confirm the role of VEGF, anti-VEGF receptor (VEGFR)-2 (a major receptor of VEGF) antibody was intracerebroventricularly administered and the effects on EBI were evaluated at 24 h. A higher dose, but not a lower dose, of anti-VEGF antibody significantly ameliorated post-SAH neurological impairments and brain edema at 24-48 h post-SAH. Post-SAH blood-brain barrier disruption was also inhibited by anti-VEGF antibody. The protective effects of anti-VEGF antibody were associated with the inhibition of post-SAH induction of VEGF, VEGFR-2, phosphorylated VEGFR-2, interleukin-1β and a matricellular protein tenascin-C (TNC). Anti-VEGFR-2 antibody also suppressed post-SAH neurological impairments and brain edema associated with VEGFR-2 inactivation and TNC downregulation. These findings demonstrated that VEGF causes post-SAH EBI via VEGFR-2 and TNC and that anti-VEGF therapy is effective for post-SAH EBI. PMID:26289408

  5. Impact of Neonatal Growth on IQ and Behavior at Early School Age

    PubMed Central

    Lynch, John W.; Yang, Seungmi; Dahhou, Mourad; Kramer, Michael S.

    2013-01-01

    OBJECTIVES: The objective was to examine associations of neonatal weight gain (NWG) and head circumference gain (HCG) with IQ scores and behavior at early school age. METHODS: We used data from the Promotion of Breastfeeding Intervention Trial, involving Belarusian infants born full term and weighing ≥2500 g. NWG and HCG were measured as the percentage gain in weight and head circumference over the first 4 weeks relative to birth size. IQ and behavior were measured at 6.5 years of age by using the Wechsler Abbreviated Scales of Intelligence and the Strengths and Difficulties Questionnaire (SDQ), respectively, with SDQ collected from parents and teachers. The associations between the exposures (NWG, HCG) and children’s IQ and SDQ were examined by using mixed models to account for clustering of measurements, and adjustment for potentially confounding perinatal and socioeconomic factors. RESULTS: Mean NWG was 26% (SD 10%) of birth weight. In fully adjusted models, infants in the highest versus lowest quartile of NWG had 1.5-point (95% confidence interval [CI] 0.8 to 2.2) higher IQ scores (n = 13 840). A weak negative (protective) association between NWG and SDQ total difficulties scores was observed for the teacher-reported (β = −0.39, 95% CI −0.71 to −0.08, n = 12 016), but not the parent-reported (β = −0.12, 95% CI −0.39 to 0.15, n = 13 815), SDQ. Similar associations were observed with HCG and IQ and behavior. CONCLUSIONS: Faster gains in weight or head circumference in the 4 weeks after birth may contribute to children’s IQ, but reverse causality (brain function affects neonatal growth) cannot be excluded. PMID:23776123

  6. DIETARY ISOTHIOCYANATE IBERIN INHIBITS GROWTH AND INDUCES APOPTOSIS IN HUMAN GLIOBLASTOMA CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we evaluated the antiproliferative and proapoptotic effects of the isothiocyanate iberin, a bioactive agent in Brassicaceae species, in human glioblastoma cells. The human glioblastoma cell cultures were treated with different concentrations of iberin and tested for growth inhibition...

  7. 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

  8. A Re-Appraisal of the Early Andean Human Remains from Lauricocha in Peru.

    PubMed

    Fehren-Schmitz, Lars; Llamas, Bastien; Lindauer, Susanne; Tomasto-Cagigao, Elsa; 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

  9. 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. PMID:22305470

  10. 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

  11. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus

    PubMed Central

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-01-01

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  12. Digit ratios predict polygyny in early apes, Ardipithecus, Neanderthals and early modern humans but not in Australopithecus.

    PubMed

    Nelson, Emma; Rolian, Campbell; Cashmore, Lisa; Shultz, Susanne

    2011-05-22

    Social behaviour of fossil hominoid species is notoriously difficult to predict owing to difficulties in estimating body size dimorphism from fragmentary remains and, in hominins, low canine size dimorphism. Recent studies have shown that the second-to-fourth digit ratio (2D : 4D), a putative biomarker for prenatal androgen effects (PAEs), covaries with intra-sexual competition and social systems across haplorrhines; non-pair-bonded polygynous taxa have significantly lower 2D : 4D ratios (high PAE) than pair-bonded monogamous species. Here, we use proximal phalanx ratios of extant and fossil specimens to reconstruct the social systems of extinct hominoids. Pierolapithecus catalaunicus, Hispanopithecus laietanus and Ardipithecus ramidus have ratios consistent with polygynous extant species, whereas the ratio of Australopithecus afarensis is consistent with monogamous extant species. The early anatomically modern human Qafzeh 9 and Neanderthals have lower digit ratios than most contemporary human populations, indicating increased androgenization and possibly higher incidence of polygyny. Although speculative owing to small sample sizes, these results suggest that digit ratios represent a supplementary approach for elucidating the social systems of fossil hominins. PMID:21047863

  13. In Vivo Mn-Enhanced MRI for Early Tumor Detection and Growth Rate Analysis in a Mouse Medulloblastoma Model12

    PubMed Central

    Suero-Abreu, Giselle A.; Praveen Raju, G.; Aristizábal, Orlando; Volkova, Eugenia; Wojcinski, Alexandre; Houston, Edward J.; Pham, Diane; Szulc, Kamila U.; Colon, Daniel; Joyner, Alexandra L.; Turnbull, Daniel H.

    2014-01-01

    Mouse models have increased our understanding of the pathogenesis of medulloblastoma (MB), the most common malignant pediatric brain tumor that often forms in the cerebellum. A major goal of ongoing research is to better understand the early stages of tumorigenesis and to establish the genetic and environmental changes that underlie MB initiation and growth. However, studies of MB progression in mouse models are difficult due to the heterogeneity of tumor onset times and growth patterns and the lack of clinical symptoms at early stages. Magnetic resonance imaging (MRI) is critical for noninvasive, longitudinal, three-dimensional (3D) brain tumor imaging in the clinic but is limited in resolution and sensitivity for imaging early MBs in mice. In this study, high-resolution (100 μm in 2 hours) and high-throughput (150 μm in 15 minutes) manganese-enhanced MRI (MEMRI) protocols were optimized for early detection and monitoring of MBs in a Patched-1 (Ptch1) conditional knockout (CKO) model. The high tissue contrast obtained with MEMRI revealed detailed cerebellar morphology and enabled detection of MBs over a wide range of stages including pretumoral lesions as early as 2 to 3 weeks postnatal with volumes close to 0.1 mm3. Furthermore, longitudinal MEMRI allowed noninvasive monitoring of tumors and demonstrated that lesions within and between individuals have different tumorigenic potentials. 3D volumetric studies allowed quantitative analysis of MB tumor morphology and growth rates in individual Ptch1-CKO mice. These results show that MEMRI provides a powerful method for early in vivo detection and longitudinal imaging of MB progression in the mouse brain. PMID:25499213

  14. Postnatal changes in the growth dynamics of the human face revealed from bone modelling patterns

    PubMed Central

    Martinez-Maza, Cayetana; Rosas, Antonio; Nieto-Díaz, Manuel

    2013-01-01

    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. PMID:23819603

  15. 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

  16. Biomolecule-Mineral Interactions in the Geochemical Environment on Early Earth and in the Human Body

    NASA Astrophysics Data System (ADS)

    Sahai, N.

    2011-12-01

    We worked on four projects consistent with the broad goals of the grant to investigate (i) the potential impacts of mineral surface chemistry and particle size on the stability and viability of cell membranes, bacteria and human cells and (ii) the influence of biomolecules on mineral nucleation and growth. The projects are of relevance to the origin and early evolution of life, biomineralization, medical mineralogy, and environmental biogeochemistry. The freedom enabled by the five-year grant to explore high-risk scientific areas, and the resulting high impact outcomes, cannot be overstated. We developed an almost entirely new field of Medical Mineralogyy and extended our concepts and knowledge-base to the potential roles of mineral surfaces in the evolution of protocells and the earliest cells. These exciting connections to medical mineralogy, and to the origin and evolution of life on early Earth are fascinating topics to the general public and even to other scientists, especially when the links to mineralogy and geochemistry are highlighted. In brief, we examined the stability of lipid bilayers representing model protocell membranes comprised of phospholipid bilayers with mineral surfaces. We found that the stability of lipid bilayers depends on mineral surface charge and increases as silica glass ~ quartz < rutile ~ mica < corundum. In a second project, we investigated whether the evolution of bacterial extra-cellular polymeric substances (EPS) may have been driven by nanomineral toxicity. Results showed that EPS does protect against mineral toxicity, and toxicity increases as amorphous SiO2 < β-TiO2 (anatase) < γ-Al2O3. A commonly accepted mechanism for Biomineralization is protein-templated nucleation. We used Molecular Dynamics and Bioinformatics computational chemistry approaches and showed that the random coil structure of a specific peptide promotes formation of an amorphous Ca-PO4 cluster, but not direct templation of hydroxyapatite. The consistency

  17. 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.

  18. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    PubMed Central

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  19. Crucial Role for Early Growth Response-1 in the Transcriptional Regulation of miR-20b in Breast Cancer

    PubMed Central

    Li, Dongping; Ilnytskyy, Yaroslav; Kovalchuk, Anna; Khachigian, Levon M.; Bronson, Roderick T.; Wang, Bo; Kovalchuk, Olga

    2013-01-01

    Transcriptional regulation of miRNAs that control the pathogenesis of breast cancer remains largely unknown. Here, we showed that ionizing radiation, a known breast carcinogen, triggered the differential expression of miR-20b in mammary tissues. We identified several GC-rich consensus binding motifs for the zinc finger transcription factor early growth response-1 (EGR1) in miR-20b promoter. miR-20b was upregulated by IR and its upregulation correlated with EGR1 expression in the breast cancer cell lin