Too Much Vitamin C: Harmful?

MedlinePlus

... too much of it. Vitamin C is a water-soluble vitamin that supports normal growth and development and helps ... Dec. 12, 2017. Pazirandeh S, et al. Overview of water-soluble vitamins. https://www.uptodate.com/contents/search. Accessed Dec. ...

Growth and development of British vegan children.

PubMed

Sanders, T A

1988-09-01

The growth and development of children born of vegan mothers and reared on a vegan diet has been studied longitudinally: All of the children were breast-fed for the first 6 mo of life and in most cases well into the second year of life. The majority of children grew and developed normally but they did tend to be smaller in stature and lighter in weight than standards for the general population. Energy, calcium, and vitamin D intakes were usually below the recommended amounts. Their diets, however, were generally adequate but a few children had low intakes of riboflavin and vitamin B-12. Most parents were aware of the need to supplement the diet with vitamin B-12. It is concluded that provided sufficient care is taken, a vegan diet can support normal growth and development.

Effect of hospital nutrition support on growth velocity and nutritional status of low birth weight infants.

PubMed

Azzeh, Firas S; Alazzeh, Awfa Y; Dabbour, Ibrahim R; Jazar, Abdelelah S; Obeidat, Ahmed A

2014-10-01

Infants with low birth weights are provided with hospital nutrition support to enhance their survivability and body weights. However, different hospitals have different nutrition support formulas. Therefore, the effectiveness of these nutrition support formulas should be investigated. To assess the effect of hospital nutrition support on growth velocity and nutritional status of low birth weight infants at Al-Noor hospital, Saudi Arabia. A cross-sectional study was conducted between October, 2010 and December, 2012. Three hundred newborns were recruited from Al-Noor Hospital in Makkah city, Saudi Arabia. Infants were selected according to their birth weights and were divided equally into three groups; (i) Low Birth Weight (LBW) infants (1501- 2500 g birth weight), (ii) Very Low Birth Weight (VLBW) infants (1001-1500 g birth weight) and (iii) Extremely Low Birth Weight (ELBW) infants (< 1000 g birth weight). Data were collected at birth and at discharged. Infants' weights were recorded and growth velocity was calculated. Some biochemical tests and mineral levels were measured. Body mass index values of VLBW and ELBW groups were lower (p < 0.05) than LBW group. The growth velocity of infants in all groups ranged between 8.7 to 10.2 g/kg/d with no differences (p > 0.05) were observed among groups. Serum calcium, phosphorus and potassium levels at discharge were higher (p < 0.05) than that at birth for ELBW and VLBW groups; while sodium level decreased in ELBW group to be within normal ranges. Albumin level was improved (p < 0.05) in ELBW group. Health care management for low birth weight infants in Al-Noor Hospital was not sufficient to achieve normal growth rate for low birth weight infants, while biochemical indicators were remarkably improved in all groups. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Breast Tissue Stromal Cells Preferentially Promote Generation of M2 Macrophages: A Novel Mechanism for Tumor Supportive Properties of Breast Microenvironment

DTIC Science & Technology

2011-08-01

macrophages (MQs), on growth of breast tumor cells, and (2) to test the hypothesis that MSCs of non -breast adipose tissues, in contrast to MSCs of...macrophages in normal and malignant tissues. In contrast to all studies focused on the role of breast tissue microenvironment in growth of primary breast...the phenotype of macrophages, provide an immune environment suitable for growth of breast cancer cells, but MSCs present in non -breast adipose

Serum IGF-1 is insufficient to restore skeletal size in the total absence of the growth hormone receptor

PubMed Central

Wu, Yingjie; Sun, Hui; Basta-Pljakic, Jelena; Cardoso, Luis; Kennedy, Oran D; Jasper, Hector; Domené, Horacio; Karabatas, Liliana; Guida, Clara; Schaffler, Mitchell B; Rosen, Clifford J; Yakar, Shoshana

2013-01-01

States of growth hormone (GH) resistance, such those observed in Laron’s dwarf patients, are characterized by mutations in the GH receptor (GHR), decreased serum and tissue IGF-1 levels, impaired glucose tolerance, and impaired skeletal acquisition. IGF-1 replacement therapy in such patients increases growth velocity but does not normalize growth. Herein we combined the GH-resistant (GHR knockout, GHRKO) mouse model with mice expressing the hepatic Igf-1 transgene (HIT) to generate the GHRKO-HIT mouse model. In GHRKOHIT mice, serum IGF-1 levels were restored via transgenic expression of Igf-1 allowing us to study how endocrine IGF-1 affects growth, metabolic homeostasis, and skeletal integrity. We show that in a GH-resistant state, normalization of serum IGF-1 improved body adiposity and restored glucose tolerance but was insufficient to support normal skeletal growth, resulting in an osteopenic skeletal phenotype. The inability of serum IGF-1 to restore skeletal integrity in the total absence of GHR likely resulted from reduced skeletal Igf-1 gene expression, blunted GH-mediated effects on the skeleton that are independent of serum or tissue IGF-1, and from poor delivery of IGF-1 to the tissues. These findings are consistent with clinical data showing that IGF-I replacement therapy in patients with Laron’s syndrome does not achieve full skeletal growth. PMID:23456957

Implementation of Combined Feather and Surface-Normal Ice Growth Models in LEWICE/X

NASA Technical Reports Server (NTRS)

Velazquez, M. T.; Hansman, R. J., Jr.

1995-01-01

Experimental observations have shown that discrete rime ice growths called feathers, which grow in approximately the direction of water droplet impingement, play an important role in the growth of ice on accreting surfaces for some thermodynamic conditions. An improved physical model of ice accretion has been implemented in the LEWICE 2D panel-based ice accretion code maintained by the NASA Lewis Research Center. The LEWICE/X model of ice accretion explicitly simulates regions of feather growth within the framework of the LEWICE model. Water droplets impinging on an accreting surface are withheld from the normal LEWICE mass/energy balance and handled in a separate routine; ice growth resulting from these droplets is performed with enhanced convective heat transfer approximately along droplet impingement directions. An independent underlying ice shape is grown along surface normals using the unmodified LEWICE method. The resulting dual-surface ice shape models roughness-induced feather growth observed in icing wind tunnel tests. Experiments indicate that the exact direction of feather growth is dependent on external conditions. Data is presented to support a linear variation of growth direction with temperature and cloud water content. Test runs of LEWICE/X indicate that the sizes of surface regions containing feathers are influenced by initial roughness element height. This suggests that a previous argument that feather region size is determined by boundary layer transition may be incorrect. Simulation results for two typical test cases give improved shape agreement over unmodified LEWICE.

Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

PubMed Central

Parkinson, Eric Kenneth

2013-01-01

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

Polyamines and Flower Development in the Male Sterile Stamenless-2 Mutant of Tomato (Lycopersicon esculentum Mill.) 1

PubMed Central

Rastogi, Rajeev; Sawhney, Vipen K.

1990-01-01

The floral organs of the male sterile stamenless-2 (sl-2/sl-2) mutant of tomato (Lycopersicon esculentum Mill.) contain significantly higher level of polyamines than those of the normal (R Rastogi, VK Sawhney [1990] Plant Physiol 93: 439-445). The effects of putrescine, spermidine and spermine, and three different inhibitors of polyamine biosynthesis on the in vitro development of floral buds of the normal and sl-2/sl-2 mutant were studied. The polyamines were inhibitory to the in vitro growth and development of both the normal and mutant floral buds and they induced abnormal stamen development in normal flowers. The inhibitors of polyamine biosynthesis also inhibited the growth and development of floral organs of the two genotypes, but the normal flowers showed greater sensitivity than the mutant. The inhibitors also promoted the formation of normal-looking pollen in stamens of some mutant flowers. The effect of the inhibitors on polyamine levels was not determined. The polyamine-induced abnormal stamen development in the normal, and the inhibitor-induced production of normal-looking pollen in mutant flowers support the suggestion that the elevated polyamine levels contribute to abnormal stamen development in the sl-2/sl-2 mutant of tomato. Images Figure 3 Figure 5 PMID:16667486

Cranial irradiation increases tumor growth in experimental breast cancer brain metastasis.

PubMed

Hamilton, Amanda M; Wong, Suzanne M; Wong, Eugene; Foster, Paula J

2018-05-01

Whole-brain radiotherapy is the standard of care for patients with breast cancer with multiple brain metastases and, although this treatment has been essential in the management of existing brain tumors, there are many known negative consequences associated with the irradiation of normal brain tissue. In our study, we used in vivo magnetic resonance imaging analysis to investigate the influence of radiotherapy-induced damage of healthy brain on the arrest and growth of metastatic breast cancer cells in a mouse model of breast cancer brain metastasis. We observed that irradiated, but otherwise healthy, neural tissue had an increased propensity to support metastatic growth compared with never-irradiated controls. The elucidation of the impact of irradiation on normal neural tissue could have implications in clinical patient management, particularly in patients with residual systemic disease or with residual radio-resistant brain cancer. Copyright © 2018 John Wiley & Sons, Ltd.

Roof Plate-Derived Radial Glial-like Cells Support Developmental Growth of Rapidly Adapting Mechanoreceptor Ascending Axons.

PubMed

Kridsada, Kim; Niu, Jingwen; Haldipur, Parthiv; Wang, Zhiping; Ding, Long; Li, Jian J; Lindgren, Anne G; Herrera, Eloisa; Thomas, Gareth M; Chizhikov, Victor V; Millen, Kathleen J; Luo, Wenqin

2018-06-05

Spinal cord longitudinal axons comprise some of the longest axons in our body. However, mechanisms that drive this extra long-distance axonal growth are largely unclear. We found that ascending axons of rapidly adapting (RA) mechanoreceptors closely abut a previously undescribed population of roof plate-derived radial glial-like cells (RGLCs) in the spinal cord dorsal column, which form a network of processes enriched with growth-promoting factors. In dreher mutant mice that lack RGLCs, the lengths of ascending RA mechanoreceptor axon branches are specifically reduced, whereas their descending and collateral branches, and other dorsal column and sensory pathways, are largely unaffected. Because the number and intrinsic growth ability of RA mechanoreceptors are normal in dreher mice, our data suggest that RGLCs provide critical non-cell autonomous growth support for the ascending axons of RA mechanoreceptors. Together, our work identifies a developmental mechanism specifically required for long-range spinal cord longitudinal axons. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Prospective long-term follow up of children with anorectal malformation: growth and development until 5years of age.

PubMed

van den Hondel, Desiree; Sloots, Cornelius E J; Gischler, Saskia J; Meeussen, Conny J H M; Wijnen, Rene M H; IJsselstijn, Hanneke

2013-04-01

To evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. Non-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5 years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. 108 children (59% male) were included. 49% had a high malformation, and 46% had ≥ 1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥ 1 additional major anomaly had lower height at all ages; at 5 years, mean (95% CI) height was -1.83 (-2.7 to -1.1) and -0.70 (-1.3 to -0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5 years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). Non-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems. Copyright © 2013 Elsevier Inc. All rights reserved.

Placental angiogenesis in sheep models of compromised pregnancy

PubMed Central

Reynolds, Lawrence P; Borowicz, Pawel P; Vonnahme, Kimberly A; Johnson, Mary Lynn; Grazul-Bilska, Anna T; Redmer, Dale A; Caton, Joel S

2005-01-01

Because the placenta is the organ that transports nutrients, respiratory gases and wastes between the maternal and fetal systems, development of its vascular beds is essential to normal placental function, and thus in supporting normal fetal growth. Compromised fetal growth and development have adverse health consequences during the neonatal period and throughout adult life. To establish the role of placental angiogenesis in compromised pregnancies, we first evaluated the pattern of placental angiogenesis and expression of angiogenic factors throughout normal pregnancy. In addition, we and others have established a variety of sheep models to evaluate the effects on fetal growth of various factors including maternal nutrient excess or deprivation and specific nutrients, maternal age, maternal and fetal genotype, increased numbers of fetuses, environmental thermal stress, and high altitude (hypobaric) conditions. Although placental angiogenesis is altered in each of these models in which fetal growth is adversely affected, the specific effect on placental angiogenesis depends on the type of ‘stress’ to which the pregnancy is subjected, and also differs between the fetal and maternal systems and between genotypes. We believe that the models of compromised pregnancy and the methods described in this review will enable us to develop a much better understanding of the mechanisms responsible for alterations in placental vascular development. PMID:15760944

Mutation of a chitinase-like gene causes ectopic deposition of lignin, aberrant cell shapes, and overproduction of ethylene.

PubMed

Zhong, Ruiqin; Kays, Stanley J; Schroeder, Betty P; Ye, Zheng-Hua

2002-01-01

Chitinase-like proteins have long been proposed to play roles in normal plant growth and development, but no mutations in chitinase-like genes have been obtained previously to support this hypothesis. In this study, we have shown that the gene responsible for the elp1 mutation in Arabidopsis encodes a chitinase-like protein (AtCTL1). Mutation of this chitinase-like gene caused ectopic deposition of lignin and aberrant shapes of cells with incomplete cell walls in the pith of inflorescence stems. The AtCTL1 gene was expressed in all organs during normal plant growth and development, but it was not induced by wounding, salicylic acid, pectin fragments, or ethylene. Consistent with its ubiquitous expression pattern, mutation of the AtCTL1 gene affected many aspects of plant growth and development, including exaggerated hook curvature, reduced length and increased diameter of hypocotyls in dark-grown seedlings, and reduced root length and increased number of root hairs in light-grown seedlings. The mutant phenotypes could be rescued partially by ethylene inhibitors, and ethylene production in the mutant was significantly greater than in the wild type. Together, these results suggest that AtCTL1, a chitinase-like gene, is essential for normal plant growth and development in Arabidopsis.

Reduced growth factor requirement of keloid-derived fibroblasts may account for tumor growth

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

Russell, S.B.; Trupin, K.M.; Rodriguez-Eaton, S.

Keloids are benign dermal tumors that form during an abnormal wound-healing process is genetically susceptible individuals. Although growth of normal and keloid cells did not differ in medium containing 10% (vol/vol) fetal bovine serum, keloid culture grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) fetal bovine serum, keloid cultures grew to significantly higher densities than normal cells in medium containing 5% (vol/vol) plasma or 1% fetal bovine serum. Conditioned medium from keloid cultures did not stimulate growth of normal cells in plasma nor did it contain detectable platelet-derived growth factor or epidermal growth factor. Keloidmore » fibroblasts responded differently than normal adult fibroblasts to transforming growth factor ..beta... Whereas transforming growth factor ..beta.. reduced growth stimulation by epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from normal adult skin or scars, it enhanced the activity of epidermal growth factor in cells from keloids. Normal and keloid fibroblasts also responded differently to hydrocortisone: growth was stimulated in normal adult cells and unaffected or inhibited in keloid cells. Fetal fibroblasts resembled keloid cells in their ability to grow in plasma and in their response to hydrocortisone. The ability of keloid fibroblasts to grow to higher cell densities in low-serum medium than cells from normal adult skin or from normal early or mature scars suggests that a reduced dependence on serum growth factors may account for their prolonged growth in vivo. Similarities between keloid and fetal cells suggest that keloids may result from the untimely expression of growth-control mechanism that is developmentally regulated.« less

Environmental Assessment Addressing the Emerald Breeze Resort, Santa Rosa Island, Fort Walton Beach, Florida

DTIC Science & Technology

2009-09-11

conditions in their upper part. Anaerobic soil conditions are conducive to the establishment of vegetation that is adapted for growth under oxygen...sufficient to support, and that under normal circumstances do support, a prevalence of vegetation typically adapted to life in saturated soil...species adapted to dense commercial development and heavy vehicular traffic would be expected to move back into the area after development of the

Gravitational force as a determinant of turtle-shell growth and shape

NASA Technical Reports Server (NTRS)

Wunder, C. C.; Dodge, C. H.; Walkup, G. A.; Clark, M. E.; Rice, J. O.; Edwards, M. T.

1974-01-01

Chronic low-gravity simulation (pedestal support, suspension by wires or foam, and/or clinostat tumbling) of 11 aquatic red-eared sliders, Pseudemys scripta elegans, and of nine box turtles, Terrapine carolina, resulted in continued but slower linear carapace growth. Decreased shell height was accompanied by drastic plastron infolding. Chronic centrifugation (1.4, 1.8, 2.8, 5, or 8.1 g) of 81 box turtles caused an eventual decrease (12% per g) in linear growth rate. No consistent decrease occurred with aquatic turtles centrifuged at below 6 g. Maximum growth of length and roundness appears near 5 g for aquatic environments and near 1 g in land environments. Present results suggest that some gravity is necessary for normal bone growth.

An immune reaction may be necessary for cancer development.

PubMed

Prehn, Richmond T

2006-02-03

The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years. In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject. The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction.

An immune reaction may be necessary for cancer development

PubMed Central

Prehn, Richmond T

2006-01-01

Background The hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. Its correctness has been debated for many years. In its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. Alternative model There is an alternative to the surveillance hypothesis; numerous studies have shown that the effect of an immune reaction on a tumor is biphasic. For each tumor, there is some quantitatively low level of immune reaction that, relative to no reaction, is facilitating, perhaps even necessary for the tumor's growth in vivo. The optimum level of this facilitating reaction may often be less than the level of immunity that the tumor might engender in a normal subject. Conclusion The failure of a tumor to grow as well in the normal as it does in the immunosuppressed host is probably not caused by a lack of tumor-cell killing in the suppressed host. Instead, the higher level of immune response in a normal animal, even if it does not rise to tumor-inhibitory levels, probably gives less positive support to tumor growth. This seems more than a semantic distinction. PMID:16457723

Effect of Hypergravity on Carbonanhydrase Reactivity in inner Ear Ioncytes of developing Cichlid Fish

NASA Astrophysics Data System (ADS)

Beier, M.; Anken, R.; Rahmann, H.

It has been shown earlier that hypergravity slows down inner ear otolith growth in developing fish. Otolith growth in terms of mineralisation mainly depends on the enzyme carboanhydrase (CAH), which is responsible for the provision of the pH- value necessary for calcium carbonate deposition and thus also is presumed to play a prominent role in Ménière's disease (a sensory - motor disorder inducing vertigo and kinetosis). Larval siblings of cichlid fish (Oreochromis mossambicus) were subjected to hypergravity (3g; 6 hours) during development and separated into normally and kinetotically swimming individuals following the transfer to 1g (i.e., stopping the centrifuge; kinetotically behaving fish performed spinning movements). Subsequently, CAH was histochemically demonstrated in inner ear ionocytes (cells involved in the endolymphatic ion exchange) and enzyme reactivity was determined densitometrically. The results showed that CAH-reactivity was significantly increased in normally behaving hyper-g specimens as compared to controls kept at 1g, whereas no difference in enzyme reactivity was evident between the controls and kinetotically behaving fish. On the background of earlier studies, according to which (1) hypergravity induces a decrease of otolith growth and (2) the otolithic calcium incorporation (visualized using the calcium -tracer alizarin complexone) of kinetotically swimming hyper - g fish was lower as compared to normally behaving hyper - g animals, the present study strongly supports the concept that an increase in CAH-reactivity may result in a decrease of otolithic calcium deposition. The mechanism regulating CAH-activity hitherto remains to be determined. Acknowledgement: This work was financially supported by the German Aerospace Center (DLR) (FKZ: 50 WB 9997).

The characterization of axenic culture systems suitable for plant propagation and experimental studies of the submersed aquatic angiosperm Potamogeton pectinatus (Sago pondweed)

USGS Publications Warehouse

Ailstock, M.S.; Fleming, W.J.; Cooke, T.J.

1991-01-01

Clonal lines of the submersed aquatic angiosperm Potamogeton pectinatus were grown in three culture systems. The first, which used sucrose as a carbon source in a liquid medium, supported vigorous vegetative growth and can be used to propagate large numbers of plants in axenic conditions. In this culture system, plants were responsive to increasing photosynthetically active radiation (PAR) photon flux density (PFD) and were photosynthetically competent. However, their growth was heterotrophic and root development was poor. When these plants were transferred to a second nonaxenic culture system, which used 16-l buckets containing artificial sediments and tap water, growth was autotrophic and plants were morphologically identical to field-harvested P. pectinatus. The last culture system which consisted of a sand substrate and inorganic nutrient bathing solution aerated with 135 ml min-1 ambient air enhanced to 3.0% CO2 was axenic and supported autotrophic growth by plants that were also morphologically normal.

Catch-up Growth: Cellular and Molecular Mechanisms

PubMed Central

Finkielstain, GP; Lui, JC; Baron, J

2012-01-01

In mammals, after a period of growth inhibition, body growth often does not just return to a normal rate but actually exceeds the normal rate, resulting in catch-up growth. Recent evidence suggests that catch-up growth occurs because growth-inhibiting conditions delay progression of the physiological mechanisms that normally cause body growth to slow and cease with age. As a result, following the period of growth inhibition, tissues retain a greater proliferative capacity than normal, and therefore grow more rapidly than normal for age. There is evidence that this mechanism contributes both to catch-up growth in terms of body length, which involves proliferation in the growth plate, and to catch-up growth in terms of organ mass, which involves proliferation in multiple non-skeletal tissues. PMID:23428687

Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth.

PubMed

Gautam, Dinesh; Jeon, Jongrye; Starost, Matthew F; Han, Sung-Jun; Hamdan, Fadi F; Cui, Yinghong; Parlow, Albert F; Gavrilova, Oksana; Szalayova, Ildiko; Mezey, Eva; Wess, Jürgen

2009-04-14

The molecular pathways that promote the proliferation and maintenance of pituitary somatotrophs and other cell types of the anterior pituitary gland are not well understood at present. However, such knowledge is likely to lead to the development of novel drugs useful for the treatment of various human growth disorders. Although muscarinic cholinergic pathways have been implicated in regulating somatotroph function, the physiological relevance of this effect and the localization and nature of the receptor subtypes involved in this activity remain unclear. We report the surprising observation that mutant mice that selectively lack the M(3) muscarinic acetylcholine receptor subtype in the brain (neurons and glial cells; Br-M3-KO mice) showed a dwarf phenotype associated with a pronounced hypoplasia of the anterior pituitary gland and a marked decrease in pituitary and serum growth hormone (GH) and prolactin. Remarkably, treatment of Br-M3-KO mice with CJC-1295, a synthetic GH-releasing hormone (GHRH) analog, rescued the growth deficit displayed by Br-M3-KO mice by restoring normal pituitary size and normal serum GH and IGF-1 levels. These findings, together with results from M(3) receptor/GHRH colocalization studies and hypothalamic hormone measurements, support a model in which central (hypothalamic) M(3) receptors are required for the proper function of hypothalamic GHRH neurons. Our data reveal an unexpected and critical role for central M(3) receptors in regulating longitudinal growth by promoting the proliferation of pituitary somatotroph cells.

77 FR 32909 - Listing Endangered and Threatened Wildlife and Designating Critical Habitat; 12-Month...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-04

... revision may be warranted, in part because in our judgment specific qualities were required to explain how... Rico. (iii) Water quality to support normal growth, reproduction, development, viability, and health... areas, rather than on any specific qualities of the physical and biological features of the habitat...

Accelerated Growth Rate Induced by Neonatal High-Protein Milk Formula Is Not Supported by Increased Tissue Protein Synthesis in Low-Birth-Weight Piglets

PubMed Central

Jamin, Agnès; Sève, Bernard; Thibault, Jean-Noël; Floc'h, Nathalie

2012-01-01

Low-birth-weight neonates are routinely fed a high-protein formula to promote catch-up growth and antibiotics are usually associated to prevent infection. Yet the effects of such practices on tissue protein metabolism are unknown. Baby pigs were fed from age 2 to 7 or 28 d with high protein formula with or without amoxicillin supplementation, in parallel with normal protein formula, to determine tissue protein metabolism modifications. Feeding high protein formula increased growth rate between 2 and 28 days of age when antibiotic was administered early in the first week of life. This could be explained by the occurrence of diarrhea when piglets were fed the high protein formula alone. Higher growth rate was associated with higher feed conversion and reduced protein synthesis rate in the small intestine, muscle and carcass, whereas proteolytic enzyme activities measured in these tissues were unchanged. In conclusion, accelerated growth rate caused by high protein formula and antibiotics was not supported by increased protein synthesis in muscle and carcass. PMID:22315674

Intermediate Nucleation State of GaN Growth

NASA Astrophysics Data System (ADS)

Zheng, L. X.; Xie, M. H.; Tong, S. Y.

2001-03-01

Homoexpitaxial nucleation of GaN during molecular-beam epitaxy is followed by scanning tunneling microcopy (STM). We observe a metastable nucleation state, which manifests as “ghost” islands in STM images. These “ghost” islands can be irreversibly driven into normal islands by continuous STM imaging. It is further established that the “ghost” island formation is related to the presence of excess Ga atoms on the surface: Normal islands are only seen under the N-rich or stoichiometric flux condition, whereas “ghost” islands are observed under Ga-rich conditions. For intermediate excess-Ga coverages, both normal and “ghost” islands are present, however, they show distinctly different sizes, suggesting different nucleation states for the two. A growth model is proposed to account for the formation of metastable, “ghost” islands. Kinetic Monte Carlo simulation is carried out and main features of the surface are reproduced. We acknowledge financial support from HK RGC under grant Nos. 7396/00P, 7142/99P, and 7121/00P.

Characteristics of mineral nutrition of plants in the bio-technical life support system with human wastes included in mass exchange

NASA Astrophysics Data System (ADS)

Tikhomirova, Natalia; Ushakova, Sofya; Kalacheva, Galina; Tikhomirov, Alexander

2016-09-01

The study addresses the effectiveness of using ion exchange substrates (IES) to optimize mineral nutrition of plants grown in the nutrient solutions containing oxidized human wastes for application in bio-technical life support systems. The study shows that the addition of IES to the root-inhabited substrate is favorable for the growth of wheat vegetative organs but causes a decrease in the grain yield. By contrast, the addition of IES to the nutrient solution does not influence the growth of vegetative organs but favors normal development of wheat reproductive organs. Thus, to choose the proper method of adjusting the solution with IES, one should take into account specific parameters of plant growth and development and the possibility of multiple recycling of IES based on the liquid products of mineralization of human wastes.

Studies on the riboflavin, pantothenic acid, nicotinic acid and choline requirements of young Embden geese

USGS Publications Warehouse

Serafin, J.A.

1981-01-01

Four experiments were conducted to examine the riboflavin, pantothenic acid, nicotinic acid, and choline requirements of young Embden geese fed purified diets. Goslings fed diets deficient in either riboflavin, pantothenic acid, nicotinic acid, or choline grew poorly. Feeding a pantothenic acid-deficient diet resulted in 100% mortality. Goslings fed diets containing 530 mg/kg of choline or less developed perosis. Under the conditions of these experiments it was found that: 1) goslings require no more than 3.84 mg/kg of riboflavin and 31.2 mg/kg of nicotinic acid in the diet for rapid growth and normal development, 2) the pantothenic acid requirement of goslings is no more than 12.6 mg/kg of diet, and 3) a dietary choline level of 1530 mg/kg is adequate for both the prevention of perosis and rapid growth of goslings. The levels of vitamins found to support normal growth and development of goslings appear to be similar to requirements of other species that have been examined.

The neurotrophins act synergistically with LIF and members of the TGF-beta superfamily to promote the survival of spiral ganglia neurons in vitro.

PubMed

Marzella, P L; Gillespie, L N; Clark, G M; Bartlett, P F; Kilpatrick, T J

1999-12-01

A number of growth factor families have been implicated in normal inner ear development, auditory neuron survival and protection. Several growth factors, including transforming growth factor-beta5 (TGF-beta5) and TGF-beta3, neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were tested for their ability, individually or in combination, to promote auditory neuron survival in dissociated cell cultures of early rat post-natal spiral ganglion cells (SGCs). The results indicate that at discrete concentrations all growth factors act in an additive fashion and some in synergy when promoting neuronal survival. These findings support the hypothesis that growth factors from different families may be interdependent when sustaining neuronal integrity.

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.

Suggested stocking levels for forest stands in northeastern Oregon and southeastern Washington.

Treesearch

P.H. Cochran; J.M. Geist; D.L. Clemens; Rodrick R. Clausnitzer; David C. Powell

1993-01-01

Catastrophes and manipulation of stocking levels are important determinants of stand development and the appearance of future forest landscapes. Managers need stocking level guides, particularly for sites incapable of supporting stocking levels presented in normal yield tables. Growth basal area (GBA) has been used by some managers in attempts to assess inherent...

Genetic and chemical reductions in protein phosphatase activity alter auxin transport, gravity response, and lateral root growth

NASA Technical Reports Server (NTRS)

Rashotte, A. M.; DeLong, A.; Muday, G. K.; Brown, C. S. (Principal Investigator)

2001-01-01

Auxin transport is required for important growth and developmental processes in plants, including gravity response and lateral root growth. Several lines of evidence suggest that reversible protein phosphorylation regulates auxin transport. Arabidopsis rcn1 mutant seedlings exhibit reduced protein phosphatase 2A activity and defects in differential cell elongation. Here we report that reduced phosphatase activity alters auxin transport and dependent physiological processes in the seedling root. Root basipetal transport was increased in rcn1 or phosphatase inhibitor-treated seedlings but showed normal sensitivity to the auxin transport inhibitor naphthylphthalamic acid (NPA). Phosphatase inhibition reduced root gravity response and delayed the establishment of differential auxin-induced gene expression across a gravity-stimulated root tip. An NPA treatment that reduced basipetal transport in rcn1 and cantharidin-treated wild-type plants also restored a normal gravity response and asymmetric auxin-induced gene expression, indicating that increased basipetal auxin transport impedes gravitropism. Increased auxin transport in rcn1 or phosphatase inhibitor-treated seedlings did not require the AGR1/EIR1/PIN2/WAV6 or AUX1 gene products. In contrast to basipetal transport, root acropetal transport was normal in phosphatase-inhibited seedlings in the absence of NPA, although it showed reduced NPA sensitivity. Lateral root growth also exhibited reduced NPA sensitivity in rcn1 seedlings, consistent with acropetal transport controlling lateral root growth. These results support the role of protein phosphorylation in regulating auxin transport and suggest that the acropetal and basipetal auxin transport streams are differentially regulated.

HRE-type genes are regulated by growth-related changes in internal oxygen concentrations during the normal development of potato (Solanum tuberosum) tubers.

PubMed

Licausi, Francesco; Giorgi, Federico Manuel; Schmälzlin, Elmar; Usadel, Björn; Perata, Pierdomenico; van Dongen, Joost Thomas; Geigenberger, Peter

2011-11-01

The occurrence of hypoxic conditions in plants not only represents a stress condition but is also associated with the normal development and growth of many organs, leading to adaptive changes in metabolism and growth to prevent internal anoxia. Internal oxygen concentrations decrease inside growing potato tubers, due to their active metabolism and increased resistance to gas diffusion as tubers grow. In the present work, we identified three hypoxia-responsive ERF (StHRE) genes whose expression is regulated by the gradual decrease in oxygen tensions that occur when potato tubers grow larger. Increasing the external oxygen concentration counteracted the modification of StHRE expression during tuber growth, supporting the idea that the actual oxygen levels inside the organs, rather than development itself, are responsible for the regulation of StHRE genes. We identified several sugar metabolism-related genes co-regulated with StHRE genes during tuber development and possibly involved in starch accumulation. All together, our data suggest a possible role for low oxygen in the regulation of sugar metabolism in the potato tuber, similar to what happens in storage tissues during seed development.

Phenotypic and Gene Expression Modification with Normal Brain Aging in GFAP-Positive Astrocytes and Neural Stem Cells

PubMed Central

Bernal, Giovanna M.; Peterson, Daniel A.

2011-01-01

Summary Astrocytes secrete growth factors that are both neuroprotective and supportive for the local environment. Identified by glial fibrillary acidic protein (GFAP) expression, astrocytes exhibit heterogeneity in morphology and in expression of phenotypic markers and growth factors throughout different adult brain regions. In adult neurogenic niches, astrocytes secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) within the neurogenic niche, and are also a source of special GFAP-positive multipotent neural stem cells (NSCs). Normal aging is accompanied by a decline in CNS function and reduced neurogenesis. We asked if a decreased availability of astrocyte-derived factors may contribute to the age-related decline in neurogenesis. Determining alterations of astrocytic activity in the aging brain is crucial for understanding CNS homeostasis in aging and for assessing appropriate therapeutic targets for an aging population. We found region-specific alterations in gene expression of GFAP, VEGF and FGF-2 and their receptors in the aged brain corresponding to changes in astrocytic reactivity, supporting astrocytic heterogeneity and demonstrating a differential aging effect. We found that GFAP-positive NSCs uniquely coexpress both VEGF and its key mitotic receptor Flk-1 in both young and aged hippocampus, indicating a possible autocrine/paracrine signaling mechanism. VEGF expression is lost once NSCs commit to a neuronal fate, but Flk-1-mediated sensitivity to VEGF signaling is maintained. We propose that age-related astrocytic changes result in reduced VEGF and FGF-2 signaling, which in turn limits neural stem cell and progenitor cell maintenance and contributes to decreased neurogenesis. PMID:21385309

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

NASA Technical Reports Server (NTRS)

Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

2003-01-01

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

Modeling error distributions of growth curve models through Bayesian methods.

PubMed

Zhang, Zhiyong

2016-06-01

Growth curve models are widely used in social and behavioral sciences. However, typical growth curve models often assume that the errors are normally distributed although non-normal data may be even more common than normal data. In order to avoid possible statistical inference problems in blindly assuming normality, a general Bayesian framework is proposed to flexibly model normal and non-normal data through the explicit specification of the error distributions. A simulation study shows when the distribution of the error is correctly specified, one can avoid the loss in the efficiency of standard error estimates. A real example on the analysis of mathematical ability growth data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998-99 is used to show the application of the proposed methods. Instructions and code on how to conduct growth curve analysis with both normal and non-normal error distributions using the the MCMC procedure of SAS are provided.

Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

PubMed

Huang, Lu; Beiting, Daniel P; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Lee, Nancy A; Lee, James J; Appleton, Judith A

2015-12-01

It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

Relationships Between Age at Menarche, Walking Gait Base of Support, and Stance Phase Frontal Plane Knee Biomechanics in Adolescent Girls.

PubMed

Froehle, Andrew W; Grannis, Kimberly A; Sherwood, Richard J; Duren, Dana L

2017-05-01

Age at menarche impacts patterns of pubertal growth and skeletal development. These effects may carry over into variation in biomechanical profiles involved in sports-related traumatic and overuse knee injuries. The present study investigated whether age at menarche is a potential indicator of knee injury risk through its influence on knee biomechanics during normal walking. To test the hypothesis that earlier menarche is related to postpubertal biomechanical risk factors for knee injuries, including a wider, more immature gait base of support, and greater valgus knee angles and moments. Cross-sectional observational study. University research facility. Healthy, postmenarcheal, adolescent girls. Age at menarche was obtained by recall questionnaire. Pubertal growth and anthropometric data were collected by using standard methods. Biomechanical data were taken from tests of walking gait at self-selected speed. Reflective marker position data were collected with a 3-dimensional quantitative motion analysis system, and 3 force plates recorded kinetic data. Age at menarche; growth and anthropometric measurements; base of support; static knee frontal plane angle; and dynamic knee frontal plane angles and moments during stance. Earlier menarche was correlated significantly with abbreviated pubertal growth and postpubertal retention of immature traits, including a wider base of support. Earlier menarche and wider base of support were both correlated with more valgus static knee angles, more valgus knee abduction angles and moments at foot-strike, and a more valgus peak knee abduction angle during stance. Peak knee abduction moment during stance was not correlated with age at menarche or base of support. Earlier menarche and its effects on growth are associated with retention of a relatively immature gait base of support and a tendency for static and dynamic valgus knee alignment. This biomechanical profile may put girls with earlier menarche at greater risk for sports-related knee injuries. Not applicable. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Relationships between age at menarche, walking gait base of support, and stance phase frontal plane knee biomechanics in adolescent females

PubMed Central

Grannis, Kimberly A.; Sherwood, Richard J.; Duren, Dana L

2016-01-01

Background Age at menarche impacts patterns of pubertal growth and skeletal development. These effects may carry over into variation in biomechanical profiles involved in sports-related traumatic and overuse knee injuries. The present study investigated whether age at menarche is a potential indicator of knee injury risk through its influence on knee biomechanics during normal walking. Objective To test the hypothesis that earlier menarche is related to post-pubertal biomechanical risk factors for knee injuries, including a wider, more immature gait base of support, and greater valgus knee angles and moments. Design Cross-sectional observational study. Setting University research facility. Participants Healthy, post-menarcheal, adolescent females. Methods Age at menarche was obtained by recall questionnaire. Pubertal growth and anthropometric data were collected using standard methods. Biomechanical data were taken from tests of walking gait at self-selected speed. Reflective marker position data were collected using a three-dimensional quantitative motion analysis system, and three force plates recorded kinetic data. Main Outcome Measures Age at menarche; growth and anthropometric measurements; base of support; static knee frontal plane angle; dynamic knee frontal plane angles and moments during stance. Results Earlier menarche was significantly correlated with abbreviated pubertal growth and post-pubertal retention of immature traits, including a wider base of support. Earlier menarche and wider base of support were both correlated with more valgus static knee angles, more valgus knee abduction angles and moments at foot-strike, and a more valgus peak knee abduction angle during stance. Peak knee abduction moment during stance was not correlated with age at menarche or base of support. Conclusions Earlier menarche and its effects on growth are associated with retention of a relatively immature gait base of support and a tendency for static and dynamic valgus knee alignment. This biomechanical profile may put girls with earlier menarche at higher risk for sports-related knee injuries. PMID:27485675

Modeling Error Distributions of Growth Curve Models through Bayesian Methods

ERIC Educational Resources Information Center

Zhang, Zhiyong

2016-01-01

Growth curve models are widely used in social and behavioral sciences. However, typical growth curve models often assume that the errors are normally distributed although non-normal data may be even more common than normal data. In order to avoid possible statistical inference problems in blindly assuming normality, a general Bayesian framework is…

Availability of essential amino acids and nitrogen in vegan diets.

PubMed

Acosta, P B

1988-09-01

Vegan children often fail to grow as well as their omnivorous cohorts despite protein intakes that exceed RDA. Explanations for inadequate growth include deficiencies of energy, calcium, zinc and vitamins B-12 and D. Due to decreased bioavailability, amino acids and nitrogen in vegan diets may be inadequate to support normal growth. Bioavailability of amino acids and nitrogen may be decreased by dietary fiber, food processing and storage, inadequate energy, and other unknown factors. Bioavailability should be considered when evaluating adequacy of intakes of protein, amino acids and nitrogen from vegan diets by infants and children.

Whisker growth studies under conditions which resemble those available on an orbiting space station

NASA Technical Reports Server (NTRS)

Hobbs, Herman H.

1992-01-01

Minimal funding was provided by NASA with one designated 'mission' being the clear demonstration of the relevance of previously supported whisker growth studies to microgravity research. While in one sense this work has shown the converse, namely, that ambient gravitational fields as high as 1 Earth normal have no relevance to growth of whiskers by hydrogen reduction of metal halides, a case is made that this does not demonstrate lack of relevance to microgravity research. On the contrary, the driving forces for this growth are precisely those which must be understood in order to understand growth in microgravity. The results described suggest that knowledge gained from this work may be highly fundamental to our understanding of the genesis of metal crystals. Time and money ran out before this work could be considered complete. At least another year's study and analysis will be required before publications could be justified.

A cellulose fiber-based diet for screwworm (Diptera: Calliphoridae) larvae.

PubMed

Chaudhury, M F; Skoda, S R

2007-02-01

A highly absorbent cellulose fiber from recycled paper was tested and compared with a polyacrylate gelling agent, Aquatain, normally used for bulking and solidifying larval rearing medium of screwworm, Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae). The absorbent fiber, when mixed with water and dietary ingredients, produced a diet medium of homogeneous texture that supported larval growth and development comparable with the standard gelled diet. Larval and pupal weights from two concentrations of cellulose fiber-based diet were significantly higher than those obtained using gelled diet. The number of pupae per tray, percentage of adult emergence, oviposition, percentage of egg hatch, and adult longevity obtained from the insects reared in the cellulose fiber-based diet were comparable or slightly better than the biological parameters recorded from flies reared in the gelled diet. Moreover, results indicate that a lesser amount of the cellulose fiber-based diet than the normal amount of gelled diet per tray would support normal larval growth. Physical properties and texture of the new diet seem to allow the larvae to move and feed more freely than they do on the semisolid gelled diet, resulting in less wasted diet. The cellulose fiber is biodegradable and inexpensive, whereas the polyacrylate gel polymer is not biodegradable and is relatively expensive. Replacing gel with cellulose fiber in the screwworm larval diet for mass rearing should result in substantial cost savings in material and labor as well as eliminating concern of environmental pollution due to diet waste disposal.

Iron availability, nitrate uptake, and exportable new production in the subarctic Pacific. [phytoplankton population growth support and atmospheric CO2 removal

NASA Technical Reports Server (NTRS)

Banse, Karl

1991-01-01

This paper presents a critique of experimental data and papers by Martin et al. (1989, 1990), who suggested that the phytoplankton growth is iron-limited and that, small additions of iron to large subarctic ocean areas might be a way of removing significant amounts of atmospheric CO2 by increasing phytoplancton growth. Data are presented to show that, in the summer of 1987, the phytoplankton assemblage as a whole was not iron limited, as measured by the bulk removal of nitrate or by the increase of chlorophyll. It is suggested that grazing normally prevents the phytoplankton from reaching concentrations that reduce the iron (and nitrate) to levels that depress division rates drastically.

Swept source optical coherence tomography for in vivo growth monitoring of capsicum annuum seeds treated with different NaCl concentrations

NASA Astrophysics Data System (ADS)

Ravichandran, Naresh Kumar; Wijesinghe, Ruchire Eranga; Lee, Seung-Yeol; Shirazi, Muhammad Faizan; Park, Kibeom; Jung, Hee-Young; Jeon, Mansik; Kim, Jeehyun

2017-04-01

In this study, Optical coherence tomography (OCT) is demonstrated as a plausible optical tool for in vivo detection of plant seeds and its morphological changes during growth. The experiment was carried out on Capsicum annuum seeds that were treated with different molar concentrations of NaCl to investigate the most optimal concentration for the seed growth. The monitoring process was carried out for 9 consecutive days. The in vivo 2D OCT images of the treated seeds were obtained and compared with seeds that were grown with sterile distilled water. The obtained results confirm the feasibility of using OCT for the proposed application. Normalized A-scan analysis method is utilized for supporting the concluded results.

Another Way To View Child Development: An Interactive Approach to the Integration of the Sensorimotor System, Communication and Temperament. Project Ta-kos.

ERIC Educational Resources Information Center

Yoches, Betty; Luera, Margarita

The purpose of this training manual is to assist parents and professionals in understanding how a child's temperament, sensorimotor system, and communication system support each other in helping the child develop a solid foundation for normal growth and development. Training is based on the premise that awareness of the interaction and integration…

Knowledge Cannot Explain the Developmental Growth of Working Memory Capacity

PubMed Central

Cowan, Nelson; Ricker, Timothy J.; Clark, Katherine M.; Hinrichs, Garrett A.; Glass, Bret A.

2014-01-01

According to some views of cognitive growth, the development of working memory capacity can account for increases in the complexity of cognition. It has been difficult to ascertain, though, that there actually is developmental growth in capacity that cannot be attributed to other developing factors. Here we assess the role of item familiarity. We document developmental increases in working memory for visual arrays of English letters versus unfamiliar characters. Although letter knowledge played a special role in development between the ages of 6 to 8 years, children with adequate letter knowledge showed practically the same developmental growth in normalized functions for letters and unfamiliar characters. The results contribute to a growing body of evidence that the developmental improvement in working memory does not wholly stem from supporting processes such as encoding, mnemonic strategies, and knowledge. PMID:24942111

Otolith growth during hypergravity

NASA Astrophysics Data System (ADS)

Lychakov, Dmitri

Background. It is suggested, that the weight of the otolith mass on the sensory epithelium is the direct regulating factor controlling the growth of the otolith via negative-feedback loop between the brain and the inner ear. This means that if the mass of the individual otolith will stand above the normal mass the afferent input arising from fish tilts will not match the expected responses based on the internal sensory model, and the feedback mechanism will slow down the otolith growth. This suggests that the altered gravity such as hyper- or microgravity can affect the normal otolith growth. Methods. Two experiments each lasted 121 and 128 days have been performed on the guppy larvae (n = 12/12 and 18/20; control/ experiment fish) raised from 10 days after birth within a centrifuge at ~2g hypergravity. The masses of utricilar, saccular and lagenar otoliths are analyzed. Results. There are no statistically significant differences between controls (1g) and experiments (2g) in masses and lengths of fishes, and in masses of uticular, saccular and lagenar otoliths. Conclusions. Otolith weight seems to be not involved in the feedback regulation of its growth. This conclusion is in accord with our previous conclusions based on results of space and centrifuge experiments on guppy larvae and Xenopus embryos (Lychakov, 2002). This work was partly supported by Russian grant RFFI 14-04-00601.

Phenotypic and gene expression modification with normal brain aging in GFAP-positive astrocytes and neural stem cells.

PubMed

Bernal, Giovanna M; Peterson, Daniel A

2011-06-01

Astrocytes secrete growth factors that are both neuroprotective and supportive for the local environment. Identified by glial fibrillary acidic protein (GFAP) expression, astrocytes exhibit heterogeneity in morphology and in the expression of phenotypic markers and growth factors throughout different adult brain regions. In adult neurogenic niches, astrocytes secrete vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) within the neurogenic niche and are also a source of special GFAP-positive multipotent neural stem cells (NSCs). Normal aging is accompanied by a decline in CNS function and reduced neurogenesis. We asked whether a decreased availability of astrocyte-derived factors may contribute to the age-related decline in neurogenesis. Determining alterations of astrocytic activity in the aging brain is crucial for understanding CNS homeostasis in aging and for assessing appropriate therapeutic targets for an aging population. We found region-specific alterations in the gene expression of GFAP, VEGF, and FGF-2 and their receptors in the aged brain corresponding to changes in astrocytic reactivity, supporting astrocytic heterogeneity and demonstrating a differential aging effect. We found that GFAP-positive NSCs uniquely coexpress both VEGF and its key mitotic receptor Flk-1 in both young and aged hippocampus, indicating a possible autocrine/paracrine signaling mechanism. VEGF expression is lost once NSCs commit to a neuronal fate, but Flk-1-mediated sensitivity to VEGF signaling is maintained. We propose that age-related astrocytic changes result in reduced VEGF and FGF-2 signaling, which in turn limits NSC and progenitor cell maintenance and contributes to decreased neurogenesis. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

Targeting monoamine oxidase A in advanced prostate cancer.

PubMed

Flamand, Vincent; Zhao, Hongjuan; Peehl, Donna M

2010-11-01

Inhibitors of monoamine oxidase A (MAOA), a mitochondrial enzyme that degrades neurotransmitters including serotonin and norepinephrine, are commonly used to treat neurological conditions including depression. Recently, we and others identified high expression of MAOA in normal basal prostatic epithelium and high-grade primary prostate cancer (PCa). In contrast, MAOA is low in normal secretory prostatic epithelium and low-grade PCa. An irreversible inhibitor of MAOA, clorgyline, induced secretory differentiation in primary cultures of normal basal epithelial cells and high-grade PCa. Furthermore, clorgyline inhibited several oncogenic pathways in PCa cells, suggesting clinical value of MAOA inhibitors as a pro-differentiation and anti-oncogenic therapy for high-risk PCa. Here, we extended our studies to a model of advanced PCa, VCaP cells, which were derived from castration-resistant metastatic PCa and express a high level of MAOA. Growth of VCaP cells in the presence or absence of clorgyline was evaluated in vitro and in vivo. Gene expression changes in response to clorgyline were determined by microarray and validated by quantitative real-time polymerase chain reaction. Treatment with clorgyline in vitro inhibited growth and altered the transcriptional pattern of VCaP cells in a manner consistent with the pro-differentiation and anti-oncogenic effects seen in treated primary PCa cells. Src, beta-catenin, and MAPK oncogenic pathways, implicated in androgen-independent growth and metastasis, were significantly downregulated. Clorgyline treatment of mice bearing VCaP xenografts slowed tumor growth and induced transcriptome changes similar to those noted in vitro. Our results support the possibility that anti-depressant drugs that target MAOA might find a new application in treating PCa.

Stability and Hopf bifurcation for a regulated logistic growth model with discrete and distributed delays

NASA Astrophysics Data System (ADS)

Fang, Shengle; Jiang, Minghui

2009-12-01

In this paper, we investigate the stability and Hopf bifurcation of a new regulated logistic growth with discrete and distributed delays. By choosing the discrete delay τ as a bifurcation parameter, we prove that the system is locally asymptotically stable in a range of the delay and Hopf bifurcation occurs as τ crosses a critical value. Furthermore, explicit algorithm for determining the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions is derived by normal form theorem and center manifold argument. Finally, an illustrative example is also given to support the theoretical results.

Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women.

PubMed

Woodson, Karen; Flood, Andrew; Green, Lisa; Tangrea, Joseph A; Hanson, Jeffrey; Cash, Brooks; Schatzkin, Arthur; Schoenfeld, Phillip

2004-03-03

Loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that is polymorphic in the population, and its presence may predispose an individual to the development of colorectal cancer. We evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. Among 40 participants, 11 (27.5%) had LOI of IGF-II in their normal colonic mucosal tissue. After adjusting for body mass index and family history of colorectal cancer, LOI status was associated with a fivefold increased risk of adenoma formation (odds ratio = 5.2, 95% confidence interval = 1.0 to 26.7). On average, IGF-II expression was more than threefold higher among women with LOI of IGF-II than among women with normal imprinting status. Our findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer. These findings are intriguing and need to be confirmed in larger studies.

Delayed growth in two German shepherd dog littermates with normal serum concentrations of growth hormone, thyroxine, and cortisol.

PubMed

Randolph, J F; Miller, C L; Cummings, J F; Lothrop, C D

1990-01-01

Four German Shepherd Dogs from a litter of 10 were evaluated because of postnatal onset of proportionate growth stunting that clinically resembled well-documented hypopituitary dwarfism in that breed. Although 2 pups had histologic evidence of hypopituitarism, the remaining 2 pups had normal serum growth hormone concentration and adrenocorticotropin secretory capability, and normal adrenal function test and thyroid function study results. Furthermore, the initially stunted German Shepherd Dogs grew at a steady rate until at 1 year, body weight and shoulder height approximated normal measurements. Seemingly, delayed growth in these pups may represent one end of a clinical spectrum associated with hypopituitarism in German Shepherd Dogs.

In Vivo Non-Destructive Monitoring of Capsicum Annuum Seed Growth with Diverse NaCl Concentrations Using Optical Detection Technique.

PubMed

Ravichandran, Naresh Kumar; Wijesinghe, Ruchire Eranga; Lee, Seung-Yeol; Shirazi, Muhammad Faizan; Jung, Hee-Young; Jeon, Mansik; Kim, Jeehyun

2017-12-12

We demonstrate that optical coherence tomography (OCT) is a plausible optical tool for in vivo detection of plant seeds and its morphological changes during growth. To investigate the direct impact of salt stress on seed germination, the experiment was conducted using Capsicum annuum seeds that were treated with different molar concentrations of NaCl. To determine the optimal concentration for the seed growth, the seeds were monitored for nine consecutive days. In vivo two-dimensional OCT images of the treated seeds were obtained and compared with the images of seeds that were grown using sterile distilled water. The obtained results confirm the feasibility of using OCT for the proposed application. Normalized depth profile analysis was utilized to support the conclusions.

In Vivo Non-Destructive Monitoring of Capsicum Annuum Seed Growth with Diverse NaCl Concentrations Using Optical Detection Technique

PubMed Central

Ravichandran, Naresh Kumar; Wijesinghe, Ruchire Eranga; Lee, Seung-Yeol; Jung, Hee-Young; Jeon, Mansik; Kim, Jeehyun

2017-01-01

We demonstrate that optical coherence tomography (OCT) is a plausible optical tool for in vivo detection of plant seeds and its morphological changes during growth. To investigate the direct impact of salt stress on seed germination, the experiment was conducted using Capsicum annuum seeds that were treated with different molar concentrations of NaCl. To determine the optimal concentration for the seed growth, the seeds were monitored for nine consecutive days. In vivo two-dimensional OCT images of the treated seeds were obtained and compared with the images of seeds that were grown using sterile distilled water. The obtained results confirm the feasibility of using OCT for the proposed application. Normalized depth profile analysis was utilized to support the conclusions. PMID:29231871

The mechanism by which nonlinearity sustains turbulence in plane Couette flow

NASA Astrophysics Data System (ADS)

Nikolaidis, M.-A.; Farrell, B. F.; Ioannou, P. J.

2018-04-01

Turbulence in wall-bounded shear flow results from a synergistic interaction between linear non-normality and nonlinearity in which non-normal growth of a subset of perturbations configured to transfer energy from the externally forced component of the turbulent state to the perturbation component maintains the perturbation energy, while the subset of energy-transferring perturbations is replenished by nonlinearity. Although it is accepted that both linear non-normality mediated energy transfer from the forced component of the mean flow and nonlinear interactions among perturbations are required to maintain the turbulent state, the detailed physical mechanism by which these processes interact in maintaining turbulence has not been determined. In this work a statistical state dynamics based analysis is performed on turbulent Couette flow at R = 600 and a comparison to DNS is used to demonstrate that the perturbation component in Couette flow turbulence is replenished by a non-normality mediated parametric growth process in which the fluctuating streamwise mean flow has been adjusted to marginal Lyapunov stability. It is further shown that the alternative mechanism in which the subspace of non-normally growing perturbations is maintained directly by perturbation-perturbation nonlinearity does not contribute to maintaining the turbulent state. This work identifies parametric interaction between the fluctuating streamwise mean flow and the streamwise varying perturbations to be the mechanism of the nonlinear interaction maintaining the perturbation component of the turbulent state, and identifies the associated Lyapunov vectors with positive energetics as the structures of the perturbation subspace supporting the turbulence.

Seed-to-seed growth of Arabidopsis thaliana on the International Space Station

NASA Technical Reports Server (NTRS)

Link, B. M.; Durst, S. J.; Zhou, W.; Stankovic, B.

2003-01-01

The assembly of the International Space Station (ISS) as a permanent experimental outpost has provided the opportunity for quality plant research in space. To take advantage of this orbital laboratory, engineers and scientists at the Wisconsin Center for Space Automation and Robotics (WCSAR), University of Wisconsin-Madison, developed a plant growth facility capable of supporting plant growth in the microgravity environment. Utilizing this Advanced Astroculture (ADVASC) plant growth facility, an experiment was conducted with the objective to grow Arabidopsis thaliana plants from seed-to-seed on the ISS. Dry Arabidopsis seeds were anchored in the root tray of the ADVASC growth chamber. These seeds were successfully germinated from May 10 until the end of June 2001. Arabidopsis plants grew and completed a full life cycle in microgravity. This experiment demonstrated that ADVASC is capable of providing environment conditions suitable for plant growth and development in microgravity. The normal progression through the life cycle, as well as the postflight morphometric analyses, demonstrate that Arabidopsis thaliana does not require the presence of gravity for growth and development. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

Effects of real or simulated microgravity on plant cell growth and proliferation

NASA Astrophysics Data System (ADS)

Medina, Francisco Javier; Manzano, Ana Isabel; Herranz, Raul; Dijkstra, Camelia; Larkin, Oliver; Hill, Richard; Carnero-Díaz, Eugénie; van Loon, Jack J. W. A.; Anthony, Paul; Davey, Michael R.; Eaves, Laurence

Experiments on seed germination and seedling growth performed in real microgravity on the International Space Station and in different facilities for simulating microgravity in Earth-based laboratories (Random Positioning Machine and Magnetic Levitation), have provided evidence that the absence of gravity (or the artificial compensation of the gravity vector) results in the uncoupling of cell growth and proliferation in root meristematic cells. These are two essential cellular functions that support plant growth and development, which are strictly coordinated under normal ground gravity conditions. Under conditions of altered gravity, we observe that cell proliferation is enhanced, whereas cell growth is reduced, according to different morphometric, cytological and immunocytochemical parameters. Since coordination of cell growth and proliferation are major features of meristematic cells, this observed uncoupling represents a major stress condition for these cells, inducing major alterations in the pattern of plant development. Moreover, the expression of the cyclin B1 gene, a regulator of the entry into mitosis and normally used as an indicator of cell proliferation, appears reduced in the smaller and more actively proliferating cells of samples grown under the conditions of our experiments. These results are compatible with an alteration of the regulation of the cell cycle, producing a shorter G2 period. Interestingly, while cyclin B1 expression is depleted in these conditions in root meristematic cells, it is enhanced in cotyledons of the same seedlings, as shown by qPCR and by the expression of the gus reporter gene. It is known that regulation of root growth (including regulation of root meristematic activity) is driven mainly by auxin, whereas cytokinin is the key hormone regulating cotyledon growth. Therefore, our results indicate a major role of auxin in the sensitivity to altered gravity of root meristematic cells. Auxin is crucial in maintaining the coupling of cell growth and proliferation under normal conditions and it should have a decisive influence in the uncoupling of these processes under altered gravity. Experiments to detect auxin distribution in roots under altered gravity produced by diamagnetic levitation have shown that the lateral balanced distribution of the growth regulator in the root cap is altered slightly and that the total concentration of the auxin detected in root tips is somewhat reduced. These effects are independent of the orientation of statoliths in columella cells.

Development and validation of the Hogan Grief Reaction Checklist.

PubMed

Hogan, N S; Greenfield, D B; Schmidt, L A

2001-01-01

The purpose of this article is to provide data on a recently developed instrument to measure the multidimensional nature of the bereavement process. In contrast to widely used grief instruments that have been developed using rational methods of instrument construction, the Hogan Grief Reaction Checklist (HGRC) was developed empirically from data collected from bereaved adults who had experienced the death of a loved one. Factor analysis of the HGRC revealed 6 factors in the normal trajectory of the grieving process: Despair, Panic Behavior, Blame and Anger, Detachment, Disorganization, and Personal Growth. Additional data are provided that support reliability and validity of the HGRC as well as its ability to discriminate variability in the grieving process as a function of cause of death and time lapsed since death. Empirical support is also provided for Personal Growth as an integral component of the bereavement process. The article concludes by considering the substantive as well as psychometric findings of this research for such issues as traumatic grief, anticipatory grief, change in the bereaved person's self-schema, and spiritual and existential growth.

Legionnaires' disease bacteria in power plant cooling systems: Phase 2

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

Tyndall, R.L.; Christensen, S.W.; Solomon, J.A.

1985-04-01

Legionnaires' Disease Bacteria (Legionella) are a normal component of the aquatic community. The study investigated various environmental factors that affect Legionella profiles in power plant cooling waters. The results indicate that each of the four factors investigated (incubation temperature, water quality, the presence and type of associated biota, and the nature of the indigenous Legionella population) is important in determining the Legionella profile of these waters. Simple predictive relationships were not found. At incubation temperatures of 32/sup 0/ and 37/sup 0/C, waters from a power plant where infectious Legionella were not observed stimulated the growth of stock Legionella cultures moremore » than did waters from plants where infectious Legionella were prevalent. This observation is consistent with Phase I results, which showed that densities of Legionella were frequently reduced in closed-cycle cooling systems despite the often higher infectivity of Legionella in closed-cycle waters. In contrast, water from power plants where infectious Legionella were prevalent supported the growth of indigenous Legionella pneumophila at 42/sup 0/C, while water from a power plant where infectious Legionella were absent did not support growth of indigenous Legionella. Some Legionella are able to withstand a water temperature of 85/sup 0/C for several hours, thus proving more tolerant than was previously realized. Finally, the observation that water from two power plants where infectious Legionella were prevalent usually supported the growth of Group A Legionella at 45/sup 0/C indicates the presence, of soluble Legionella growth promoters in these waters. This test system could allow for future identification and control of these growth promoters and, hence, of Legionella. 25 refs., 23 figs., 10 tabs.« less

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Relative shortening and functional tethering of spinal cord in adolescent scoliosis - Result of asynchronous neuro-osseous growth, summary of an electronic focus group debate of the IBSE.

PubMed

Chu, Winnie Cw; Lam, Wynnie Mw; Ng, Bobby Kw; Tze-Ping, Lam; Lee, Kwong-Man; Guo, Xia; Cheng, Jack Cy; Burwell, R Geoffrey; Dangerfield, Peter H; Jaspan, Tim

2008-06-27

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The Statement for this debate was written by Dr WCW Chu and colleagues who examine the spinal cord to vertebral growth interaction during adolescence in scoliosis. Using the multi-planar reconstruction technique of magnetic resonance imaging they investigated the relative length of spinal cord to vertebral column including ratios in 28 girls with AIS (mainly thoracic or double major curves) and 14 age-matched normal girls. Also evaluated were cerebellar tonsillar position, somatosensory evoked potentials (SSEPs), and clinical neurological examination. In severe AIS compared with normal controls, the vertebral column is significantly longer without detectable spinal cord lengthening. They speculate that anterior spinal column overgrowth relative to a normal length spinal cord exerts a stretching tethering force between the two ends, cranially and caudally leading to the initiation and progression of thoracic AIS. They support and develop the Roth-Porter concept of uncoupled neuro-osseous growth in the pathogenesis of AIS which now they prefer to term 'asynchronous neuro-osseous growth'. Morphological evidence about the curve apex suggests that the spinal cord is also affected, and a 'double pathology' is suggested. AIS is viewed as a disorder with a wide spectrum and a common neuroanatomical abnormality namely, a spinal cord of normal length but short relative to an abnormally lengthened anterior vertebral column. Neuroanatomical changes and/or abnormal neural function may be expressed only in severe cases. This asynchronous neuro-osseous growth concept is regarded as one component of a larger concept. The other component relates to the brain and cranium of AIS subjects because abnormalities have been found in brain (infratentorial and supratentorial) and skull (vault and base). The possible relevance of systemic melatonin-signaling pathway dysfunction, platelet calmodulin levels and putative vertebral vascular biology to the asynchronous neuro-osseous growth concept is discussed. A biomechanical model to test the spinal component of the concept is in hand. There is no published research on the biomechanical properties of the spinal cord for scoliosis specimens. Such research on normal spinal cords includes movements (kinematics), stress-strain responses to uniaxial loading, and anterior forces created by the stretched cord in forward flexion that may alter sagittal spinal shape during adolescent growth. The asynchronous neuro-osseous growth concept for the spine evokes controversy. Dr Chu and colleagues respond to five other concepts of pathogenesis for AIS and suggest that relative anterior spinal overgrowth and biomechanical growth modulation may also contribute to AIS pathogenesis.

Evolution of graphene islands growing on Cu foils

NASA Astrophysics Data System (ADS)

Wofford, Joseph; Nie, Shu; Bartelt, Norman; McCarty, Kevin; Dubon, Oscar

2011-03-01

Using low-energy electron microscopy we investigate, in real time, the growth of graphene monolayers on Cu foils. Graphene islands evolve from an initially compact form into an increasingly ramified, four-lobed shape, reflecting the symmetry of the (100)-textured Cu surface. Diffraction analysis reveals that each lobe is an individual graphene domain, differentiated by a rotation about the film normal, making the islands polycrystalline. An inspection of the morphological evolution of the graphene lobes shows the growth fronts posses an angularly dependent velocity, which is consistent with a growth mode dominated by edge kinetics. The fast growth direction of each lobe tends to align with the 001 in-plane directions of the Cu surface but not with a high symmetry direction of the graphene lattice. Finally, the implications of this unexpected growth mechanism on the formation of high-quality graphene films on Cu foils are evaluated. Supported by BES/USDOE under contracts #DE-AC04-94AL85000 and #DE-AC02-05CH11231.

Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development.

PubMed

Lange, Clemens A K; Luhmann, Ulrich F O; Mowat, Freya M; Georgiadis, Anastasios; West, Emma L; Abrahams, Sabu; Sayed, Haroon; Powner, Michael B; Fruttiger, Marcus; Smith, Alexander J; Sowden, Jane C; Maxwell, Patrick H; Ali, Robin R; Bainbridge, James W B

2012-07-01

Molecular oxygen is essential for the development, growth and survival of multicellular organisms. Hypoxic microenvironments and oxygen gradients are generated physiologically during embryogenesis and organogenesis. In the eye, oxygen plays a crucial role in both physiological vascular development and common blinding diseases. The retinal pigment epithelium (RPE) is a monolayer of cells essential for normal ocular development and in the mature retina provides support for overlying photoreceptors and their vascular supply. Hypoxia at the level of the RPE is closely implicated in pathogenesis of age-related macular degeneration. Adaptive tissue responses to hypoxia are orchestrated by sophisticated oxygen sensing mechanisms. In particular, the von Hippel-Lindau tumour suppressor protein (pVhl) controls hypoxia-inducible transcription factor (HIF)-mediated adaptation. However, the role of Vhl/Hif1a in the RPE in the development of the eye and its vasculature is unknown. In this study we explored the function of Vhl and Hif1a in the developing RPE using a tissue-specific conditional-knockout approach. We found that deletion of Vhl in the RPE results in RPE apoptosis, aniridia and microphthalmia. Increased levels of Hif1a, Hif2a, Epo and Vegf are associated with a highly disorganised retinal vasculature, chorioretinal anastomoses and the persistence of embryonic vascular structures into adulthood. Additional inactivation of Hif1a in the RPE rescues the RPE morphology, aniridia, microphthalmia and anterior vasoproliferation, but does not rescue retinal vasoproliferation. These data demonstrate that Vhl-dependent regulation of Hif1a in the RPE is essential for normal RPE and iris development, ocular growth and vascular development in the anterior chamber, whereas Vhl-dependent regulation of other downstream pathways is crucial for normal development and maintenance of the retinal vasculature.

Age-related changes in spatiotemporal characteristics of gait accompany ongoing lower limb linear growth in late childhood and early adolescence.

PubMed

Froehle, Andrew W; Nahhas, Ramzi W; Sherwood, Richard J; Duren, Dana L

2013-05-01

Walking gait is generally held to reach maturity, including walking at adult-like velocities, by 7-8 years of age. Lower limb length, however, is a major determinant of gait, and continues to increase until 13-15 years of age. This study used a sample from the Fels Longitudinal Study (ages 8-30 years) to test the hypothesis that walking with adult-like velocity on immature lower limbs results in the retention of immature gait characteristics during late childhood and early adolescence. There was no relationship between walking velocity and age in this sample, whereas the lower limb continued to grow, reaching maturity at 13.2 years in females and 15.6 years in males. Piecewise linear mixed models regression analysis revealed significant age-related trends in normalized cadence, initial double support time, single support time, base of support, and normalized step length in both sexes. Each trend reached its own, variable-specific age at maturity, after which the gait variables' relationships with age reached plateaus and did not differ significantly from zero. Offsets in ages at maturity occurred among the gait variables, and between the gait variables and lower limb length. The sexes also differed in their patterns of maturation. Generally, however, immature walkers of both sexes took more frequent and relatively longer steps than did mature walkers. These results support the hypothesis that maturational changes in gait accompany ongoing lower limb growth, with implications for diagnosing, preventing, and treating movement-related disorders and injuries during late childhood and early adolescence. Copyright © 2012 Elsevier B.V. All rights reserved.

X-linked mental retardation syndrome: Three brothers with the Brooks-Wisniewski-Brown syndrome

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

Morava, E.; Storcz, J.; Kosztolanyi, G.

1996-07-12

We report on 3 brothers with growth and mental retardation, bifrontal narrowness, short palpebral fissures, deeply set eyes with entropion, wide bulbous nose, small mouth, myopia, and spastic diplegia. The patients were born to normal and non-consanguineous parents. The similarity of our cases with those recently reported by Brooks et al. supports their suggestion that these patients are representative of a distinct entity. 8 refs., 3 figs., 1 tab.

What Is a Growth Disorder? (For Parents)

MedlinePlus

... hormone, which is essential for normal bone growth. Turner syndrome , one of the most common genetic growth disorders, ... chromosome. In addition to short stature, girls with Turner syndrome usually don't undergo normal sexual development because ...

Composition and metabolism of fecal microbiota from normal and overweight children are differentially affected by melibiose, raffinose and raffinose-derived fructans.

PubMed

Adamberg, Kaarel; Adamberg, Signe; Ernits, Karin; Larionova, Anneli; Voor, Tiia; Jaagura, Madis; Visnapuu, Triinu; Alamäe, Tiina

2018-06-20

The aim of the study was to investigate the metabolism of non-digestible oligo- and polysaccharides by fecal microbiota, using isothermal microcalorimetry. The five tested substrates were raffinose, melibiose, a mixture of oligo- and polysaccharides produced from raffinose by levansucrase, levan synthesized from raffinose, and levan from timothy grass. Two inocula were comprised of pooled fecal samples from overweight or normal-weight children, from healthy adult volunteers and a pure culture of Bacteroides thetaiotaomicron as a reference bacterium for colon microbiota. The growth was analyzed based on the heat evolution curves, and the production of organic acids and gases. Taxonomic profiles of the microbiota were assessed by 16S rDNA sequencing. Raffinose and melibiose promoted the growth of bifidobacteria in all fecal pools. Several pool-specific substrate-related responses to raffinose and melibiose were revealed. Lactate-producing bacteria (Streptococcus and Enterococcus) became enriched in the pool of overweight children resulting in lactic acid as the major fermentation product on short saccharides. Acetic and butyric acids were prevalent at fermentation in the normal-weight pool coinciding with the enrichment of Catenibacterium. In the adult pool, the specific promotion of Bacteroides and Lachnospiraceae by levans was disclosed. In the fecal pool of normal-weight children, levans stimulated the growth of Senegalimassilia and Lachnoclostridium and this particular pool also showed the highest maximum heat production rate at levan fermentation. Levans and raffinose-derived oligosaccharides, but not raffinose and melibiose were completely fermented by a pure culture of Bacteroides thetaiotaomicron. The main conclusion from the study is that fecal microbiota of normal and overweight children have different compositions and they respond in specific manners to non-digestible oligo- and polysaccharides: raffinose, melibiose, raffinose-derived oligosaccharides and levans. The potential of the tested saccharides to support a healthy balance of colon microbiota requires further studies. Copyright © 2018. Published by Elsevier Ltd.

Elevated levels of insulin-like growth factor (IGF)-I in serum rescue the severe growth retardation of IGF-I null mice.

PubMed

Wu, Yingjie; Sun, Hui; Yakar, Shoshana; LeRoith, Derek

2009-09-01

IGF-I plays a vital role in growth and development and acts in an endocrine and an autocrine/paracrine fashion. The purpose of the current study was to clarify whether elevated levels of IGF-I in serum can rescue the severe growth retardation and organ development and function of igf-I null mice. To address that, we overexpressed a rat igf-I transgene specifically in the liver of igf-I null mice. We found that in the total absence of tissue IGF-I, elevated levels of IGF-I in serum can support normal body size at puberty and after puberty but are insufficient to fully support the female reproductive system (evident by irregular estrous cycle, impaired development of ovarian corpus luteum, reduced number of uterine glands and endometrial hypoplasia, all leading to decreased number of pregnancies and litter size). We conclude that most autocrine/paracrine actions of IGF-I that determine organ growth and function can be compensated by elevated levels of endocrine IGF-I. However, in mice, full compensatory responses are evident later in development, suggesting that autocrine/paracrine IGF-I is critical for neonatal development. Furthermore, we show that tissue IGF-I is necessary for the development of the female reproductive system and cannot be compensated by elevated levels of serum IGF-I.

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Recurrent chronic histiocytic intervillositis with intrauterine growth restriction, osteopenia, and fractures.

PubMed

Crawford, April; Moore, Lynette; Bennett, Gregory; Savarirayan, Ravi; Manton, Nicholas; Khong, Yee; Barnett, Christopher P; Haan, Eric

2016-11-01

Chronic histiocytic intervillositis (CHI) is characterized by the presence of histiocytes within the intervillous space of the placenta. The pathogenesis is unclear but available evidence supports an alloimmune mechanism on the basis of the presence in maternal blood of HLA antibodies directed against paternal HLA antigens. CHI has a high risk of recurrence and of abnormal perinatal outcomes. Little is known about the effects of CHI on the developing fetus, in particular on the growth and development of the skeleton. We have studied a woman whose third pregnancy was terminated after ultrasonography showed severe intrauterine growth restriction, raising the possibility of a lethal skeletal dysplasia. Postmortem radiographs showed multiple fractures and other signs of osteogenesis imperfecta (OI). However, bone histology was not typical of OI and no abnormalities were identified by sequencing OI genes. The subsequent pregnancy was also severely growth restricted and was terminated. The placenta showed chronic histiocytic intervillositis, which, on retrospective review, had also been present in her second and third pregnancies. Her fifth pregnancy was again associated with intrauterine growth restriction and CHI but resulted in a premature birth. CHI can be associated with radiographic features that mimic OI and should be considered when fetal fractures occur in the context of recurrent miscarriage, fetal death in utero, and intrauterine growth restriction. The correct diagnosis can be made by histopathology of the placenta, supported by bone histology and normal results of molecular studies for OI. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Metabolomic analysis of the longissimus from underperforming piglets suggests impaired carbohydrate metabolism, increased lipid utilization and higher protein breakdown in comparison to piglets with normal preweaning growth

USDA-ARS?s Scientific Manuscript database

The present study was designed to determine if normal birth weight pigs that grow poorly during the pre-weaning period have altered skeletal muscle metabolism, as previously reported for intrauterine growth retarded pigs relative to littermates with normal growth rates. Eight pairs of average birth...

Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans

PubMed Central

Chauhan, Nitin M; Shinde, Ravikumar B; Karuppayil, S. Mohan

2013-01-01

In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation. PMID:24688528

Effect of alcohols on filamentation, growth, viability and biofilm development in Candida albicans.

PubMed

Chauhan, Nitin M; Shinde, Ravikumar B; Karuppayil, S Mohan

2013-12-01

In this study we report the potential of alcohols as morphogenetic regulators in Candida albicans. All the alcohols tested influenced various modes of growth like planktonic as well as biofilm forms. Viability was affected at high concentrations. Among the alcohols, the response of C. albicans to amyl alcohol (pentanol) was noteworthy. Amyl alcohol at a concentration 0.5% which was not inhibitory to growth and viability specifically inhibited morphogenetic switching from yeast to hyphal forms. It also inhibited normal biofilm development favoring yeast dominated biofilms. Based on this study we hypothesize that alcohols produced under anaerobic conditions may not favor biofilm development and support dissemination of yeast cells. Since anaerobic conditions are not found to favor production of quorum sensing molecules like farnesol, the alcohols may play a role in morphogenetic regulation.

The Bone-specific Expression of Runx2 Oscillates during the Cell Cycle to Support a G1-related Antiproliferative Function in Osteoblasts*

PubMed Central

Galindo, Mario; Pratap, Jitesh; Young, Daniel W.; Hovhannisyan, Hayk; Im, Hee-Jeong; Choi, Je-Yong; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; van Wijnen, Andre J.

2010-01-01

The Runx2 (CBFA1/AML3/PEBP2αA) transcription factor promotes skeletal cell differentiation, but it also has a novel cell growth regulatory activity in osteoblasts. We addressed here whether Runx2 activity is functionally linked to cell cycle-related mechanisms that control normal osteoblast proliferation and differentiation. We found that the levels of Runx2 gene transcription, mRNA and protein, are each up-regulated with cessation of cell growth (i.e. G0/G1 transition) in preconfluent MC3T3 osteoblastic cells that do not yet express mature bone phenotypic gene expression. Cell growth regulation of Runx2 is also observed in primary calvarial osteoblasts and other osteoblastic cells with relatively normal cell growth characteristics, but not in osteosarcoma cells (e.g. SAOS-2 and ROS17/2.8). Runx2 levels are cell cycle-regulated in MC3T3 cells with respect to the G1/S and M/G1 transitions: expression oscillates from maximal levels during early G1 to minimal levels during early S phase and mitosis. However, in normal or immortalized (e.g. ATDC5) chondrocytic cells, Runx2 expression is suppressed during quiescence, and Runx2 levels are not regulated during G1 and S phase in ATDC5 cells. Antisense or small interfering RNA-mediated reduction of the low physiological levels of Runx2 in proliferating MC3T3 cells does not accelerate cell cycle progression. However, forced expression of Runx2 suppresses proliferation of MC3T3 preosteoblasts or C2C12 mesenchymal cells which have osteogenic potential. Forced elevation of Runx2 in synchronized MC3T3 cells causes a delay in G1. We propose that Runx2 levels and function are biologically linked to a cell growth-related G1 transition in osteoblastic cells. PMID:15781466

Basal Lamina Mimetic Nanofibrous Peptide Networks for Skeletal Myogenesis

NASA Astrophysics Data System (ADS)

Yasa, I. Ceren; Gunduz, Nuray; Kilinc, Murat; Guler, Mustafa O.; Tekinay, Ayse B.

2015-11-01

Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells’ growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, “IKVAV”, and fibronectin-derived well known adhesive sequence, “RGD”, into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes.

DNA polymeric films as a support for cell growth as a new material for regenerative medicine: Compatibility and applicability.

PubMed

Jayme, Cristiano Ceron; de Paula, Leonardo Barcelos; Rezende, Nayara; Calori, Italo Rodrigo; Franchi, Leonardo Pereira; Tedesco, Antonio Claudio

2017-11-15

DNA polymeric films (DNA-PFs) are a promising drug delivery system (DDS) in modern medicine. In this study, we evaluated the growth behavior of oral squamous cell carcinoma (OSCC) cells on DNA-PFs. The morphological, biochemical, and cytometric features of OSCC cell adhesion on DNA-PFs were also assessed. An initial, temporary alteration in cell morphology was observed at early time points owing to the inhibition of cell attachment to the film, which then returned to a normal morphological state at later time points. MTT and resazurin assays showed a moderate reduction in cell viability related to increased DNA concentration in the DNA-PFs. Flow cytometry studies showed low cytotoxicity of DNA-PFs, with cell viabilities higher than 90% in all the DNA-PFs tested. Flow cytometric cell cycle analysis also showed average cell cycle phase distributions at later time points, indicating that OSCC cell growth is maintained in the presence of DNA-PFs. These results show high biocompatibility of DNA-PFs and suggest their use in designing "dressing material," where the DNA film acts as a support for cell growth, or with incorporation of active or photoactive compounds, which can induce tissue regeneration and are useful to treat many diseases, especially oral cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Basal Lamina Mimetic Nanofibrous Peptide Networks for Skeletal Myogenesis

PubMed Central

Yasa, I. Ceren; Gunduz, Nuray; Kilinc, Murat; Guler, Mustafa O.; Tekinay, Ayse B.

2015-01-01

Extracellular matrix (ECM) is crucial for the coordination and regulation of cell adhesion, recruitment, differentiation and death. Therefore, equilibrium between cell-cell and cell-matrix interactions and matrix-associated signals are important for the normal functioning of cells, as well as for regeneration. In this work, we describe importance of adhesive signals for myoblast cells’ growth and differentiation by generating a novel ECM mimetic peptide nanofiber scaffold system. We show that not only structure but also composition of bioactive signals are important for cell adhesion, growth and differentiation by mimicking the compositional and structural properties of native skeletal muscle basal lamina. We conjugated laminin-derived integrin binding peptide sequence, “IKVAV”, and fibronectin-derived well known adhesive sequence, “RGD”, into peptide nanostructures to provide adhesive and myogenic cues on a nanofibrous morphology. The myogenic and adhesive signals exhibited a synergistic effect on model myoblasts, C2C12 cells. Our results showed that self-assembled peptide nanofibers presenting laminin derived epitopes support adhesion, growth and proliferation of the cells and significantly promote the expression of skeletal muscle-specific marker genes. The functional peptide nanofibers used in this study present a biocompatible and biodegradable microenvironment, which is capable of supporting the growth and differentiation of C2C12 myoblasts into myotubes. PMID:26555958

Associations Between Changes in Normal Personality Traits and Borderline Personality Disorder Symptoms over 16 years

PubMed Central

Wright, Aidan G.C.; Hopwood, Christopher J.; Zanarini, Mary C.

2014-01-01

There has been significant movement toward conceptualizing borderline personality disorder (BPD) with normal personality traits. However one critical assumption underlying this transition, that longitudinal trajectories of BPD symptoms and normal traits track together, has not been tested. We evaluated the prospective longitudinal associations of changes in five-factor model traits and BPD symptoms over the course of 16 years using parallel process latent growth curve models in 362 patients with BPD (N=290) or other PDs (N=72). Moderate to strong cross-sectional and longitudinal associations were observed between BPD symptoms and Neuroticism, Extraversion, Agreeableness, and Conscientiousness. This study is the first to demonstrate a longitudinal link between changes in BPD symptoms and changes in traits over an extended interval in a clinical sample. These findings imply that changes in BPD symptoms occur in concert with changes in normal traits, and support the proposed transition to conceptualizing BPD, at least in part, with trait dimensions. PMID:25364942

Associations between changes in normal personality traits and borderline personality disorder symptoms over 16 years.

PubMed

Wright, Aidan G C; Hopwood, Christopher J; Zanarini, Mary C

2015-01-01

There has been significant movement toward conceptualizing borderline personality disorder (BPD) with normal personality traits. However, 1 critical assumption underlying this transition, that longitudinal trajectories of BPD symptoms and normal traits track together, has not been tested. We evaluated the prospective longitudinal associations of changes in Five-Factor Model traits and BPD symptoms over the course of 16 years using parallel process latent growth curve models in 362 patients with BPD (n = 290) or other PDs (n = 72). Moderate to strong cross-sectional and longitudinal associations were observed between BPD symptoms and Neuroticism, Extraversion, Agreeableness, and Conscientiousness. This study is the first to demonstrate a longitudinal link between changes in BPD symptoms and changes in traits over an extended interval in a clinical sample. These findings imply that changes in BPD symptoms occur in concert with changes in normal traits, and support the proposed transition to conceptualizing BPD, at least in part, with trait dimensions. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Development of Mandarin spoken language after pediatric cochlear implantation.

PubMed

Li, Bei; Soli, Sigfrid D; Zheng, Yun; Li, Gang; Meng, Zhaoli

2014-07-01

The purpose of this study was to evaluate early spoken language development in young Mandarin-speaking children during the first 24 months after cochlear implantation, as measured by receptive and expressive vocabulary growth rates. Growth rates were compared with those of normally hearing children and with growth rates for English-speaking children with cochlear implants. Receptive and expressive vocabularies were measured with the simplified short form (SSF) version of the Mandarin Communicative Development Inventory (MCDI) in a sample of 112 pediatric implant recipients at baseline, 3, 6, 12, and 24 months after implantation. Implant ages ranged from 1 to 5 years. Scores were expressed in terms of normal equivalent ages, allowing normalized vocabulary growth rates to be determined. Scores for English-speaking children were re-expressed in these terms, allowing direct comparisons of Mandarin and English early spoken language development. Vocabulary growth rates during the first 12 months after implantation were similar to those for normally hearing children less than 16 months of age. Comparisons with growth rates for normally hearing children 16-30 months of age showed that the youngest implant age group (1-2 years) had an average growth rate of 0.68 that of normally hearing children; while the middle implant age group (2-3 years) had an average growth rate of 0.65; and the oldest implant age group (>3 years) had an average growth rate of 0.56, significantly less than the other two rates. Growth rates for English-speaking children with cochlear implants were 0.68 in the youngest group, 0.54 in the middle group, and 0.57 in the oldest group. Growth rates in the middle implant age groups for the two languages differed significantly. The SSF version of the MCDI is suitable for assessment of Mandarin language development during the first 24 months after cochlear implantation. Effects of implant age and duration of implantation can be compared directly across languages using normalized vocabulary growth rates. These comparisons for Mandarin and English reveal comparable results, despite the diversity of these languages, underscoring the universal role of plasticity in the developing auditory system. Copyright © 2014. Published by Elsevier Ireland Ltd.

Increased efficiency of gamma-irradiated versus mitomycin C-treated feeder cells for the expansion of normal human cells in long-term cultures.

PubMed

Roy, A; Krzykwa, E; Lemieux, R; Néron, S

2001-12-01

Several normal human cells, such as hematopoietic stem cells, dendritic cells, and B cells, can be cultured in vitro in defined optimal conditions. Several ex vivo culture systems require the use of feeder cells to support the growth of target cells. In such systems, proliferation of feeder cells has to be stopped, so that they can be used as nonreplicating viable support cells. Because feeder cells need to provide one or few active signals, it is important to maintain them in an metabolically active state, allowing continued expression of specific ligands or cytokines. Mitomycin C and gamma-irradiation treatments are commonly used to prepare nonproliferating feeder cells and are usually considered to be equivalent. Normal human B lymphocytes can be expanded in vitro in the presence of feeder cells expressing the CD40 ligand CD154. Here we compared the ability of gamma-irradiation- and mitomycin C-treated feeder cells to support the expansion of normal human B lymphocytes. The results indicate that expansion of B cells during a long-term culture was 100 times more potent using gamma-irradiated feeder cells compared to mitomycin C-treated cells. This difference could be related to a significant reduction in both cellular metabolism and level of CD154 expression observed in mitomycin C-treated feeder cells, but not in gamma-irradiated cells nor in control untreated cells. These results indicate that mitomycin C-treated feeder cells are metabolically altered, and consequently less efficient at maintaining cell expansion in the long-term cell culture system used.

Evaluation of genetic variability among "Early Mature" Juglans regia using microsatellite markers and morphological traits.

PubMed

Ebrahimi, Aziz; Zarei, Abdolkarim; Zamani Fardadonbeh, Mojtaba; Lawson, Shaneka

2017-01-01

Limiting the juvenile phase and reducing tree size are the two main challenges for breeders to improve most fruit crops. Early maturation and dwarf cultivars have been reported for many fruit species. "Early mature" and low vigor walnut genotypes were found among seedlings of Persian walnut. Nine microsatellite markers were used to evaluate genetic diversity among "Early Mature" Persian walnut accessions and provide a comparison with "normal growth" accessions. Six maturation related characteristics were also measured in "Early Mature" samples. Phenotypic traits and diversity indices showed relatively high levels of genetic diversity in "Early Mature" seedlings and indicated high differentiation between individuals. Seedling height, the most diverse phenotypic trait, has an important role in the clustering of "Early Mature" accessions. The "Early Mature" type had higher number of alleles, number of effective allele, and Shannon index compared to the "Normal Growth" group. The two types of studied walnuts had different alleles, with more than half of produced alleles specific to a specific group. "Early Mature" and "Normal Growth" walnuts had 27 and 17 private alleles, respectively. Grouping with different methods separated "Early Mature" and "Normal Growth" samples entirely. The presence of moderate to high genetic diversity in "Early Mature" walnuts and high genetic differentiation with "Normal Growth" walnuts, indicated that "Early Mature" walnuts were more diverse and distinct from "Normal Growth" samples. Moreover, our results showed SSR markers were useful for differentiating between "Early Mature" and "Normal Growth" walnuts. A number of identified loci have potential in breeding programs for identification of "Early Mature" walnuts at the germination phase.

Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in normal human urothelial cells.

PubMed

Varley, Claire Lucy; Stahlschmidt, Jens; Smith, Barbara; Stower, Michael; Southgate, Jennifer

2004-05-01

We observed that in urothelium, both cornifying and noncornifying forms of squamous metaplasia are accompanied by changes in the localization of the nuclear hormone receptors, peroxisome proliferator activated receptor gamma (PPAR-gamma) and retinoid X receptor (RXR-alpha). To obtain objective evidence for a role for PPAR-gamma-mediated signaling in urothelial differentiation, we examined expression of the cytokeratin isotypes CK13, CK20, and CK14 as indicators of transitional, terminal transitional, and squamous differentiation, respectively, in cultures of normal human urothelial cells. In control culture conditions, normal human urothelial cells showed evidence of squamous differentiation (CK14+, CK13-, CK20-). Treatment with the high-affinity PPAR-gamma agonist, troglitazone (TZ), resulted in gain of CK13 and loss of CK14 protein expression. The effect of TZ was significantly augmented when the autocrine-stimulated epidermal growth factor receptor pathway was inhibited and this resulted in induction of CK20 expression. The RXR-specific inhibitors PA452, HX531, and HX603 inhibited the TZ-induced CK13 expression, supporting a role for RXR in the induction of CK13 expression. Thus, signaling through PPAR-gamma can mediate transitional differentiation of urothelial cells and this is modulated by growth regulatory programs.

Valyl-tRNA synthetase modification-dependent restriction of bacteriophage T4.

PubMed Central

Olson, N J; Marchin, G L

1984-01-01

A strain of Escherichia coli, CP 790302, severely restricts the growth of wild-type bacteriophage T4. In broth culture, most infections of single cells are abortive, although a few infected cells exhibit reduced burst sizes. In contrast, bacteriophage T4 mutants impaired in the ability to modify valyl-tRNA synthetase develop normally on this strain. Biochemical evidence indicates that the phage-modified valyl-tRNA synthetase in CP 790302 is different from that previously described. Although the enzyme is able to support normal protein synthesis, a disproportionate amount of phage structural protein (serum blocking power) fails to mature into particles of the appropriate density. The results with host strain CP 790302 are consistent with either a gratuitous inhibition of phage assembly by faulty modification or abrogation of an unknown role that valyl-tRNA synthetase might normally play in viral assembly. PMID:6374167

Cell proliferation and differentiation in chemical leukemogenesis

NASA Technical Reports Server (NTRS)

Irons, R. D.; Stillman, W. S.; Clarkson, T. W. (Principal Investigator)

1993-01-01

In tissues such as bone marrow with normally high rates of cell division, proliferation is tightly coordinated with cell differentiation. Survival, proliferation and differentiation of early hematopoietic progenitor cells depend on the growth factors, interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF) and their synergism with other cytokines. We provide evidence that a characteristic shared by a diverse group of compounds with demonstrated leukemogenic potential is the ability to act synergistically with GM-CSF. This results in an increase in recruitment of a resting population of hematopoietic progenitor cells normally unresponsive to the cytokine and a twofold increase in the size of the proliferating cell population normally regarded to be at risk of transformation in leukemogenesis. These findings support the possibility that transient alterations in hematopoietic progenitor cell differentiation may be an important factor in the early stages of development of leukemia secondary to chemical or drug exposure.

Childbirth Educators, Doulas, Nurses, and Women Respond to the Six Care Practices for Normal Birth

PubMed Central

Curl, Marilyn; Davies, Rae; Lothian, Sheila; Pascali-Bonaro, Debra; Scaer, Roberta M.; Walsh, Allison

2004-01-01

This collection of commentaries by childbirth educators, doulas, a labor and delivery nurse, and a woman preparing for the birth of her second baby provide an overall response to all six of Lamaze International's care practice papers that promote normal birth: Labor Begins on Its Own; Freedom of Movement throughout Labor; Continuous Labor Support; No Routine Interventions; Non-Supine (e.g., Upright or Side-Lying) Positions for Birth; and No Separation of Mother and Baby with Unlimited Opportunity for Breastfeeding. Strategies for using the position papers to facilitate learning in childbirth classes and for helping expectant parents access and understand research are presented. The commentaries describe the value of the position papers as a catalyst for professional growth, a foundation for creating change, a way to encourage reflection among professionals and women planning for the births of their babies, and an inspiration for everyone who advocates normal birth. PMID:17273388

Effects of protein or amino-acid supplementation on the physical growth of young children in low-income countries

PubMed Central

Arsenault, Joanne E; Brown, Kenneth H

2017-01-01

Abstract Child growth stunting is common in low-income countries, possibly due to insufficient protein intakes. Most previous studies have concluded that children’s protein intakes are adequate in relation to estimated requirements, but these studies did not consider issues of protein digestibility and effects of infection on dietary protein utilization. Using an alternative approach to assess the possible role of protein inadequacy in children’s growth restriction, the results of 18 intervention trials in which supplementary protein or amino acids were provided to children ages 6–35 months and growth outcomes were reviewed. Eight studies conducted in hospitalized children recovering from acute malnutrition found that the recommended protein intake levels for healthy children supported normal growth rates, but higher intakes were needed for accelerated rates of “catch-up” growth. Ten community-based studies did not demonstrate a consistent benefit of supplemental protein on children’s growth. However, weaknesses in the study designs limit the conclusions that can be drawn from these studies, and additional appropriately designed trials are needed to answer this question definitively. Recommendations for optimizing future study designs are provided herein. PMID:28938793

Human body frequency modulation by 0.9% sodium chloride solutions: a new paradigm and perspective for human health.

PubMed

Sudan, B J

2000-08-01

This case study demonstrates that the normal human body frequency, which can be disturbed by electromagnetic influences of the environment, can be modulated by 0.9% sodium chloride solutions (physiological saline) and that occurrence of allergic reactions have subsequently been suppressed as a result of this modulation. The use of distilled water as control showed no effect on occurrence of allergic reactions. Further observations on the growth of various plants in a greenhouse exposed to various geomagnetic fields support the previous observations on humans. The neutralization of electromagnetic influences on humans using 0.9% sodium chloride solution or by enclosure of plants within a copper wire Faraday cage resulting in a normal and uniform growth of plants as compared with disturbed and irregular growth in unenclosed controls, is demonstrated. These original observations propose a new strategy to suppress or prevent allergic reactions and possibly other effects observed in various human pathologies in relation to a disturbance of human body frequencies. It is hypothesized that the double helix structure of desoxyribonucleic acid (DNA) could be modified by environmental electromagnetic fields and that disresonance between the two chains of DNA could lead to the expression of specific pathology. Copyright 2000 Harcourt Publishers Ltd.

Evaluation of short stature, carbohydrate metabolism and other endocrinopathies in Bloom's syndrome.

PubMed

Diaz, Alejandro; Vogiatzi, Maria G; Sanz, Maureen M; German, James

2006-01-01

To obtain an understanding of the etiology of proportional dwarfism and endocrinopathies of Bloom's syndrome BS. Admission for 5-day periods to an NIH-supported Clinical Research Center of a randomly selected population of persons with BS (n = 11; mean age 11.5 years, range 9 months to 28.5 years) for clinical and genetic history-taking, physical examination, and endocrinological, gastroenterological and immunological testing. An oral glucose tolerance test was performed in all participants. Impaired glucose tolerance was present in 4 individuals, insulin resistance was observed in 6 individuals, and previously unrecognized diabetes was found in 1. Growth hormone provocation was normal in the 10 individuals tested. Overnight frequent GH sampling was suggestive of neurosecretory dysfunction in 3. Compensated hypothyroidism was found in 2 participants. Lipid profile abnormalities were present in 5 of 10 individuals. Low immunoglobulin concentrations (IgG and/or IgM) were seen in all tested. Intestinal absorption by D-xylose and/or fecal fat measurement was normal in all individuals tested as well. Altered carbohydrate metabolism is very common in BS, and is present from childhood. BS dwarfism is not related to growth hormone deficiency or malabsorption. The basis for the growth restriction in BS remains to be elucidated. Copyright (c) 2006 S. Karger AG, Basel.

{l_angle}110{r_angle} dendrite growth in aluminum feathery grains

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

Henry, S.; Rappaz, M.; Jarry, P.

1998-11-01

Automatic indexing of electron backscattered diffraction patterns, scanning electron microscopy, and optical microscopy observations have been carried out on aluminum-magnesium-silicon, aluminum-copper, and aluminum-silicon alloys directionally solidified or semicontinuously cast using the direct chill casting process. From these combined observations, it is shown that the feathery grains are made of {l_angle}110{r_angle} primary dendrite trunks (e.g., [011{bar 1}]) split in their centers by a coherent (111) twin plane. The average spacing of the dendrite trunks in the twin plane (about 10 to 20 {micro}m) is typically one order of magnitude smaller than that separating successive rows of trunks (or twin planes). Themore » [011{bar 1}] orientation of these trunks is close to the thermal gradient direction (typically within 15 deg)--a feature probably resulting from a growth competition mechanism similar to that occurring during normal <100> columnar dendrite growth. On both sides of these trunks, secondary dendrite arms also grow along {l_angle}110{r_angle} directions. Their impingement creates wavy noncoherent twin boundaries between the coherent twin planes. In the twin plane, evidence is shown that {l_angle}110{r_angle} branching mechanisms lead to the propagation of the twinned regions, to the regular arrangement of the primary dendrite trunks along a [{bar 2}11] direction, and to coherent planar twin boundaries. From these observations, it is concluded that the feathery grains are probably the result of a change from a normal <100> to a {l_angle}110{r_angle} surface tension/attachment kinetics anisotropy growth mode. Finally, the proposed mechanisms of leathery grain growth are further supported by the observation of {l_angle}110{r_angle} dendrite growth morphologies in thin aluminum-zinc coatings.« less

Aberrant, ectopic expression of VEGF and VEGF receptors 1 and 2 in malignant colonic epithelial cells. Implications for these cells growth via an autocrine mechanism

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

Ahluwalia, Amrita; Jones, Michael K.; Department of Medicine, University of California, Irvine, CA

2013-08-09

Highlights: •Malignant colonic epithelial cells express VEGF and its receptors. •Cultured colon cancer cells secrete VEGF into the medium. •Inhibition of VEGF receptor significantly decreases colon cancer cell proliferation. •VEGF is critical for colon cancer cell growth. -- Abstract: Vascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 andmore » VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy. Material and methods: We examined and quantified expression of VEGF, VEGF-R1 and VEGF-R2 in three different human colonic tissue arrays containing sections of adenocarcinoma (n = 43) and normal mucosa (n = 41). In human colon cancer cell lines HCT116 and HT29 and normal colon cell lines NCM356 and NCM460, we examined expression of VEGF, VEGF-R1 and VEGF-R2 mRNA and protein, VEGF production and secretion into the culture medium; and, the effect of a potent, selective inhibitor of VEGF receptors, AL-993, on cell proliferation. Results: Human colorectal cancer specimens had strong expression of VEGF in cancer cells and also expressed VEGF-R1 and VEGF-R2.In vitro studies showed that human colon cancer cell lines, HCT116 and HT29, but not normal colonic cell lines, express VEGF, VEGF-R1 and VEGF-R2 and secrete VEGF into the medium up to a concentration 2000 pg/ml within 48 h. Furthermore, we showed that inhibition of VEGF receptors using a specific VEGF-R inhibitor significantly reduced proliferation (by >50%) of cultured colon cancer cell lines. Conclusions: Our findings support the contention that VEGF generated by colon cancer cells stimulates their growth directly through an autocrine mechanism that is independent of its primary function in the induction of angiogenesis.« less

Early recognition of growth abnormalities permitting early intervention

USDA-ARS?s Scientific Manuscript database

Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children's health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height. This rev...

Knowledge cannot explain the developmental growth of working memory capacity.

PubMed

Cowan, Nelson; Ricker, Timothy J; Clark, Katherine M; Hinrichs, Garrett A; Glass, Bret A

2015-01-01

According to some views of cognitive growth, the development of working memory capacity can account for increases in the complexity of cognition. It has been difficult to ascertain, though, that there actually is developmental growth in capacity that cannot be attributed to other developing factors. Here we assess the role of item familiarity. We document developmental increases in working memory for visual arrays of English letters versus unfamiliar characters. Although letter knowledge played a special role in development between the ages of 6 and 8 years, children with adequate letter knowledge showed practically the same developmental growth in normalized functions for letters and unfamiliar characters. The results contribute to a growing body of evidence that the developmental improvement in working memory does not wholly stem from supporting processes such as encoding, mnemonic strategies, and knowledge. A video abstract is available at: https://www.youtube.com/watch?v=LJdqErLR2Hs&feature=youtu.be. © 2014 John Wiley & Sons Ltd.

Ethylene Production by Plants in a Closed Environment

NASA Technical Reports Server (NTRS)

Wheeler, R. M.; Peterson, B. V.; Sager, J. C.; Knott, W. M.

1996-01-01

Ethylene production by 20-sq m stands of wheat, soybean, lettuce and potato was monitored throughout growth and development in NASA's Controlled Ecological Life Support System (CELSS) Biomass Production Chamber. Chamber ethylene concentrations rose during periods of rapid growth for all four species, reaching 120 parts per billion (ppb) for wheat, 60 ppb for soybean, and 40 to 50 ppb for lettuce and potato. Following this, ethylene concentrations declined during seed fill and maturation (wheat and soybean), or remained relatively constant (potato). Lettuce plants were harvested during rapid growth and peak ethylene production. The highest ethylene production rates (unadjusted for chamber leakage) ranged from 0.04 to 0.06 ml/sq m/day during rapid growth of lettuce and wheat stands, or approximately 0.8 to 1.1 ml/g fresh weight/h. Results suggest that ethylene production by plants is a normal event coupled to periods of rapid metabolic activity, and that ethylene removal or control measures should be considered for growing crops in a tightly closed CELSS.

Intercepted photosynthetically active radiation in wheat canopies estimated by spectral reflectance. [Phoenix, Arizona

NASA Technical Reports Server (NTRS)

Hatfield, J. L.; Asrar, G.; Kanemasu, E. T.

1982-01-01

The interception of photosynthetically active radiation (PAR) was evaluated relative to greenness and normalized difference (MSS 7-5/7+5) for five planting dates of wheat for 1978-79 and 1979-80 in Phoenix. Intercepted PAR was calculated from a model driven by leaf area index and stage of growth. Linear relationships were found between greenness and normalized difference with a separate model representing growth and senescence of the crop. Normalized difference was a significantly better model and would be easier to apply than the empirically derived greenness parameter. For the leaf area growth portion of the season the model between PAR interception and normalized difference was the same over years, however, for the leaf senescence the models showed more variability due to the lack of data on measured interception in sparse canopies. Normalized difference could be used to estimate PAR interception directly for crop growth models.

Characterization of Antisense Transformed Plants Deficient in the Tobacco Anionic Peroxidase.

PubMed Central

Lagrimini, L. M.; Gingas, V.; Finger, F.; Rothstein, S.; Liu, TTY.

1997-01-01

On the basis of the biological compounds that they metabolize, plant peroxidases have long been implicated in plant growth, cell wall biogenesis, lignification, and host defenses. Transgenic tobacco (Nicotiana tabacum L.) plants that underexpress anionic peroxidase were generated using antisense RNA. The antisense RNA was found to be specific for the anionic isoenzyme and highly effective, reducing endogenous transcript levels and total peroxidase activity by as much as 1600-fold. Antisense-transformed plants appeared normal at initial observation; however, growth studies showed that plants with reduced peroxidase activity grow taller and flower sooner than control plants. In contrast, previously transformed plants overproducing anionic peroxidase were shorter and flowered later than controls. Axillary buds were more developed in antisense-transformed plants and less developed in plants overproducing this enzyme. It was found that the lignin content in leaf, stem, and root was unchanged in antisense-transformed plants, which does not support a role for anionic peroxidase in the lignification of secondary xylem vessels. However, studies of wounded tissue show some reduction in wound-induced deposition of lignin-like polymers. The data support a possible role for tobacco anionic peroxidase in host defenses but not without a reduction in growth potential. PMID:12223765

Characterization of Antisense Transformed Plants Deficient in the Tobacco Anionic Peroxidase.

PubMed

Lagrimini, L. M.; Gingas, V.; Finger, F.; Rothstein, S.; Liu, TTY.

1997-08-01

On the basis of the biological compounds that they metabolize, plant peroxidases have long been implicated in plant growth, cell wall biogenesis, lignification, and host defenses. Transgenic tobacco (Nicotiana tabacum L.) plants that underexpress anionic peroxidase were generated using antisense RNA. The antisense RNA was found to be specific for the anionic isoenzyme and highly effective, reducing endogenous transcript levels and total peroxidase activity by as much as 1600-fold. Antisense-transformed plants appeared normal at initial observation; however, growth studies showed that plants with reduced peroxidase activity grow taller and flower sooner than control plants. In contrast, previously transformed plants overproducing anionic peroxidase were shorter and flowered later than controls. Axillary buds were more developed in antisense-transformed plants and less developed in plants overproducing this enzyme. It was found that the lignin content in leaf, stem, and root was unchanged in antisense-transformed plants, which does not support a role for anionic peroxidase in the lignification of secondary xylem vessels. However, studies of wounded tissue show some reduction in wound-induced deposition of lignin-like polymers. The data support a possible role for tobacco anionic peroxidase in host defenses but not without a reduction in growth potential.

Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors.

PubMed

Giraudier, Stéphane; Chagraoui, Hédia; Komura, Emiko; Barnache, Stéphane; Blanchet, Benoit; LeCouedic, Jean Pierre; Smith, David F; Larbret, Frédéric; Taksin, Anne-Laure; Moreau-Gachelin, Françoise; Casadevall, Nicole; Tulliez, Michel; Hulin, Anne; Debili, Najet; Vainchenker, William

2002-10-15

Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by megakaryocyte hyperplasia and bone marrow fibrosis. Biologically, an autonomous megakaryocyte growth and differentiation is noticed, which contributes to the megakaryocyte accumulation. To better understand the molecular mechanisms involved in this spontaneous growth, we searched for genes differentially expressed between normal megakaryocytes requiring cytokines to grow and IMF spontaneously proliferating megakaryocytes. Using a differential display technique, we found that the immunophilin FKBP51 was 2 to 8 times overexpressed in megakaryocytes derived from patients' CD34(+) cells in comparison to normal megakaryocytes. Overexpression was moderate and confirmed in 8 of 10 patients, both at the mRNA and protein levels. Overexpression of FKBP51 in a UT-7/Mpl cell line and in normal CD34(+) cells induced a resistance to apoptosis mediated by cytokine deprivation with no effect on proliferation. FKBP51 interacts with both calcineurin and heat shock protein (HSP)70/HSP90. However, a mutant FKBP51 deleted in the HSP70/HSP90 binding site kept the antiapoptotic effect, suggesting that the calcineurin pathway was responsible for the FKBP51 effect. Overexpression of FKBP51 in UT-7/Mpl cells induced a marked inhibition of calcineurin activity. Pharmacologic inhibition of calcineurin by cyclosporin A mimicked the effect of FKBP51. The data support the conclusion that FKBP51 inhibits apoptosis through a calcineurin-dependent pathway. In conclusion, FKBP51 is overexpressed in IMF megakaryocytes and this overexpression could be, in part, responsible for the megakaryocytic accumulation observed in this disorder by regulating their apoptotic program.

Culture of human cell lines by a pathogen-inactivated human platelet lysate.

PubMed

Fazzina, R; Iudicone, P; Mariotti, A; Fioravanti, D; Procoli, A; Cicchetti, E; Scambia, G; Bonanno, G; Pierelli, L

2016-08-01

Alternatives to the use of fetal bovine serum (FBS) have been investigated to ensure xeno-free growth condition. In this study we evaluated the efficacy of human platelet lysate (PL) as a substitute of FBS for the in vitro culture of some human cell lines. PL was obtained by pools of pathogen inactivated human donor platelet (PLT) concentrates. Human leukemia cell lines (KG-1, K562, JURKAT, HL-60) and epithelial tumor cell lines (HeLa and MCF-7) were cultured with either FBS or PL. Changes in cell proliferation, viability, morphology, surface markers and cell cycle were evaluated for each cell line. Functional characteristics were analysed by drug sensitivity test and cytotoxicity assay. Our results demonstrated that PL can support growth and expansion of all cell lines, although the cells cultured in presence of PL experienced a less massive proliferation compared to those grown with FBS. We found a comparable percentage of viable specific marker-expressing cells in both conditions, confirming lineage fidelity in all cultures. Functionality assays showed that cells in both FBS- and PL-supported cultures maintained their normal responsiveness to adriamycin and NK cell-mediated lysis. Our findings indicate that PL is a feasible serum substitute for supporting growth and propagation of haematopoietic and epithelial cell lines with many advantages from a perspective of process standardization, ethicality and product safety.

Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts.

PubMed

Kabiri, Zahra; Greicius, Gediminas; Madan, Babita; Biechele, Steffen; Zhong, Zhendong; Zaribafzadeh, Hamed; Edison; Aliyev, Jamal; Wu, Yonghui; Bunte, Ralph; Williams, Bart O; Rossant, Janet; Virshup, David M

2014-06-01

Wnt/β-catenin signaling supports intestinal homeostasis by regulating proliferation in the crypt. Multiple Wnts are expressed in Paneth cells as well as other intestinal epithelial and stromal cells. Ex vivo, Wnts secreted by Paneth cells can support intestinal stem cells when Wnt signaling is enhanced with supplemental R-Spondin 1 (RSPO1). However, in vivo, the source of Wnts in the stem cell niche is less clear. Genetic ablation of Porcn, an endoplasmic reticulum resident O-acyltransferase that is essential for the secretion and activity of all vertebrate Wnts, confirmed the role of intestinal epithelial Wnts in ex vivo culture. Unexpectedly, mice lacking epithelial Wnt activity (Porcn(Del)/Villin-Cre mice) had normal intestinal proliferation and differentiation, as well as successful regeneration after radiation injury, indicating that epithelial Wnts are dispensable for these processes. Consistent with a key role for stroma in the crypt niche, intestinal stromal cells endogenously expressing Wnts and Rspo3 support the growth of Porcn(Del) organoids ex vivo without RSPO1 supplementation. Conversely, increasing pharmacologic PORCN inhibition, affecting both stroma and epithelium, reduced Lgr5 intestinal stem cells, inhibited recovery from radiation injury, and at the highest dose fully blocked intestinal proliferation. We conclude that epithelial Wnts are dispensable and that stromal production of Wnts can fully support normal murine intestinal homeostasis.

Enhanced polarization and dielectric properties of Pb(Zr1-xTix)O3 thin films

NASA Astrophysics Data System (ADS)

Ortega, N.; Kumar, Ashok; Katiyar, R. S.

2008-10-01

We report the fabrication of PbZr0.57Ti0.43O3 (PZT) thin films with preferential growth along (111) and random crystalline orientation on the platinized silicon substrates using pulsed laser deposition technique. X-ray diffraction patterns and surface morphology indicate increase in grain size and nucleation, which support better perovskite matrix with increase in annealing temperature. We observed large dielectric constant (˜4000) and enhanced remanent polarization 70 μC/cm2 at room temperature attributed to grain growth and intermetallic Pt-Pb transient phase. Frequency dependent polarization showed minor reduction in polarization above 10 kHz frequencies. Normalized fatigue characteristic of PZT thin films showed minimal 25% degradation in remanent polarization after 109 cycles, which may be useful for memory devices. ac conductivity spectra illustrated that anomaly near the phase transition temperature with activation energy (Ea˜0.60-0.75 eV) supports the intrinsic nature of ferroelectric phase transition.

Low fat diet with omega-3 fatty acids increases plasma insulin-like growth factor concentration in healthy postmenopausal women

USDA-ARS?s Scientific Manuscript database

The insulin-like growth factor pathway plays a central role in the normal and abnormal growth of tissues; however, the nutritional determinants of insulin-like growth factor I (IGF-I) and its binding proteins in normal individuals are not well-defined. The purpose of this study was to determine the ...

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity

PubMed Central

Lewis, John D.; Elman, Jeffrey L.

2009-01-01

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory – as occurs in autism – should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth – indicating a reduced reliance on long-distance connections – for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects. PMID:18171375

Genetics and Genomics of Longitudinal Lung Function Patterns in Individuals with Asthma

PubMed Central

Yates, Katherine P.; Zhou, Xiaobo; Guo, Feng; Sternberg, Alice L.; Van Natta, Mark L.; Wise, Robert A.; Szefler, Stanley J.; Sharma, Sunita; Kho, Alvin T.; Cho, Michael H.; Croteau-Chonka, Damien C.; Castaldi, Peter J.; Jain, Gaurav; Sanyal, Amartya; Zhan, Ye; Lajoie, Bryan R.; Dekker, Job; Stamatoyannopoulos, John; Covar, Ronina A.; Zeiger, Robert S.; Adkinson, N. Franklin; Williams, Paul V.; Kelly, H. William; Grasemann, Hartmut; Vonk, Judith M.; Koppelman, Gerard H.; Postma, Dirkje S.; Raby, Benjamin A.; Houston, Isaac; Lu, Quan; Fuhlbrigge, Anne L.; Tantisira, Kelan G.; Silverman, Edwin K.; Tonascia, James; Strunk, Robert C.; Weiss, Scott T.

2016-01-01

Rationale: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease. Objectives: To determine the genetic underpinnings of lung function patterns in subjects with childhood asthma. Methods: We performed a genome-wide association study of 581 non-Hispanic white individuals with asthma that were previously classified by patterns of lung function growth and decline (normal growth, normal growth with early decline, reduced growth, and reduced growth with early decline). The strongest association was also measured in two additional cohorts: a small asthma cohort and a large chronic obstructive pulmonary disease metaanalysis cohort. Interaction between the genomic region encompassing the most strongly associated single-nucleotide polymorphism and nearby genes was assessed by two chromosome conformation capture assays. Measurements and Main Results: An intergenic single-nucleotide polymorphism (rs4445257) on chromosome 8 was strongly associated with the normal growth with early decline pattern compared with all other pattern groups (P = 6.7 × 10−9; odds ratio, 2.8; 95% confidence interval, 2.0–4.0); replication analysis suggested this variant had opposite effects in normal growth with early decline and reduced growth with early decline pattern groups. Chromosome conformation capture experiments indicated a chromatin interaction between rs4445257 and the promoter of the distal CSMD3 gene. Conclusions: Early decline in lung function after normal growth is associated with a genetic polymorphism that may also protect against early decline in reduced growth groups. Clinical trial registered with www.clinicaltrials.gov (NCT00000575). PMID:27367781

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non-Small Cell Lung Carcinoma.

PubMed

Imbs, Diane-Charlotte; El Cheikh, Raouf; Boyer, Arnaud; Ciccolini, Joseph; Mascaux, Céline; Lacarelle, Bruno; Barlesi, Fabrice; Barbolosi, Dominique; Benzekry, Sébastien

2018-01-01

Concomitant administration of bevacizumab and pemetrexed-cisplatin is a common treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC-bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Logistic and Multiple Regression: A Two-Pronged Approach to Accurately Estimate Cost Growth in Major DoD Weapon Systems

DTIC Science & Technology

2004-03-01

Breusch - Pagan test for constant variance of the residuals. Using Microsoft Excel® we calculate a p-value of 0.841237. This high p-value, which is above...our alpha of 0.05, indicates that our residuals indeed pass the Breusch - Pagan test for constant variance. In addition to the assumption tests , we...Wilk Test for Normality – Support (Reduced) Model (OLS) Finally, we perform a Breusch - Pagan test for constant variance of the residuals. Using

RNA Expression Profiling Reveals Differentially Regulated Growth Factor and Receptor Expression in Redirected Cancer Cells.

PubMed

Schmucker, Hannah S; Park, Jang Pyo; Coissieux, Marie-May; Bentires-Alj, Mohamed; Feltus, F Alex; Booth, Brian W

2017-05-01

Tumorigenic cells can be redirected to adopt a normal phenotype when transplanted into cleared mammary fat pads of juvenile female mice in specific ratios with normal epithelial cells. The redirected tumorigenic cells enter stem cell niches and provide progeny that differentiate into all mammary epithelial subtypes. We have developed an in vitro model that mimics the in vivo phenomenon. The shift in phenotype to redirection should be accomplished through a return to a normal gene expression state. To measure this shift, we interrogated the transcriptome of various in vitro model states in search for casual genes. For this study, expression of growth factors, cytokines, and their associated receptors was examined. In all, we queried 251 growth factor and cytokine-related genes. We found numerous growth factor and cytokine genes whose expression levels switched from expression levels seen in cancer cells to expression levels observed in normal cells. The comparisons of gene expression between normal mammary epithelial cells, tumor-derived cells, and redirected cancer cells have revealed insight into active and inactive growth factors and cytokines in cancer cell redirection.

Low body temperature in long-lived Ames dwarf mice at rest and during stress.

PubMed

Hunter, W S; Croson, W B; Bartke, A; Gentry, M V; Meliska, C J

1999-09-01

Among homeothermic animals, larger species generally have lower metabolic rates and live longer than do smaller species. Because Ames dwarf mice (dwarfs) live approximately 1 year longer than their larger normal sex- and age-matched siblings (normals), we hypothesized that they would have lower body core temperature (Tco). We, therefore, measured Tco of six dwarfs and six normals during 24-h periods of ad lib feeding, 24-h food deprivation, and emotional stress induced by cage switching. With ad lib feeding, Tco of dwarfs averaged 1.6 degrees C lower than normals; during food deprivation, Tco of both dwarfs and controls was significantly lower than when food was available ad lib; and following cage switch, Tco was elevated in both groups. However, during all three experiments, Tco was significantly lower in dwarfs than in normals. These data support the hypothesis that Ames dwarf mice, which live longer than normal size controls, maintain lower Tco than normals. Because dwarfs are deficient in thyroid stimulating hormone (TSH) and growth hormone (GH), their low Tco may be a result of reduced thermogenesis due to lack of those hormones. However, whether low Tco per se is related to the increased longevity of the dwarf mice remains an interesting possibility to be investigated.

Pregnancy after Bariatric Surgery: Obstetric and Perinatal Outcomes and the Growth and Development of Children.

PubMed

Dell'Agnolo, Cátia Millene; Cyr, Caroline; de Montigny, Francine; de Barros Carvalho, Maria Dalva; Pelloso, Sandra Marisa

2015-11-01

Several outcomes of pregnancy after bariatric surgery are currently being studied. This cross-sectional, retrospective study evaluated the obstetric and perinatal outcomes of pregnancies in 19 women who underwent bariatric surgery, as well as the growth and development of their children, in the Southern Brazil. Among these women, 11 children were born prior to surgery and 32 were born post-surgery. The mean time between the surgery and the first pregnancy was 42.96 months. Preterm newborns were more common among the pre-surgery childbirths. Regarding growth, normal weights were observed in 27.3 % of the children in the pre-surgery births and obesity was observed in 54.5 %. In contrast, normal weights were observed in 59.4 % of the children born during the postoperative period and obesity was observed in 31.2 %. The average excess weight that the women lost prior to pregnancy was 64.88. Speech delays were found in three male children evaluated using the Denver Developmental Screening Test II. A statistical association was found between the interval from the surgery to the pregnancy and the outcome of the questionable Denver II test results (p = 0.011). Except for the large index of low birth weight, it can be concluded that pregnancy after bariatric surgery is safe. The growth rate was found to be adequate in the children born after the surgery, with reduced obesity. Although changes in speech development were detected, no factors were supported an association with pregnancy after bariatric surgery.

Cancer cell metabolism: one hallmark, many faces.

PubMed

Cantor, Jason R; Sabatini, David M

2012-10-01

Cancer cells must rewire cellular metabolism to satisfy the demands of growth and proliferation. Although many of the metabolic alterations are largely similar to those in normal proliferating cells, they are aberrantly driven in cancer by a combination of genetic lesions and nongenetic factors such as the tumor microenvironment. However, a single model of altered tumor metabolism does not describe the sum of metabolic changes that can support cell growth. Instead, the diversity of such changes within the metabolic program of a cancer cell can dictate by what means proliferative rewiring is driven, and can also impart heterogeneity in the metabolic dependencies of the cell. A better understanding of this heterogeneity may enable the development and optimization of therapeutic strategies that target tumor metabolism.

Constitutive Uncoupling of Pathways of Gene Expression That Control Growth and Differentiation in Myeloid Leukemia: A Model for the Origin and Progression of Malignancy

NASA Astrophysics Data System (ADS)

Sachs, Leo

1980-10-01

Chemical carcinogens and tumor promoters have pleiotropic effects. Tumor initiators can produce a variety of mutations and tumor promoters can regulate a variety of physiological molecules that control growth and differentiation. The appropriate mutation and the regulation of the appropriate molecules to induce cell growth can initiate and promote the sequence of changes required for transformation of normal cells into malignant cells. After this sequence of changes, some tumors can still be induced to revert with a high frequency from a malignant phenotype to a nonmalignant phenotype. Results obtained from analysis of regulation of growth and differentiation in normal and leukemic myeloid cells, the phenotypic reversion of malignancy by induction of normal differentiation in myeloid leukemia, and the blocks in differentiation-defective leukemic cell mutants have been used to propose a general model for the origin and progression of malignancy. The model states that malignancy originates by changing specific pathways of gene expression required for growth from inducible to constitutive in cells that can still be induced to differentiate normally by the physiological inducer of differentiation. The malignant cells, unlike the normal cells, then no longer require the physiological inducer for growth. This changes the requirements for growth and uncouples growth from differentiation. Constitutive expression of other specific pathways can uncouple other controls, which then causes blocks in differentiation and the further progression of malignancy. The existence of specific constitutive pathways of gene expression that uncouple controls in malignant cells can also explain the expression of fetal proteins, hormones, and some other specialized products of normal development in various types of tumors.

Growth hormone and early treatment.

PubMed

Antoniazzi, F; Cavarzere, P; Gaudino, R

2015-06-01

Growth hormone (GH) treatment is approved by the US Food and Drug Administration (FDA) not only for GH deficiency (GHD) but also for other childhood growth disorders with growth failure and/or short stature. GHD is the most frequent endocrine disorder presenting with short stature in childhood. During neonatal period, metabolic effects due to congenital GHD require a prompt replacement therapy to avoid possible life-threatening complications. In childhood and adolescence, growth impairment is the most evident effect of GHD and early treatment has the aim of restore normal growth and to reach normal adult height. We reassume in this review the conditions causing GHD and the diagnostic challenge to reach an early diagnosis, and an early treatment, necessary to obtain the best results. Finally, we summarize results obtained in clinical studies about pediatric patients with GHD treated at an early age, in which a marked early catch-up growth and a normalization of adult height were obtained.

Evaluation of growth hormone release and human growth hormone treatment in children with cranial irradiation-associated short stature

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

Romshe, C.A.; Zipf, W.B.; Miser, A.

1984-02-01

We studied nine children who had received cranial irradiation for various malignancies and subsequently experienced decreased growth velocity. Their response to standard growth hormone stimulation and release tests were compared with that in seven children with classic GH deficiency and in 24 short normal control subjects. With arginine and L-dopa stimulation, six of nine patients who received radiation had a normal GH response (greater than 7 ng/ml), whereas by design none of the GH deficient and all of the normal children had a positive response. Only two of nine patients had a normal response to insulin hypoglycemia, with no significantmore » differences in the mean maximal response of the radiation and the GH-deficient groups. Pulsatile secretion was not significantly different in the radiation and GH-deficient groups, but was different in the radiation and normal groups. All subjects in the GH-deficient and radiation groups were given human growth hormone for 1 year. Growth velocity increased in all, with no significant difference in the response of the two groups when comparing the z scores for growth velocity of each subject's bone age. We recommend a 6-month trial of hGH in children who have had cranial radiation and are in prolonged remission with a decreased growth velocity, as there is no completely reliable combination of GH stimulation or release tests to determine their response.« less

Hepatocyte Growth Factor and MET Support Mouse Enteric Nervous System Development, the Peristaltic Response, and Intestinal Epithelial Proliferation in Response to Injury

PubMed Central

Avetisyan, Marina; Wang, Hongtao; Schill, Ellen Merrick; Bery, Saya; Grider, John R.; Hassell, John A.; Stappenbeck, Thaddeus

2015-01-01

Factors providing trophic support to diverse enteric neuron subtypes remain poorly understood. We tested the hypothesis that hepatocyte growth factor (HGF) and the HGF receptor MET might support some types of enteric neurons. HGF and MET are expressed in fetal and adult enteric nervous system. In vitro, HGF increased enteric neuron differentiation and neurite length, but only if vanishingly small amounts (1 pg/ml) of glial cell line-derived neurotrophic factor were included in culture media. HGF effects were blocked by phosphatidylinositol-3 kinase inhibitor and by MET-blocking antibody. Both of these inhibitors and MEK inhibition reduced neurite length. In adult mice, MET was restricted to a subset of calcitonin gene-related peptide-immunoreactive (IR) myenteric plexus neurons thought to be intrinsic primary afferent neurons (IPANs). Conditional MET kinase domain inactivation (Metfl/fl; Wnt1Cre+) caused a dramatic loss of myenteric plexus MET-IR neurites and 1–1′-dioctodecyl-3,3,3′,3′-tetramethylindocarbocyamine perchlorate (DiI) labeling suggested reduced MET-IR neurite length. In vitro, Metfl/fl; Wnt1Cre+ mouse bowel had markedly reduced peristalsis in response to mucosal deformation, but normal response to radial muscle stretch. However, whole-bowel transit, small-bowel transit, and colonic-bead expulsion were normal in Metfl/fl; Wnt1Cre+ mice. Finally, Metfl/fl; Wnt1Cre+ mice had more bowel injury and reduced epithelial cell proliferation compared with WT animals after dextran sodium sulfate treatment. These results suggest that HGF/MET signaling is important for development and function of a subset IPANs and that these cells regulate intestinal motility and epithelial cell proliferation in response to bowel injury. SIGNIFICANCE STATEMENT The enteric nervous system has many neuronal subtypes that coordinate and control intestinal activity. Trophic factors that support these neuron types and enhance neurite growth after fetal development are not well understood. We show that a subset of adult calcitonin gene-related peptide (CGRP)-expressing myenteric neurons produce MET, the receptor for hepatocyte growth factor, and that loss of MET activity affects peristalsis in response to mucosal stroking, reduces MET-immunoreactive neurites, and increases susceptibility to dextran sodium sulfate-induced bowel injury. These observations may be relevant for understanding and treating intestinal motility disorders and also suggest that enhancing the activity of MET-expressing CGRP neurons might be a useful strategy to reduce bowel inflammation. PMID:26290232

Effect of transforming growth factor-beta1 on embryonic and posthatch muscle growth and development in normal and low score normal chicken.

PubMed

Li, X; Velleman, S G

2009-02-01

During skeletal muscle development, transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of muscle cell proliferation and differentiation. The TGF-beta1 signal is carried by Smad proteins into the cell nucleus, inhibiting the expression of key myogenic regulatory factors including MyoD and myogenin. However, the molecular mechanism by which TGF-beta1 inhibits muscle cell proliferation and differentiation has not been well documented in vivo. The present study investigated the effect of TGF-beta1 on in vivo skeletal muscle growth and development. A chicken line, Low Score Normal (LSN) with reduced muscling and upregulated TGF-beta1 expression, was used and compared to a normal chicken line. The injection of TGF-beta1 at embryonic day (ED) 3 significantly reduced the pectoralis major (p. major) muscle weight in the normal birds at 1 wk posthatch, whereas no significant difference was observed in the LSN birds. The difference between normal and LSN birds in response to TGF-beta1 is likely due to different levels of endogenous TGF-beta1 where the LSN birds have increased TGF-beta1 expression in their p. major muscle at both 17 ED and 6 wk posthatch. Smad3 expression was reduced by TGF-beta1 from 10 ED to 1 wk posthatch in normal p. major muscle. Unlike Smad3, Smad7 expression was not significantly affected by TGF-beta1 until posthatch in both normal and LSN p. major muscle. Expression of MyoD was reduced 35% by TGF-beta1 during embryonic development in normal p. major muscle, whereas LSN p. major muscle showed a delayed decrease at 1 d posthatch in MyoD expression in response to the TGF-beta1 treatment. Myogenin expression was reduced 29% by TGF-beta1 after hatch in normal p. major muscle. In LSN p. major muscle, TGF-beta1 treatment significantly decreased myogenin expression by 43% at 1 d posthatch and 32% at 1 wk posthatch. These data suggested that TGF-beta1 reduced p. major muscle growth by inhibiting MyoD and myogenin expression during both embryonic and posthatch development. Furthermore, TGF-beta1 also reduced the expression of the cell adhesion receptor beta1 integrin subunit during embryonic and posthatch muscle growth in normal and LSN chickens. Therefore, the reduction of beta1 integrin in response to TGF-beta1 is also associated with decreased posthatch muscle growth. The results from this study indicate that TGF-beta1 inhibits skeletal muscle growth by regulating MyoD and myogenin expression. These data also suggest that a beta1 integrin-mediated alternative pathway is likely involved in the TGF-beta1-induced reduction of muscle growth.

Interactions between the thyroid hormones and the hormones of the growth hormone axis.

PubMed

Laron, Zvi

2003-12-01

The normal secretion and action of the thyroid hormones and the hormones of the GH/IGF-I (growth hormone/ insulin-like growth factor I) axis are interdependent. Their interactions often differ in man from animal studies in rodents and sheep. Thus neonates with congenital hypothyroidism are of normal length in humans but IUGR (intrauterine growth retardation) in sheep. Postnatally normal GH/IGF-I secretion and action depends on an euthyroid state. Present knowledge on the interactions between the two axes is reviewed in states of hypo- and hyperthyroidism, states of GH/IGF-I deprivation and hypersecretion, as well as the relationship between IGF-I and thyroid cancer. Emphasis is given to data in children and aspects of linear growth and skeletal maturation.

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

PubMed

Friede, H

1981-01-01

The literature on normal development and growth of certain areas of the human head is reviewed, starting with the early induction of the desmal neurocranium. the development of the brain capsule with its dural reinforcement bands and their connection with the basicranium is discussed, as is the primordial chondrocranium, including its bone replacement. Growth of the calvaria and the three cranial fossae is also analysed. Special interest is focused on the anterior fossa, as knowledge of the growth in this area is very important for an understanding of pathogenesis and possibilities of treating premature craniosynostosis. Finally it is stressed that close observation of the effects of treatment on this pathology may increase our knowledge of normal growth.

Evaluation of the in vitro growth of urinary tract infection-causing gram-negative and gram-positive bacteria in a proposed synthetic human urine (SHU) medium.

PubMed

Ipe, Deepak S; Ulett, Glen C

2016-08-01

Bacteriuria is a hallmark of urinary tract infection (UTI) and asymptomatic bacteriuria (ABU), which are among the most frequent infections in humans. A variety of gram-negative and gram-positive bacteria are associated with these infections but Escherichia coli contributes up to 80% of cases. Multiple bacterial species including E. coli can grow in human urine as a means to maintain colonization during infections. In vitro bacteriuria studies aimed at modeling microbial growth in urine have utilized various compositions of synthetic human urine (SHU) and a Composite SHU formulation was recently proposed. In this study, we sought to validate the recently proposed Composite SHU as a medium that supports the growth of several bacterial species that are known to grow in normal human urine and/or artificial urine. Comparative growth assays of gram-negative and gram-positive bacteria E. coli, Pseudomonas aeruginosa, Proteus mirabilis, Streptococcus agalactiae, Staphylococcus saprophyticus and Enterococcus faecalis were undertaken using viable bacterial count and optical density measurements over a 48h culture period. Three different SHU formulations were tested in various culture vessels, shaking conditions and volumes and showed that Composite SHU can support the robust growth of gram-negative bacteria but requires supplementation with 0.2% yeast extract to support the growth of gram-positive bacteria. Experiments are also presented that show an unexpected but major influence of P. mirabilis towards the ability to measure bacterial growth in generally accepted multiwell assays using absorbance readings, predicted to have a basis in the release of volatile organic compound(s) from P. mirabilis during growth in Composite SHU medium. This study represents an essential methodological validation of a more chemically defined type of synthetic urine that can be applied to study mechanisms of bacteriuria and we conclude will offer a useful in vitro model to investigate the basis of some of the most common infections of humans. Copyright © 2016 Elsevier B.V. All rights reserved.

Titanium oxide as substrate for neural cell growth.

PubMed

Carballo-Vila, Mónica; Moreno-Burriel, Berta; Chinarro, Eva; Jurado, José R; Casañ-Pastor, Nieves; Collazos-Castro, Jorge E

2009-07-01

Titanium oxide has antiinflammatory activity and tunable electrochemical behavior that make it an attractive material for the fabrication of implantable devices. The most stable composition is TiO2 and occurs mainly in three polymorphs, namely, anatase, rutile, and brookite, which differ in its crystallochemical properties. Here, we report the preparation of rutile surfaces that permit good adherence and axonal growth of cultured rat cerebral cortex neurons. Rutile disks were obtained by sinterization of TiO2 powders of commercial origin or precipitated from hydrolysis of Ti(IV)-isopropoxide. Commercial powders sintered at 1300-1600 degrees C produced rutile surfaces with abnormal grain growth, probably because of impurities of the powders. Neurons cultured on those surfaces survived in variable numbers and showed fewer neurites than on control materials. On the other hand, rutile sintered from precipitated powders had less contaminants and more homogenous grain growth. By adjusting the thermal treatment it was possible to obtain surfaces performing well as substrate for neuron survival for at least 10 days. Some surfaces permitted normal axonal elongation, whereas dendrite growth was generally impaired. These findings support the potential use of titanium oxide in neuroprostheses and other devices demanding materials with enhanced properties in terms of biocompatibility and axon growth promotion.

Spatial decision supporting for winter wheat irrigation and fertilizer optimizing in North China Plain

NASA Astrophysics Data System (ADS)

Yang, Xiaodong; Yang, Hao; Dong, Yansheng; Yu, Haiyang

2014-11-01

Production management of winter wheat is more complicated than other crops since its growth period is covered all four seasons and growth environment is very complex with frozen injury, drought, insect or disease injury and others. In traditional irrigation and fertilizer management, agricultural technicians or farmers mainly make decision based on phenology, planting experience to carry out artificial fertilizer and irrigation management. For example, wheat needs more nitrogen fertilizer in jointing and booting stage by experience, then when the wheat grow to the two growth periods, the farmer will fertilize to the wheat whether it needs or not. We developed a spatial decision support system for optimizing irrigation and fertilizer measures based on WebGIS, which monitoring winter wheat growth and soil moisture content by combining a crop model, remote sensing data and wireless sensors data, then reasoning professional management schedule from expert knowledge warehouse. This system is developed by ArcIMS, IDL in server-side and JQuery, Google Maps API, ASP.NET in client-side. All computing tasks are run on server-side, such as computing 11 normal vegetable indexes (NDVI/ NDWI/ NDWI2/ NRI/ NSI/ WI/ G_SWIR/ G_SWIR2/ SPSI/ TVDI/ VSWI) and custom VI of remote sensing image by IDL; while real-time building map configuration file and generating thematic map by ArcIMS.

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering.

PubMed

Jabbarzadeh, Ehsan; Deng, Meng; Lv, Qing; Jiang, Tao; Khan, Yusuf M; Nair, Lakshmi S; Laurencin, Cato T

2012-11-01

Regenerative engineering approaches utilizing biomimetic synthetic scaffolds provide alternative strategies to repair and restore damaged bone. The efficacy of the scaffolds for functional bone regeneration critically depends on their ability to induce and support vascular infiltration. In the present study, three-dimensional (3D) biomimetic poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds were developed by sintering together PLAGA microspheres followed by nucleation of minerals in a simulated body fluid. Further, the angiogenic potential of vascular endothelial growth factor (VEGF)-incorporated mineralized PLAGA scaffolds were examined by monitoring the growth and phenotypic expression of endothelial cells on scaffolds. Scanning electron microscopy micrographs confirmed the growth of bone-like mineral layers on the surface of microspheres. The mineralized PLAGA scaffolds possessed interconnectivity and a compressive modulus of 402 ± 61 MPa and compressive strength of 14.6 ± 2.9 MPa. Mineralized scaffolds supported the attachment and growth and normal phenotypic expression of endothelial cells. Further, precipitation of apatite layer on PLAGA scaffolds resulted in an enhanced VEGF adsorption and prolonged release compared to nonmineralized PLAGA and, thus, a significant increase in endothelial cell proliferation. Together, these results demonstrated the potential of VEGF-incorporated biomimetic PLAGA sintered microsphere scaffolds for bone tissue engineering as they possess the combined effects of osteointegrativity and angiogenesis. Copyright © 2012 Wiley Periodicals, Inc.

Swimming Behavior and Calcium Incorporation into inner Ear Otoliths of Fish after vestibular Nerve Transection

NASA Astrophysics Data System (ADS)

Edelmann, E.; Anken, R.; Rahmann, H.

Previous investigations on neonate swordtail fish (Xiphophorus helleri) revealed that otolithic calcium incorporation (visualized using the calcium-tracer alizarin- complexone) and thus otolith growth had ceased after nerve transection, supporting a hypothesis according to which the gravity-dependent otolith growth is regulated neuronally. Subsequent investigations on larval cichlid fish (Oreochromis mossambicus) yielded contrasting results, repeatedly depending on the particular batch of cichlids investigated: Like neonate swordtails, type I cichlids revealed a stop of calcium incorporation after unilateral vestibular nerve transection. Their behaviour after transection was normal and the otolithic calcium incorporation in controls of the same batch was symmetrical. In type II cichlids, however, vestibular nerve transection had no effect on otolithic calcium incorporation. They behaved kinetotically after transection (this kind of kinetosis was qualitatively similar to the swimming behaviour exhibited by larval cichlids during microgravity in the course of parabolic aircraft flights). The otolithic calcium incorporation in control animals was asymmetrical. These results stongly suggest that the effects of vestibular nerve transection as well as the efficacy of the mechanism, which regulates otolith growth/otolithic calcium incorporation, are - depending on the particular batch of animals - genetically predispositioned. Thus, it is assumed that the mechanisms regulating otolith growth and equlibibrium differ in the two types of cichlid fish. This work was financially supported by the German Aerospace Center (DLR) e.V. (FKZ: 50 WB 9997).

Trichohyalin is a potential major autoantigen in human alopecia areata.

PubMed

Leung, Man Ching; Sutton, Chris W; Fenton, David A; Tobin, Desmond J

2010-10-01

Several lines of evidence support an autoimmune basis for alopecia areata (AA), a common putative autoimmune hair loss disorder. However, definitive support is lacking largely because the identity of hair follicle (HF) autoantigen(s) involved in its pathogenesis remains unknown. Here, we isolated AA-reactive HF-specific antigens from normal human scalp anagen HF extracts by immunoprecipitation using serum antibodies from 10 AA patients. Samples were analyzed by LC-MALDI-TOF/TOF mass spectrometry, which indicated strong reactivity to the hair growth phase-specific structural protein trichohyalin in all AA sera. Keratin 16 (K16) was also identified as another potential AA-relevant target HF antigen. Double immunofluorescence studies using AA (and control sera) together with a monoclonal antibody to trichohyalin revealed that AA sera contained immunoreactivity that colocalized with trichohyalin in the growth phase-specific inner root sheath of HF. Furthermore, a partial colocalization of AA serum reactivity with anti-K16 antibody was observed in the outer root sheath of the HF. In summary, this study supports the involvement of an immune response to anagen-specific HFs antigens in AA and specifically suggests that an immune response to trichohyalin and K16 may have a role in the pathogenesis of the enigmatic disorder.

Substrate flexibility regulates growth and apoptosis of normal but not transformed cells

NASA Technical Reports Server (NTRS)

Wang, H. B.; Dembo, M.; Wang, Y. L.

2000-01-01

One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.

Choline pathways during normal and stimulated renal growth in rats.

PubMed Central

Bean, G H; Lowenstein, L M

1978-01-01

Cellular membrane synthesis occurs during normal and stimulated renal growth. Choline in the kidney is utilized as a precursor for membrane synthesis via the choline kinase reaction. We investigated choline phosphorylation during normal and stimulated renal growth. Rapidly growing neonatal rat kidneys contained relatively high levels of choline kinase activity (61 pmol phosphorylcholine/min per mg protein). Choline kinase activity and phosphorylcholine production then fell gradually over the 1st mo of life; by 1 mo phosphorylcholine production was 34 pmol phosphorylcholine/min per mg protein. Choline kinase activity increased by 27% (P less than 0.001) in 28-day-old rats when renal growth was stimulated by contralateral nephrectomy; the increase occurred within 2 h after surgery. Thus, changes in the activity of this important enzyme in the initiation of membrane synthesis is associated both with normal renal development and with adaptation to nephron loss. The findings further suggest that the cell membrane may be involved in the initiation of compensatory renal growth. PMID:659614

The Hippo effector Yorkie controls normal tissue growth by antagonizing scalloped-mediated default repression.

PubMed

Koontz, Laura M; Liu-Chittenden, Yi; Yin, Feng; Zheng, Yonggang; Yu, Jianzhong; Huang, Bo; Chen, Qian; Wu, Shian; Pan, Duojia

2013-05-28

The Hippo tumor suppressor pathway restricts tissue growth by inactivating the transcriptional coactivator Yki. Although Sd has been implicated as a DNA-binding transcription factor partner for Yki and can genetically account for gain-of-function Yki phenotypes, how Yki regulates normal tissue growth remains a long-standing puzzle because Sd, unlike Yki, is dispensable for normal growth in most Drosophila tissues. Here we show that the yki mutant phenotypes in multiple developmental contexts are rescued by inactivation of Sd, suggesting that Sd functions as a default repressor and that Yki promotes normal tissue growth by relieving Sd-mediated default repression. We further identify Tgi as a cofactor involved in Sd's default repressor function and demonstrate that the mammalian ortholog of Tgi potently suppresses the YAP oncoprotein in transgenic mice. These findings fill a major gap in Hippo-mediated transcriptional regulation and open up possibilities for modulating the YAP oncoprotein in cancer and regenerative medicine. Copyright © 2013 Elsevier Inc. All rights reserved.

EPHA4 haploinsufficiency is responsible for the short stature of a patient with 2q35-q36.2 deletion and Waardenburg syndrome.

PubMed

Li, Chuan; Chen, Rongyu; Fan, Xin; Luo, Jingsi; Qian, Jiale; Wang, Jin; Xie, Bobo; Shen, Yiping; Chen, Shaoke

2015-04-11

Waardenburg syndrome type I (WS1), an auditory-pigmentary genetic disorder, is caused by heterozygous loss-of-function mutations in PAX3. Abnormal physical signs such as dystopia canthorum, patchy hypopigmentation and sensorineural hearing loss are common, but short stature is not associated with WS1. We reported a 4-year and 6 month-old boy with a rare combination of WS1 and severe short stature (83.5 cm (-5.8SD)). His facial features include dystopia canthorum, mild synophrys, slightly up-slanted palpebral fissure, posteriorly rotated ears, alae nasi hypoplasia and micrognathia. No heterochromia was noticed. He had a normal intelligence quotient and hearing. Insulin-like growth factor-1 (IGF-1) was 52.7 ng/ml, lower than the normal range (55 ~ 452 ng/ml) and the peak growth hormone level was 7.57 ng/ml at 90 minutes after taking moderate levodopa and pyridostigmine bromide. The patient exhibited a good response to human growth hormone (rhGH) replacement therapy, showing a 9.2 cm/year growth rate and an improvement of 1 standard deviation (SD) of height after one year treatment. CMA test of patient's DNA revealed a 4.46 Mb de novo deletion at 2q35-q36.2 (hg19; chr2:221,234,146-225,697,363). PAX3 haploinsufficiency is known to cause Waardenburg syndrome. Examining overlapping deletions in patients led to the conclusion that EPHA4 is a novel short stature gene. The finding is supported by the splotch-retarded and epha4 knockout mouse models which both showed growth retardation. We believe this rare condition is caused by the haploinsufficiency of both PAX3 and EPH4 genes. We further reported a growth response to recombinant human growth hormone treatment in this patient.

Effects of calcium and vitamin D3 on transforming growth factors in rectal mucosa of sporadic colorectal adenoma patients: a randomized controlled trial.

PubMed

Tu, Huakang; Flanders, W Dana; Ahearn, Thomas U; Daniel, Carrie R; Gonzalez-Feliciano, Amparo G; Long, Qi; Rutherford, Robin E; Bostick, Roberd M

2015-04-01

Transforming growth factor alpha (TGFα) and TGFβ1 are growth-promoting and -inhibiting autocrine/paracrine growth factors, respectively, that may (1) affect risk for colorectal cancer and (2) be modifiable by anti-proliferative exposures. The effects of supplemental calcium and vitamin D3 on these two markers in the normal-appearing colorectal mucosa in humans are unknown. We conducted a pilot, randomized, double-blind, placebo-controlled, 2 × 2 factorial clinical trial (n = 92; 23/treatment group) of calcium 2 g and/or vitamin D3 800 IU/d versus placebo over 6 mo. TGFα and TGFβ1 expression was measured in biopsies of normal-appearing rectal mucosa using automated immunohistochemistry and quantitative image analysis at baseline and 6-mo follow-up. In the calcium, vitamin D3 , and calcium plus vitamin D3 groups relative to the placebo group (1) the mean overall expression of TGFβ1 increased by 14% (P= 0.25), 19% (P = 0.17), and 22% (P = 0.09); (2) the ratio of TGFα expression in the upper 40% (differentiation zone) to that in the lower 60 (proliferation zone) of the crypts decreased by 34% (P = 0.11), 31% (P = 0.22), and 26% (P = 0.33); and (3) the TGFα/TGFβ1 ratio in the upper 40% of the crypts decreased by 28% (P = 0.09), 14% (P = 0.41), and 22% (P = 0.24), respectively. These preliminary results, although not statistically significant, suggest that supplemental calcium and vitamin D3 may increase TGFβ1 expression and shift TGFα expression downward from the differentiation to the proliferation zone in the crypts in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients, and support further investigation in a larger clinical trial. © 2013 Wiley Periodicals, Inc.

In vitro 3D regeneration-like growth of human patient brain tissue.

PubMed

Tang-Schomer, M D; Wu, W B; Kaplan, D L; Bookland, M J

2018-05-01

In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models. Copyright © 2018 John Wiley & Sons, Ltd.

Abnormal Mammary Development in 129:STAT1-Null Mice is Stroma-Dependent

PubMed Central

Cardiff, Robert D.; Trott, Josephine F.; Hovey, Russell C.; Hubbard, Neil E.; Engelberg, Jesse A.; Tepper, Clifford G.; Willis, Brandon J.; Khan, Imran H.; Ravindran, Resmi K.; Chan, Szeman R.; Schreiber, Robert D.; Borowsky, Alexander D.

2015-01-01

Female 129:Stat1-null mice (129S6/SvEvTac-Stat1tm1Rds homozygous) uniquely develop estrogen-receptor (ER)-positive mammary tumors. Herein we report that the mammary glands (MG) of these mice have altered growth and development with abnormal terminal end buds alongside defective branching morphogenesis and ductal elongation. We also find that the 129:Stat1-null mammary fat pad (MFP) fails to sustain the growth of 129S6/SvEv wild-type and Stat1-null epithelium. These abnormalities are partially reversed by elevated serum progesterone and prolactin whereas transplantation of wild-type bone marrow into 129:Stat1-null mice does not reverse the MG developmental defects. Medium conditioned by 129:Stat1-null epithelium-cleared MFP does not stimulate epithelial proliferation, whereas it is stimulated by medium conditioned by epithelium-cleared MFP from either wild-type or 129:Stat1-null females having elevated progesterone and prolactin. Microarrays and multiplexed cytokine assays reveal that the MG of 129:Stat1-null mice has lower levels of growth factors that have been implicated in normal MG growth and development. Transplanted 129:Stat1-null tumors and their isolated cells also grow slower in 129:Stat1-null MG compared to wild-type recipient MG. These studies demonstrate that growth of normal and neoplastic 129:Stat1-null epithelium is dependent on the hormonal milieu and on factors from the mammary stroma such as cytokines. While the individual or combined effects of these factors remains to be resolved, our data supports the role of STAT1 in maintaining a tumor-suppressive MG microenvironment. PMID:26075897

Perinatal and lifestyle factors mediate the association between maternal education and preschool children's weight status: the ToyBox study.

PubMed

Androutsos, Odysseas; Moschonis, George; Ierodiakonou, Despo; Karatzi, Kalliopi; De Bourdeaudhuij, Ilse; Iotova, Violeta; Zych, Kamila; Moreno, Luis A; Koletzko, Berthold; Manios, Yannis

2018-04-01

This study aimed to explore the associations among perinatal, sociodemographic, and behavioral factors and preschool overweight/obesity. Data were collected from 7541 European preschoolers in May/June 2012. Children's anthropometrics were measured, and parents self-reported all other data via questionnaires. Level of statistical significance was set at P ≤ 0.05. Certain perinatal factors (i.e., maternal prepregnancy overweight/obesity, maternal excess gestational weight gain, excess birth weight, and "rapid growth velocity"), children's energy balance-related behaviors (i.e., high sugar-sweetened beverage consumption, increased screen time, reduced active-play time), family sociodemographic characteristics (i.e., Eastern or Southern Europe, low maternal and paternal education), and parental overweight/obesity were identified as correlates of preschoolers' overweight/obesity. Furthermore, maternal prepregnancy overweight/obesity, children's "rapid growth velocity," and increased screen time mediated by 21.2%, 12.5%, and 5.7%, respectively, the association between maternal education and preschoolers' body mass index. This study highlighted positive associations of preschooler's overweight/obesity with excess maternal prepregnancy and gestational weight gain, excess birth weight and "rapid growth velocity," Southern or Eastern European region, and parental overweight/obesity. Moreover, maternal prepregnancy overweight/obesity, children's "rapid growth velocity," and increased screen time partially mediated the association between maternal education and preschoolers' body mass index. The findings of the present study may support childhood obesity prevention initiatives, because vulnerable population groups and most specifically low-educated families should be prioritized. Among other fields, these intervention initiatives should also focus on the importance of normal prepregnancy maternal weight status, normal growth velocity during infancy, and retaining preschool children's screen time within recommendations. Copyright © 2017 Elsevier Inc. All rights reserved.

TRAJECTORY AND CORRELATES OF GROWTH OF EXTREMELY LOW BIRTH WEIGHT ADOLESCENTS

PubMed Central

Hack, Maureen; Schluchter, Mark; Margevicius, Seunghee; Andreias, Laura; Taylor, Gerry; Cuttler, Leona

2014-01-01

Background Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch-up among extremely low birth weight (ELBW, <1 kg) adolescents. Methods Cohort study of 148 neurologically normal ELBW children and 115 normal birth weight (NBW) controls born 1992 through 1995. Longitudinal measures of gender-specific growth of ELBW children from birth, and growth and measures of obesity of ELBW and NBW children at 14 years. Results Following neonatal growth failure, ELBW children had accelerated growth, but at 8 years they still had lower weight and height z scores than NBW children. By 14 years ELBW boys had caught up in growth to their NBW controls but ELBW girls remained significantly smaller. ELBW children however did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses only maternal BMI and weight gain during infancy and childhood predicted the ELBW children’s 14-year weight z scores, BMI z scores and abdominal circumference. Perinatal risk factors including intrauterine growth only predicted growth up to 20 months. Conclusion Maternal BMI and rate of growth, rather than perinatal factors, predict 14-year obesity among neurologically normal ELBW adolescents. PMID:24216539

Intraoperative cervix location and apical support stiffness in women with and without pelvic organ prolapse.

PubMed

Swenson, Carolyn W; Smith, Tovia M; Luo, Jiajia; Kolenic, Giselle E; Ashton-Miller, James A; DeLancey, John O

2017-02-01

It is unknown how initial cervix location and cervical support resistance to traction, which we term "apical support stiffness," compare in women with different patterns of pelvic organ support. Defining a normal range of apical support stiffness is important to better understand the pathophysiology of apical support loss. The aims of our study were to determine whether: (1) women with normal apical support on clinic Pelvic Organ Prolapse Quantification, but with vaginal wall prolapse (cystocele and/or rectocele), have the same intraoperative cervix location and apical support stiffness as women with normal pelvic support; and (2) all women with apical prolapse have abnormal intraoperative cervix location and apical support stiffness. A third objective was to identify clinical and biomechanical factors independently associated with clinic Pelvic Organ Prolapse Quantification point C. We conducted an observational study of women with a full spectrum of pelvic organ support scheduled to undergo gynecologic surgery. All women underwent a preoperative clinic examination, including Pelvic Organ Prolapse Quantification. Cervix starting location and the resistance (stiffness) of its supports to being moved steadily in the direction of a traction force that increased from 0-18 N was measured intraoperatively using a computer-controlled servoactuator device. Women were divided into 3 groups for analysis according to their pelvic support as classified using the clinic Pelvic Organ Prolapse Quantification: (1) "normal/normal" was women with normal apical (C < -5 cm) and vaginal (Ba and Bp < 0 cm) support; (2) normal/prolapse had normal apical support (C < -5 cm) but prolapse of the anterior or posterior vaginal walls (Ba and/or Bp ≥ 0 cm); and (3) prolapse/prolapse had both apical and vaginal wall prolapse (C > -5 cm and Ba and/or Bp ≥ 0 cm). Demographics, intraoperative cervix locations, and apical support stiffness values were then compared. Normal range of cervix location during clinic examination and operative testing was defined by the total range of values observed in the normal/normal group. The proportion of women in each group with cervix locations within and outside the normal range was determined. Linear regression was performed to identify variables independently associated with clinic Pelvic Organ Prolapse Quantification point C. In all, 52 women were included: 14 in the normal/normal group, 11 in the normal/prolapse group, and 27 in the prolapse/prolapse group. At 1 N of traction force in the operating room, 50% of women in the normal/prolapse group had cervix locations outside the normal range while 10% had apical support stiffness outside the normal range. Of women in the prolapse/prolapse group, 81% had cervix locations outside the normal range and 8% had apical support stiffness outside the normal range. Similar results for cervix locations were observed at 18 N of traction force; however the proportion of women with apical support stiffness outside the normal range increased to 50% in the normal/prolapse group and 59% in the prolapse/prolapse group. The prolapse/prolapse group had statistically lower apical support stiffness compared to the normal/normal group with increased traction from 1-18 N (0.47 ± 0.18 N/mm vs 0.63 ± 0.20 N/mm, P = .006), but all other comparisons were nonsignificant. After controlling for age, parity, body mass index, and apical support stiffness, cervix location at 1 N traction force remained an independent predictor of clinic Pelvic Organ Prolapse Quantification point C, but only in the prolapse/prolapse group. Approximately 50% of women with cystocele and/or rectocele but normal apical support in the clinic had cervix locations outside the normal range under intraoperative traction, while 19% of women with uterine prolapse had normal apical support. Identifying women whose apical support falls outside a defined normal range may be a more accurate way to identify those who truly need a hysterectomy and/or an apical support procedure and to spare those who do not. Copyright © 2016 Elsevier Inc. All rights reserved.

Hyperthyroidism and acromegaly due to a thyrotropin- and growth hormone-secreting pituitary tumor. Lack of hormonal response to bromocriptine.

PubMed

Carlson, H E; Linfoot, J A; Braunstein, G D; Kovacs, K; Young, R T

1983-05-01

A 47-year-old woman with acromegaly and hyperthyroidism was found to have an inappropriately normal serum thyrotropin level (1.5 to 2.5 microU/ml) that responded poorly to thyrotropin-releasing hormone but showed partial responsiveness to changes in circulating thyroid hormones. Serum alpha-subunit levels were high-normal and showed a normal response to thyrotropin-releasing hormone. Growth hormone and thyrotropin hypersecretion persisted despite radiotherapy and bromocriptine treatment. Selective trans-sphenoidal removal of a pituitary adenoma led to normalization of both growth hormone and thyrotropin levels. Both thyrotropes and somatotropes were demonstrated in the adenoma by the immunoperoxidase technique and electron microscopy.

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

PubMed

Stubbs, Sharron A; Webber, Lisa J; Stark, Jaroslav; Rice, Suman; Margara, Raul; Lavery, Stuart; Trew, Geoffrey H; Hardy, Kate; Franks, Stephen

2013-08-01

Polycystic ovary syndrome (PCOS), the commonest cause of anovulatory infertility, is characterized by disordered follicle development including increased activation and accelerated growth of preantral follicles. Data from experimental animals and preliminary results from studies of human ovarian tissue suggest that IGFs affect preantral follicle development. Our objectives were to investigate the expression of the type-1 IGF receptor (IGFR-1) in the human ovary and to determine whether IGFs are involved in stimulating the transition of follicles from primordial to primary stage in normal and polycystic ovaries. We used archived ovarian tissue for protein expression studies and small cortical biopsies for follicle isolation and for tissue culture. This was a laboratory-based study, using clinical tissue samples. A total of 54 women, 33 with normal ovaries and 21 with polycystic ovaries, were classified by reference to menstrual cycle history and ultrasonography. We evaluated expression of IGFR-1 mRNA in isolated preantral follicles and of IGFR-1 protein in archived ovarian tissue samples from normal and polycystic ovaries and effects of exogenous IGF-1 on preantral follicle development and survival in cultured fragments of normal and polycystic ovaries. IGFR-1 mRNA and protein was expressed in preantral follicles at all stages of development and enhanced expression was noted in PCOS follicles during early preantral development. IGF-1 stimulated initiation of follicle growth in normal tissue but had little effect on preantral follicle growth in polycystic ovaries in which, characteristically, there was a higher proportion of follicles that had entered the growing phase even before culture. IGFs are plausible candidates in regulation of initiation of human follicle growth, and accelerated preantral follicle growth in PCOS may be due to increased activity of endogenous IGFs.

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

PubMed

Wolf, Myles; White, Kenneth E

2014-07-01

High levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. Autosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Is "treat your child normally" helpful advice for parents of survivors of treatment of hypoplastic left heart syndrome?

PubMed

Rempel, Gwen R; Harrison, Margaret J; Williamson, Deanna L

2009-04-01

Developing technology affords children with complex congenitally malformed hearts a chance for survival. Parents gratefully pursue life-saving options on behalf of their children, despite the risks to the life of their child, and uncertainty about outcomes. Little is known about how mothers and fathers experience parenting a child whose new state as a survivor may include less than optimal developmental sequels. Our study involved multiple interactive interviews with 9 mothers and 7 fathers of infants and preschool children with hypoplastic left heart syndrome who had survived the Norwood surgical approach. Qualitative methodology included grounded theory methods of simultaneous collection and analysis of data, and we used open and selective coding of transcribed interviews. Parents used normalization in the context of uncertainty regarding the ongoing survival of their child. Parents described their underweight children as being on their own growth curve, and viewed their developmental progress, however delayed, as reason for celebration, as they had been prepared for their child to die. There is growing evidence that children with congenitally malformed hearts who require surgical intervention during the first year of life may experience developmental delay. The use of normalization by their parents may be effective in decreasing their worry regarding the uncertain future faced by their child, but may negatively affect the developmental progress of the child if they do not seek resources to assist development. Advice from paediatric specialists for parents to view their children as normal needs to be balanced with assistance for parents to access services to support optimal growth and development of their child.

Effects of Growth Hormone/IGF-I and Exercise on Unloaded Bones

NASA Technical Reports Server (NTRS)

Harper, J. S.; Arnaud, S. B.; Gosselink, K. L.; Grindeland, R. E.

1994-01-01

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) in combination with exercise prevent muscle atrophy induced by unloading in the tail-suspension rat model for space flight (Gosselink et al, FASEB J 1994). This study evaluated the effects of these treatments on bone. Hypophysectomized rats were suspended (S) and treated with 1mg/kg/day CH plus IGF-I (H) or vehicle (Sal) daily by injection and exercised (Ex) by 3 climbs up a 1m ladder carrying a load equal to 30% the initial body weight (BW) 3x/day for 10 days. Tibial epiphysis (Epi) widths were measured by micrometry and femoral Bone Mineral Content (fBMC) in excised femurs by DEXA (Lunar DPX-L). Serum calcium (Ca) and phosphorus (Pi) were measured by COBAS Autoanalyzer (Roche Diag.). Ambulatory (Amb)-H treated rats showed growth rates of 6.6+-0.9 g/day, similar to S-H-Ex and higher than S-H (3.210.6, p less than 0.05) and S-Sal (-0.711.0, p less than 0.05). Epi widths were 10% lower in S-Sal, and S-Sal-Ex, and increased 100% in all H groups. fBMC was less in S than Amb, only when all S groups are compared to both Amb groups (p less than 0.03). H treatment increased fBMC (p less than 0.05) but reduced fBMC/100g BW in all H groups (p less than 0.001). The reduced density of H bone cannot be attributed to low circulating Ca. and Pi since they were higher in H than Sal (p less than 0.001). H treatment for 10 days in doses sufficient to support normal growth in BW failed to produce normal Epi widths or fBMC, even when combined with exercise. The suspension effect observed in Epi widths was not corrected by H or Ex alone, but was improved by H plus a This regimen. although effective in preventing muscle atrophy, failed to return bone measures, Epi widths and fBMC, to normal.

The Potential Role of Systemic Buffers in Reducing Intratumoral Extracellular pH and Acid-Mediated Invasion

PubMed Central

Silva, Ariosto S.; Yunes, Jose A.; Gillies, Robert J.; Gatenby, Robert A.

2013-01-01

A number of studies have shown that the extracellular pH (pHe) in cancers is typically lower than that in normal tissue and that an acidic pHe promotes invasive tumor growth in primary and metastatic cancers. Here, we investigate the hypothesis that increased systemic concentrations of pH buffers reduce intratumoral and peritumoral acidosis and, as a result, inhibit malignant growth. Computer simulations are used to quantify the ability of systemic pH buffers to increase the acidic pHe of tumors in vivo and investigate the chemical specifications of an optimal buffer for such purpose. We show that increased serum concentrations of the sodium bicarbonate (NaHCO3) can be achieved by ingesting amounts that have been used in published clinical trials. Furthermore, we find that consequent reduction of tumor acid concentrations significantly reduces tumor growth and invasion without altering the pH of blood or normal tissues. The simulations also show that the critical parameter governing buffer effectiveness is its pKa. This indicates that NaHCO3, with a pKa of 6.1, is not an ideal intratumoral buffer and that greater intratumoral pHe changes could be obtained using a buffer with a pKa of ~7. The simulations support the hypothesis that systemic pH buffers can be used to increase the tumor pHe and inhibit tumor invasion. PMID:19276380

Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures.

PubMed

Fox, Emily P; Cowley, Elise S; Nobile, Clarissa J; Hartooni, Nairi; Newman, Dianne K; Johnson, Alexander D

2014-10-20

The human microbiome contains diverse microorganisms, which share and compete for the same environmental niches. A major microbial growth form in the human body is the biofilm state, where tightly packed bacterial, archaeal, and fungal cells must cooperate and/or compete for resources in order to survive. We examined mixed biofilms composed of the major fungal species of the gut microbiome, Candida albicans, and each of five prevalent bacterial gastrointestinal inhabitants: Bacteroides fragilis, Clostridium perfringens, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis. We observed that biofilms formed by C. albicans provide a hypoxic microenvironment that supports the growth of two anaerobic bacteria, even when cultured in ambient oxic conditions that are normally toxic to the bacteria. We also found that coculture with bacteria in biofilms induces massive gene expression changes in C. albicans, including upregulation of WOR1, which encodes a transcription regulator that controls a phenotypic switch in C. albicans, from the "white" cell type to the "opaque" cell type. Finally, we observed that in suspension cultures, C. perfringens induces aggregation of C. albicans into "mini-biofilms," which allow C. perfringens cells to survive in a normally toxic environment. This work indicates that bacteria and C. albicans interactions modulate the local chemistry of their environment in multiple ways to create niches favorable to their growth and survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

Growth hormone therapy in hypochondroplasia.

PubMed

Ramaswami, U; Hindmarsh, P C; Brook, C G

1999-02-01

Patients with hypochondroplasia present with variable phenotypes. Children with severe short stature and disproportion of the body segments usually have the mutation Asn540Lys. They respond to growth hormone (GH) therapy with an increase in spinal length and, coupled with a surgical leg-lengthening procedure, it is possible for some patients to achieve adult heights within the normal range. Some children who present with proportionate short stature and hypochondroplasia fail to increase their growth rate at puberty, although the growth spurt can be restored by GH therapy. Others, with an identical presentation, seem to grow normally during puberty. At present, there is no way of predicting who will undergo a normal pubertal growth spurt. We therefore monitor all patients during childhood and give GH treatment only to those patients who fail to develop a growth spurt at puberty. Severe cases may occasionally need treatment before puberty if their growth velocity is compromised, but these will probably also be candidates for a surgical leg-lengthening procedure.

The Success of Thread-embedding Therapy in Generating Hair Re-growth in Mice Points to Its Possibly Having a Similar Effect in Humans

PubMed Central

Shin, Hyun Jong; Lee, Dong-Jin; Kwon, Kang; Seo, Hyung-Sik; Jeong, Han-Sol; Lee, Ji-Yeon; Ha, Ki-Tae; Lee, Chang-Hyun; Jang, Yong-Suk; Lee, Byung-Wook; Kim, Byung Joo; Jung, Myeong-Ho

2015-01-01

Objectives: Recently, thread-embedding therapy (TET) has been widely applied in Korean medicine for cosmetic purposes such as reducing skin wrinkles. An inserted thread was reported to have induced continuous stimulation, followed by support for connective tissue regeneration. However, the potential role of TET in hairgrowth has not yet been reported. Methods: We designed this study to evaluate whether TET has a hair-growth-promoting effect. C57 black 6 (C57BL/6) mice were divided into three groups: normal saline-treated, minoxidil-treated, and thread-embedded groups. Normal saline or 5% minoxidil was topically sprayed on the dorsal skin of the mice once a day for 16 days. Medical threads were embedded into the dorsal skin of the mice in a single application. Hair growth activity was evaluated by using dermoscopic and microscopic observations. Sections of the dorsal skin were stained with hematoxylin and eosin. Expressions of bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA), fibroblast growth factor-7 (FGF-7), and fibroblast growth factor-5 (FGF-5) were detected by using immunohistochemical staining. A reverse transcription-polymerase chain reaction (RT-PCR) analysis was adopted to measure the messenger RNA (mRNA) expressions of FGF-7 and FGF-5. Results: TET enhanced anagen development in the hair follicles of C57BL/6 mice. The expressions of BrdU and PCNA, both of which imply active cellular proliferation, were increased by using TET. Moreover, TET increased the expression of FGF-7, an anagen-inducing growth factor, while decreasing the expression of FGF-5, an anagen-cessation growth factor, both at the protein and the mRNA levels. Conclusion: TET enhanced hair re-growth in C57BL/6 mice. TET regulated the expressions of anagen-associated growth factors and activated the proliferation of hair follicular cells in depilated skin lesions. Considering its long-lasting effect, TET may be a good alternative therapeutic for the treatment of alopecia. PMID:26998386

Hyphal Growth in Human Fungal Pathogens and Its Role in Virulence

PubMed Central

Brand, Alexandra

2012-01-01

Most of the fungal species that infect humans can grow in more than one morphological form but only a subset of pathogens produce filamentous hyphae during the infection process. This subset is phylogenetically unrelated and includes the commonly carried yeasts, Candida albicans, C. dubliniensis, and Malassezia spp., and the acquired pathogens, Aspergillus fumigatus and dermatophytes such as Trichophyton rubrum and T. mentagrophytes. The primary function of hypha formation in these opportunistic pathogens is to invade the substrate they are adhered to, whether biotic or abiotic, but other functions include the directional translocation between host environments, consolidation of the colony, nutrient acquisition and the formation of 3-dimensional matrices. To support these functions, polarised hyphal growth is co-regulated with other factors that are essential for normal hypha function in vivo. PMID:22121367

Steady-state and dynamic gene expression programs in Saccharomyces cerevisiae in response to variation in environmental nitrogen

PubMed Central

Airoldi, Edoardo M.; Miller, Darach; Athanasiadou, Rodoniki; Brandt, Nathan; Abdul-Rahman, Farah; Neymotin, Benjamin; Hashimoto, Tatsu; Bahmani, Tayebeh; Gresham, David

2016-01-01

Cell growth rate is regulated in response to the abundance and molecular form of essential nutrients. In Saccharomyces cerevisiae (budding yeast), the molecular form of environmental nitrogen is a major determinant of cell growth rate, supporting growth rates that vary at least threefold. Transcriptional control of nitrogen use is mediated in large part by nitrogen catabolite repression (NCR), which results in the repression of specific transcripts in the presence of a preferred nitrogen source that supports a fast growth rate, such as glutamine, that are otherwise expressed in the presence of a nonpreferred nitrogen source, such as proline, which supports a slower growth rate. Differential expression of the NCR regulon and additional nitrogen-responsive genes results in >500 transcripts that are differentially expressed in cells growing in the presence of different nitrogen sources in batch cultures. Here we find that in growth rate–controlled cultures using nitrogen-limited chemostats, gene expression programs are strikingly similar regardless of nitrogen source. NCR expression is derepressed in all nitrogen-limiting chemostat conditions regardless of nitrogen source, and in these conditions, only 34 transcripts exhibit nitrogen source–specific differential gene expression. Addition of either the preferred nitrogen source, glutamine, or the nonpreferred nitrogen source, proline, to cells growing in nitrogen-limited chemostats results in rapid, dose-dependent repression of the NCR regulon. Using a novel means of computational normalization to compare global gene expression programs in steady-state and dynamic conditions, we find evidence that the addition of nitrogen to nitrogen-limited cells results in the transient overproduction of transcripts required for protein translation. Simultaneously, we find that that accelerated mRNA degradation underlies the rapid clearing of a subset of transcripts, which is most pronounced for the highly expressed NCR-regulated permease genes GAP1, MEP2, DAL5, PUT4, and DIP5. Our results reveal novel aspects of nitrogen-regulated gene expression and highlight the need for a quantitative approach to study how the cell coordinates protein translation and nitrogen assimilation to optimize cell growth in different environments. PMID:26941329

A patient with cystinosis presenting like bartter syndrome and review of literature.

PubMed

Ertan, Pelin; Evrengul, Havva; Ozen, Serkan; Emre, Sinan

2012-12-01

Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder presenting with metabolic acidosis, Fanconi syndrome and renal failure. We present a 6-year-old girl with severe growth failure, hyponatremia and hypokalemia. Her parents were 4(th) degree relatives. Two relatives were diagnosed as end stage renal failure. She also had persistant hypokalemic hypochloremic metabolic alkalosis. Her renal function was normal at presentation. She was thought to have Bartter syndrome with supporting findings of elevated levels of renin and aldosterone with normal blood pressure, and hyperplasia of juxtaglomerular apparatus. Her metabolic alkalosis did not resolve despite supportive treatment. At 6(th) month of follow-up proteinuria, glucosuria and deterioration of renal function developed. Diagnosis of cystinosis was made with slit lamp examination and leukocyte cystine levels. At 12(th) month of follow-up her metabolic alkalosis has converted to metabolic acidosis. In children presenting with persistant metabolic alkalosis, with family history of renal failure, and parental consanguinity, cystinosis should always be kept in mind as this disease is an important cause of end stage renal failure which may have features mimmicking Bartter syndrome.

Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.

PubMed

Pawar, Archana; Meier, Jeremy A; Dasgupta, Anwesha; Diwanji, Neha; Deshpande, Neha; Saxena, Kritika; Buwa, Natasha; Inchanalkar, Siddhi; Schwartz, Martin Alexander; Balasubramanian, Nagaraj

2016-09-01

Integrin dependent regulation of growth factor signalling confers anchorage dependence that is deregulated in cancers. Downstream of integrins and oncogenic Ras the small GTPase Ral is a vital mediator of adhesion dependent trafficking and signalling. This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells. In re-adherent mouse fibroblasts (MEFs) integrin dependent activation of RalA drives Arf6 activation. Independent of adhesion constitutively active RalA and RalB could both however activate Arf6. This is further conserved in oncogenic H-Ras containing bladder cancer T24 cells, which express anchorage independent active Ral that supports Arf6 activation. Arf6 mediates active Ral-exocyst dependent delivery of raft microdomains to the plasma membrane that supports anchorage independent growth signalling. Accordingly in T24 cells the RalB-Arf6 crosstalk is seen to preferentially regulate anchorage independent Erk signalling. Active Ral we further find uses a Ral-RalBP1-ARNO-Arf6 pathway to mediate Arf6 activation. This study hence identifies Arf6, through this regulatory crosstalk, to be a key downstream mediator of Ral isoform function along adhesion dependent pathways in normal and cancer cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Plasma growth hormone, insulin, and glucagon responses to arginine infusion in children and adolescents with idiopathic short stature, isolated growth hormone deficiency, panhypopituitarism, and anorexia nervosa.

PubMed

Sizonenko, P C; Rabinovitch, A; Schneider, P; Paunier, L; Wollheim, C B; Zahnd, G

1975-09-01

The effects of intravenous infusion of arginine (20 g/m2) after an overnight fast on plasma immunoreactive growth hormone (GH), insulin (IRI), and glucagon (IRG), and blood glucose were examined in five groups of children and adolescents: 10 normal individuals, 18 with idiopathic short stature, 6 with isolated growth hormone deficiency, 8 with panhypopituitarism, and 6 with anorexia nervosa. The mean fasting plasma GH concentration was significantly elevated in the group with anorexia nervosa (P less than 0.05), and similar to the value for the normal group in all other groups. After arginine infusion, four- to sixfold increases of plasma GH were observed in the normal children, and similar increases were seen in those with idiopathic short stature as well as in those with anorexia nervosa; whereas, in the children with isolated growth hormone deficiency or panhypopituitarism, there was no significant increase in plasma GH. Fasting blood glucose concentrations were significantly lower than normal in subjects with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.001), whereas fasting plasma IRI and IRG concentrations were similar to the values in the normal group. Plasma IRI increased eightfold at the end of the 30-min arginine infusion in the normal subjects; the increase was slightly but not significantly less in those with idiopathic short stature, and significantly less in those with isolated growth hormone deficiency (P less than 0.05), panhypopituitarism (P less than 0.001), and anorexia nervosa (P less than 0.05). Arginine infusion resulted in two- to threefold increases of plasma IRG in the normal group, and similar increases were observed in all of the other groups tested. These results suggest that whereas pancreatic beta cell responsiveness may be deficient in children and adolescents with isolated growth hormone deficiency, panhypopituitarism, or anorexia nervosa, pancreatic alpha cell responsiveness, to arginine at least, appears to be intact under these conditions.

Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia.

PubMed Central

Soliman, A T; Alsalmi, I; Darwish, A; Asfour, M G

1996-01-01

Seven children, with a mean (SD) age of 4.6 (2.1) years, who as infants (21 (7.5) days) underwent near total (95-98%) pancreatectomy for persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) were studied. At birth all the infants were macrosomic. Four infants had been born after a difficult labour, of whom three had moderate birth asphyxia and respiratory distress. All had normal thyroid function. After surgery transient hyperglycaemia was manifest in six of the children and required insulin treatment for 5.8 (3.8) weeks, and transient hypoglycaemia was encountered in one child and responded well to increased carbohydrate intake and diazoxide for three weeks. Six of the children rapidly crossed down their length and weight centiles during the first year after surgery. At the end of the first year these children were at or below the 5th centile of height and weight for their age and gender. After a period of 4.6 (2.1) years, their mean (SD) height score was -2.57 (0.5), growth velocity 3.9 (0.75) cm/year, and growth velocity SD score -2.1 (0.55)l these were significantly low and denoted significant growth retardation. The growth hormone peak responses to provocation with clonidine were normal (13.5 (2.8) micrograms/l). However, the circulating insulin-like growth factor-I (IGF-I) concentrations were significantly decreased (79 (34) ng/ml). Three of the children developed diabetes at two and a half, five, and seven years after surgery, two others had impaired oral glucose tolerance and six out of the seven children had an impaired C peptide response to glucagon. Defective insulin secretion in these children might directly inhibit IGF-I synthesis in the liver. The body mass index of the pancreatectomised children was 14.9 (0.5) and was normal for age and gender; they had a normal 72 hour faecal fat content and normal serum albumin concentration. These data indicated grossly adequate exocrine pancreatic function. It appears that children requiring near total pancreatectomy for PHHI have normal developmental milestones but defective linear growth with impaired insulin secretion and low IGF-I production despite normal growth hormone response to provocation. PMID:8669952

The Underlying Ecological Processes of Gut Microbiota Among Cohabitating Retarded, Overgrown and Normal Shrimp.

PubMed

Xiong, Jinbo; Dai, Wenfang; Zhu, Jinyong; Liu, Keshao; Dong, Chunming; Qiu, Qiongfen

2017-05-01

Increasing evidence of tight links among the gut microbiota, obesity, and host health has emerged, but knowledge of the ecological processes that shape the variation in microbial assemblages across growth rates remains elusive. Moreover, inadequately control for differences in factors that profoundly affect the gut microbial community, hampers evaluation of the gut microbiota roles in regulating growth rates. To address this gap, we evaluated the composition and ecological processes of the gut bacterial community in cohabitating retarded, overgrown, and normal shrimps from identically managed ponds. Gut bacterial community structures were distinct (P = 0.0006) among the shrimp categories. Using a structural equation modeling (SEM), we found that changes in the gut bacterial community were positively related to digestive activities, which subsequently affected shrimp growth rate. This association was further supported by intensified interspecies interaction and enriched lineages with high nutrient intake efficiencies in overgrown shrimps. However, the less phylogenetic clustering of gut microbiota in overgrown and retarded subjects may offer empty niches for pathogens invasion, as evidenced by higher abundances of predicted functional pathways involved in disease infection. Given no differences in biotic and abiotic factors among the cohabitating shrimps, we speculated that the distinct gut community assembly could be attributed to random colonization in larval shrimp (e.g., priority effects) and that an altered microbiota could be a causative factor in overgrowth or retardation in shrimp. To our knowledge, this is the first study to provide an integrated overview of the direct roles of gut microbiota in shaping shrimp growth rate and the underlying ecological mechanisms.

Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

PubMed

Haffner, D; Schaefer, F; Nissel, R; Wühl, E; Tönshoff, B; Mehls, O

2000-09-28

Growth hormone treatment stimulates growth in short children with chronic renal failure. However, the extent to which this therapy increases final adult height is not known. We followed 38 initially prepubertal children with chronic renal failure treated with growth hormone for a mean of 5.3 years until they reached their final adult height. The mean (+/-SD) age at the start of treatment was 10.4+/-2.2 years, the mean bone age was 7.1+/-2.3 years, and the mean height was 3.1+/-1.2 SD below normal. Fifty matched children with chronic renal failure who were not treated with growth hormone served as controls. The children treated with growth hormone had sustained catch-up growth, whereas the control children had progressive growth failure. The mean final height of the growth hormone-treated children was 165 cm for boys and 156 cm for girls. The mean final adult height of the growth hormone-treated children was 1.6+/-1.2 SD below normal, which was 1.4 SD above their standardized height at base line (P< 0.001). In contrast, the final height of the untreated children (2.1+/-1.2 SD below normal) was 0.6 SD below their standardized height at base line (P<0.001). Although prepubertal bone maturation was accelerated in growth hormone-treated children, treatment was not associated with a shortening of the pubertal growth spurt. The total height gain was positively associated with the initial target-height deficit and the duration of growth hormone therapy and was negatively associated with the percentage of the observation period spent receiving dialysis treatment. Long-term growth hormone treatment of children with chronic renal failure induces persistent catch-up growth, and the majority of patients achieve normal adult height.

Differences in the association between maternal serum homocysteine and ADMA levels in women with pregnancies complicated by preeclampsia and/or intrauterine growth restriction.

PubMed

Laskowska, Marzena; Laskowska, Katarzyna; Oleszczuk, Jan

2013-01-01

The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction. The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays. A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia. These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

Ovine prenatal growth restriction impacts glucose metabolism and body composition throughout life in both sexes.

PubMed

Wallace, Jacqueline M; Milne, John S; Aitken, Raymond P; Horgan, Graham W; Adam, Clare L

2018-05-22

Low birthweight is a risk factor for later adverse health. Here the impact of placentally-mediated prenatal growth-restriction followed by postnatal nutrient abundance on growth, glucose metabolism and body composition was assessed in both sexes at key stages from birth to mid-adult life. Singleton-bearing adolescent dams were fed control or high nutrient intakes to induce normal or growth-restricted pregnancies, respectively. Restricted lambs had ~40% reduced birthweight. Fractional growth rates were higher in restricted lambs of both sexes predominantly during suckling/juvenile phases. Thereafter, rates and patterns of growth differed by sex. Absolute catch-up was not achieved and restricted offspring had modestly reduced weight and stature at mid-adulthood necropsy (~109 weeks). Dual-energy X-ray absorptiometry revealed lower bone mineral density in restricted versus normal lambs at 11, 41, 64 and 107 weeks, with males>females from 41 weeks onwards. Body fat percentage was higher in females versus males throughout, in restricted versus normal lambs at weaning (both sexes), and in restricted versus normal females at mid-adulthood. Insulin secretion after glucose-challenge was greater in restricted versus normal of both sexes at 7 weeks, and in restricted-males at 32 weeks. In both sexes fasting glucose concentrations were greater in restricted offspring across the life-course, while glucose area-under-the-curve after challenge was higher in restricted offspring at 32, 60, 85 and 106 weeks, indicative of persistent glucose intolerance. Therefore prenatal growth-restriction has negative consequences for body composition and metabolism throughout the life-course with the effects modulated by sex differences in postnatal growth rates, fat deposition and bone mass accrual.

Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth.

PubMed

Grier, Alex; Qiu, Xing; Bandyopadhyay, Sanjukta; Holden-Wiltse, Jeanne; Kessler, Haeja A; Gill, Ann L; Hamilton, Brooke; Huyck, Heidie; Misra, Sara; Mariani, Thomas J; Ryan, Rita M; Scholer, Lori; Scheible, Kristin M; Lee, Yi-Horng; Caserta, Mary T; Pryhuber, Gloria S; Gill, Steven R

2017-12-11

Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.

Growth is required for perception of water availability to pattern root branches in plants.

PubMed

Robbins, Neil E; Dinneny, José R

2018-01-23

Water availability is a potent regulator of plant development and induces root branching through a process termed hydropatterning. Hydropatterning enables roots to position lateral branches toward regions of high water availability, such as wet soil or agar media, while preventing their emergence where water is less available, such as in air. The mechanism by which roots perceive the spatial distribution of water during hydropatterning is unknown. Using primary roots of Zea mays (maize) we reveal that developmental competence for hydropatterning is limited to the growth zone of the root tip. Past work has shown that growth generates gradients in water potential across an organ when asymmetries exist in the distribution of available water. Using mathematical modeling, we predict that substantial growth-sustained water potential gradients are also generated in the hydropatterning competent zone and that such biophysical cues inform the patterning of lateral roots. Using diverse chemical and environmental treatments we experimentally demonstrate that growth is necessary for normal hydropatterning of lateral roots. Transcriptomic characterization of the local response of tissues to a moist surface or air revealed extensive regulation of signaling and physiological pathways, some of which we show are growth-dependent. Our work supports a "sense-by-growth" mechanism governing hydropatterning, by which water availability cues are rendered interpretable through growth-sustained water movement. Copyright © 2018 the Author(s). Published by PNAS.

Exposure of Arabidopsis thaliana to Hypobaric Environments: Implications for Low-Pressure Bioregenerative Life Support Systems for Human Exploration Missions and Terraforming on Mars

NASA Astrophysics Data System (ADS)

Richards, Jeffrey T.; Corey, Kenneth A.; Paul, Anna-Lisa; Ferl, Robert J.; Wheeler, Raymond M.; Schuerger, Andrew C.

2006-12-01

Understanding how hypobaria can affect net photosynthetic (P net) and net evapotranspiration rates of plants is important for the Mars Exploration Program because low-pressured environments may be used to reduce the equivalent system mass of near-term plant biology experiments on landers or future bioregenerative advanced life support systems. Furthermore, introductions of plants to the surface of a partially terraformed Mars will be constrained by the limits of sustainable growth and reproduction of plants to hypobaric conditions. To explore the effects of hypobaria on plant physiology, a low-pressure growth chamber (LPGC) was constructed that maintained hypobaric environments capable of supporting short-term plant physiological studies. Experiments were conducted on Arabidopsis thaliana maintained in the LPGC with total atmospheric pressures set at 101 (Earth sea-level control), 75, 50, 25 or 10 kPa. Plants were grown in a separate incubator at 101 kPa for 6 weeks, transferred to the LPGC, and acclimated to low-pressure atmospheres for either 1 or 16 h. After 1 or 16 h of acclimation, CO2 levels were allowed to drawdown from 0.1 kPa to CO2 compensation points to assess P net rates under different hypobaric conditions. Results showed that P net increased as the pressures decreased from 101 to 10 kPa when CO2 partial pressure (pp) values were below 0.04 kPa (i.e., when ppCO2 was considered limiting). In contrast, when ppCO2 was in the nonlimiting range from 0.10 to 0.07 kPa, the P net rates were insensitive to decreasing pressures. Thus, if CO2 concentrations can be kept elevated in hypobaric plant growth modules or on the surface of a partially terraformed Mars, P net rates may be relatively unaffected by hypobaria. Results support the conclusions that (i) hypobaric plant growth modules might be operated around 10 kPa without undue inhibition of photosynthesis and (ii) terraforming efforts on Mars might require a surface pressure of at least 10 kPa (100 mb) for normal growth of deployed plant species.

Exposure of Arabidopsis thaliana to hypobaric environments: implications for low-pressure bioregenerative life support systems for human exploration missions and terraforming on Mars.

PubMed

Richards, Jeffrey T; Corey, Kenneth A; Paul, Anna-Lisa; Ferl, Robert J; Wheeler, Raymond M; Schuerger, Andrew C

2006-12-01

Understanding how hypobaria can affect net photosynthetic (P (net)) and net evapotranspiration rates of plants is important for the Mars Exploration Program because low-pressured environments may be used to reduce the equivalent system mass of near-term plant biology experiments on landers or future bioregenerative advanced life support systems. Furthermore, introductions of plants to the surface of a partially terraformed Mars will be constrained by the limits of sustainable growth and reproduction of plants to hypobaric conditions. To explore the effects of hypobaria on plant physiology, a low-pressure growth chamber (LPGC) was constructed that maintained hypobaric environments capable of supporting short-term plant physiological studies. Experiments were conducted on Arabidopsis thaliana maintained in the LPGC with total atmospheric pressures set at 101 (Earth sea-level control), 75, 50, 25 or 10 kPa. Plants were grown in a separate incubator at 101 kPa for 6 weeks, transferred to the LPGC, and acclimated to low-pressure atmospheres for either 1 or 16 h. After 1 or 16 h of acclimation, CO(2) levels were allowed to drawdown from 0.1 kPa to CO(2) compensation points to assess P (net) rates under different hypobaric conditions. Results showed that P (net) increased as the pressures decreased from 101 to 10 kPa when CO(2) partial pressure (pp) values were below 0.04 kPa (i.e., when ppCO2 was considered limiting). In contrast, when ppCO(2) was in the nonlimiting range from 0.10 to 0.07 kPa, the P (net) rates were insensitive to decreasing pressures. Thus, if CO(2 )concentrations can be kept elevated in hypobaric plant growth modules or on the surface of a partially terraformed Mars, P (net) rates may be relatively unaffected by hypobaria. Results support the conclusions that (i) hypobaric plant growth modules might be operated around 10 kPa without undue inhibition of photosynthesis and (ii) terraforming efforts on Mars might require a surface pressure of at least 10 kPa (100 mb) for normal growth of deployed plant species.

Trajectory and correlates of growth of extremely-low-birth-weight adolescents.

PubMed

Hack, Maureen; Schluchter, Mark; Margevicius, Seunghee; Andreias, Laura; Taylor, H Gerry; Cuttler, Leona

2014-02-01

Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch up among extremely-low-birth-weight (ELBW) (<1 kg) adolescents. A cohort study of 148 neurologically normal ELBW children and 115 normal-birth-weight (NBW) controls born during the period 1992-1995 was conducted. Longitudinal measures of gender-specific growth of ELBW children from birth, in addition to growth and measures of obesity of ELBW and NBW children at 14 y, were evaluated. Following neonatal growth failure, ELBW children had accelerated growth, but at 8 y, they still had lower weight and height z scores than NBW children. By 14 y, ELBW boys had caught up in growth to their NBW controls, but ELBW girls remained significantly smaller. ELBW children, however, did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses, only maternal BMI and weight gain during infancy and childhood predicted the ELBW children's 14-y weight z scores, BMI z scores, and abdominal circumference. Perinatal risk factors, including intrauterine growth, only predicted growth up to 20 mo. Maternal BMI and rate of growth, rather than perinatal factors, predict 14-y obesity among neurologically normal ELBW adolescents.

Immobilization and Application of Electrospun Nanofiber Scaffold-based Growth Factor in Bone Tissue Engineering.

PubMed

Chen, Guobao; Lv, Yonggang

2015-01-01

Electrospun nanofibers have been extensively used in growth factor delivery and regenerative medicine due to many advantages including large surface area to volume ratio, high porosity, excellent loading capacity, ease of access and cost effectiveness. Their relatively large surface area is helpful for cell adhesion and growth factor loading, while storage and release of growth factor are essential to guide cellular behaviors and tissue formation and organization. In bone tissue engineering, growth factors are expected to transmit signals that stimulate cellular proliferation, migration, differentiation, metabolism, apoptosis and extracellular matrix (ECM) deposition. Bolus administration is not always an effective method for the delivery of growth factors because of their rapid diffusion from the target site and quick deactivation. Therefore, the integration of controlled release strategy within electrospun nanofibers can provide protection for growth factors against in vivo degradation, and can manipulate desired signal at an effective level with extended duration in local microenvironment to support tissue regeneration and repair which normally takes a much longer time. In this review, we provide an overview of growth factor delivery using biomimetic electrospun nanofiber scaffolds in bone tissue engineering. It begins with a brief introduction of different kinds of polymers that were used in electrospinning and their applications in bone tissue engineering. The review further focuses on the nanofiber-based growth factor delivery and summarizes the strategies of growth factors loading on the nanofiber scaffolds for bone tissue engineering applications. The perspectives on future challenges in this area are also pointed out.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

PubMed

McGeachie, M J; Yates, K P; Zhou, X; Guo, F; Sternberg, A L; Van Natta, M L; Wise, R A; Szefler, S J; Sharma, S; Kho, A T; Cho, M H; Croteau-Chonka, D C; Castaldi, P J; Jain, G; Sanyal, A; Zhan, Y; Lajoie, B R; Dekker, J; Stamatoyannopoulos, J; Covar, R A; Zeiger, R S; Adkinson, N F; Williams, P V; Kelly, H W; Grasemann, H; Vonk, J M; Koppelman, G H; Postma, D S; Raby, B A; Houston, I; Lu, Q; Fuhlbrigge, A L; Tantisira, K G; Silverman, E K; Tonascia, J; Weiss, S T; Strunk, R C

2016-05-12

Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

The effects of early-life seizures on hippocampal dendrite development and later-life learning and memory.

PubMed

Casanova, J R; Nishimura, Masataka; Swann, John W

2014-04-01

Severe childhood epilepsy is commonly associated with intellectual developmental disabilities. The reasons for these cognitive deficits are likely multifactorial and will vary between epilepsy syndromes and even among children with the same syndrome. However, one factor these children have in common is the recurring seizures they experience - sometimes on a daily basis. Supporting the idea that the seizures themselves can contribute to intellectual disabilities are laboratory results demonstrating spatial learning and memory deficits in normal mice and rats that have experienced recurrent seizures in infancy. Studies reviewed here have shown that seizures in vivo and electrographic seizure activity in vitro both suppress the growth of hippocampal pyramidal cell dendrites. A simplification of dendritic arborization and a resulting decrease in the number and/or properties of the excitatory synapses on them could help explain the observed cognitive disabilities. There are a wide variety of candidate mechanisms that could be involved in seizure-induced growth suppression. The challenge is designing experiments that will help focus research on a limited number of potential molecular events. Thus far, results suggest that growth suppression is NMDA receptor-dependent and associated with a decrease in activation of the transcription factor CREB. The latter result is intriguing since CREB is known to play an important role in dendrite growth. Seizure-induced dendrite growth suppression may not occur as a single process in which pyramidal cells dendrites simply stop growing or grow slower compared to normal neurons. Instead, recent results suggest that after only a few hours of synchronized epileptiform activity in vitro dendrites appear to partially retract. This acute response is also NMDA receptor dependent and appears to be mediated by the Ca(+2)/calmodulin-dependent phosphatase, calcineurin. An understanding of the staging of seizure-induced growth suppression and the underlying molecular mechanisms will likely prove crucial for developing therapeutic strategies aimed at ameliorating the intellectual developmental disabilities associated with intractable childhood epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Mutations in the NHEJ Component XRCC4 Cause Primordial Dwarfism

PubMed Central

Murray, Jennie E.; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S.; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A.; Graham, Gail E.; Ranza, Emmanuelle; Blundell, Tom L.; Jackson, Andrew P.; Stewart, Grant S.; Bicknell, Louise S.

2015-01-01

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. PMID:25728776

Gravitational Effects on Reproduction, Growth, and Development of Mammals

NASA Technical Reports Server (NTRS)

Oyama, J.

1985-01-01

The broad objective of this research program is to determine the role which gravity plays in the growth and development of mammalian animals. Current studies are focused on the effects of graded hypergravitatinal field intensities on mice, rats and other small sized laboratory animals using the chronic centrifugation technique. They include studies on reproduction and prenatal and postnatel growth and development. Among the important questions addressed are: (1) what stage or stages in animal development are affected by hypergravity and what are the effects? (2) is there a minimum or critical body size for hypergravity to produce a significant effect on growth and development? (3) are there field intensity thresholds for the preceding questions? From analysis of the body masses at birth of rats conceived and allowed to undergo gestation under 2.1G and under normal gravity (1G), it was found that there was no significant difference between the two groups. Futhermore, their growth rates postnatally were the same until they reached a body mass of approximately 50 grams when the 2.1G group showed a significantly slower rate. Results from these studies support the conclusion that prenatal as well as the early postnatal stages of growth and development of the rat are refractory to hyper-G.

GENOMIC IMPRINTING, DISRUPTED PLACENTAL EXPRESSION, AND SPECIATION

PubMed Central

Brekke, Thomas D.; Henry, Lindy A.; Good, Jeffrey M.

2016-01-01

The importance of regulatory incompatibilities to the early stages of speciation remains unclear. Hybrid mammals often show extreme parent-of-origin growth effects that are thought to be a consequence of disrupted genetic imprinting (parent-specific epigenetic gene silencing) during early development. Here we test the long-standing hypothesis that abnormal hybrid growth reflects disrupted gene expression due to loss of imprinting (LOI) in hybrid placentas, resulting in dosage imbalances between paternal growth factors and maternal growth repressors. We analyzed placental gene expression in reciprocal dwarf hamster hybrids that show extreme parent-of-origin growth effects relative to their parental species. In massively enlarged hybrid placentas, we observed both extensive transgressive expression of growth-related genes and bi-allelic expression of many genes that were paternally silenced in normal sized hybrids. However, the apparent widespread disruption of paternal silencing was coupled with reduced gene expression levels overall. These patterns are contrary to the predictions of the LOI model and indicate that hybrid misexpression of dosage sensitive genes is caused by other regulatory mechanisms in this system. Collectively, our results support a central role for disrupted gene expression and imprinting in the evolution of mammalian hybrid inviability, but call into question the generality of the widely invoked LOI model. PMID:27714796

Rapid Engineering of Three-Dimensional, Multicellular Tissues With Polymeric Scaffolds

NASA Technical Reports Server (NTRS)

Gonda, Steve R.; Jordan, Jacqueline; Fraga, Denise N.

2007-01-01

A process has been developed for the rapid tissue engineering of multicellular-tissue-equivalent assemblies by the controlled enzymatic degradation of polymeric beads in a low-fluid-shear bioreactor. In this process, the porous polymeric beads serve as temporary scaffolds to support the assemblies of cells in a tissuelike 3D configuration during the critical initial growth phases of attachment of anchorage-dependent cells, aggregation of the cells, and formation of a 3D extracellular matrix. Once the cells are assembled into a 3D array and enmeshed in a structural supportive 3D extracellular matrix (ECM), the polymeric scaffolds can be degraded in the low-fluid-shear environment of the NASA-designed bioreactor. The natural 3D tissuelike assembly, devoid of any artificial support structure, is maintained in the low-shear bioreactor environment by the newly formed natural cellular/ECM. The elimination of the artificial scaffold allows normal tissue structure and function.

9-AAA inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.

PubMed

Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew

2016-11-01

The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-AAA) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-AAA had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-AAA, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-AAA. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-AAA show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.

Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency.

PubMed

Mazzola, A; Meazza, C; Travaglino, P; Pagani, S; Frattini, D; Bozzola, E; Corneli, G; Aimaretti, G; Bozzola, M

2008-02-01

In this study we investigated 9 prepubertal children with blunted GH response to classic pharmacological stimuli in contrast with normal auxological evaluation. The children were followed to evaluate their growth velocity for a longer period before starting replacement GH therapy. To evaluate the pituitary reserve a supraphysiologic stimulus such as GHRH plus arginine was used. Serum GH levels were measured by a time-resolved immunofluorimetric assay before and after 1 microg/kg body weight iv injection of GHRH, while serum PRL, IGF-I, and insulin were evaluated only in basal conditions using an automatic immunometric assay. Out of 9 studied subjects, 7 underwent GHRH plus arginine administration and showed a normal GH response; the parents of the remaining 2 children refused the test. Normal serum levels of PRL, IGF-I, insulin, and a normal insulin sensitivity were observed in all children. After 1 yr, the growth rate in each patient was further improved and reached almost normal values. Our results further confirm that the decision to start replacement GH therapy should be based on both auxological parameters and laboratory findings. The GHRH plus arginine test appears to be useful to identify false GH deficiency in children showing a blunted GH response to classic stimuli in contrast with normal growth rate.

Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

PubMed Central

Shi, Xiao-Lei; Gu, Jin-Yang; Zhang, Yue; Han, Bing; Xiao, Jiang-Qiang; Yuan, Xian-Wen; Zhang, Ning; Ding, Yi-Tao

2011-01-01

AIM: To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-on-chronic liver failure (ACLF) patients. METHODS: Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemokine profile was also examined for the normal serum and liver failure serum. RESULTS: Hepatocyte growth factor (HGF) and Tumor necrosis factor; tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver support functions in the homo-hepatocyte culture. Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro. In addition, co-cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum. CONCLUSION: ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro. PMID:21633639

Comparison and evaluation of gene therapy and epigenetic approaches for wound healing.

PubMed

Cutroneo, K R; Chiu, J F

2000-01-01

During the past decade considerable evidence has mounted concerning the importance of growth factors in the wound healing process both for cell replication and for stimulating reparative cells to synthesize and secrete extracellular matrix components. During normal wound healing the growth factor concentration has to be maintained at a certain level. If the growth factor concentration is too low, normal healing fails to occur. Whereas if the growth factor concentration is too high due to either over-expression of the growth factor or too much growth factor being applied to the wound, aberrant wound healing will occur. One approach for controlling the amount of growth factor at the wound site during normal healing is through gene therapy and the titration of gene dosage. However if a narrow window exists between the beneficial therapeutic effect and toxic effects with increasing gene dosage, an agent may be necessary to give in combination with gene therapy to regulate the over-expression of growth factor. In addition to genetic approaches to regulate wound healing, epigenetic approaches also exist. Antisense oligodeoxynucleotides have been shown to regulate wound repair in certain model systems and to determine the protein(s) necessary for normal wound healing. A novel approach to regulate the activity of collagen genes, thereby affecting fibrosis, is to use a sense oligodeoxynucleotide having the same sequence of the cis element which regulates the promoter activity of a particular collagen gene. This exogenous oligodeoxynucleotide will compete with the cis element in the collagen gene for the trans-acting factor which regulates promoter activity. These epigenetic approaches afford the opportunity to regulate over-expression of growth factor and therefore preclude the potential toxic effects of gene therapy. Both genetic and epigenetic approaches for regulating the wound healing process, either normal or aberrant wound healing, have certain advantages and disadvantages which are discussed in the present article.

[Relationship between breast milk composition and weight growth velocity of infants fed with exclusive breast milk].

PubMed

Huang, Li-Li; Xiong, Fei; Yang, Fan

2016-10-01

To study the effect of breast milk composition on weight growth velocity of infants fed with exclusive breast milk. One hundred and thirty-eight full-term singleton infants who received regular follow-up visits and fed with exclusive breast milk and their mothers were recruited. Body height, weight and head circumference of these infants were measured at regular visits. Z scores were used to evaluate growth velocity. The subjects were classified into a failure to thrive group (ΔZ scores≤-0.67), a poor growth group (-0.67<ΔZ scores<0) and a normal control group (ΔZ scores≥0). The samples of mature breast milk were collected for composition analysis. The differences in the levels of the protein, fats, energy, carbohydrates and minerals in breast milk were compared among the three groups. ΔZ scores for weight in the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). There was no significant difference in the levels of protein, fats and energy in breast milk among the failure to thrive, poor growth and normal control groups. However, the levels of carbohydrates and minerals in both the failure to thrive and poor growth groups were lower than in the normal control group (P<0.05). Weight growth velocity of infants can be affected by the composition of breast milk to a certain degree in a short period. In order to maintain a good weight growth velocity of infants, mothers should have a balanced diet to improve the quality of breast milk.

Economics of Future Growth in Photovoltaics Manufacturing

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

Basore, Paul A.; Chung, Donald; Buonassisi, Tonio

2015-06-14

The past decade's record of growth in the photovoltaics manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life ofmore » the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.« less

Plasma-electric field controlled growth of oriented graphene for energy storage applications

NASA Astrophysics Data System (ADS)

Ghosh, Subrata; Polaki, S. R.; Kamruddin, M.; Jeong, Sang Mun; (Ken Ostrikov, Kostya

2018-04-01

It is well known that graphene grows as flat sheets aligned with the growth substrate. Oriented graphene structures typically normal to the substrate have recently attracted major attention. Most often, the normal orientation is achieved in a plasma-assisted growth and is believed to be due to the plasma-induced in-built electric field, which is usually oriented normal to the substrate. This work focuses on the effect of an in-built electric field on the growth direction, morphology, interconnectedness, structural properties and also the supercapacitor performance of various configurations of graphene structures and reveals the unique dependence of these features on the electric field orientation. It is shown that tilting of growth substrates from parallel to the normal direction with respect to the direction of in-built plasma electric field leads to the morphological transitions from horizontal graphene layers, to oriented individual graphene sheets and then interconnected 3D networks of oriented graphene sheets. The revealed transition of the growth orientation leads to a change in structural properties, wetting nature, types of defect in graphitic structures and also affects their charge storage capacity when used as supercapacitor electrodes. This simple and versatile approach opens new opportunities for the production of potentially large batches of differently oriented and structured graphene sheets in one production run.

Oscillatory Increases in Alkalinity Anticipate Growth and May Regulate Actin Dynamics in Pollen Tubes of Lily[W][OA

PubMed Central

Lovy-Wheeler, Alenka; Kunkel, Joseph G.; Allwood, Ellen G.; Hussey, Patrick J.; Hepler, Peter K.

2006-01-01

Lily (Lilium formosanum or Lilium longiflorum) pollen tubes, microinjected with a low concentration of the pH-sensitive dye bis-carboxyethyl carboxyfluorescein dextran, show oscillating pH changes in their apical domain relative to growth. An increase in pH in the apex precedes the fastest growth velocities, whereas a decline follows growth, suggesting a possible relationship between alkalinity and cell extension. A target for pH may be the actin cytoskeleton, because the apical cortical actin fringe resides in the same region as the alkaline band in lily pollen tubes and elongation requires actin polymerization. A pH-sensitive actin binding protein, actin-depolymerizing factor (ADF), together with actin-interacting protein (AIP) localize to the cortical actin fringe region. Modifying intracellular pH leads to reorganization of the actin cytoskeleton, especially in the apical domain. Acidification causes actin filament destabilization and inhibits growth by 80%. Upon complete growth inhibition, the actin fringe is the first actin cytoskeleton component to disappear. We propose that during normal growth, the pH increase in the alkaline band stimulates the fragmenting activity of ADF/AIP, which in turn generates more sites for actin polymerization. Increased actin polymerization supports faster growth rates and a proton influx, which inactivates ADF/AIP, decreases actin polymerization, and retards growth. As pH stabilizes and increases, the activity of ADF/AIP again increases, repeating the cycle of events. PMID:16920777

A frozen-thawed in vitro-matured bovine oocyte derived calf with normal growth and fertility.

PubMed

Otoi, T; Yamamoto, K; Koyama, N; Tachikawa, S; Suzuki, T

1996-08-01

The growth and fertility of a female calf obtained from a frozen-thawed bovine oocyte was assessed. The birth weight of the calf was lower than the mean birth weight of calves from in vitro fertilized embryos (IVF-controls) and calves obtained by artificial insemination (AI-controls). The growth rate of the calf up to 6 months was slower than that of the IVF-controls, but similar to that of the AI-controls. When the calf developed into a heifer (200 kg), she was inseminated with frozen semen and 280 days later delivered a male calf. The chromosoms of this cow were normal. These findings suggest that the growth and fertility of the calf derived from the frozen oocyte are normal.

Optical aberrations, retinal image quality and eye growth: Experimentation and modeling

NASA Astrophysics Data System (ADS)

Tian, Yibin

2007-12-01

Retinal image quality is important for normal eye growth. Optical aberrations are of interest for two reasons: first, they degrade retinal images; second, they might provide some cues to defocus. Higher than normal ocular aberrations have been previously associated with human myopia. However, these studies were cross-sectional in design, and only reported aberrations in terms of root mean square (RMS) errors of Zernike coefficients, a poor metric of optical quality. This dissertation presents results from investigations of ocular optical aberrations, retinal image quality and eye growth in chicks and humans. A number of techniques were utilized, including Shack-Hartmann aberrometry, high-frequency A-scan ultrasonography, ciliary nerve section (CNX), photorefractive keratectomy (PRK) as well as computer simulations and modeling. A technique to extract light scatter information from Shack-Hartmann images was also developed. The main findings of the dissertation are summarized below. In young chicks, most ocular aberrations decreased with growth in both normal and CNX eyes, and there were diurnal fluctuations in some aberrations. Modeling suggested active reduction in higher order aberrations (HOAs) during early development. Although CNX eyes manifested greater than normal HOAs, they showed near normal growth. Retinal image degradation varied greatly among individual eyes post-PRK in young chicks. Including light scatter information into analyses of retinal image quality better estimated the latter. Albino eyes showed more severe retinal image degradation than normal eyes, due to increased optical aberrations and light scatter, but their growth was similar to those of normal eyes, implying that they are relatively insensitive to retina image quality. Although the above results questioned the influence of optical aberrations on early ocular growth, some optical quality metrics, derived from optical aberrations data, could predict how much the eyes of young chicks subsequently elongated. The performance of some focus measures was very poor when non-defocus aberrations exceeded a certain level; presumably, these non-defocus aberrations might interfere with the eye's ability to interpret defocus. In anisomyopic human adults, more myopic eyes had larger anterior and vitreous chambers, greater astigmatism, and more positive spherical aberration. However, compared to isometropes, only interocular differences in spherical equivalent refractive errors were significantly increased.

Growth and development after hematopoietic cell transplant in children.

PubMed

Sanders, J E

2008-01-01

Hematopoietic cell transplantation (HCT) following high-dose chemotherapy or chemoradiotherapy for children with malignant or nonmalignant hematologic disorders has resulted in an increasing number of long-term disease-free survivors. The preparative regimens include high doses of alkylating agents, such as CY with or without BU, and may include TBI. These agents impact the neuroendocrine system in growing children and their subsequent growth and development. Children receiving high-dose CY or BUCY have normal thyroid function, but those who receive TBI-containing regimens may develop thyroid function abnormalities. Growth is not impacted by chemotherapy-only preparative regimens, but TBI is likely to result in growth hormone deficiency and decreased growth rates that need to be treated with synthetic growth hormone therapy. Children who receive high-dose CY-only have normal development through puberty, whereas those who receive BUCY have a high incidence of delayed pubertal development. Following fractionated TBI preparative regimens, approximately half of the patients have normal pubertal development. These data demonstrate that the growth and development problems after HCT are dependent upon the preparative regimen received. All children should be followed for years after HCT for detection of growth and development abnormalities that are treatable with appropriate hormone therapy.

Difference in C3-C4 metabolism underlies tradeoff between growth rate and biomass yield in Methylobacterium extorquens AM1.

PubMed

Fu, Yanfen; Beck, David A C; Lidstrom, Mary E

2016-07-19

Two variants of Methylobacterium extorquens AM1 demonstrated a trade-off between growth rate and biomass yield. In addition, growth rate and biomass yield were also affected by supplementation of growth medium with different amounts of cobalt. The metabolism changes relating to these growth phenomena as well as the trade-off were investigated in this study. (13)C metabolic flux analysis was used to generate a detailed central carbon metabolic flux map with both absolute and normalized flux values. The major differences between the two variants occurred at the formate node as well as within C3-C4 inter-conversion pathways. Higher relative fluxes through formyltetrahydrofolate ligase, phosphoenolpyruvate carboxylase, and malic enzyme led to higher biomass yield, while higher relative fluxes through pyruvate kinase and pyruvate dehydrogenase led to higher growth rate. These results were then tested by phenotypic studies on three mutants (null pyk, null pck mutant and null dme mutant) in both variants, which agreed with the model prediction. In this study, (13)C metabolic flux analysis for two strain variants of M. extorquens AM1 successfully identified metabolic pathways contributing to the trade-off between cell growth and biomass yield. Phenotypic analysis of mutants deficient in corresponding genes supported the conclusion that C3-C4 inter-conversion strategies were the major response to the trade-off.

Direct uptake of canopy rainwater causes turgor-driven growth spurts in the mangrove Avicennia marina.

PubMed

Steppe, Kathy; Vandegehuchte, Maurits W; Van de Wal, Bart A E; Hoste, Pieter; Guyot, Adrien; Lovelock, Catherine E; Lockington, David A

2018-03-17

Mangrove forests depend on a dense structure of sufficiently large trees to fulfil their essential functions as providers of food and wood for animals and people, CO2 sinks and protection from storms. Growth of these forests is known to be dependent on the salinity of soil water, but the influence of foliar uptake of rainwater as a freshwater source, additional to soil water, has hardly been investigated. Under field conditions in Australia, stem diameter variation, sap flow and stem water potential of the grey mangrove (Avicennia marina (Forssk.) Vierh.) were simultaneously measured during alternating dry and rainy periods. We found that sap flow in A. marina was reversed, from canopy to roots, during and shortly after rainfall events. Simultaneously, stem diameters rapidly increased with growth rates up to 70 μm h-1, which is about 25-75 times the normal growth rate reported in temperate trees. A mechanistic tree model was applied to provide evidence that A. marina trees take up water through their leaves, and that this water contributes to turgor-driven stem growth. Our results indicate that direct uptake of freshwater by the canopy during rainfall supports mangrove tree growth and serve as a call to consider this water uptake pathway if we aspire to correctly assess influences of changing rainfall patterns on mangrove tree growth.

Growth is required for perception of water availability to pattern root branches in plants

PubMed Central

2018-01-01

Water availability is a potent regulator of plant development and induces root branching through a process termed hydropatterning. Hydropatterning enables roots to position lateral branches toward regions of high water availability, such as wet soil or agar media, while preventing their emergence where water is less available, such as in air. The mechanism by which roots perceive the spatial distribution of water during hydropatterning is unknown. Using primary roots of Zea mays (maize) we reveal that developmental competence for hydropatterning is limited to the growth zone of the root tip. Past work has shown that growth generates gradients in water potential across an organ when asymmetries exist in the distribution of available water. Using mathematical modeling, we predict that substantial growth-sustained water potential gradients are also generated in the hydropatterning competent zone and that such biophysical cues inform the patterning of lateral roots. Using diverse chemical and environmental treatments we experimentally demonstrate that growth is necessary for normal hydropatterning of lateral roots. Transcriptomic characterization of the local response of tissues to a moist surface or air revealed extensive regulation of signaling and physiological pathways, some of which we show are growth-dependent. Our work supports a “sense-by-growth” mechanism governing hydropatterning, by which water availability cues are rendered interpretable through growth-sustained water movement. PMID:29317538

Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes

PubMed Central

Ericson, Megan E.; Frank, Matthew W.

2016-01-01

Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogen Listeria monocytogenes encode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype of Escherichia coli strain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate of L. monocytogenes in laboratory medium. Robust exogenous fatty acid incorporation was not detected in L. monocytogenes unless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth of L. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth of L. monocytogenes. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth of L. monocytogenes. PMID:27736774

Growth and Remodeling in Blood Vessels Studied In Vivo With Fractal Analysis

NASA Technical Reports Server (NTRS)

Parsons-Wingerter, Patricia A.

2003-01-01

Every cell in the human body must reside in close proximity to a blood vessel (within approximately 200 mm) because blood vessels provide the oxygen, metabolite, and fluid exchanges required for cellular existence. The growth and remodeling of blood vessels are required to support the normal physiology of embryonic development, reproductive biology, wound healing and adaptive remodeling to exercise, as well as abnormal tissue change in diseases such as cancer, diabetes, and coronary heart disease. Cardiovascular and hemodynamic (blood flow dynamics) alterations experienced by astronauts during long-term spaceflight, including orthostatic intolerance, fluid shifts in the body, and reduced numbers of red (erythrocyte) and white (immune) blood cells, are identified as risk factors of very high priority in the NASA task force report on risk reduction for human spaceflight, the "Critical Path Roadmap."

FoxA and LIPG endothelial lipase control the uptake of extracellular lipids for breast cancer growth

PubMed Central

Slebe, Felipe; Rojo, Federico; Vinaixa, Maria; García-Rocha, Mar; Testoni, Giorgia; Guiu, Marc; Planet, Evarist; Samino, Sara; Arenas, Enrique J.; Beltran, Antoni; Rovira, Ana; Lluch, Ana; Salvatella, Xavier; Yanes, Oscar; Albanell, Joan; Guinovart, Joan J.; Gomis, Roger R.

2016-01-01

The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report that BCa cells are dependent on a mechanism to supply precursors for intracellular lipid production derived from extracellular sources and that the endothelial lipase (LIPG) fulfils this function. LIPG expression allows the import of lipid precursors, thereby contributing to BCa proliferation. LIPG stands out as an essential component of the lipid metabolic adaptations that BCa cells, and not normal tissue, must undergo to support high proliferation rates. LIPG is ubiquitously and highly expressed under the control of FoxA1 or FoxA2 in all BCa subtypes. The downregulation of either LIPG or FoxA in transformed cells results in decreased proliferation and impaired synthesis of intracellular lipids. PMID:27045898

Growth impairment due to transient hypercortisolism.

PubMed

Armour, K; Chalew, S; Kowarski, A A

1986-01-01

Cushing's syndrome in childhood is generally recognized by classical features such as truncal obesity, striae, easy bruising, moon facies, hypertension and growth retardation. Exceptionally, Cushing's syndrome has been reported to present as growth failure alone. We diagnosed transient hypercortisolism in 6 children who had poor growth as their only presenting abnormality. The 6 children all had integrated concentrations of cortisols (IC-F) (14.1 +/- 1.7 micrograms/dl; mean +/- 1 SD) which exceeded the IC-F in healthy children and adults (5.7 +/- 1.5 micrograms/dl; P less than 0.001). The IC-F of these 6 index cases overlapped the range of IC-F in patients with pathologically proven Cushing's syndrome (20.2 +/- 4.7 micrograms/dl). Four of the 6 patients were treated with human growth hormone for 8 months and showed a marked improvement in their growth rates. Four patients have entered puberty and are growing at normal rates. Three of the 6 children had normal repeat IC-Fs, subsequently, at a time they had normal growth rates. In 1-1/2 to 3 years of follow-up, none of the patients developed any other stigmata of Cushing's syndrome. We conclude that transient hypercortisolism, documented by the IC-F, may cause growth failure without other symptoms of Cushing's syndrome. Growth hormone therapy may improve the growth rate of these children at the time of their poor growth.

QRC Evaluation of Materials and Processes.

DTIC Science & Technology

1982-10-01

Fatigue Crack Growth Data for Normal and "Soft" Aluminum 2024 - T351 65 27...Spectrum Fatigue Crack Growth Data for Normal and "Soft" Aluminum 7075-T651 66 28 Constant Amplitude FCGR Data for Normal and "Soft" Aluminum 2024 - T351 67...in Figure 29. The same trends observed in the spectrum fatigue tests are repeated in the S constant amplitude data: for aluminum 2024 - T351 , the

The epidermal growth factor receptor (EGF-R) is present on the basolateral, but not the apical, surface of enterocytes in the human gastrointestinal tract.

PubMed Central

Playford, R J; Hanby, A M; Gschmeissner, S; Peiffer, L P; Wright, N A; McGarrity, T

1996-01-01

BACKGROUND: While it is clear that luminal epidermal growth factor (EGF) stimulates repair of the damaged bowel, its significance in maintaining normal gut growth remains uncertain. If EGF is important in maintaining normal gut growth, the EGF receptor (EGF-R) should be present on the apical (luminal) surface in addition to the basolateral surface. AIMS/SUBJECTS/METHODS: This study examined the distribution of the EGF-R in the epithelium throughout the human gastro-intestinal tract using immunohistochemistry, electron microscopy, and western blotting of brush border preparations. RESULTS: Immunostaining of the oesophagus showed circumferential EGF-R positivity in the cells of the basal portions of the stratified squamous epithelium but surface cells were EGF-R negative. In the normal stomach, small intestine, and colon, immunostaining localised the receptor to the basolateral surface with the apical membranes being consistently negative. EGF-R positivity within the small intestine appeared to be almost entirely restricted to the proliferative (crypt) region. Western blotting demonstrated a 170 kDa protein in whole tissue homogenates but not in the brush border vesicle preparations. CONCLUSIONS: As the EGF-R is located only on the basolateral surfaces in the normal adult gastrointestinal tract, the major role of luminal EGF is probably to stimulate repair rather than to maintain normal gut growth. Images Figure 1 Figure 2 Figure 3 PMID:8977341

Paths to future growth in photovoltaics manufacturing

DOE PAGES

Basore, Paul A.

2016-03-01

The past decade has seen rapid growth in the photovoltaics industry, followed in the past few years by a period of much slower growth. A simple model that is consistent with this historical record can be used to predict the future evolution of the industry. Two key parameters are identified that determine the outcome. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units dollar/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service lifemore » of the assets (capacity-normalized capital demand rate, CapDR, units dollar/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a modest improvement in CapIR to ensure future growth in photovoltaics. Here, several approaches are presented that can enable the required improvement in CapIR. If, in addition, there is an accompanying improvement in CapDR, the rate of growth can be substantially accelerated.« less

Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance.

PubMed

Mita, Sakura; de Monasterio-Schrader, Patricia; Fünfschilling, Ursula; Kawasaki, Takahiko; Mizuno, Hidenobu; Iwasato, Takuji; Nave, Klaus-Armin; Werner, Hauke B; Hirata, Tatsumi

2015-11-01

The function of mature neurons critically relies on the developmental outgrowth and projection of their cellular processes. It has long been postulated that the neuronal glycoproteins M6a and M6b are involved in axon growth because these four-transmembrane domain-proteins of the proteolipid protein family are highly enriched on growth cones, but in vivo evidence has been lacking. Here, we report that the function of M6 proteins is required for normal axonal extension and guidance in vivo. In mice lacking both M6a and M6b, a severe hypoplasia of axon tracts was manifested. Most strikingly, the corpus callosum was reduced in thickness despite normal densities of cortical projection neurons. In single neuron tracing, many axons appeared shorter and disorganized in the double-mutant cortex, and some of them were even misdirected laterally toward the subcortex. Probst bundles were not observed. Upon culturing, double-mutant cortical and cerebellar neurons displayed impaired neurite outgrowth, indicating a cell-intrinsic function of M6 proteins. A rescue experiment showed that the intracellular loop of M6a is essential for the support of neurite extension. We propose that M6 proteins are required for proper extension and guidance of callosal axons that follow one of the most complex trajectories in the mammalian nervous system. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

FGF7 supports hematopoietic stem and progenitor cells and niche-dependent myeloblastoma cells via autocrine action on bone marrow stromal cells in vitro

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

Ishino, Ruri; Minami, Kaori; Tanaka, Satowa

2013-10-11

Highlights: •FGF7 is downregulated in MED1-deficient mesenchymal cells. •FGF7 produced by mesenchymal stromal cells is a novel hematopoietic niche molecule. •FGF7 supports hematopoietic progenitor cells and niche-dependent leukemia cells. •FGF7 activates FGFR2IIIb of bone marrow stromal cells in an autocrine manner. •FGF7 indirectly acts on hematopoietic cells lacking FGFR2IIIb via stromal cells. -- Abstract: FGF1 and FGF2 support hematopoietic stem and progenitor cells (HSPCs) under stress conditions. In this study, we show that fibroblast growth factor (FGF7) may be a novel niche factor for HSPC support and leukemic growth. FGF7 expression was attenuated in mouse embryonic fibroblasts (MEFs) deficient formore » the MED1 subunit of the Mediator transcriptional coregulator complex. When normal mouse bone marrow (BM) cells were cocultured with Med1{sup +/+} MEFs or BM stromal cells in the presence of anti-FGF7 antibody, the growth of BM cells and the number of long-time culture-initiating cells (LTC-ICs) decreased significantly. Anti-FGF7 antibody also attenuated the proliferation and cobblestone formation of MB1 stromal cell-dependent myeloblastoma cells. The addition of recombinant FGF7 to the coculture of BM cells and Med1{sup −/−} MEFs increased BM cells and LTC-ICs. FGF7 and its cognate receptor, FGFR2IIIb, were undetectable in BM cells, but MEFs and BM stromal cells expressed both. FGF7 activated downstream targets of FGFR2IIIb in Med1{sup +/+} and Med1{sup −/−} MEFs and BM stromal cells. Taken together, we propose that FGF7 supports HSPCs and leukemia-initiating cells indirectly via FGFR2IIIb expressed on stromal cells.« less

Adult's Responses to the Physical Appearance of Children with Growth Disorders.

ERIC Educational Resources Information Center

Alley, Thomas R.; Hall, Debora L.

1989-01-01

Reports reactions of university students to the physical appearance of children with growth disorders of dwarfism, or sex-linked trisomy, compared to children with normal body proportions. Normal children were rated more favorably on physical attractiveness. Discussed the impact of perceived age and height-weight characteristics on…

Antibodies neutralizing hepsin protease activity do not impact cell growth but inhibit invasion of prostate and ovarian tumor cells in culture.

PubMed

Xuan, Jian-Ai; Schneider, Doug; Toy, Pam; Lin, Rick; Newton, Alicia; Zhu, Ying; Finster, Silke; Vogel, David; Mintzer, Bob; Dinter, Harald; Light, David; Parry, Renate; Polokoff, Mark; Whitlow, Marc; Wu, Qingyu; Parry, Gordon

2006-04-01

Hepsin is a type II transmembrane serine protease that is expressed in normal liver, and at lower levels in kidney, pancreas, and testis. Several studies have shown that hepsin mRNA is significantly elevated in most prostate tumors, as well as a significant fraction of ovarian and renal cell carcinomas and hepatomas. Although the overexpression of mRNA in these tumors has been extensively documented, there has been conflicting literature on whether hepsin plays a role in tumor cell growth and progression. Early literature implied a role for hepsin in human tumor cell proliferation, whereas recent studies with a transgenic mouse model for prostate cancer support a role for hepsin in tumor progression and metastases. To evaluate this issue further, we have expressed an activatable form of hepsin, and have generated a set of monoclonal antibodies that neutralize enzyme activity. The neutralizing antibodies inhibit hepsin enzymatic activity in biochemical and cell-based assays. Selected neutralizing and nonneutralizing antibodies were used in cell-based assays with tumor cells to evaluate the effect of antibodies on tumor cell growth and invasion. Neutralizing antibodies failed to inhibit the growth of prostate, ovarian, and hepatoma cell lines in culture. However, potent inhibitory effects of the antibodies were seen on invasion of ovarian and prostate cells in transwell-based invasion assays. These results support a role for hepsin in tumor cell progression but not in primary tumor growth. Consistent with this, immunohistochemical experiments with a mouse monoclonal antibody reveal progressively increased staining of prostate tumors with advanced disease, and in particular, extensive staining of bone metastatic lesions.

Development of an Autonomous, Dual Chamber Bioreactor for the Growth of 3-Dimensional Epithelial-Stromal Tissues in Microgravity

NASA Technical Reports Server (NTRS)

Patel, Zarana S.; Wettergreen, Matthew A.; Huff, Janice L.

2014-01-01

We are developing a novel, autonomous bioreactor that can provide for the growth and maintenance in microgravity of 3-D organotypic epithelial-stromal cultures that require an air-liquid interface. These complex 3-D tissue models accurately represent the morphological features, differentiation markers, and growth characteristics observed in normal human epithelial tissues, including the skin, esophagus, lung, breast, pancreas, and colon. However, because of their precise and complex culture requirements, including that of an air-liquid interface, these 3-D models have yet to be utilized for life sciences research aboard the International Space Station. The development of a bioreactor for these cultures will provide the capability to perform biological research on the ISS using these realistic, tissue-like human epithelial-stromal cell models and will contribute significantly to advances in fundamental space biology research on questions regarding microgravity effects on normal tissue development, aging, cancer, and other disease processes. It will also allow for the study of how combined stressors, such as microgravity with radiation and nutritional deficiencies, affect multiple biological processes and will provide a platform for conducting countermeasure investigations on the ISS without the use of animal models. The technology will be autonomous and consist of a cell culture chamber that provides for air-liquid, liquid-liquid, and liquid-air exchanges within the chambers while maintaining the growth and development of the biological samples. The bioreactor will support multiple tissue types and its modular design will provide for incorporation of add-on capabilities such as microfluidics drug delivery, media sampling, and in situ biomarker analysis. Preliminary flight testing of the hardware will be conducted on a parabolic platform through NASA's Flight Opportunities Program.

Dioxin inhibition of swim bladder development in zebrafish: is it secondary to heart failure?

PubMed

Yue, Monica S; Peterson, Richard E; Heideman, Warren

2015-05-01

The swim bladder is a gas-filled organ that is used for regulating buoyancy and is essential for survival in most teleost species. In zebrafish, swim bladder development begins during embryogenesis and inflation occurs within 5 days post fertilization (dpf). Embryos exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) before 96 h post fertilization (hpf) developed swim bladders normally until the growth/elongation phase, at which point growth was arrested. It is known that TCDD exposure causes heart malformations that lead to heart failure in zebrafish larvae, and that blood circulation is a key factor in normal development of the swim bladder. The adverse effects of TCDD exposure on the heart occur during the same period of time that swim bladder development and growth occurs. Based on this coincident timing, and the dependence of swim bladder development on proper circulatory development, we hypothesized that the adverse effects of TCDD on swim bladder development were secondary to heart failure. We compared swim bladder development in TCDD-exposed embryos to: (1) silent heart morphants, which lack cardiac contractility, and (2) transiently transgenic cmlc2:caAHR-2AtRFP embryos, which mimic TCDD-induced heart failure via heart-specific, constitutive activation of AHR signaling. Both of these treatment groups, which were not exposed to TCDD, developed hypoplastic swim bladders of comparable size and morphology to those found in TCDD-exposed embryos. Furthermore, in all treatment groups swim bladder development was arrested during the growth/elongation phase. Together, these findings support a potential role for heart failure in the inhibition of swim bladder development caused by TCDD. Copyright © 2015 Elsevier B.V. All rights reserved.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

PubMed

Ahrens, Birgit; Hellmuth, Christian; Haiden, Nadja; Olbertz, Dirk; Hamelmann, Eckard; Vusurovic, Milica; Fleddermann, Manja; Roehle, Robert; Knoll, Anette; Koletzko, Berthold; Wahn, Ulrich; Beyer, Kirsten

2018-05-01

A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Information dynamics in carcinogenesis and tumor growth.

PubMed

Gatenby, Robert A; Frieden, B Roy

2004-12-21

The storage and transmission of information is vital to the function of normal and transformed cells. We use methods from information theory and Monte Carlo theory to analyze the role of information in carcinogenesis. Our analysis demonstrates that, during somatic evolution of the malignant phenotype, the accumulation of genomic mutations degrades intracellular information. However, the degradation is constrained by the Darwinian somatic ecology in which mutant clones proliferate only when the mutation confers a selective growth advantage. In that environment, genes that normally decrease cellular proliferation, such as tumor suppressor or differentiation genes, suffer maximum information degradation. Conversely, those that increase proliferation, such as oncogenes, are conserved or exhibit only gain of function mutations. These constraints shield most cellular populations from catastrophic mutator-induced loss of the transmembrane entropy gradient and, therefore, cell death. The dynamics of constrained information degradation during carcinogenesis cause the tumor genome to asymptotically approach a minimum information state that is manifested clinically as dedifferentiation and unconstrained proliferation. Extreme physical information (EPI) theory demonstrates that altered information flow from cancer cells to their environment will manifest in-vivo as power law tumor growth with an exponent of size 1.62. This prediction is based only on the assumption that tumor cells are at an absolute information minimum and are capable of "free field" growth that is, they are unconstrained by external biological parameters. The prediction agrees remarkably well with several studies demonstrating power law growth in small human breast cancers with an exponent of 1.72+/-0.24. This successful derivation of an analytic expression for cancer growth from EPI alone supports the conceptual model that carcinogenesis is a process of constrained information degradation and that malignant cells are minimum information systems. EPI theory also predicts that the estimated age of a clinically observed tumor is subject to a root-mean square error of about 30%. This is due to information loss and tissue disorganization and probably manifests as a randomly variable lag phase in the growth pattern that has been observed experimentally. This difference between tumor size and age may impose a fundamental limit on the efficacy of screening based on early detection of small tumors. Independent of the EPI analysis, Monte Carlo methods are applied to predict statistical tumor growth due to perturbed information flow from the environment into transformed cells. A "simplest" Monte Carlo model is suggested by the findings in the EPI approach that tumor growth arises out of a minimally complex mechanism. The outputs of large numbers of simulations show that (a) about 40% of the populations do not survive the first two-generations due to mutations in critical gene segments; but (b) those that do survive will experience power law growth identical to the predicted rate obtained from the independent EPI approach. The agreement between these two very different approaches to the problem strongly supports the idea that tumor cells regress to a state of minimum information during carcinogenesis, and that information dynamics are integrally related to tumor development and growth.

Corn response to climate stress detected with satellite-based NDVI time series

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

Wang, Ruoyu; Cherkauer, Keith; Bowling, Laura

Corn growth conditions and yield are closely dependent on climate variability. Leaf growth, measured as the leaf area index, can be used to identify changes in crop growth in response to climate stress. This research was conducted to capture patterns of spatial and temporal corn leaf growth under climate stress for the St. Joseph River watershed, in northeastern Indiana. Leaf growth is represented by the Normalized Difference Vegetative Index (NDVI) retrieved from multiple years (2000–2010) of Landsat 5 TM images. By comparing NDVI values for individual image dates with the derived normal curve, the response of crop growth to environmentalmore » factors is quantified as NDVI residuals. Regression analysis revealed a significant relationship between yield and NDVI residual during the pre-silking period, indicating that NDVI residuals reflect crop stress in the early growing period that impacts yield. Both the mean NDVI residuals and the percentage of image pixels where corn was under stress (risky pixel rate) are significantly correlated with water stress. Dry weather is prone to hamper potential crop growth, with stress affecting most of the observed corn pixels in the area. Oversupply of rainfall at the end of the growing season was not found to have a measurable effect on crop growth, while above normal precipitation earlier in the growing season reduces the risk of yield loss at the watershed scale. Furthermore, the spatial extent of stress is much lower when precipitation is above normal than under dry conditions, masking the impact of small areas of yield loss at the watershed scale.« less

Corn response to climate stress detected with satellite-based NDVI time series

DOE PAGES

Wang, Ruoyu; Cherkauer, Keith; Bowling, Laura

2016-03-23

Corn growth conditions and yield are closely dependent on climate variability. Leaf growth, measured as the leaf area index, can be used to identify changes in crop growth in response to climate stress. This research was conducted to capture patterns of spatial and temporal corn leaf growth under climate stress for the St. Joseph River watershed, in northeastern Indiana. Leaf growth is represented by the Normalized Difference Vegetative Index (NDVI) retrieved from multiple years (2000–2010) of Landsat 5 TM images. By comparing NDVI values for individual image dates with the derived normal curve, the response of crop growth to environmentalmore » factors is quantified as NDVI residuals. Regression analysis revealed a significant relationship between yield and NDVI residual during the pre-silking period, indicating that NDVI residuals reflect crop stress in the early growing period that impacts yield. Both the mean NDVI residuals and the percentage of image pixels where corn was under stress (risky pixel rate) are significantly correlated with water stress. Dry weather is prone to hamper potential crop growth, with stress affecting most of the observed corn pixels in the area. Oversupply of rainfall at the end of the growing season was not found to have a measurable effect on crop growth, while above normal precipitation earlier in the growing season reduces the risk of yield loss at the watershed scale. Furthermore, the spatial extent of stress is much lower when precipitation is above normal than under dry conditions, masking the impact of small areas of yield loss at the watershed scale.« less

The Application of Advanced Cultivation Techniques in the Long Term Maintenance of Space Flight Plant Biological Systems

NASA Technical Reports Server (NTRS)

Heyenga, A. G.

2003-01-01

The development of the International Space Station (ISS) presents extensive opportunities for the implementation of long duration space life sciences studies. Continued attention has been placed in the development of plant growth chamber facilities capable of supporting the cultivation of plants in space flight microgravity conditions. The success of these facilities is largely dependent on their capacity to support the various growth requirements of test plant species. The cultivation requirements for higher plant species are generally complex, requiring specific levels of illumination, temperature, humidity, water, nutrients, and gas composition in order to achieve normal physiological growth and development. The supply of water, nutrients, and oxygen to the plant root system is a factor, which has proven to be particularly challenging in a microgravity space flight environment. The resolution of this issue is particularly important for the more intensive crop cultivation of plants envisaged in Nasa's advanced life support initiative. BioServe Space Technologies is a NASA, Research Partnership Center (RPC) at the University of Colorado, Boulder. BioServe has designed and operated various space flight plant habitat systems, and placed specific emphasis on the development and enhanced performance of subsystem components such as water and nutrient delivery, illumination, gas exchange and atmosphere control, temperature and humidity control. The further development and application of these subsystems to next generation habitats is of significant benefit and contribution towards the development of both the Space Plant biology and the Advanced Life Support Programs. The cooperative agreement between NASA Ames Research center and BioServe was established to support the further implementation of advanced cultivation techniques and protocols to plant habitat systems being coordinated at NASA Ames Research Center. Emphasis was placed on the implementation of passive-based water and nutrient support systems and techniques, which can be used to minimize demands on power, mass, and operational complexity in space flight studies. This effort has direct application to the development of next-generation space flight plant chambers such as the Plant Research Unit (PRU). Work was also directed at the development of in-flight plant preservation techniques and protocols consistent with the interest in applying recent developments in gene chip micro array technologies. Cultivation technologies and protocols were evaluated in a 55 day space flight plant growth study, conducted on the ISS, mission 9A (10/7/02 - 12/7/02).

Growth hormone transgenesis in coho salmon disrupts muscle immune function impacting cross-talk with growth systems.

PubMed

Alzaid, Abdullah; Kim, Jin-Hyoung; Devlin, Robert H; Martin, Samuel A M; Macqueen, Daniel J

2018-04-26

Suppression of growth during infection may aid resource allocation towards effective immune function. Past work supporting this hypothesis in salmonid fish revealed an immune-responsive regulation of the insulin-like growth factor (IGF) system, an endocrine pathway downstream of growth hormone (GH). Skeletal muscle is the main target for growth and energetic storage in fish, yet little is known about how its growth is regulated during an immune response. We addressed this knowledge gap by characterizing muscle immune responses in size-matched coho salmon ( Oncorhynchus kisutch ) achieving different growth rates. We compared a wild-type strain with two GH transgenic groups from the same genetic background achieving either maximal or suppressed growth, a design separating GH's direct effects from its influence on growth rate and nutritional state. Fish were sampled 30h post-injection with PBS (control) or mimics of bacterial or viral infection. We quantified mRNA expression levels for genes from the GH, GH receptor, IGF hormone, IGF1 receptor and IGF-binding protein families, along with immune genes involved in inflammatory or antiviral responses and muscle growth status marker genes. We demonstrate dampened immune function in GH transgenics compared to wild-type. The muscle of GH transgenics achieving rapid growth showed no detectable antiviral response, coupled with evidence of a constitutive inflammatory state. GH and IGF system gene expression was strongly altered by GH transgenesis and fast growth, both for baseline expression and responses to immune stimulation. Thus, GH transgenesis strongly disrupts muscle immune status and normal GH and IGF system expression responses to immune stimulation. © 2018. Published by The Company of Biologists Ltd.

Mechanism-based model for tumor drug resistance.

PubMed

Kuczek, T; Chan, T C

1992-01-01

The development of tumor resistance to cytotoxic agents has important implications in the treatment of cancer. If supported by experimental data, mathematical models of resistance can provide useful information on the underlying mechanisms and aid in the design of therapeutic regimens. We report on the development of a model of tumor-growth kinetics based on the assumption that the rates of cell growth in a tumor are normally distributed. We further assumed that the growth rate of each cell is proportional to its rate of total pyrimidine synthesis (de novo plus salvage). Using an ovarian carcinoma cell line (2008) and resistant variants selected for chronic exposure to a pyrimidine antimetabolite, N-phosphonacetyl-L-aspartate (PALA), we derived a simple and specific analytical form describing the growth curves generated in 72 h growth assays. The model assumes that the rate of de novo pyrimidine synthesis, denoted alpha, is shifted down by an amount proportional to the log10 PALA concentration and that cells whose rate of pyrimidine synthesis falls below a critical level, denoted alpha 0, can no longer grow. This is described by the equation: Probability (growth) = probability (alpha 0 less than alpha-constant x log10 [PALA]). This model predicts that when growth curves are plotted on probit paper, they will produce straight lines. This prediction is in agreement with the data we obtained for the 2008 cells. Another prediction of this model is that the same probit plots for the resistant variants should shift to the right in a parallel fashion. Probit plots of the dose-response data obtained for each resistant 2008 line following chronic exposure to PALA again confirmed this prediction. Correlation of the rightward shift of dose responses to uridine transport (r = 0.99) also suggests that salvage metabolism plays a key role in tumor-cell resistance to PALA. Furthermore, the slope of the regression lines enables the detection of synergy such as that observed between dipyridamole and PALA. Although the rate-normal model was used to study the rate of salvage metabolism in PALA resistance in the present study, it may be widely applicable to modeling of other resistance mechanisms such as gene amplification of target enzymes.

Constitutional growth delay pattern of growth in velo-cardio-facial syndrome: longitudinal follow up and final height of two cases.

PubMed

Turan, Serap; Ozdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo-cardio-facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS -3.4 SDS), but showed spontaneous catch-up and ended up with a final height of -2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty.

Orientations of dendritic growth during solidification

NASA Astrophysics Data System (ADS)

Lee, Dong Nyung

2017-03-01

Dendrites are crystalline forms which grow far from the limit of stability of the plane front and adopt an orientation which is as close as possible to the heat flux direction. Dendritic growth orientations for cubic metals, bct Sn, and hcp Zn, can be controlled by thermal conductivity, Young's modulus, and surface energy. The control factors have been elaborated. Since the dendrite is a single crystal, its properties such as thermal conductivity that influences the heat flux direction, the minimum Young's modulus direction that influences the strain energy minimization, and the minimum surface energy plane that influences the crystal/liquid interface energy minimization have been proved to control the dendritic growth direction. The dendritic growth directions of cubic metals are determined by the minimum Young's modulus direction and/or axis direction of symmetry of the minimum crystal surface energy plane. The dendritic growth direction of bct Sn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction. The primary dendritic growth direction of hcp Zn is determined by its maximum thermal conductivity direction and the minimum surface energy plane normal direction and the secondary dendrite arm direction of hcp Zn is normal to the primary dendritic growth direction.

In vitro cholesteatoma growth and secretion of cytokines.

PubMed

Helgaland, Tore; Engelen, Bart; Olsnes, Carla; Aarstad, Hans Jørgen; Vassbotn, Flemming S

2010-07-01

Our results show a significant difference between skin and cholesteatoma biology in vitro. Cholesteatoma disease is a process of destruction characterized by uncontrolled growth of squamous epithelial cells in the middle ear or temporal bone. The pathophysiology behind the cholesteatoma development is controversial, and the mechanisms driving the cholesteatoma growth, migration and destructive properties is still unclear. We aimed to provide a method to study the effect of various compounds on cholesteatoma and skin tissue growth, as well as to further investigate the biological differences between normal skin and cholesteatoma tissue. We have established a method to study cholesteatoma biopsy tissue in vitro. Cholesteatoma tissues from patients undergoing surgery for chronic otitis were grown in culture medium and compared to growth patterns and behaviour of normal retroauricular skin. Conditioned medium was analysed for various secreted cytokines. We found a radial outgrowth of keratinocyte epithelium from the circular biopsies. After 5 days of culture we found a significant growth of both cholesteatoma and skin-derived cells. Cholesteatoma samples showed higher growth rate as compared with skin control cultures from the same patient. Moreover, the cholesteatoma cells showed higher production of monocyte chemoattractant protein-1 (MCP-1) and interleukin (IL)-6 as compared with normal skin.

Aberrant expression of erythropoietin in uterine leiomyoma: implications in tumor growth.

PubMed

Asano, Ryoko; Asai-Sato, Mikiko; Miyagi, Yohei; Mizushima, Taichi; Koyama-Sato, Makiko; Nagashima, Yoji; Taguri, Masataka; Sakakibara, Hideya; Hirahara, Fumiki; Miyagi, Etsuko

2015-08-01

Myomatous erythrocytosis syndrome is a rare complication of uterine leiomyoma caused by erythropoietin (EPO) that is produced by tumor cells. We assessed the EPO expression in leiomyomas and investigated the effects of EPO on the tumor growth. Tissue samples were collected from 114 patients with uterine leiomyomas who underwent myomectomy or hysterectomy in Yokohama City University Hospital. From 17 patients, the corresponding normal myometrium was also collected. All samples were analyzed for EPO messenger RNA (mRNA) expression by real-time reverse transcription-polymerase chain reaction. EPO protein expression was determined by an enzyme-linked immunosorbent assay. The relationships between EPO expression and clinicopathological features were retrospectively analyzed using the patients' charts. Blood vessel density and maturity were assessed using hematoxylin-eosin staining and CD34 immunohistochemistry. EPO mRNA expression was detected in 108 of 114, or 95%, of the leiomyomas. The mean EPO mRNA expression in the leiomyoma was higher than the corresponding normal myometrium (3836 ± 4122 vs 1455 ± 2141; P = .025 by Wilcoxon rank test). The EPO mRNA expression in the leiomyomas varied extensively among samples, ranging from undetectable levels to 18-fold above the mean EPO mRNA of normal myometrium. EPO protein production was observed concomitant with mRNA expression. A positive correlation of leiomyoma size and EPO mRNA expression was shown by Spearman rank correlation coefficient (ρ = 0.294; P = .001), suggesting the involvement of EPO in leiomyoma growth. The blood vessel maturity was also significantly increased in EPO-producing leiomyomas (high vessel maturity in high vs low EPO group: 67% vs 20%; P = .013 by Fisher exact test). This report demonstrates that EPO is produced in most of conventional leiomyomas and supports a model in which EPO accelerates tumor growth, possibly by inducing vessel maturity. Our study suggests one possible mechanism by which some uterine leiomyomas reach a large size, and the understanding of EPO expression patterns in these tumors may be useful for management of the patients with leiomyomas. Copyright © 2015 Elsevier Inc. All rights reserved.

Growth of contact area between rough surfaces under normal stress

NASA Astrophysics Data System (ADS)

Stesky, R. M.; Hannan, S. S.

1987-05-01

The contact area between deforming rough surfaces in marble, alabaster, and quartz was measured from thin sections of surfaces bonded under load with low viscosity resin epoxy. The marble and alabaster samples had contact areas that increased with stress at an accelerating rate. This result suggests that the strength of the asperity contacts decreased progressively during the deformation, following some form of strain weakening relationship. This conclusion is supported by petrographic observation of the thin sections that indicate that much of the deformation was cataclastic, with minor twinning of calcite and kinking of gypsum. In the case of the quartz, the observed contact area was small and increased approximately linearly with normal stress. Only the irreversible cataclastic deformation was observed; however strain-induced birefringence and cracking of the epoxy, not observed with the other rocks, suggests that significant elastic deformation occurred, but recovered during unloading.

Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects.

PubMed

Zemishlany, Z; Davidson, M

1996-08-15

The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10 young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations. The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety.

Gastric cancer stem cells: A novel therapeutic target

PubMed Central

Singh, Shree Ram

2013-01-01

Gastric cancer remains one of the leading causes of global cancer mortality. Multipotent gastric stem cells have been identified in both mouse and human stomachs, and they play an essential role in the self-renewal and homeostasis of gastric mucosa. There are several environmental and genetic factors known to promote gastric cancer. In recent years, numerous in vitro and in vivo studies suggest that gastric cancer may originate from normal stem cells or bone marrow–derived mesenchymal cells, and that gastric tumors contain cancer stem cells. Cancer stem cells are believed to share a common microenvironment with normal niche, which play an important role in gastric cancer and tumor growth. This mini-review presents a brief overview of the recent developments in gastric cancer stem cell research. The knowledge gained by studying cancer stem cells in gastric mucosa will support the development of novel therapeutic strategies for gastric cancer. PMID:23583679

Productivity and food value of Amaranthus cruentus under non-lethal salt stress

NASA Technical Reports Server (NTRS)

Macler, Bruce A.; Macelroy, Robert D.

1989-01-01

Experiments were carried out to analyze the effects of increasing salinity stress on growth, photosynthesis, and carbon allocation in the crop plant Amaranthus. Plants were germinated and grown in Hoagland's solution with NaCl concentrations of 0 to 1.0 percent. The limits of total salinity in the plant growth medium are investigated. For Amaranthus cruentus, germination, vegetative growth, flowering, seed development and yield were normal at salinities from 0 to 0.2 percent. Inhibition of these phases increased from o.2 to 0.4 percent salinity and was total above 0.5 percent with 1 percent salinity was lethal to all developmental phases. Onset of growth phases were not affected by salinity. Plants could not be adapted by gradually increasing salinity over days or weeks. Water uptake increased, while photosynthetic CO2 uptake decreased with increasing salinity on a dry weight basis during vegetative growth. Protein levels were unchanged with increasing salinity. Leaf starch levels were lower at salinities of 0.5 percent and above, while stem starch levels were not affected by these salinities. The evidence supports salt inhibition arising frm changes in primary biochemical processes rather than from effects on water relations. While not addressing the toxic effects of specific ions, it suggests that moderate salinity per se need not be a problem in space systems.

SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

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

Wu, Feng; Jordan, Ashley; Kluz, Thomas

The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealedmore » the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.« less

Professional Growth & Support System Self-Assessment

ERIC Educational Resources Information Center

Education Resource Strategies, 2013

2013-01-01

The "Professional Growth & Support System Self-Assessment" is designed to help school systems evaluate their current Professional Growth & Support strategy. The self-assessment is organized around the "Eight Principles of Strategic Professional Growth & Support." Each section allows school leaders to identify the…

Outgrowth of fibroblast cells from goat skin explants in three different culture media and the establishment of cell lines.

PubMed

Singh, Mahipal; Sharma, Anil K

2011-02-01

Three different commercially available media, known to support human and porcine-specific fibroblast cultures, were tested for their growth potential on goat skin explants. Although outgrowth of fibroblasts was observed in all media tested, irrespective of breed, porcine-specific media exhibited higher rate of growth. Using this media, three fibroblast cell lines (GSF289, GSF737, and GSF2010) from ear skin explants of normal healthy dairy goats of Kiko and Saanen breed were successfully established in culture. Liquid nitrogen stocks of these frozen cells had a viability rate of 96.2% in in vitro cultures. These cells were morphologically indistinguishable from the cell stocks prior to freezing. Analysis of the growth of a fifth passage culture revealed an 'S' shaped growth curve with a population doubling time of 25 h. The cell lines were found negative for microbial, fungal, and mycoplasma contaminations. These goat skin fibroblast lines and the simple method of their isolation and freezing with high rate of viability will provide additional tools to study molecular mechanisms that regulate fibroblast function and for genetic manipulation of small ruminants.

The effect of growth temperature on the irreversibility line of MPMG YBCO bulk with Y2O3 layer

NASA Astrophysics Data System (ADS)

Kurnaz, Sedat; Çakır, Bakiye; Aydıner, Alev

2017-07-01

In this study, three kinds of YBCO samples which are named Y1040, Y1050 and Y1060 were fabricated by Melt-Powder-Melt-Growth (MPMG) method without a seed crystal. Samples seem to be single crystal. The compacted powders were located on a crucible with a buffer layer of Y2O3 to avoid liquid to spread on the furnace plate and also to support crystal growth. YBCO samples were investigated by magnetoresistivity (ρ-T) and magnetization (M-T) measurements in dc magnetic fields (parallel to c-axis) up to 5 T. Irreversibility fields (Hirr) and upper critical fields (Hc2) were obtained using 10% and 90% criteria of the normal state resistivity value from ρ-T curves. M-T measurements were carried out using the zero field cooling (ZFC) and field cooling (FC) processes to get irreversible temperature (Tirr). Fitting of the irreversibility line results to giant flux creep and vortex glass models were discussed. The results were found to be consistent with the results of the samples fabricated using a seed crystal. At the fabrication of MPMG YBCO, optimized temperature for crystal growth was determined to be around 1050-1060 °C.

A Patient with Cystinosis Presenting Like Bartter Syndrome and Review of Literature

PubMed Central

Ertan, Pelin; Evrengul, Havva; Ozen, Serkan; Emre, Sinan

2012-01-01

Background Nephropathic cystinosis is an autosomal recessively inherited metabolic disorder presenting with metabolic acidosis, Fanconi syndrome and renal failure. Case Presentation We present a 6-year-old girl with severe growth failure, hyponatremia and hypokalemia. Her parents were 4th degree relatives. Two relatives were diagnosed as end stage renal failure. She also had persistant hypokalemic hypochloremic metabolic alkalosis. Her renal function was normal at presentation. She was thought to have Bartter syndrome with supporting findings of elevated levels of renin and aldosterone with normal blood pressure, and hyperplasia of juxtaglomerular apparatus. Her metabolic alkalosis did not resolve despite supportive treatment. At 6th month of follow-up proteinuria, glucosuria and deterioration of renal function developed. Diagnosis of cystinosis was made with slit lamp examination and leukocyte cystine levels. At 12th month of follow-up her metabolic alkalosis has converted to metabolic acidosis. Conclusion In children presenting with persistant metabolic alkalosis, with family history of renal failure, and parental consanguinity, cystinosis should always be kept in mind as this disease is an important cause of end stage renal failure which may have features mimmicking Bartter syndrome. PMID:23431081

Gingival crevicular fluid protein content and alkaline phosphatase activity in relation to pubertal growth phase.

PubMed

Perinetti, Giuseppe; Franchi, Lorenzo; Castaldo, Attilio; Contardo, Luca

2012-11-01

To evaluate gingival crevicular fluid (GCF) protein content and alkaline phosphatase (ALP) activity in growing subjects in relation to stages of skeletal maturation, ie, the growth phase, as prepubertal, pubertal, and postpubertal. Fifty healthy growing subjects (31 girls and 19 boys; age range, 7.8-17.7 years) were enrolled in this study that followed a double-blind, prospective, cross-sectional design. Collection of GCF was performed at the mesial and distal sites of both central incisors, for the maxilla and mandible. Growth phase was assessed through the cervical vertebral maturation method. GCF parameters were expressed as total protein content, total ALP activity, and normalized ALP activity. The total GCF protein content was similar between the different growth phases. On the contrary, the total ALP activity showed a peak for the pubertal growth phase. The normalized GCF ALP activity was only poorly associated with growth phase. No differences were seen between the maxillary and mandibular sites, or between the sexes, for any GCF parameter. The total GCF protein content is not sensitive to the growth phase. However, GCF ALP activity has potential as a diagnostic aid for identification of the pubertal growth phase in individual subjects when expressed as total, but not normalized, values.

78 FR 47612 - Endangered and Threatened Wildlife and Plants; Designation of Critical Habitat for the Sharpnose...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-06

... (primary constituent elements such as roost sites, nesting grounds, seasonal wetlands, water quality, tide... individual and population growth and for normal behavior; (2) Food, water, air, light, minerals, or other... Growth and for Normal Behavior Sharpnose shiners occur in fairly shallow, flowing water, often less than...

Economics of Future Growth in Photovoltaics Manufacturing; NREL (National Renewable Energy Laboratory)

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

Basore, Paul; Chung, Donald; Buonassisi, Tonio

2015-06-14

The past decade’s record of growth in the photovoltaic manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life ofmore » the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.« less

Abnormal grain growth in AISI 304L stainless steel

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

Shirdel, M., E-mail: mshirdel1989@ut.ac.ir; Mirzadeh, H., E-mail: hmirzadeh@ut.ac.ir; Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran

2014-11-15

The microstructural evolution during abnormal grain growth (secondary recrystallization) in 304L stainless steel was studied in a wide range of annealing temperatures and times. At relatively low temperatures, the grain growth mode was identified as normal. However, at homologous temperatures between 0.65 (850 °C) and 0.7 (900 °C), the observed transition in grain growth mode from normal to abnormal, which was also evident from the bimodality in grain size distribution histograms, was detected to be caused by the dissolution/coarsening of carbides. The microstructural features such as dispersed carbides were characterized by optical metallography, X-ray diffraction, scanning electron microscopy, energy dispersivemore » X-ray analysis, and microhardness. Continued annealing to a long time led to the completion of secondary recrystallization and the subsequent reappearance of normal growth mode. Another instance of abnormal grain growth was observed at homologous temperatures higher than 0.8, which may be attributed to the grain boundary faceting/defaceting phenomenon. It was also found that when the size of abnormal grains reached a critical value, their size will not change too much and the grain growth behavior becomes practically stagnant. - Highlights: • Abnormal grain growth (secondary recrystallization) in AISI 304L stainless steel • Exaggerated grain growth due to dissolution/coarsening of carbides • The enrichment of carbide particles by titanium • Abnormal grain growth due to grain boundary faceting at very high temperatures • The stagnancy of abnormal grain growth by annealing beyond a critical time.« less

Mutations in the NHEJ component XRCC4 cause primordial dwarfism.

PubMed

Murray, Jennie E; van der Burg, Mirjam; IJspeert, Hanna; Carroll, Paula; Wu, Qian; Ochi, Takashi; Leitch, Andrea; Miller, Edward S; Kysela, Boris; Jawad, Alireza; Bottani, Armand; Brancati, Francesco; Cappa, Marco; Cormier-Daire, Valerie; Deshpande, Charu; Faqeih, Eissa A; Graham, Gail E; Ranza, Emmanuelle; Blundell, Tom L; Jackson, Andrew P; Stewart, Grant S; Bicknell, Louise S

2015-03-05

Non-homologous end joining (NHEJ) is a key cellular process ensuring genome integrity. Mutations in several components of the NHEJ pathway have been identified, often associated with severe combined immunodeficiency (SCID), consistent with the requirement for NHEJ during V(D)J recombination to ensure diversity of the adaptive immune system. In contrast, we have recently found that biallelic mutations in LIG4 are a common cause of microcephalic primordial dwarfism (MPD), a phenotype characterized by prenatal-onset extreme global growth failure. Here we provide definitive molecular genetic evidence supported by biochemical, cellular, and immunological data for mutations in XRCC4, encoding the obligate binding partner of LIG4, causing MPD. We report the identification of biallelic mutations in XRCC4 in five families. Biochemical and cellular studies demonstrate that these alterations substantially decrease XRCC4 protein levels leading to reduced cellular ligase IV activity. Consequently, NHEJ-dependent repair of ionizing-radiation-induced DNA double-strand breaks is compromised in XRCC4 cells. Similarly, immunoglobulin junctional diversification is impaired in cells. However, immunoglobulin levels are normal, and individuals lack overt signs of immunodeficiency. Additionally, in contrast to individuals with LIG4 mutations, pancytopenia leading to bone marrow failure has not been observed. Hence, alterations that alter different NHEJ proteins give rise to a phenotypic spectrum, from SCID to extreme growth failure, with deficiencies in certain key components of this repair pathway predominantly exhibiting growth deficits, reflecting differential developmental requirements for NHEJ proteins to support growth and immune maturation. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Soy-based infant formula supplemented with DHA and ARA supports growth and increases circulating levels of these fatty acids in infants.

PubMed

Hoffman, Dennis; Ziegler, Ekhard; Mitmesser, Susan H; Harris, Cheryl L; Diersen-Schade, Deborah A

2008-01-01

Healthy term infants (n = 244) were randomized to receive: (1) control, soy-based formula without supplementation or (2) docosahexaenoic acid-arachidonic acid (DHA + ARA), soy-based formula supplemented with at least 17 mg DHA/100 kcal (from algal oil) and 34 mg ARA/100 kcal (from fungal oil) in a double-blind, parallel group trial to evaluate safety, benefits, and growth from 14 to 120 days of age. Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age and 24-h dietary and tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study. Blood samples were drawn from subsets of 25 infants in each group. Capillary column gas chromatography was used to analyze the percentages of fatty acids in red blood cell (RBC) lipids and plasma phospholipids. Compared with the control group, percentages of fatty acids such as DHA and ARA in total RBC and plasma phospholipids were significantly higher in infants in the DHA + ARA group at 120 days of age (P < 0.001). Growth rates did not differ significantly between feeding groups at any assessed time point. Supplementation did not affect the tolerance of formula or the incidence of adverse events. Feeding healthy term infants soy-based formula supplemented with DHA and ARA from single cell oil sources at concentrations similar to human milk significantly increased circulating levels of DHA and ARA when compared with the control group. Both formulas supported normal growth and were well tolerated.

Growth and yield of Giant Sequoia

Treesearch

David J. Dulitz

1986-01-01

Very little information exists concerning growth and yield of giant sequoia (Sequoiadendron giganteum [Lindl.] Buchholz). For old-growth trees, diameter growth is the single factor adding increment since maximum height has been obtained. Diameter growth averages 0.04 inches per year in normal old-growth trees but will fluctuate with changes in the...

[Polyamines and their role in tumor growth].

PubMed

Godlewska, Joanna; Peczyńska-Czoch, Wanda

2002-01-01

The polyamines-putrescine, spermidine and spermine--are normal constituents of prokariotic and eukariotic cells. These small polycationic, aliphatic compounds are essential for normal cell proliferation. Cells cease to proliferate, when they are depleted of their polyamines, but resume a normal growth rate after supplementation with these compounds. Because of the sustained increase in polyamine biosynthesis in preneoplastic and neoplastic tissues, a great deal of interest has been given to the polyamine biosynthesis, network, and uptake systems as a target in antineoplastic strategies.

Routing and wavelength assignment based on normalized resource and constraints for all-optical network

NASA Astrophysics Data System (ADS)

Joo, Seong-Soon; Nam, Hyun-Soon; Lim, Chang-Kyu

2003-08-01

With the rapid growth of the Optical Internet, high capacity pipes is finally destined to support end-to-end IP on the WDM optical network. Newly launched 2D MEMS optical switching module in the market supports that expectations of upcoming a transparent optical cross-connect in the network have encouraged the field applicable research on establishing real all-optical transparent network. To open up a customer-driven bandwidth services, design of the optical transport network becomes more challenging task in terms of optimal network resource usage. This paper presents a practical approach to finding a route and wavelength assignment for wavelength routed all-optical network, which has λ-plane OXC switches and wavelength converters, and supports that optical paths are randomly set up and released by dynamic wavelength provisioning to create bandwidth between end users with timescales on the order of seconds or milliseconds. We suggest three constraints to make the RWA problem become more practical one on deployment for wavelength routed all-optical network in network view: limitation on maximum hop of a route within bearable optical network impairments, limitation on minimum hops to travel before converting a wavelength, and limitation on calculation time to find all routes for connections requested at once. We design the NRCD (Normalized Resource and Constraints for All-Optical Network RWA Design) algorithm for the Tera OXC: network resource for a route is calculated by the number of internal switching paths established in each OXC nodes on the route, and is normalized by ratio of number of paths established and number of paths equipped in a node. We show that it fits for the RWA algorithm of the wavelength routed all-optical network through real experiments on the distributed objects platform.

Growth pattern and age at menarche of obese girls in a transitional society.

PubMed

Jaruratanasirikul, S; Mo-suwan, L; Lebel, L

1997-01-01

Childhood obesity is an increasing problem in a transitional society such as Thailand. To study physical growth and puberty in obese children, a cross-sectional survey of growth and age at menarche was carried out in schoolgirls aged between 8 and 16 years old. The 3,120 girls were divided into two groups based on weight-for-height criteria. Girls with weight-for-height between 80 and 120% were classified as normal stature (2,625; 84.1%) and those more than 120% were obese (495; 15.9%). Using probit analysis, age at menarche in obese girls was 0.9 year earlier than normal stature girls (11.5 years vs 12.4 years). At age 12, obese girls were reaching menarche 2.8 times more when compared with the normal stature girls. In terms of growth pattern, obese girls were taller and grew faster during the prepubertal period, and then reached their final height earlier than the normal stature girls (13 years vs 15 years). The final height in obese girls was significantly shorter (153.0 cm and 155.0 cm, p = 0.01). We conclude that: 1) obese girls grow faster, have earlier menarche and then stop growing earlier, and 2) obese girls tend to be shorter as adults, compared with normal stature girls.

Biomechanical Analysis of Normal Brain Development during the First Year of Life Using Finite Strain Theory.

PubMed

Kim, Jeong Chul; Wang, Li; Shen, Dinggang; Lin, Weili

2016-12-02

The first year of life is the most critical time period for structural and functional development of the human brain. Combining longitudinal MR imaging and finite strain theory, this study aimed to provide new insights into normal brain development through a biomechanical framework. Thirty-three normal infants were longitudinally imaged using MRI from 2 weeks to 1 year of age. Voxel-wise Jacobian determinant was estimated to elucidate volumetric changes while Lagrange strains (both normal and shear strains) were measured to reveal directional growth information every 3 months during the first year of life. Directional normal strain maps revealed that, during the first 6 months, the growth pattern of gray matter is anisotropic and spatially inhomogeneous with higher left-right stretch around the temporal lobe and interhemispheric fissure, anterior-posterior stretch in the frontal and occipital lobes, and superior-inferior stretch in right inferior occipital and right inferior temporal gyri. In contrast, anterior lateral ventricles and insula showed an isotropic stretch pattern. Volumetric and directional growth rates were linearly decreased with age for most of the cortical regions. Our results revealed anisotropic and inhomogeneous brain growth patterns of the human brain during the first year of life using longitudinal MRI and a biomechanical framework.

Human Keratinocytes That Express hTERT and Also Bypass a p16INK4a-Enforced Mechanism That Limits Life Span Become Immortal yet Retain Normal Growth and Differentiation Characteristics

PubMed Central

Dickson, Mark A.; Hahn, William C.; Ino, Yasushi; Ronfard, Vincent; Wu, Jenny Y.; Weinberg, Robert A.; Louis, David N.; Li, Frederick P.; Rheinwald, James G.

2000-01-01

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in normal human fibroblasts and retinal pigment epithelial cells, as ectopic expression of the telomerase catalytic subunit, hTERT, immortalizes these cell types directly. Telomerase expression alone is insufficient to enable certain other cell types to evade senescence, however. Such cells, including keratinocytes and mammary epithelial cells, appear to require loss of the pRB/p16INK4a cell cycle control mechanism in addition to hTERT expression to achieve immortality. To investigate the relationships among telomerase activity, cell cycle control, senescence, and differentiation, we expressed hTERT in two epithelial cell types, keratinocytes and mesothelial cells, and determined the effect on proliferation potential and on the function of cell-type-specific growth control and differentiation systems. Ectopic hTERT expression immortalized normal mesothelial cells and a premalignant, p16INK4a-negative keratinocyte line. In contrast, when four keratinocyte strains cultured from normal tissue were transduced to express hTERT, they were incompletely rescued from senescence. After reaching the population doubling limit of their parent cell strains, hTERT+ keratinocytes entered a slow growth phase of indefinite length, from which rare, rapidly dividing immortal cells emerged. These immortal cell lines frequently had sustained deletions of the CDK2NA/INK4A locus or otherwise were deficient in p16INK4a expression. They nevertheless typically retained other keratinocyte growth controls and differentiated normally in culture and in xenografts. Thus, keratinocyte replicative potential is limited by a p16INK4a-dependent mechanism, the activation of which can occur independent of telomere length. Abrogation of this mechanism together with telomerase expression immortalizes keratinocytes without affecting other major growth control or differentiation systems. PMID:10648628

A biologically based model of growth and senescence of Syrian hamster embryo (SHE) cells after exposure to arsenic.

PubMed Central

Liao, K H; Gustafson, D L; Fox, M H; Chubb, L S; Reardon, K F; Yang, R S

2001-01-01

We modified the two-stage Moolgavkar-Venzon-Knudson (MVK) model for use with Syrian hamster embryo (SHE) cell neoplastic progression. Five phenotypic stages are proposed in this model: Normal cells can either become senescent or mutate into immortal cells followed by anchorage-independent growth and tumorigenic stages. The growth of normal SHE cells was controlled by their division, death, and senescence rates, and all senescent cells were converted from normal cells. In this report, we tested the modeling of cell kinetics of the first two phenotypic stages against experimental data evaluating the effects of arsenic on SHE cells. We assessed cell division and death rates using flow cytometry and correlated cell division rates to the degree of confluence of cell cultures. The mean cell death rate was approximately equal to 1% of the average division rate. Arsenic did not induce immortalization or further mutations of SHE cells at concentrations of 2 microM and below, and chromium (3.6 microM) and lead (100 microM) had similar negative results. However, the growth of SHE cells was inhibited by 5.4 microM arsenic after a 2-day exposure, with cells becoming senescent after only 16 population doublings. In contrast, normal cells and cells exposed to lower arsenic concentrations grew normally for at least 30 population doublings. The biologically based model successfully predicted the growth of normal and arsenic-treated cells, as well as the senescence rates. Mechanisms responsible for inducing cellular senescence in SHE cells exposed to arsenic may help explain the apparent inability of arsenic to induce neoplasia in experimental animals. PMID:11748027

Bone marrow mesenchymal stem cells are abnormal in multiple myeloma

PubMed Central

Corre, Jill; Mahtouk, Karène; Attal, Michel; Gadelorge, Mélanie; Huynh, Anne; Fleury-Cappellesso, Sandrine; Danho, Clotaire; Laharrague, Patrick; Klein, Bernard; Rème, Thierry; Bourin, Philippe

2007-01-01

Recent literature suggested that cell of the microenvironment of solid tumors could be abnormal as well. To address this hypothesis in multiple myeloma (MM), we studied bone marrow mesenchymal stem cells (BMMSCs), the only long-lived cells of the bone marrow microenvironment, by gene expression with Affymetrix arrays and phenotypic and functional study in 3 groups of individuals: patients with MM and those with monoclonal gamopathy of undefined significance (MGUS), and healthy aged-matched subjects. Gene expression profile independently classified the BMMSCs of these individuals in a normal and in a MM group. MGUS BMMSCs were interspersed between those 2 groups. Among the 145 distinct genes differentially expressed in MM and normal BMMSCs 46% were involved in tumor-microenvironment cross-talk. Known soluble factors involved in MM pathophysiologic features, (interleukin (IL)-6, IL-1β, DKK1 and amphiregulin, were revealed and new ones found. In particular, GDF-15 was found to induce dose-dependant growth of MOLP-6, a stromal cell-dependent myeloma cell line. Functionally, MM BMMSCs induced an over-growth of MOLP-6, and their capacity to differentiate into an osteoblastic lineage was impaired. Thus, BMMSCs from MM patients could create a very efficient niche to support the survival and proliferation of the myeloma stem cells. PMID:17344918

RRx-001: a systemically non-toxic M2-to-M1 macrophage stimulating and prosensitizing agent in Phase II clinical trials.

PubMed

Oronsky, Bryan; Paulmurugan, Ramasamy; Foygel, Kira; Scicinski, Jan; Knox, Susan J; Peehl, Donna; Zhao, Hongjuan; Ning, Shoucheng; Cabrales, Pedro; Summers, Thomas A; Reid, Tony R; Fitch, William L; Kim, Michelle M; Trepel, Jane B; Lee, Min-Jung; Kesari, Santosh; Abrouk, Nacer D; Day, Regina M; Oronsky, Arnold; Ray, Carolyn M; Carter, Corey A

2017-01-01

According to Hanahan and Weinberg, cancer manifests as six essential physiologic hallmarks: (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) invasion and metastasis. As a facilitator of these traits as well as immunosuppression and chemoresistance, the presence of tumor-associated macrophages (TAMs) may serve as the seventh hallmark of cancer. Anticancer agents that successfully reprogram TAMs to target rather than support tumor cells may hold the key to better therapeutic outcomes. Areas covered: This article summarizes the characteristics of the macrophage-stimulating agent RRx-001, a molecular iconoclast, sourced from the aerospace industry, with a particular emphasis on the cell-to-cell transfer mechanism of action (RBCs to TAMs) underlying its antitumor activity as well as its chemo and radioprotective properties, consolidated from various preclinical and clinical studies. Expert opinion: RRx-001 is macrophage-stimulating agent with the potential to synergize with chemotherapy, radiotherapy and immunotherapy while simultaneously protecting normal tissues from their cytotoxic effects. Given the promising indications of activity in multiple tumor types and these normal tissue protective properties, RRx-001 may be used to treat a broad spectrum of malignancies, if it is approved in the future.

Intersection of FOXO- and RUNX1-mediated gene expression programs in single breast epithelial cells during morphogenesis and tumor progression.

PubMed

Wang, Lixin; Brugge, Joan S; Janes, Kevin A

2011-10-04

Gene expression networks are complicated by the assortment of regulatory factors that bind DNA and modulate transcription combinatorially. Single-cell measurements can reveal biological mechanisms hidden by population averages, but their value has not been fully explored in the context of mRNA regulation. Here, we adapted a single-cell expression profiling technique to examine the gene expression program downstream of Forkhead box O (FOXO) transcription factors during 3D breast epithelial acinar morphogenesis. By analyzing patterns of mRNA fluctuations among individual matrix-attached epithelial cells, we found that a subset of FOXO target genes was jointly regulated by the transcription factor Runt-related transcription factor 1 (RUNX1). Knockdown of RUNX1 causes hyperproliferation and abnormal morphogenesis, both of which require normal FOXO function. Down-regulating RUNX1 and FOXOs simultaneously causes widespread oxidative stress, which arrests proliferation and restores normal acinar morphology. In hormone-negative breast cancers lacking human epidermal growth factor receptor 2 (HER2) amplification, we find that RUNX1 down-regulation is strongly associated with up-regulation of FOXO1, which may be required to support growth of RUNX1-negative tumors. The coordinate function of these two tumor suppressors may provide a failsafe mechanism that inhibits cancer progression.

Heterogeneity in development of adolescent anxiety disorder symptoms in an 8-year longitudinal community study.

PubMed

Nelemans, Stefanie A; Hale, William W; Branje, Susan J T; Raaijmakers, Quinten A W; Frijns, Tom; van Lier, Pol A C; Meeus, Wim H J

2014-02-01

In this study, we prospectively examined developmental trajectories of five anxiety disorder symptom dimensions (generalized anxiety disorder, panic disorder, school anxiety, separation anxiety disorder, and social anxiety disorder) from early to late adolescence in a community sample of 239 adolescents, assessed annually over 8 years. Latent growth modeling indicated different developmental trajectories from early into late adolescence for the different anxiety disorder symptoms, with some symptoms decreasing and other symptoms increasing over time. Sex differences in developmental trajectories were found for some symptoms, but not all. Furthermore, latent class growth analysis identified a normal developmental profile (including a majority of adolescents reporting persistent low anxiety disorder symptoms over 8 years) and an at-risk developmental profile (including a minority of adolescents reporting persistent high anxiety disorder symptoms over 8 years) for all of the anxiety disorder symptom dimensions except panic disorder. Additional analyses longitudinally supported the validity of these normal and at-risk developmental profiles and suggested differential associations between different anxiety disorder symptom dimensions and developmental trajectories of substance use, parenting, and identity development. Taken together, our results emphasize the importance of examining separate dimensions of anxiety disorder symptoms in contrast to a using a global, one-dimensional approach to anxiety.

Fibroblast growth factor receptor two (FGFR2) regulates uterine epithelial integrity and fertility in mice.

PubMed

Filant, Justyna; DeMayo, Franco J; Pru, James K; Lydon, John P; Spencer, Thomas E

2014-01-01

Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate luminal epithelial (LE) cell proliferation in the adult mouse uterus. This study tested the hypothesis that FGFR2 has a biological role in postnatal development and function of the uterus by conditionally deleting Fgfr2 after birth using progesterone receptor (Pgr)-Cre mice. Adult Fgfr2 mutant female mice were initially subfertile and became infertile with increasing parity. No defects in uterine gland development were observed in conditional Fgfr2 mutant mice. In the adult, Fgfr2 mutant mice possessed a histologically normal reproductive tract with the exception of the uterus. The LE of the Fgfr2 mutant uterus was stratified, but no obvious histological differences were observed in the glandular epithelium, stroma, or myometrium. Within the stratified LE, cuboidal basal cells were present and positive for basal cell markers (KRT14 and TRP63). Nulliparous bred Fgfr2 mutants contained normal numbers of blastocysts on Day 3.5 postmating, but the number of embryo implantation sites was substantially reduced on Day 5.5 postmating. These results support the idea that loss of FGFR2 in the uterus after birth alters its development, resulting in LE stratification and peri-implantation pregnancy loss.

Wavelength-normalized spectroscopic analysis of Staphylococcus aureus and Pseudomonas aeruginosa growth rates.

PubMed

McBirney, Samantha E; Trinh, Kristy; Wong-Beringer, Annie; Armani, Andrea M

2016-10-01

Optical density (OD) measurements are the standard approach used in microbiology for characterizing bacteria concentrations in culture media. OD is based on measuring the optical absorbance of a sample at a single wavelength, and any error will propagate through all calculations, leading to reproducibility issues. Here, we use the conventional OD technique to measure the growth rates of two different species of bacteria, Pseudomonas aeruginosa and Staphylococcus aureus. The same samples are also analyzed over the entire UV-Vis wavelength spectrum, allowing a distinctly different strategy for data analysis to be performed. Specifically, instead of only analyzing a single wavelength, a multi-wavelength normalization process is implemented. When the OD method is used, the detected signal does not follow the log growth curve. In contrast, the multi-wavelength normalization process minimizes the impact of bacteria byproducts and environmental noise on the signal, thereby accurately quantifying growth rates with high fidelity at low concentrations.

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures

NASA Astrophysics Data System (ADS)

Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.

1983-07-01

Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.

Clinical and laboratory parameters predicting a requirement for the reevaluation of growth hormone status during growth hormone treatment: Retesting early in the course of GH treatment.

PubMed

Vuralli, Dogus; Gonc, E Nazli; Ozon, Z Alev; Alikasifoglu, Ayfer; Kandemir, Nurgun

2017-06-01

We aimed to define the predictive criteria, in the form of specific clinical, hormonal and radiological parameters, for children with growth hormone deficiency (GHD) who may benefit from the reevaluation of GH status early in the course of growth hormone (GH) treatment. Two hundred sixty-five children with growth hormone deficiency were retested by GH stimulation at the end of the first year of GH treatment. The initial clinical and laboratory characteristics of those with a normal (GH≥10ng/ml) response and those with a subnormal (GH<10ng/ml) response were compared to predict a normal GH status during reassessment. Sixty-nine patients (40.6%) out of the 170 patients with isolated growth hormone deficiency (IGHD) had a peak GH of ≥10ng/ml during the retest. None of the patients with multiple pituitary hormone deficiency (MPHD) had a peak GH of ≥10ng/ml. Puberty and sex steroid priming in peripubertal cases increased the probability of a normal GH response. Only one patient with IGHD who had an ectopic posterior pituitary without stalk interruption on MRI analysis showed a normal GH response during the retest. Patients with a peak GH between 5 and 10ng/ml, an age at diagnosis of ≥9years or a height gain below 0.61 SDS during the first year of treatment had an increased probability of having a normal GH response at the retest. Early reassessment of GH status during GH treatment is unnecessary in patients who have MPHD with at least 3 hormone deficiencies. Retesting at the end of the first year of therapy is recommended for patients with IGHD who have a height gain of <0.61 SDS in the first year of treatment, especially those with a normal or 'hypoplastic' pituitary on imaging. Priming can increase the likelihood of a normal response in patients in the pubertal age group who do not show overt signs of pubertal development. Copyright © 2017. Published by Elsevier Ltd.

Normal growth and muscle dysfunction in X-linked hypophosphatemic rickets associated with a novel mutation in the PHEX gene.

PubMed

Makras, Polyzois; Hamdy, Neveen A T; Kant, Sarina G; Papapoulos, Socrates E

2008-04-01

X-linked hypophosphatemic rickets (XLH) is characterized by hypophosphatemia and growth retardation. Early diagnosis and treatment improve growth. Our objective was to describe long-term observations of a family with XLH due to a novel mutation of the PHEX gene with unusual clinical features, including normal growth. The mother and her two sons were followed in the same institution for nearly 30 yr. The mother had hypophosphatemia and normal height (Z score, -0.6) without ever receiving any treatment. Her two sons achieved final heights of 183.7 cm (Z score, -0.01) and 182.7 cm (Z score, -0.18), respectively, despite late initiation of treatment with phosphate and low serum phosphate levels. In addition, they had reversible proximal myopathy that took about 7 yr to resolve in one of them. Direct sequencing of the PHEX gene revealed a new splice site mutation in intron 4 of the gene (IVS4+6T-->C) resulting in skipping of exon 4. Three members of a family with XLH due to a novel mutation of the PHEX gene had a normal growth pattern despite late diagnosis and treatment of the two boys and no treatment at all of their mother. The pathophysiological basis of this phenotype-genotype association warrants further investigation.

Slow Crack Growth Analysis of Brittle Materials with Finite Thickness Subjected to Constant Stress-Rate Flexural Loading

NASA Technical Reports Server (NTRS)

Chio, S. R.; Gyekenyesi, J. P.

1999-01-01

A two-dimensional, numerical analysis of slow crack growth (SCG) was performed for brittle materials with finite thickness subjected to constant stress-rate ("dynamic fatigue") loading in flexure. The numerical solution showed that the conventional, simple, one-dimensional analytical solution can be used with a maximum error of about 5% in determining the SCG parameters of a brittle material with the conditions of a normalized thickness (a ratio of specimen thickness to initial crack size) T > 3.3 and of a SCG parameter n > 10. The change in crack shape from semicircular to elliptical configurations was significant particularly at both low stress rate and low T, attributed to predominant difference in stress intensity factor along the crack front. The numerical solution of SCG parameters was supported within the experimental range by the data obtained from constant stress-rate flexural testing for soda-lime glass microslides at ambient temperature.

Flaw growth of 7075, 7475, 7050 and 7049 aluminum alloy plate in stress corrosion environments: 4-year marine atmosphere results

NASA Technical Reports Server (NTRS)

Hasse, K. R.; Dorward, R. C.

1981-01-01

After nearly 53 months of exposure to marine atmosphere, crack growth in SL DCB specimens from 7075, 7475, 7050, and 7049-T7X plate has slowed to the arbitrary 10 to the -10 power m/sec used to define threshold stress intensity. Because some specimens appear to be approaching crack arrest, the importance of self-loading from corrosion product wedging as a significant driving force for crack propagation in overaged materials is questioned. Crack length-time data were analyzed using a computer curve fitting program which minimized the effects of normal data scatter, and provided a clearer picture of material performance. Precracked specimen data are supported by the results of smooth specimen tests. Transgranular stress corrosion cracking was observed in TL DCB specimens from all four alloys. This process is extremely slow and is characterized by a striated surface morphology.

The Kenny-Caffey syndrome: growth retardation and hypocalcemia in a young boy.

PubMed

Lee, W K; Vargas, A; Barnes, J; Root, A W

1983-04-01

A 2-year-old black boy with the Kenny-Caffey syndrome was first evaluated because of growth retardation and hypocalcemia. Hypothalamic-pituitary function was normal. Basal serum somatomedin C levels were normal for age, but did not increase during short-term administration of human growth hormone. Serum immunoreactive parathyroid hormone levels remained inappropriately low during spontaneous and induced hypocalcemia, indicating that hypocalcemia was the consequence of hypoparathyroidism. The manifestations of 15 patients with this syndrome are tabulated.

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

PubMed

Tutton, P J; Barkla, D H

1987-01-01

The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same embryonic origin and that cells exhibiting an admixture of endocrine and proliferative properties exist in colonic tumours, but not in the normal intestinal epithelium. Thus, it appears that in the normal intestine a clear structural and functional distinction exists between the regulating cells (i.e. the sympathetic neurones and enteroendocrine cells) and the regulated cells (i.e. the undifferentiated crypt cells): cells that have acquired a regulating role are no longer able to divide and cells which are able to divide do not take up or store amines.(ABSTRACT TRUNCATED AT 400 WORDS)

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development

PubMed Central

Contreras, Esteban G.; Sierralta, Jimena

2018-01-01

Background Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called ‘brain sparing’. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Results Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Conclusions Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals. PMID:29621246

p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

PubMed

Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

2018-01-01

Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

Linguistic pattern analysis of misspellings of typically developing writers in grades 1-9.

PubMed

Bahr, Ruth Huntley; Sillian, Elaine R; Berninger, Virginia W; Dow, Michael

2012-12-01

A mixed-methods approach, evaluating triple word-form theory, was used to describe linguistic patterns of misspellings. Spelling errors were taken from narrative and expository writing samples provided by 888 typically developing students in Grades 1-9. Errors were coded by category (phonological, orthographic, and morphological) and specific linguistic feature affected. Grade-level effects were analyzed with trend analysis. Qualitative analyses determined frequent error types and how use of specific linguistic features varied across grades. Phonological, orthographic, and morphological errors were noted across all grades, but orthographic errors predominated. Linear trends revealed developmental shifts in error proportions for the orthographic and morphological categories between Grades 4 and 5. Similar error types were noted across age groups, but the nature of linguistic feature error changed with age. Triple word-form theory was supported. By Grade 1, orthographic errors predominated, and phonological and morphological error patterns were evident. Morphological errors increased in relative frequency in older students, probably due to a combination of word-formation issues and vocabulary growth. These patterns suggest that normal spelling development reflects nonlinear growth and that it takes a long time to develop a robust orthographic lexicon that coordinates phonology, orthography, and morphology and supports word-specific, conventional spelling.

Translation Initiation Factor AteIF(iso)4E Is Involved in Selective mRNA Translation in Arabidopsis Thaliana Seedlings

PubMed Central

Martínez-Silva, Ana Valeria; Aguirre-Martínez, César; Flores-Tinoco, Carlos E.; Alejandri-Ramírez, Naholi D.; Dinkova, Tzvetanka D.

2012-01-01

One of the most regulated steps of translation initiation is the recruitment of mRNA by the translation machinery. In eukaryotes, this step is mediated by the 5′end cap-binding factor eIF4E bound to the bridge protein eIF4G and forming the eIF4F complex. In plants, different isoforms of eIF4E and eIF4G form the antigenically distinct eIF4F and eIF(iso)4F complexes proposed to mediate selective translation. Using a microarray analysis of polyribosome- and non-polyribosome-purified mRNAs from 15 day-old Arabidopsis thaliana wild type [WT] and eIF(iso)4E knockout mutant [(iso)4E-1] seedlings we found 79 transcripts shifted from polyribosomes toward non-polyribosomes, and 47 mRNAs with the opposite behavior in the knockout mutant. The translationally decreased mRNAs were overrepresented in root-preferentially expressed genes and proteins from the endomembrane system, including several transporters such as the phosphate transporter PHOSPHATE1 (PHO1), Sucrose transporter 3 (SUC3), ABC transporter-like with ATPase activity (MRP11) and five electron transporters, as well as signal transduction-, protein modification- and transcription-related proteins. Under normal growth conditions, eIF(iso)4E expression under the constitutive promoter 35 S enhanced the polyribosomal recruitment of PHO1 supporting its translational preference for eIF(iso)4E. Furthermore, under phosphate deficiency, the PHO1 protein increased in the eIF(iso)4E overexpressing plants and decreased in the knockout mutant as compared to wild type. In addition, the knockout mutant had larger root, whereas the 35 S directed expression of eIF(iso)4E caused shorter root under normal growth conditions, but not under phosphate deficiency. These results indicate that selective translation mediated by eIF(iso)4E is relevant for Arabidopsis root development under normal growth conditions. PMID:22363683

Constitutional Growth Delay Pattern of Growth in Velo−Cardio−Facial Syndrome: Longitudinal follow up and final height of two cases

PubMed Central

Özdemir, Nihal; Güran, Tülay; Akalın, Figen; Akçay, Teoman; Ayabakan, Canan; Yılmaz, Yüksel; Bereket, Abdullah

2008-01-01

We report two patients with velo−cardio−facial syndrome (VCFS) who were admitted to our pediatric endocrinology clinic because of short stature and followed longitudinally until attainment of final height. Both patients followed a growth pattern consistent with constitutional delay of puberty with normal and near normal final height. Case 2 also had partial growth hormone (GH) deficiency and severe short stature (height SDS −3.4 SDS), but showed spontaneous catch−up and ended up with a final height of −2 SDS. These cases suggest that short stature in children with VCFS is due to a pattern of growth similar to that observed in constitutional delay of growth and puberty. Conflict of interest:None declared. PMID:21318064

The relationship between loudness intensity functions and the click-ABR wave V latency.

PubMed

Serpanos, Y C; O'Malley, H; Gravel, J S

1997-10-01

To assess the relationship of loudness growth and the click-evoked auditory brain stem response (ABR) wave V latency-intensity function (LIF) in listeners with normal hearing or cochlear hearing loss. The effect of hearing loss configuration on the intensity functions was also examined. Behavioral and electrophysiological intensity functions were obtained using click stimuli of comparable intensities in listeners with normal hearing (Group I; n = 10), and cochlear hearing loss of flat (Group II; n = 10) or sloping (Group III; n = 10) configurations. Individual intensity functions were obtained from measures of loudness growth using the psychophysical methods of absolute magnitude estimation and production of loudness (geometrically averaged to provide the measured loudness function), and from the wave V latency measures of the ABR. Slope analyses for the behavioral and electrophysiological intensity functions were separately performed by group. The loudness growth functions for the groups with cochlear hearing loss approximated the normal function at high intensities, with overall slope values consistent with those reported from previous psychophysical research. The ABR wave V LIF for the group with a flat configuration of cochlear hearing loss approximated the normal function at high intensities, and was displaced parallel to the normal function for the group with sloping configuration. The relationship between the behavioral and electrophysiological intensity functions was examined at individual intensities across the range of the functions for each subject. A significant relationship was obtained between loudness and the ABR wave V LIFs for the groups with normal hearing and flat configuration of cochlear hearing loss; the association was not significant (p = 0.10) for the group with a sloping configuration of cochlear hearing loss. The results of this study established a relationship between loudness and the ABR wave V latency for listeners with normal hearing, and flat cochlear hearing loss. In listeners with a sloping configuration of cochlear hearing loss, the relationship was not significant. This suggests that the click-evoked ABR may be used to estimate loudness growth at least for individuals with normal hearing and those with a flat configuration of cochlear hearing loss. Predictive equations were derived to estimate loudness growth for these groups. The use of frequency-specific stimuli may provide more precise information on the nature of the relationship between loudness growth and the ABR wave V latency, particularly for listeners with sloping configurations of cochlear hearing loss.

The Ubiquitin Ligase Component Siah1a Is Required for Completion of Meiosis I in Male Mice

PubMed Central

Dickins, Ross A.; Frew, Ian J.; House, Colin M.; O'Bryan, Moira K.; Holloway, Andrew J.; Haviv, Izhak; Traficante, Nadia; de Kretser, David M.; Bowtell, David D. L.

2002-01-01

The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including β-catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytes in mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division. PMID:11884614

Using wavelength-normalized optical spectroscopy to improve the accuracy of bacteria growth rate quantification

NASA Astrophysics Data System (ADS)

McBirney, Samantha E.; Trinh, Kristy; Wong-Beringer, Annie; Armani, Andrea M.

2017-02-01

One of the fundamental analytical measurements performed in microbiology is monitoring and characterizing cell concentration in culture media. Measurement error will give rise to reproducibility problems in a wide range of applications, from biomanufacturing to basic research. Therefore, it is critical that the generated results are consistent. Single wavelength optical density (OD) measurements have become the preferred approach. Here, we compare the conventional OD600 technique with a multi-wavelength normalized scattering optical spectroscopy method to measure the growth rates of Pseudomonas aeruginosa and Staphylococcus aureus, two of the leading nosocomial pathogens with proven abilities to develop resistance. The multi-wavelength normalization process minimizes the impact of bacteria byproducts and environmental noise on the signal, thereby accurately quantifying growth rates with high fidelity at low concentrations. In contrast, due to poor absorbance and scattering at 600 nm, the classic OD600 measurement method is able to detect bacteria but cannot quantify the growth rate reliably. Our wavelength-normalization protocol to detect bacteria growth rates can be readily and easily adopted by research labs, given that it only requires the use of a standard spectrophotometer and implementation of straightforward data analysis. Measuring and monitoring bacteria growth rates play a critical role in a wide range of settings, spanning from therapeutic design and development to diagnostics and disease prevention. Having a full understanding of the growth cycles of bacteria known to cause severe infections and diseases will lead to a better understanding of the pathogenesis of these illnesses, leading to better treatment and, ultimately, the development of a cure.

Difference in C3–C4 metabolism underlies tradeoff between growth rate and biomass yield in Methylobacterium extorquens AM1

DOE PAGES

Fu, Yanfen; Beck, David A. C.; Lidstrom, Mary E.

2016-07-19

In this study, two variants of Methylobacterium extorquens AM1 demonstrated a trade-off between growth rate and biomass yield. In addition, growth rate and biomass yield were also affected by supplementation of growth medium with different amounts of cobalt. The metabolism changes relating to these growth phenomena as well as the trade-off were investigated in this study. 13C metabolic flux analysis was used to generate a detailed central carbon metabolic flux map with both absolute and normalized flux values. As a result, the major differences between the two variants occurred at the formate node as well as within C3-C4 inter-conversion pathways.more » Higher relative fluxes through formyltetrahydrofolate ligase, phosphoenolpyruvate carboxylase, and malic enzyme led to higher biomass yield, while higher relative fluxes through pyruvate kinase and pyruvate dehydrogenase led to higher growth rate. These results were then tested by phenotypic studies on three mutants (null pyk, null pck mutant and null dme mutant) in both variants, which agreed with the model prediction. In this study, 13C metabolic flux analysis for two strain variants of M. extorquens AM1 successfully identified metabolic pathways contributing to the trade-off between cell growth and biomass yield. Phenotypic analysis of mutants deficient in corresponding genes supported the conclusion that C3-C4 inter-conversion strategies were the major response to the trade-off.« less

Difference in C3–C4 metabolism underlies tradeoff between growth rate and biomass yield in Methylobacterium extorquens AM1

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

Fu, Yanfen; Beck, David A. C.; Lidstrom, Mary E.

In this study, two variants of Methylobacterium extorquens AM1 demonstrated a trade-off between growth rate and biomass yield. In addition, growth rate and biomass yield were also affected by supplementation of growth medium with different amounts of cobalt. The metabolism changes relating to these growth phenomena as well as the trade-off were investigated in this study. 13C metabolic flux analysis was used to generate a detailed central carbon metabolic flux map with both absolute and normalized flux values. As a result, the major differences between the two variants occurred at the formate node as well as within C3-C4 inter-conversion pathways.more » Higher relative fluxes through formyltetrahydrofolate ligase, phosphoenolpyruvate carboxylase, and malic enzyme led to higher biomass yield, while higher relative fluxes through pyruvate kinase and pyruvate dehydrogenase led to higher growth rate. These results were then tested by phenotypic studies on three mutants (null pyk, null pck mutant and null dme mutant) in both variants, which agreed with the model prediction. In this study, 13C metabolic flux analysis for two strain variants of M. extorquens AM1 successfully identified metabolic pathways contributing to the trade-off between cell growth and biomass yield. Phenotypic analysis of mutants deficient in corresponding genes supported the conclusion that C3-C4 inter-conversion strategies were the major response to the trade-off.« less

Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes.

PubMed

Yao, Jiangwei; Ericson, Megan E; Frank, Matthew W; Rock, Charles O

2016-12-01

Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogen Listeria monocytogenes encode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype of Escherichia coli strain JP1111 [fabI(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate of L. monocytogenes in laboratory medium. Robust exogenous fatty acid incorporation was not detected in L. monocytogenes unless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth of L. monocytogenes, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth of L. monocytogenes Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth of L. monocytogenes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Separation of metabolic supply and demand: aerobic glycolysis as a normal physiological response to fluctuating energetic demands in the membrane.

PubMed

Epstein, Tamir; Xu, Liping; Gillies, Robert J; Gatenby, Robert A

2014-01-01

Cancer cells, and a variety of normal cells, exhibit aerobic glycolysis, high rates of glucose fermentation in the presence of normal oxygen concentrations, also known as the Warburg effect. This metabolism is considered abnormal because it violates the standard model of cellular energy production that assumes glucose metabolism is predominantly governed by oxygen concentrations and, therefore, fermentative glycolysis is an emergency back-up for periods of hypoxia. Though several hypotheses have been proposed for the origin of aerobic glycolysis, its biological basis in cancer and normal cells is still not well understood. We examined changes in glucose metabolism following perturbations in membrane activity in different normal and tumor cell lines and found that inhibition or activation of pumps on the cell membrane led to reduction or increase in glycolysis, respectively, while oxidative phosphorylation remained unchanged. Computational simulations demonstrated that these findings are consistent with a new model of normal physiological cellular metabolism in which efficient mitochondrial oxidative phosphorylation supplies chronic energy demand primarily for macromolecule synthesis and glycolysis is necessary to supply rapid energy demands primarily to support membrane pumps. A specific model prediction was that the spatial distribution of ATP-producing enzymes in the glycolytic pathway must be primarily localized adjacent to the cell membrane, while mitochondria should be predominantly peri-nuclear. The predictions were confirmed experimentally. Our results show that glycolytic metabolism serves a critical physiological function under normoxic conditions by responding to rapid energetic demand, mainly from membrane transport activities, even in the presence of oxygen. This supports a new model for glucose metabolism in which glycolysis and oxidative phosphorylation supply different types of energy demand. Cells use efficient but slow-responding aerobic metabolism to meet baseline, steady energy demand and glycolytic metabolism, which is inefficient but can rapidly increase adenosine triphosphate (ATP) production, to meet short-timescale energy demands, mainly from membrane transport activities. In this model, the origin of the Warburg effect in cancer cells and aerobic glycolysis in general represents a normal physiological function due to enhanced energy demand for membrane transporters activity required for cell division, growth, and migration.

Extracting Spurious Latent Classes in Growth Mixture Modeling with Nonnormal Errors

ERIC Educational Resources Information Center

Guerra-Peña, Kiero; Steinley, Douglas

2016-01-01

Growth mixture modeling is generally used for two purposes: (1) to identify mixtures of normal subgroups and (2) to approximate oddly shaped distributions by a mixture of normal components. Often in applied research this methodology is applied to both of these situations indistinctly: using the same fit statistics and likelihood ratio tests. This…

Effects of an advanced temperature cycle on smolt development and endocrinology indicate that temperature is not a zeitgeber for smolting in Atlantic salmon

USGS Publications Warehouse

McCormick, S.D.; Shrimpton, J.M.; Moriyama, S.; Bjornsson, Bjorn Thrandur

2002-01-01

Atlantic salmon (Salmo salar) juveniles were reared under simulated conditions of normal photoperiod (LDN) or short days (LD 9:15) and ambient temperature (AMB: normal temperature increases in April) or an advanced temperature cycle (ADV: temperature increases in February). Under both photoperiod conditions, the timing of increased and peak levels of gill Na+,K+-ATPase activity were not altered by temperature, although the rate of increase was initially greater under ADV. ADV/LD 9:15 resulted in peak gill Na+,K+-ATPase activity that was half of that seen under normal photoperiod and temperature conditions. Plasma growth hormone (GH) levels increased threefold in late March under ADV/LDN, but not under ADV/LD 9:15, indicating that there is a photoperiod-dependent effect of temperature on levels of this hormone. Plasma insulin-like growth factor I (IGF-I) increased in spring in all groups, with increases occurring significantly earlier in the ADV/LDN group. In each photoperiod condition, the advanced temperature cycle resulted in large decreases in plasma thyroxine (T4) levels in March, which subsequently recovered, whereas plasma 3,5,3???-triiodo-L-thyronine (T3) levels were not substantially affected by either photoperiod or temperature. There was no consistent pattern of change in plasma cortisol levels. The results do not provide support for the role of temperature as a zeitgeber, but do indicate that temperature has a role in the timing of smolting by affecting the rate of development and interacting with the photoperiod.

Parenthood by design.

PubMed

Sleep, J

1986-02-01

Parenthood by design involves realistic preparation for practical aspects of parenting as well as the romantic illusions fostered by relatives, social pressure, and the media. The ideals do not mention the physical discomfort, exhaustion, jealousy, anger and frustration encountered in a normal puerperium. Many women have not returned to normal sexual activity, work and sports even by 6 weeks after delivery. Perineal discomfort is still experienced by 70% after 10 days, especially in cases of assisted vaginal delivery. Urinary incontinence is present in 20% up to 3 months after normal vaginal delivery. Many women report fatigue as the reason for not resuming sexual intercourse. Family interactions are stressed by the newcomer: rivalry on the part of the husband or siblings is common. Modern education in the attempt to train people for vocational competence has left out parenting. In England, midwives teach classes of 20 women for 5 contact hours in late pregnancy, and are expected to cover all aspects of pregnancy, labor, delivery, baby care, postnatal adjustment and support services. The schools have sex education, fostering freedom in life styles for young people, but little emphasis on responsibility. There are some community organizations such as the La Leche League, the National Childbirth Trust and the Meet-A-Mum Association that offer support during and after pregnancy. Accidental pregnancy with education as crisis intervention is inadequate for the future; parenthood by design would permit couples to experience parenthood as a period of growth based on a fuller understanding of practical reality.

Fatty acid profile of maternal and fetal erythrocytes and placental expression of fatty acid transport proteins in normal and intrauterine growth restriction pregnancies.

PubMed

Assumpção, Renata P; Mucci, Daniela B; Fonseca, Fernanda C P; Marcondes, Henrique; Sardinha, Fátima L C; Citelli, Marta; Tavares do Carmo, Maria G

2017-10-01

Long-chain polyunsaturated fatty acids (LC-PUFA), mainly docosahexaenoic (DHA) and arachidonic acids (AA), are critical for adequate fetal growth and development. We investigated mRNA expression of proteins involved in hydrolysis, uptake and/or transport of fatty acids in placenta of fifteen full term normal pregnancies and eleven pregnancies complicated by intrauterine growth restriction (IUGR) with normal umbilical blood flows. The mRNA expression of LPL, FATPs (-1, -2 and -4) and FABPs (-1 and -3) was increased in IUGR placentas, however, tissue profile of LC-PUFA was not different between groups. Erythrocytes from both mothers and fetuses of the IUGR group showed lower concentrations of AA and DHA and inferior DHA/ALA ratio compared to normal pregnancies (P < 0.05). We hypothesize that reduced circulating levels of AA and DHA could up-regulate mRNA expression of placental fatty acids transporters, as a compensatory mechanism, however this failed to sustain normal LC-PUFA supply to the fetus in IUGR. Copyright © 2017 Elsevier Ltd. All rights reserved.

Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses.

PubMed

Tse, J Y; Lao, T T; Chan, C C; Chiu, P M; Cheung, A N

2001-01-01

Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.

Impact of sickle cell trait on physical growth in tribal children of Mandla district in Madhya Pradesh, India.

PubMed

Qamra, Suneel; Roy, Jyotirmoy; Srivastava, Praval

2011-11-01

Reliable reports on growth impairment in sickle cell trait (SCT) children in India are lacking despite contradictory findings reported earlier. The present study assessed the impact of SCT on physical growth of tribal children of Mandla district. Weight, height, circumferences, breadths, lengths and skinfolds were recorded on 6190 children, inclusive of 732 SCT children, from birth to 12 years of age using a cross-sectional design. The sickle test was conducted in the field using 2% sodium metabisulphite followed by electrophoresis. No significant difference in mean values was observed in the majority of the age groups between SCT and normal children for all 11 body measurements. However, inconsistent growth patterns in these measurements among SCT children were evident. Body weight was more deficient than height or other body measurements in the children when compared to Indian and National Centre for Health Statistics (NCHS) standards, while bicristal breadth was comparable with Indian standards. There was no significant impact of SCT observed on growth of children irrespective of sex. Notably, growth of SCT girls was comparable to their normal counterparts. The actual growth difference between normal and SCT children may have been masked on account of poor attainment of annual gain in each successive age group.

Epoxyeicosanoids promote organ and tissue regeneration.

PubMed

Panigrahy, Dipak; Kalish, Brian T; Huang, Sui; Bielenberg, Diane R; Le, Hau D; Yang, Jun; Edin, Matthew L; Lee, Craig R; Benny, Ofra; Mudge, Dayna K; Butterfield, Catherine E; Mammoto, Akiko; Mammoto, Tadanori; Inceoglu, Bora; Jenkins, Roger L; Simpson, Mary A; Akino, Tomoshige; Lih, Fred B; Tomer, Kenneth B; Ingber, Donald E; Hammock, Bruce D; Falck, John R; Manthati, Vijaya L; Kaipainen, Arja; D'Amore, Patricia A; Puder, Mark; Zeldin, Darryl C; Kieran, Mark W

2013-08-13

Epoxyeicosatrienoic acids (EETs), lipid mediators produced by cytochrome P450 epoxygenases, regulate inflammation, angiogenesis, and vascular tone. Despite pleiotropic effects on cells, the role of these epoxyeicosanoids in normal organ and tissue regeneration remains unknown. EETs are produced predominantly in the endothelium. Normal organ and tissue regeneration require an active paracrine role of the microvascular endothelium, which in turn depends on angiogenic growth factors. Thus, we hypothesize that endothelial cells stimulate organ and tissue regeneration via production of bioactive EETs. To determine whether endothelial-derived EETs affect physiologic tissue growth in vivo, we used genetic and pharmacological tools to manipulate endogenous EET levels. We show that endothelial-derived EETs play a critical role in accelerating tissue growth in vivo, including liver regeneration, kidney compensatory growth, lung compensatory growth, wound healing, corneal neovascularization, and retinal vascularization. Administration of synthetic EETs recapitulated these results, whereas lowering EET levels, either genetically or pharmacologically, delayed tissue regeneration, demonstrating that pharmacological modulation of EETs can affect normal organ and tissue growth. We also show that soluble epoxide hydrolase inhibitors, which elevate endogenous EET levels, promote liver and lung regeneration. Thus, our observations indicate a central role for EETs in organ and tissue regeneration and their contribution to tissue homeostasis.

Psychological and emotional development, intellectual capabilities, and body image in short normal children.

PubMed

Molinari, E; Sartori, A; Ceccarelli, A; Marchi, S

2002-04-01

It is well established that children with short stature frequently have problems in cognitive development, personality, self-esteem and social relations. This is partly due to the fact that many parents view them as more vulnerable than other children of normal stature and do not allow them to face the normal experiences that correspond to their actual age. The aim of the present study was to assess, through the administration of appropriate psychological tools, a series of psychological and cognitive characteristics [i.e. anxiety, depression, good adjustment, social functioning, feeling of guilt, interpersonal relationship, intelligence quotient (IQ)], as well as variables linked to development of body image, in a group of children suffering from normal growth variants [familial short stature (FSS), no. 10, 4 males/6 females; with constitutional growth delay (CGD), no. 4,4 males; height standard deviation score (HSDS) ranging between -2.4 and -1.9] and in a control group children of normal stature (HSDS between -0.1 and +0.1). Children with short stature significantly differed from normal statured controls as far as Colored Progressive Matrices (CPMs, centiles), IQ (IQ, obtained using the Goodenough test), "Good Adjustment" (Draw-a-Person index, DAP), "Feelings of Guilt" (DAP index), "Height" (as emerges from drawings of the body) are concerned. Significant relationships were found between the height of the subjects (in centiles) and cognitive skills, measured both using CPMs (r=0.408; p=0.017) and Draw-a-Man (DAM) (r=0.359; p=0.037) and between height and feelings of guilt (r=0.325; p=0.027), measured using DAP. CPM scores correlated positively with the "Good Adjustment" index of DAP (r=0.354; p=0.05) and negatively with Children's Depression Inventory (CDI) (r=-0.609; p=0.01), "School Anxiety" index (r=-0.427; p=0.05) and "Total Anxiety" index (r=-0.436; p=0.05) of the Anxiety Scale Questionnaire for the Age of Development, and with 2 indices of DAP, namely, "Feelings of Guilt" (r=-0.461; p=0.01) and "Interpersonal Relationships (Difficulty in Establishing)" (r=-0.455; p=0.01). A significant positive correlation was found between the height of the subject and both the measurement of the "Body of Drawing 3" (r=0.450, p=0.01) and the measurement of the "Body of Drawing 4" (r=0.461, p=0.01), as well as the with the "Total Height of Drawing 4" (r=0.464, p=0.01). Higher indices for anxiety, depression, feelings of guilt and difficulty in establishing interpersonal relationships and lower indices for good adjustment were found in children with CGD as compared to subjects with FSS or normal statured children. Although further additional studies on larger samples are needed to confirm these preliminary observations, the present study underlines the importance of psychological support also during the growth and development in short normal children.

Normal growth and development in the absence of hepatic insulin-like growth factor I

PubMed Central

Yakar, Shoshana; Liu, Jun-Li; Stannard, Bethel; Butler, Andrew; Accili, Domenici; Sauer, Brian; LeRoith, Derek

1999-01-01

The somatomedin hypothesis proposed that insulin-like growth factor I (IGF-I) was a hepatically derived circulating mediator of growth hormone and is a crucial factor for postnatal growth and development. To reassess this hypothesis, we have used the Cre/loxP recombination system to delete the igf1 gene exclusively in the liver. igf1 gene deletion in the liver abrogated expression of igf1 mRNA and caused a dramatic reduction in circulating IGF-I levels. However, growth as determined by body weight, body length, and femoral length did not differ from wild-type littermates. Although our model proves that hepatic IGF-I is indeed the major contributor to circulating IGF-I levels in mice it challenges the concept that circulating IGF-I is crucial for normal postnatal growth. Rather, our model provides direct evidence for the importance of the autocrine/paracrine role of IGF-I. PMID:10377413

Circulating levels of IGF-1 directly regulate bone growth and density

PubMed Central

Yakar, Shoshana; Rosen, Clifford J.; Beamer, Wesley G.; Ackert-Bicknell, Cheryl L.; Wu, Yiping; Liu, Jun-Li; Ooi, Guck T.; Setser, Jennifer; Frystyk, Jan; Boisclair, Yves R.; LeRoith, Derek

2002-01-01

IGF-1 is a growth-promoting polypeptide that is essential for normal growth and development. In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS). This complex prolongs the half-life of serum IGFs and facilitates their endocrine actions. Liver IGF-1–deficient (LID) mice and ALS knockout (ALSKO) mice exhibited relatively normal growth and development, despite having 75% and 65% reductions in serum IGF-1 levels, respectively. Double gene disrupted mice were generated by crossing LID+ALSKO mice. These mice exhibited further reductions in serum IGF-1 levels and a significant reduction in linear growth. The proximal growth plates of the tibiae of LID+ALSKO mice were smaller in total height as well as in the height of the proliferative and hypertrophic zones of chondrocytes. There was also a 10% decrease in bone mineral density and a greater than 35% decrease in periosteal circumference and cortical thickness in these mice. IGF-1 treatment for 4 weeks restored the total height of the proximal growth plate of the tibia. Thus, the double gene disruption LID+ALSKO mouse model demonstrates that a threshold concentration of circulating IGF-1 is necessary for normal bone growth and suggests that IGF-1, IGFBP-3, and ALS play a prominent role in the pathophysiology of osteoporosis. PMID:12235108

Developmental milestones record - 6 months

MedlinePlus

Normal childhood growth milestones - 6 months; Childhood growth milestones - 6 months; Growth milestones for children - 6 months ... the weight on hands (often occurs by 4 months) Able to pick up a dropped object Able ...

The protective effect of curcumin in Olfactory Ensheathing Cells exposed to hypoxia.

PubMed

Bonfanti, Roberta; Musumeci, Teresa; Russo, Cristina; Pellitteri, Rosalia

2017-02-05

Curcumin, a phytochemical component derived from the rhizomes of Curcuma longa, has shown a great variety of pharmacological activities, such as anti-inflammatory, anti-tumor, anti-depression and anti-oxidant activity. Therefore, in the last years it has been used as a therapeutic agent since it confers protection in different neurodegenerative diseases, cerebral ischemia and excitotoxicity. Olfactory Ensheathing Cells (OECs) are glial cells of the olfactory system. They are able to secrete several neurotrophic growth factors, promote axonal growth and support the remyelination of damaged axons. OEC transplantation has emerged as a possible experimental therapy to induce repair of spinal cord injury, even if the functional recovery is still limited. Since hypoxia is a secondary effect in spinal cord injury, this in vitro study investigates the protective effect of curcumin in OECs exposed to hypoxia. Primary OECs were obtained from neonatal rat olfactory bulbs and placed both in normal and hypoxic conditions. Furthermore, some cells were grown with basic Fibroblast Growth Factor (bFGF) and/or curcumin at different concentration and times. The results obtained through immunocytochemical procedures and MTT test show that curcumin stimulates cell viability in OECs grown in normal and hypoxic conditions. Furthermore, the synergistic effect of curcumin and bFGF is the most effective exerting protection on OECs. Since spinal cord injury is often accompanied by secondary insults, such as ischemia or hypoxia, our results suggest that curcumin in combination with bFGF might be considered a possible approach for restoration in injuries. Copyright © 2016 Elsevier B.V. All rights reserved.

Inadequate thickness of the weight-bearing surface of claws in ruminants.

PubMed

Shakespeare, A S

2009-12-01

The term 'thin soles' refers to the suboptimal thickness of the weight-bearing surface of claws in ruminants. These palmar/plantar surfaces of the claws support the weight of the animal and consist of the distal wall horn, the sole proper, the heel and the minute white line area. The sole should normally only bear weight on uneven or undulating surfaces. A decrease in the thickness of the weight-bearing claw surface will decrease the protective function of this structure and may alter the proportion of weight-bearing by each section with possible detrimental effects on hoof function. Horn tissue readily absorbs water and becomes softer which can lead to increased wear rates. Growth rates normally match wear rates but, unlike the latter, time is needed for the growth rate response to adapt to changes in wear rate. Concrete surfaces can be abrasive and dairy cows that spend their lactation cycle on these floors should be let out to pasture in the dry period so that their claws can recoup lost horn. Frictional coefficient is a measure of the'slipperiness' of hooves on various surfaces. Newly laid or fresh concrete is not only abrasive but the thin surface suspension of calcium hydroxide that forms has a very alkaline pH which causes keratin degradation and is mostly responsible for the excessive claw wear that occurs. Four case studies are used to illustrate the importance of the distal wall horn, the dangers of over-trimming and the effects of disease and concrete on horn growth and wear rates.

Orchestrating the Tumor Microenvironment to Improve Survival for Patients With Pancreatic Cancer: Normalization, Not Destruction.

PubMed

Whatcott, Clifford J; Han, Haiyong; Von Hoff, Daniel D

2015-01-01

Pancreatic cancer is the fourth leading cause of cancer death in the United States. The microenvironment of pancreatic cancer could be one of the "perfect storms" that support the growth of a cancer. Indeed, pancreatic cancer may be the poster child of a problem with the microenvironment. In this article, we review the rationale and attempts to date on modifying or targeting structural proteins in the microenvironment including hyaluronan (HA) (in primary and metastases), collagen, and SPARC (secreted protein, acidic, and rich in cysteine). Indeed, working in this area has produced a regimen that improves survival for patients with advanced pancreatic cancer (nab-paclitaxel + gemcitabine). In addition, in initial clinical trials, PEGylated hyaluronidase appears promising. We also review a new approach that is different than targeting/destroying the microenvironment and that is orchestrating, reengineering, reprogramming, or normalizing the microenvironment (including normalizing structural proteins, normalizing an immunologically tumor-friendly environment to a less friendly environment, reversing epithelial-to-mesenchymal transition, and so on). We believe this will be most effectively done by agents that have global effects on transcription. There is initial evidence that this can be done by agents such as vitamin D derivatives and other new agents. There is no doubt these opportunities can now be tried in the clinic with hopefully beneficial effects.

Thyroid Cells Exposed to Simulated Microgravity Conditions - Comparison of the Fast Rotating Clinostat and the Random Positioning Machine

NASA Astrophysics Data System (ADS)

Warnke, Elisabeth; Kopp, Sascha; Wehland, Markus; Hemmersbach, Ruth; Bauer, Johann; Pietsch, Jessica; Infanger, Manfred; Grimm, Daniela

2016-06-01

The ground-based facilities 2D clinostat (CN) and Random Positioning Machine (RPM) were designed to simulate microgravity conditions on Earth. With support of the CORA-ESA-GBF program we could use both facilities to investigate the impact of simulated microgravity on normal and malignant thyroid cells. In this review we report about the current knowledge of thyroid cancer cells and normal thyrocytes grown under altered gravity conditions with a special focus on growth behaviour, changes in the gene expression pattern and protein content, as well as on altered secretion behaviour of the cells. We reviewed data obtained from normal thyrocytes and cell lines (two poorly differentiated follicular thyroid cancer cell lines FTC-133 and ML-1, as well as the normal thyroid cell lines Nthy-ori 3-1 and HTU-5). Thyroid cells cultured under conditions of simulated microgravity (RPM and CN) and in Space showed similar changes with respect to spheroid formation. In static 1 g control cultures no spheroids were detectable. Changes in the regulation of cytokines are discussed to be involved in MCS (multicellular spheroids) formation. The ESA-GBF program helps the scientists to prepare future spaceflight experiments and furthermore, it might help to identify targets for drug therapy against thyroid cancer.

Immobilization of Growth Factors to Collagen Surfaces Using Pulsed Visible Light.

PubMed

Fernandes-Cunha, Gabriella M; Lee, Hyun Jong; Kumar, Alisha; Kreymerman, Alexander; Heilshorn, Sarah; Myung, David

2017-10-09

In the treatment of traumatic injuries, burns, and ulcers of the eye, inadequate epithelial tissue healing remains a major challenge. Wound healing is a complex process involving the temporal and spatial interplay between cells and their extracellular milieu. It can be impaired by a variety of causes including infection, poor circulation, loss of critical cells, and/or proteins, and a deficiency in normal neural signaling (e.g., neurotrophic ulcers). Ocular anatomy is particularly vulnerable to lasting morbidity from delayed healing, whether it be scarring or perforation of the cornea, destruction of the conjunctival mucous membrane, or cicatricial changes to the eyelids and surrounding skin. Therefore, there is a major clinical need for new modalities for controlling and accelerating wound healing, particularly in the eye. Collagen matrices have long been explored as scaffolds to support cell growth as both two-dimensional coatings and substrates, as well as three-dimensional matrices. Meanwhile, the immobilization of growth factors to various substrates has also been extensively studied as a way to promote enhanced cellular adhesion and proliferation. Herein we present a new strategy for photochemically immobilizing growth factors to collagen using riboflavin as a photosensitizer and exposure to visible light (∼458 nm). Epidermal growth factor (EGF) was successfully bound to collagen-coated surfaces as well as directly to endogenous collagen from porcine corneas. The initial concentration of riboflavin and EGF as well as the blue light exposure time were keys to the successful binding of growth factors to these surfaces. The photocrosslinking reaction increased EGF residence time on collagen surfaces over 7 days. EGF activity was maintained after the photocrosslinking reaction with a short duration of pulsed blue light exposure. Bound EGF accelerated in vitro corneal epithelial cell proliferation and migration and maintained normal cell phenotype. Additionally, the treated surfaces were cytocompatible, and the photocrosslinking reaction was proven to be safe, preserving nearly 100% cell viability. These results suggest that this general approach is safe and versatile may be used for targeting and immobilizing bioactive factors onto collagen matrices in a variety of applications, including in the presence of live, seeded cells or in vivo onto endogenous extracellular matrix collagen.

Suppressing magnetic island growth by resonant magnetic perturbation

NASA Astrophysics Data System (ADS)

Yu, Q.; Günter, S.; Lackner, K.

2018-05-01

The effect of externally applied resonant magnetic perturbations (RMPs) on the growth of magnetic islands is investigated based on two-fluid equations. It is found that if the local bi-normal electron fluid velocity at the resonant surface is sufficiently large, static RMPs of the same helicity and of moderate amplitude can suppress the growth of magnetic islands in high-temperature plasmas. These islands will otherwise grow, driven by an unfavorable plasma current density profile and bootstrap current perturbation. These results indicate that the error field can stabilize island growth, if the error field amplitude is not too large and the local bi-normal electron fluid velocity is not too low. They also indicate that applied rotating RMPs with an appropriate frequency can be utilized to suppress island growth in high-temperature plasmas, even for a low bi-normal electron fluid velocity. A significant change in the local equilibrium plasma current density gradient by small amplitude RMPs is found for realistic plasma parameters, which are important for the island stability and are expected to be more important for fusion reactors with low plasma resistivity.

Effect of Growth Hormone Deficiency on Brain Structure, Motor Function and Cognition

ERIC Educational Resources Information Center

Webb, Emma A.; O'Reilly, Michelle A.; Clayden, Jonathan D.; Seunarine, Kiran K.; Chong, Wui K.; Dale, Naomi; Salt, Alison; Clark, Chris A.; Dattani, Mehul T.

2012-01-01

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone less than 6.7 [micro]g/l) and idiopathic short stature (peak growth hormone greater than 10 [micro]g/l)…

Testosterone inhibits the growth of prostate cancer xenografts in nude mice.

PubMed

Song, Weitao; Soni, Vikram; Soni, Samit; Khera, Mohit

2017-09-07

Traditional beliefs of androgen's stimulating effects on the growth of prostate cancer (PCa) have been challenged in recent years. Our previous in vitro study indicated that physiological normal levels of androgens inhibited the proliferation of PCa cells. In this in vivo study, the ability of testosterone (T) to inhibit PCa growth was assessed by testing the tumor incidence rate and tumor growth rate of PCa xenografts on nude mice. Different serum testosterone levels were manipulated in male nude/nude athymic mice by orchiectomy or inserting different dosages of T pellets subcutaneously. PCa cells were injected subcutaneously to nude mice and tumor incidence rate and tumor growth rate of PCa xenografts were tested. The data demonstrated that low levels of serum T resulted in the highest PCa incidence rate (50%). This PCa incidence rate in mice with low T levels was significantly higher than that in mice treated with higher doses of T (24%, P < 0.01) and mice that underwent orchiectomy (8%, P < 0.001). Mice that had low serum T levels had the shortest tumor volume doubling time (112 h). This doubling time was significantly shorter than that in the high dose 5 mg T arm (158 h, P < 0.001) and in the orchiectomy arm (468 h, P < 0.001). These results indicated that low T levels are optimal for PCa cell growth. Castrate T levels, as seen after orchiectomy, are not sufficient to support PCa cell growth. Higher levels of serum T inhibited PCa cell growth.

[Growth hormone treatment update].

PubMed

2014-02-01

Short stature in children is a common cause for referral to pediatric endocrinologists, corresponding most times to normal variants of growth. Initially growth hormone therapy was circumscribed to children presenting growth hormone deficiency. Since the production of recombinant human hormone its use had spread to other pathologies.

Growth in pediatric renal transplant recipients.

PubMed

Vasudevan, A; Phadke, K

2007-04-01

One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.

Bradykinin-induced growth inhibition of normal rat kidney (NRK) cells is paralleled by a decrease in epidermal-growth-factor receptor expression.

PubMed Central

Van Zoelen, E J; Peters, P H; Afink, G B; Van Genesen, S; De Roos, D G; Van Rotterdam, W; Theuvenet, A P

1994-01-01

Normal rat kidney fibroblasts, grown to density arrest in the presence of epidermal growth factor (EGF), can be induced to undergo phenotypic transformation by treatment with transforming growth factor beta or retinoic acid. Here we show that bradykinin blocks this growth-stimulus-induced loss of density-dependent growth arrest by a specific receptor-mediated mechanism. The effects of bradykinin are specific, and are not mimicked by other phosphoinositide-mobilizing agents such as prostaglandin F2 alpha. Northern-blot analysis and receptor-binding studies demonstrate that bradykinin also inhibits the retinoic acid-induced increase in EGF receptor levels in these cells. These studies provide additional evidence that EGF receptor levels modulate EGF-induced expression of the transformed phenotype in these cells. Images Figure 5 PMID:8135739

Studies on the growth of the fetal guinea pig. The effects of ligation of the uterine artery on organ growth and development.

PubMed

Lafeber, H N; Rolph, T P; Jones, C T

1984-12-01

The effects of reduced maternal placental blood flow on the growth and development of the fetal guinea pig have been studied by unilateral ligation of the uterine artery at day 30 of pregnancy. Fetal guinea pigs were investigated about 20 or 30 days later. In about one-third of cases fetal death occurred, in another third fetuses less than 60% of normal weight were observed and in the remainder all fetuses were in the normal weight range. In the growth retarded fetuses prenatal growth occurred at about 50% of the rate in control. There was no postnatal 'catch up' as growth still remained lower than in controls. Restricted fetal growth affected particularly development of the visceral tissues in which case size declined in proportion to body weight. Brain and adrenal by comparison were less affected as their contribution to total body weight increased, but even so in the severely retarded fetuses the mass of both fell. The responses of the liver were in general consistent with a delay in the pattern of development. Thus DNA, RNA, protein and haematopoietic cell content changes occurred later than normal. In contrast an enhanced deposition of glycogen was apparent in the liver of the growth-retarded fetus. The results indicate some of the ways in which nutritional deprivation of the fetuses leads to reprogramming of growth and maturation of selected fetal tissues to allow non-essential changes to await more favourable times.

Expression of von Willebrand factor and caldesmon in the placental tissues of pregnancies complicated with intrauterine growth restriction.

PubMed

Göksever Çelik, Hale; Uhri, Mehmet; Yildirim, Gökhan

2017-11-02

The decreased placental perfusion is the underlying reason for intrauterine growth restriction that in turn leads to reduced placental perfusion and ischemia. However, there are several issues to be understood in the pathophysiology of intrauterine growth restriction. We aimed to study whether any compensatory response in placental vascular bed occur in pregnancies complicated with intrauterine growth restriction by the immunohistochemical staining of von Willebrand factor and caldesmon in placental tissues. A total of 103 pregnant women was enrolled in the study including 50 patients who were complicated with IUGR and 50 uncomplicated control patients. The study was designed in a prospective manner. All placentas were also stained with von Willebrand factor and caldesmon monoclonal kits. The immunohistochemical staining of von Willebrand factor and caldesmon expressions in placental tissues were different between normal and intrauterine growth restriction group. The percentages of 2+ and 3+ von Willebrand factor expression were higher in the intrauterine growth restriction group comparing with the normal group, although the difference was not statistically significant. The intensity of caldesmon expression was significantly lower in the intrauterine growth restriction group in comparison with the normal group (p < .001). Angiogenesis occurs as a placental response to intrauterine growth restriction which is a hypoxic condition. But newly formed vessels are immature and not strong enough. Our study is important to clarify the pathophysiology and placental compensatory responses in intrauterine growth restriction.

Growth curves of preschool children in the northeast of iran: a population based study using quantile regression approach.

PubMed

Payande, Abolfazl; Tabesh, Hamed; Shakeri, Mohammad Taghi; Saki, Azadeh; Safarian, Mohammad

2013-01-14

Growth charts are widely used to assess children's growth status and can provide a trajectory of growth during early important months of life. The objectives of this study are going to construct growth charts and normal values of weight-for-age for children aged 0 to 5 years using a powerful and applicable methodology. The results compare with the World Health Organization (WHO) references and semi-parametric LMS method of Cole and Green. A total of 70737 apparently healthy boys and girls aged 0 to 5 years were recruited in July 2004 for 20 days from those attending community clinics for routine health checks as a part of a national survey. Anthropometric measurements were done by trained health staff using WHO methodology. The nonparametric quantile regression method obtained by local constant kernel estimation of conditional quantiles curves using for estimation of curves and normal values. The weight-for-age growth curves for boys and girls aged from 0 to 5 years were derived utilizing a population of children living in the northeast of Iran. The results were similar to the ones obtained by the semi-parametric LMS method in the same data. Among all age groups from 0 to 5 years, the median values of children's weight living in the northeast of Iran were lower than the corresponding values in WHO reference data. The weight curves of boys were higher than those of girls in all age groups. The differences between growth patterns of children living in the northeast of Iran versus international ones necessitate using local and regional growth charts. International normal values may not properly recognize the populations at risk for growth problems in Iranian children. Quantile regression (QR) as a flexible method which doesn't require restricted assumptions, proposed for estimation reference curves and normal values.

Growth Curves of Preschool Children in the Northeast of Iran: A Population Based Study Using Quantile Regression Approach

PubMed Central

Payande, Abolfazl; Tabesh, Hamed; Shakeri, Mohammad Taghi; Saki, Azadeh; Safarian, Mohammad

2013-01-01

Introduction: Growth charts are widely used to assess children’s growth status and can provide a trajectory of growth during early important months of life. The objectives of this study are going to construct growth charts and normal values of weight-for-age for children aged 0 to 5 years using a powerful and applicable methodology. The results compare with the World Health Organization (WHO) references and semi-parametric LMS method of Cole and Green. Methods: A total of 70737 apparently healthy boys and girls aged 0 to 5 years were recruited in July 2004 for 20 days from those attending community clinics for routine health checks as a part of a national survey. Anthropometric measurements were done by trained health staff using WHO methodology. The nonparametric quantile regression method obtained by local constant kernel estimation of conditional quantiles curves using for estimation of curves and normal values. Results: The weight-for-age growth curves for boys and girls aged from 0 to 5 years were derived utilizing a population of children living in the northeast of Iran. The results were similar to the ones obtained by the semi-parametric LMS method in the same data. Among all age groups from 0 to 5 years, the median values of children’s weight living in the northeast of Iran were lower than the corresponding values in WHO reference data. The weight curves of boys were higher than those of girls in all age groups. Conclusion: The differences between growth patterns of children living in the northeast of Iran versus international ones necessitate using local and regional growth charts. International normal values may not properly recognize the populations at risk for growth problems in Iranian children. Quantile regression (QR) as a flexible method which doesn’t require restricted assumptions, proposed for estimation reference curves and normal values. PMID:23618470

Slow Growth and Urban Sprawl: Support for a New Regional Agenda?

ERIC Educational Resources Information Center

Gainsborough, Juliet F.

2002-01-01

Assessed the possibilities for coalition building around growth related concerns, exploring support for slowing growth in New York City and Los Angeles. Analyzed data from surveys of urban and suburban dwellers regarding support for growth control measures. Suburbanites were much more receptive to slow growth policies than were urbanites, though…

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure.

PubMed

Massie, Isobel; Dale, Sarah B; Daniels, Julie T

2015-06-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE- RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP.

Limbal Fibroblasts Maintain Normal Phenotype in 3D RAFT Tissue Equivalents Suggesting Potential for Safe Clinical Use in Treatment of Ocular Surface Failure

PubMed Central

Dale, Sarah B.; Daniels, Julie T.

2015-01-01

Limbal epithelial stem cell deficiency can cause blindness, but transplantation of these cells on a carrier such as human amniotic membrane can restore vision. Unfortunately, clinical graft manufacture using amnion can be inconsistent. Therefore, we have developed an alternative substrate, Real Architecture for 3D Tissue (RAFT), which supports human limbal epithelial cells (hLE) expansion. Epithelial organization is improved when human limbal fibroblasts (hLF) are incorporated into RAFT tissue equivalent (TE). However, hLF have the potential to transdifferentiate into a pro-scarring cell type, which would be incompatible with therapeutic transplantation. The aim of this work was to assess the scarring phenotype of hLF in RAFT TEs in hLE+ and hLE− RAFT TEs and in nonairlifted and airlifted RAFT TEs. Diseased fibroblasts (dFib) isolated from the fibrotic conjunctivae of ocular mucous membrane pemphigoid (Oc-MMP) patients were used as a pro-scarring positive control against which hLF were compared using surrogate scarring parameters: matrix metalloproteinase (MMP) activity, de novo collagen synthesis, α-smooth muscle actin (α-SMA) expression, and transforming growth factor-β (TGF-β) secretion. Normal hLF and dFib maintained different phenotypes in RAFT TE. MMP-2 and -9 activity, de novo collagen synthesis, and α-SMA expression were all increased in dFib cf. normal hLF RAFT TEs, although TGF-β1 secretion did not differ between normal hLF and dFib RAFT TEs. Normal hLF do not progress toward a scarring-like phenotype during culture in RAFT TEs and, therefore, may be safe to include in therapeutic RAFT TE, where they can support hLE, although in vivo work is required to confirm this. dFib RAFT TEs (used in this study as a positive control) may be useful toward the development of an ex vivo disease model of Oc-MMP. PMID:25380529

Normal Brain-Skull Development with Hybrid Deformable VR Models Simulation.

PubMed

Jin, Jing; De Ribaupierre, Sandrine; Eagleson, Roy

2016-01-01

This paper describes a simulation framework for a clinical application involving skull-brain co-development in infants, leading to a platform for craniosynostosis modeling. Craniosynostosis occurs when one or more sutures are fused early in life, resulting in an abnormal skull shape. Surgery is required to reopen the suture and reduce intracranial pressure, but is difficult without any predictive model to assist surgical planning. We aim to study normal brain-skull growth by computer simulation, which requires a head model and appropriate mathematical methods for brain and skull growth respectively. On the basis of our previous model, we further specified suture model into fibrous and cartilaginous sutures and develop algorithm for skull extension. We evaluate the resulting simulation by comparison with datasets of cases and normal growth.

Synergy between TGF-beta 3 and NT-3 to promote the survival of spiral ganglia neurones in vitro.

PubMed

Marzella, P L; Clark, G M; Shepherd, R K; Bartlett, P F; Kilpatrick, T J

1998-01-09

Transforming growth factor-betas (TGF-betas) have been implicated in normal inner ear development and in promoting neuronal survival. Early rat post-natal spiral ganglion cells (SGC) in dissociated cell culture were used as a model of auditory innervation to test the trophic factors TGF-beta3 and neurotrophin-3 (NT-3) for their ability, individually or in combination, to promote neuronal survival. The findings from this study suggest that TGF-beta3 supports neuronal survival in a concentration-dependent manner. Moreover TGF-beta3 and NT-3-potentiated spiral ganglion neuronal survival in a synergistic fashion.

Flow cytometric analysis of normal and neoplastic mast cells: role in diagnosis and follow-up of mast cell disease.

PubMed

Escribano, Luis; Garcia Montero, Andres C; Núñez, Rosa; Orfao, Alberto

2006-08-01

Human mast cells (MCs) are directly derived from human pluripotent CD34+ stem and progenitor hematopoietic cells with stem cell factor being a critical growth factor supporting human MC proliferation, differentiation, and survival. Because of the advantages that flow cytometry offers (it allows rapid, objective, and sensitive multiparameter analysis of high numbers of cells from a sample, with information being provided on the basis of a single cell), it has become the method of choice in the past decade for immunophenotypic identification, enumeration, and characterization of human MCs in bone marrow and other tissue specimens.

Bayesian Inference and Application of Robust Growth Curve Models Using Student's "t" Distribution

ERIC Educational Resources Information Center

Zhang, Zhiyong; Lai, Keke; Lu, Zhenqiu; Tong, Xin

2013-01-01

Despite the widespread popularity of growth curve analysis, few studies have investigated robust growth curve models. In this article, the "t" distribution is applied to model heavy-tailed data and contaminated normal data with outliers for growth curve analysis. The derived robust growth curve models are estimated through Bayesian…

Tall stature without growth hormone: four male patients with aromatase deficiency.

PubMed

Rochira, Vincenzo; Zirilli, Lucia; Maffei, Laura; Premrou, Valeria; Aranda, Claudio; Baldi, Matteo; Ghigo, Ezio; Aimaretti, Gianluca; Carani, Cesare; Lanfranco, Fabio

2010-04-01

From preliminary observations, GH-IGF-I seems to be compromised in men with aromatase deficiency. The GH deficiency (GHD) coexists paradoxically with tall stature, raising the question whether or not a true GHD is part of this rare syndrome. To evaluate the GH secretion in aromatase-deficient men, their GH response to the GHRH plus arginine (GHRH-ARG) test was compared with that of normal subjects. The effect of estrogen replacement treatment on the GH-IGF-I axis in aromatase-deficient men was evaluated before and during therapy. A case-control study was conducted. Four adult men with aromatase deficiency were compared with 12 normal subjects. We measured the GH response to GHRH-ARG in aromatase-deficient men (at baseline and during estrogen treatment) and in normal subjects. Basal serum IGF-I was measured in both patients and controls. The response of GH to GHRH-ARG was severely impaired in men with aromatase deficiency and resulted in significantly lower (P < 0.001) levels than in normal subjects. Although normal, serum IGF-I levels were also significantly lower (P < 0.001) than in normal subjects. Both GH peak and IGF-I concentrations were not modified by estrogen therapy in men with aromatase deficiency. In aromatase-deficient men, GH response to potent provocative stimuli is impaired and is not restored by exogenous estrogens. Furthermore, a tall stature may be reached, notwithstanding the coexistence of GHD, if a prolonged time for growth is available due to a delay in bone maturation, and other growth factors different from GH (mainly insulin) promote growth.

Tumor formation of prostate cancer cells influenced by stromal cells from the transitional or peripheral zones of the normal prostate

PubMed Central

Zhao, Fu-Jun; Han, Bang-Min; Yu, Sheng-Qiang; Xia, Shu-Jie

2009-01-01

This study was designed to investigate the different involvements of prostatic stromal cells from the normal transitional zone (TZ) or peripheral zone (PZ) in the carcinogenesis of prostate cancer (PCa) epithelial cells (PC-3) in vitro and in vivo co-culture models. Ultra-structures and gene expression profiles of primary cultures of human prostatic stromal cells from the normal TZ or PZ were analyzed by electron microscopy and microarray analysis. In vitro and in vivo co-culture models composed of normal TZ or PZ stromal cells and human PCa PC-3 cells were established. We assessed tumor growth and weight in the in vivo nude mice model. There are morphological and ultra-structural differences in stromal cells from TZ and PZ of the normal prostate. In all, 514 differentially expressed genes were selected by microarray analysis; 483 genes were more highly expressed in stromal cells from TZ and 31 were more highly expressed in those from PZ. Co-culture with PZ stromal cells and transforming growth factor-β1 (TGF-β1) increased the tumor growth of PC-3 cells in vitro and in vivo, as well as Bcl-2 expression. On the other hand, stromal cells of TZ suppressed PC-3 cell tumor growth in the mouse model. We conclude that ultra-structures and gene expression differ between the stromal cells from TZ or PZ of the normal prostate, and stroma–epithelium interactions from TZ or PZ might be responsible for the distinct zonal localization of prostate tumor formation. PMID:19122679

Growth Hormone Studies in Growth Retardation—Therapeutic Response to Administration of Androgen

PubMed Central

Deller, John J.; Plunket, Daniel C.; Forsham, Peter H.

1966-01-01

Growth hormone assays were performed before and after androgen administration in a 12-year-old boy with unexplained growth retardation. A subnormal growth hormone secretion in response to a standard hypoglycemic stimulus was demonstrated, and it was corrected by androgen pretreatment. After that, a normal serum growth hormone level and a temporary growth spurt were demonstrated. ImagesFigure 1. PMID:5942009

Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation.

PubMed

Garelli, Andres; Gontijo, Alisson M; Miguela, Veronica; Caparros, Esther; Dominguez, Maria

2012-05-04

Developing animals frequently adjust their growth programs and/or their maturation or metamorphosis to compensate for growth disturbances (such as injury or tumor) and ensure normal adult size. Such plasticity entails tissue and organ communication to preserve their proportions and symmetry. Here, we show that imaginal discs autonomously activate DILP8, a Drosophila insulin-like peptide, to communicate abnormal growth and postpone maturation. DILP8 delays metamorphosis by inhibiting ecdysone biosynthesis, slowing growth in the imaginal discs, and generating normal-sized animals. Loss of dilp8 yields asymmetric individuals with an unusually large variation in size and a more varied time of maturation. Thus, DILP8 is a fundamental element of the hitherto ill-defined machinery governing the plasticity that ensures developmental stability and robustness.

Globally Increased Crop Growth and Cropping Intensity from the Long-Term Satellite-Based Observations

NASA Astrophysics Data System (ADS)

Chen, Bin

2018-04-01

Understanding the spatiotemporal change trend of global crop growth and multiple cropping system under climate change scenarios is a critical requirement for supporting the food security issue that maintains the function of human society. Many studies have predicted the effects of climate changes on crop production using a combination of filed studies and models, but there has been limited evidence relating decadal-scale climate change to global crop growth and the spatiotemporal distribution of multiple cropping system. Using long-term satellite-derived Normalized Difference Vegetation Index (NDVI) and observed climate data from 1982 to 2012, we investigated the crop growth trend, spatiotemporal pattern trend of agricultural cropping intensity, and their potential correlations with respect to the climate change drivers at a global scale. Results show that 82.97 % of global cropland maximum NDVI witnesses an increased trend while 17.03 % of that shows a decreased trend over the past three decades. The spatial distribution of multiple cropping system is observed to expand from lower latitude to higher latitude, and the increased cropping intensity is also witnessed globally. In terms of regional major crop zones, results show that all nine selected zones have an obvious upward trend of crop maximum NDVI (p < 0.001), and as for climatic drivers, the gradual temperature and precipitation changes have had a measurable impact on the crop growth trend.

Cardiomyocyte hypertrophy induced by Endonuclease G deficiency requires reactive oxygen radicals accumulation and is inhibitable by the micropeptide humanin.

PubMed

Blasco, Natividad; Cámara, Yolanda; Núñez, Estefanía; Beà, Aida; Barés, Gisel; Forné, Carles; Ruíz-Meana, Marisol; Girón, Cristina; Barba, Ignasi; García-Arumí, Elena; García-Dorado, David; Vázquez, Jesús; Martí, Ramon; Llovera, Marta; Sanchis, Daniel

2018-06-01

The endonuclease G gene (Endog), which codes for a mitochondrial nuclease, was identified as a determinant of cardiac hypertrophy. How ENDOG controls cardiomyocyte growth is still unknown. Thus, we aimed at finding the link between ENDOG activity and cardiomyocyte growth. Endog deficiency induced reactive oxygen species (ROS) accumulation and abnormal growth in neonatal rodent cardiomyocytes, altering the AKT-GSK3β and Class-II histone deacethylases (HDAC) signal transduction pathways. These effects were blocked by ROS scavengers. Lack of ENDOG reduced mitochondrial DNA (mtDNA) replication independently of ROS accumulation. Because mtDNA encodes several subunits of the mitochondrial electron transport chain, whose activity is an important source of cellular ROS, we investigated whether Endog deficiency compromised the expression and activity of the respiratory chain complexes but found no changes in these parameters nor in ATP content. MtDNA also codes for humanin, a micropeptide with possible metabolic functions. Nanomolar concentrations of synthetic humanin restored normal ROS levels and cell size in Endog-deficient cardiomyocytes. These results support the involvement of redox signaling in the control of cardiomyocyte growth by ENDOG and suggest a pathway relating mtDNA content to the regulation of cell growth probably involving humanin, which prevents reactive oxygen radicals accumulation and hypertrophy induced by Endog deficiency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Adamantanyl-Histone Deacetylase Inhibitor H6CAHA Exhibits Favorable Pharmacokinetics and Augments Prostate Cancer Radiation Sensitivity

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

Konsoula, Zacharoula; Cao Hong; Velena, Alfredo

2011-04-01

Purpose: To evaluate pharmacological properties of H6CAHA, an adamantyl-hydroxamate histone deacetylase inhibitor, and to investigate its effect on prostate cancer cells following exposure to {gamma}-radiation in vitro and in vivo. Methods and Materials: H6CAHA was assessed for in vitro solubility, lipophilicity and growth inhibition, and in vivo plasma pharmacokinetics. The effect of H6CAHA on radiation clonogenic survival and DNA damage repair was evaluated in human prostate cancer (PC3, DU145, LNCaP) and nonmalignant control epithelial (RWPE1 and 267B1) cell lines. The effect of this agent on the growth of prostate cancer xenografts was also assessed in mice. Results: H6CAHA demonstrated goodmore » solubility and permeability profiles and preferentially inhibited the growth of prostate cancer cells over nonmalignant cells. Plasma pharmacokinetics revealed that the area under the curve of H6CAHA was 8.08 {+-} 0.91 {mu}M x h, and its half-life was 11.17 {+-} 0.87 h. Radiation clonogenic assays revealed that H6CAHA decreased the survival of prostate cancer cells at the dose that exerted limited effect on normal cells. Concomitantly, delayed DNA damage repair following combination treatment was evident in cancer cells, indicated by the prolonged appearance of {gamma}H2AX and Rad51 foci and suppression of DNA damage repair genes (ATM, BRCA1, and BRCA2). Combined modality of H6CAHA (daily intraperitoneal injections for 10 days) with {gamma}-radiation (10 x 2 Gy) completely blocked the growth of PC3 tumor xenografts (p < 0.001) over 60 days. Conclusion: These results support the potential therapeutic value of H6CAHA in combination with radiation and support the rationale for further clinical investigation.« less

Melatonin and associated signaling pathways that control normal breast epithelium and breast cancer.

PubMed

Hill, Steven M; Blask, David E; Xiang, Shulin; Yuan, Lin; Mao, Lulu; Dauchy, Robert T; Dauchy, Erin M; Frasch, Tripp; Duplesis, Tamika

2011-09-01

This review article discusses recent work on the melatonin-mediated circadian regulation and integration of molecular and metabolic signaling mechanisms involved in human breast cancer growth and the associated consequences of circadian disruption by exposure to light-at-night (LAN). The anti-proliferative effects of the circadian melatonin signal are, in general, mediated through mechanisms involving the activation of MT(1) melatonin receptors expressed in human breast cancer cell lines and xenografts. In estrogen receptor-positive (ERα+) human breast cancer cells, melatonin suppresses both ERα mRNA expression and estrogen-induced transcriptional activity of the ERα via MT(1)-induced activation of G(αi2) signaling and reduction of cAMP levels. Melatonin also regulates the transcriptional activity of additional members of the nuclear receptor super-family, enzymes involved in estrogen metabolism, and the expression of core clock and clock-related genes. The anti-invasive/anti-metastatic actions of melatonin involve the blockade of p38 phosphorylation and matrix metalloproteinase expression. Melatonin also inhibits the growth of human breast cancer xenografts via MT(1)-mediated suppression of cAMP leading to a blockade of linoleic acid (LA) uptake and its metabolism to the mitogenic signaling molecule 13-hydroxyoctadecadienoic acid (13-HODE). Down-regulation of 13-HODE reduces the activation of growth factor pathways supporting cell proliferation and survival. Finally, studies in both rats and humans indicate that light-at-night (LAN) induced circadian disruption of the nocturnal melatonin signal activates human breast cancer growth, metabolism, and signaling, providing the strongest mechanistic support, thus far, for epidemiological studies demonstrating the elevated breast cancer risk in night shift workers and other individuals increasingly exposed to LAN.

Recombinant IGF-I: Past, present and future.

PubMed

Bright, George M

2016-06-01

Normal linear growth in humans requires GH and IGF-I. Diminished GH action resulting in reduced availability of IGF-I and IGF-binding proteins is the hallmarks of GH Insensitivity Syndromes (GHIS). The deficiencies are the perceived mechanisms for the growth failure of affected patients and the therapeutic targets for the restoration of normal growth. Early treatment attempts with pituitary-derived GH had limited effects in GHIS patients. Recombinant human insulin-like growth factor-I (rhIGF-I) treatment initially provides accelerated growth to GHIS children and provides substantial benefit. But, in general, catch up growth is less substantial with rhIGF-I treatment of GHIS than with rhGH treatment of GH Deficiency. Few classic GHIS patients have reached heights in the normal range (height SD score between -2.0 SD and +2.0 SD) with rhIGF-I monotherapy. A potential explanation is that while rhIGF-I treatment increases circulating concentrations of IGF-1 and IGFBP-3, such treatment reduces endogenous GH levels by negative feedback inhibition of pituitary GH release. In as much as both GH and IGF-I are required for good catch up growth, the loss of any residual GH signaling during IGF-I monotherapy in GHIS patients may attenuate possible catch up growth. Consistent with this explanation is the finding that, as predicted by the preclinical studies by Ross Clark, combination of rhGH & rhIGF-1 provides better growth responses than rhIGF-1 monotherapy in prepubertal children with short stature and low IGF-I levels despite normal stimulated GH responses. In the future, rhGH and rhIGF-I combination therapy can potentially improve growth outcomes over that seen with rhIGF-I monotherapy in all GHIS patients except in those with a total lack of functional GH signaling. Future alternative treatments for GHIS subjects may also include the use of post-growth hormone receptor signaling agonists which restore both GH signaling and IGF-I exposures or the addition of long-acting rhGH species to rhIGF-I. Additional etiologic factors for the growth failure in GHIS should be considered if the growth deficits of GHIS do not resolve with treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Seasonal Differences in Climatic Controls of Vegetation Growth in the Beijing-Tianjin Sand Source Region of China.

NASA Astrophysics Data System (ADS)

Wang, H.

2017-12-01

Seasonal differences in climatic controls of vegetation growth in the Beijing-Tianjin Sand Source Region of China Bin He1 , Haiyan Wan11 State Key Laboratory of Earth Surface Processes and Resource Ecology, College of Global Change and Earth System Science, Beijing Normal University, Beijing 100875, China Corresponding author: Bin He, email addresses: hebin@bnu.edu.cnPhone:+861058806506, Address: Beijing Normal University, College of Global Change and Earth System Science, Beijing Normal University, Beijing 100875, China. Email addresses of co-authors: wanghaiyan@mail.bnu.edu.cnABSTRACTLaunched in 2000, the Beiing-Tainjin Sand Source Controlling Project (BTSSCP) is an ecological restoration project intended to prevent desertification in China. Evidence from multiple sources has confirmed increases in vegetation growth in the BTSSCP region since the initiation of the project. Precipitation and related soil moisture conditions typically are considered to be the main drivers of vegetation growth in this arid region. However, by investigating the relationships between vegetation growth and corresponding climatic factors, we identified seasonal variation in the climatic constraints of vegetation growth. In spring, vegetation growth is stimulated mainly by elevated temperature, whereas precipitation is the lead driver of summer greening. In autumn, positive effects of both temperature and precipitation on vegetation growth were observed. Furthermore, strong biosphere-atmosphere interactions were observed in this region. Spring warming promotes vegetation growth, but also reduces soil moisture. Summer greening has a strong cooling effect on land surface temperature. These results indicate that 1) precipitation-based projections of vegetation growth may be misleading; and 2) the ecological and environment consequences of ecological projects should be comprehensively evaluated. KEYWORDS: vegetation growth, climatic drivers, seasonal variation, BTSSCP

Development of a Novel Tissue Specific Aromatase Activity Regulation Therapeutic Method

DTIC Science & Technology

2009-09-01

Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Estrogen is essential for normal growth and development of the female ...the ovaries and other tissues of the body using an enzyme called aromatase. Once women have reached menopause, the ovaries no longer produce estrogen...Introduction Estrogen is essential for normal growth and development of the female reproductive system, including breast tissue, and lifetime

Truncated Hormone Inhibits Breast Tumor Blood Vessel Formation, Not Tumor Growth | Center for Cancer Research

Cancer.gov

The hormone prolactin (PRL) plays a critical role in normal breast development by stimulating the proliferation of mammary cells, the production of milk proteins, and the formation of new mammary blood vessels. Unfortunately, the same cell and vessel growth pathways controlled by PRL in normal cells also operate in breast cancer cells, and elevated plasma PRL is a risk factor

Influence of Student Engagement, Moods and Completed Assignments with on Normalized Gains and Growth in Reading Literature Using iPads

ERIC Educational Resources Information Center

Hepworth, A. J.

2014-01-01

The purpose of this study was to investigate how engagement, mood and number of assignments completed on computerized differentiated homework using an iPad in a one-to-one mobile device environment influenced the growth index and normalized gain in reading literature benchmark assessments of students in grades five, six, and seven. Furthermore,…

Growth, reproductive performance, carcass characteristics and meat quality in F1 and F2 progenies of somatic cell-cloned pigs.

PubMed

Adachi, Noritaka; Yamaguchi, Daisuke; Watanabe, Akiyuki; Miura, Narumi; Sunaga, Seiji; Oishi, Hitoshi; Hashimoto, Michiko; Oishi, Takatsugu; Iwamoto, Masaki; Hanada, Hirofumi; Kubo, Masanori; Onishi, Akira

2014-04-24

The objective of this study was to examine the health and meat production of cloned sows and their progenies in order to demonstrate the application of somatic cell cloning to the pig industry. This study compared the growth, reproductive performance, carcass characteristics and meat quality of Landrace cloned sows, F1 progenies and F2 progenies. We measured their body weight, growth rate and feed conversion and performed a pathological analysis of their anatomy to detect abnormalities. Three of the five cloned pigs were used for a growth test. Cloned pigs grew normally and had characteristics similar to those of the control purebred Landrace pigs. Two cloned gilts were bred with a Landrace boar and used for a progeny test. F1 progenies had characteristics similar to those of the controls. Two of the F1 progeny gilts were bred with a Duroc or Large White boar and used for the progeny test. F2 progenies grew normally. There were no biological differences in growth, carcass characteristics and amino acid composition among cloned sows, F1 progenies, F2 progenies and conventional pigs. The cloned sows and F1 progenies showed normal reproductive performance. No specific abnormalities were observed by pathological analysis, with the exception of periarteritis in the F1 progenies. All pigs had a normal karyotype. These results demonstrate that cloned female pigs and their progenies have similar growth, reproductive performance and carcass quality characteristics and that somatic cell cloning could be a useful technique for conserving superior pig breeds in conventional meat production.

Growth, Reproductive Performance, Carcass Characteristics and Meat Quality in F1 and F2 Progenies of Somatic Cell-Cloned Pigs

PubMed Central

ADACHI, Noritaka; YAMAGUCHI, Daisuke; WATANABE, Akiyuki; MIURA, Narumi; SUNAGA, Seiji; OISHI, Hitoshi; HASHIMOTO, Michiko; OISHI, Takatsugu; IWAMOTO, Masaki; HANADA, Hirofumi; KUBO, Masanori; ONISHI, Akira

2014-01-01

The objective of this study was to examine the health and meat production of cloned sows and their progenies in order to demonstrate the application of somatic cell cloning to the pig industry. This study compared the growth, reproductive performance, carcass characteristics and meat quality of Landrace cloned sows, F1 progenies and F2 progenies. We measured their body weight, growth rate and feed conversion and performed a pathological analysis of their anatomy to detect abnormalities. Three of the five cloned pigs were used for a growth test. Cloned pigs grew normally and had characteristics similar to those of the control purebred Landrace pigs. Two cloned gilts were bred with a Landrace boar and used for a progeny test. F1 progenies had characteristics similar to those of the controls. Two of the F1 progeny gilts were bred with a Duroc or Large White boar and used for the progeny test. F2 progenies grew normally. There were no biological differences in growth, carcass characteristics and amino acid composition among cloned sows, F1 progenies, F2 progenies and conventional pigs. The cloned sows and F1 progenies showed normal reproductive performance. No specific abnormalities were observed by pathological analysis, with the exception of periarteritis in the F1 progenies. All pigs had a normal karyotype. These results demonstrate that cloned female pigs and their progenies have similar growth, reproductive performance and carcass quality characteristics and that somatic cell cloning could be a useful technique for conserving superior pig breeds in conventional meat production. PMID:24492641

Childhood growth and development associated with need for full-time special education at school age.

PubMed

Mannerkoski, Minna; Aberg, Laura; Hoikkala, Marianne; Sarna, Seppo; Kaski, Markus; Autti, Taina; Heiskala, Hannu

2009-01-01

To explore how growth measurements and attainment of developmental milestones in early childhood reflect the need for full-time special education (SE). After stratification in this population-based study, 900 pupils in full-time SE groups (age-range 7-16 years, mean 12 years 8 months) at three levels and 301 pupils in mainstream education (age-range 7-16, mean 12 years 9 months) provided data on height and weight from birth to age 7 years and head circumference to age 1 year. Developmental screening was evaluated from age 1 month to 48 months. Statistical methods included a general linear model (growth measurements), binary logistic regression analysis (odds ratios for growth), and multinomial logistic regression analysis (odds ratios for developmental milestones). At 1 year, a 1 standard deviation score (SDS) decrease in height raised the probability of SE placement by 40%, and a 1 SDS decrease in head size by 28%. In developmental screening, during the first months of life the gross motor milestones, especially head support, differentiated the children at levels 0-3. Thereafter, the fine motor milestones and those related to speech and social skills became more important. Children whose growth is mildly impaired, though in the normal range, and who fail to attain certain developmental milestones have an increased probability for SE and thus a need for special attention when toddlers age. Similar to the growth curves, these children seem to have consistent developmental curves (patterns).

The Arabidopsis SUMO E3 ligase SIZ1 mediates the temperature dependent trade-off between plant immunity and growth

PubMed Central

Vlachakis, Georgios; Chatterjee, Sayantani; Arroyo-Mateos, Manuel; Wackers, Paul F. K.; Jonker, Martijs J.

2018-01-01

Increased ambient temperature is inhibitory to plant immunity including auto-immunity. SNC1-dependent auto-immunity is, for example, fully suppressed at 28°C. We found that the Arabidopsis sumoylation mutant siz1 displays SNC1-dependent auto-immunity at 22°C but also at 28°C, which was EDS1 dependent at both temperatures. This siz1 auto-immune phenotype provided enhanced resistance to Pseudomonas at both temperatures. Moreover, the rosette size of siz1 recovered only weakly at 28°C, while this temperature fully rescues the growth defects of other SNC1-dependent auto-immune mutants. This thermo-insensitivity of siz1 correlated with a compromised thermosensory growth response, which was independent of the immune regulators PAD4 or SNC1. Our data reveal that this high temperature induced growth response strongly depends on COP1, while SIZ1 controls the amplitude of this growth response. This latter notion is supported by transcriptomics data, i.e. SIZ1 controls the amplitude and timing of high temperature transcriptional changes including a subset of the PIF4/BZR1 gene targets. Combined our data signify that SIZ1 suppresses an SNC1-dependent resistance response at both normal and high temperatures. At the same time, SIZ1 amplifies the dark and high temperature growth response, likely via COP1 and upstream of gene regulation by PIF4 and BRZ1. PMID:29357355

Normal and leukaemic human haemopoietic cells in diffusion chamber. A morphological and functional CFU-C study.

PubMed

Laurent, M; Clémancey-Marcille, G; Hollard, D

1980-03-01

Leukaemic human bone marrow and peripheral blood cells were cultured for 25 d in diffusion chambers implanted into cyclophosphamide treated mice. Normal bone marrow cells were cultured simultaneously. These cells were studied both morphologically and functionally (CFU-C). The leukaemic cells behaved heterogeneously, 2 groups being distinguishable in accordance with their initial in vitro growth pattern (1: no growth or microcluster growth. 2: macrocluster growth). Group I showed progressive cellular death with a diminution of granulocytic progenitors and the appearance of a predominantly macrophagic population. This behaviour resembled that of the control group. The initial microcluster growth pattern remained identical throughout the entire culture period. Group 2, after considerable cellular death up to d 5, showed an explosive proliferation of the granulocytic progenitors and incomplete differentiation (up to myelocyte). The initial macrocluster growth pattern remained identical.

Loss of expression of the recycling receptor, FcRn, promotes tumor cell growth by increasing albumin consumption

PubMed Central

Khare, Priyanka; Schneider, Zita; Ober, Raimund J; Ward, Elizabeth Sally

2017-01-01

Tumor cells rely on high concentrations of amino acids to support their growth and proliferation. Although increased macropinocytic uptake and lysosomal degradation of the most abundant serum protein, albumin, in Ras-transformed cells can meet these demands, it is not understood how the majority of tumor cells that express wild type Ras achieve this. In the current study we reveal that the neonatal Fc receptor, FcRn, regulates tumor cell proliferation through the ability to recycle its ligand, albumin. By contrast with normal epithelial cells, we show that human FcRn is present at very low or undetectable levels in the majority of tumor cell lines analyzed. Remarkably, shRNA-mediated ablation of FcRn expression in an FcRn-positive tumor cell line results in a substantial growth increase of tumor xenografts, whereas enforced expression of this receptor by lentiviral transduction has the reverse effect. Moreover, intracellular albumin and glutamate levels are increased by the loss of FcRn-mediated recycling of albumin, combined with hypoalbuminemia in tumor-bearing mice. These studies identify a novel role for FcRn as a suppressor of tumor growth and have implications for the use of this receptor as a prognostic indicator and therapeutic target. PMID:27974681

Study of Selecting on Light Source Used for Micro-algae Cultivation in Space

NASA Astrophysics Data System (ADS)

Ai, Weidang; Ai, Weidang; Guo, Shuang-Sheng; Gao, Feng; Tang, Yong-Kang; Qin, Li-Feng

To select suitable light source for micro-algae cultivation in future space station, the selected Spirulina plastensis(No.7) were cultured under different lightening qualities, including six light sources that were made up of different combinations of red and blue light-emitting diode(LED). The growth, photosynthetic efficiency and nutrition quality of the Spirulina, were analyzed. From the experiments, the red light may promote the cumulation of biomass of the Spirulina, and the cumulating rate was the highest under all red light source, but the syntheses of protein, phycobiliprotein, β-carotene, VE and other nutrients needs a certain portion of blue light; yet, the complete blue light condition is not favorable to the growth of Spirulina, and may bring pollution by chlorella and other kinds of micro-algae. It is concluded that the LEDs can be used as the light resource of micro-algae cultivation. The normal growth and development of microalgae need two light sources of both red and blue LEDs. The comprehensive analyses of the various factors that affect the growth of Spirulina, such as nutrition quality and photosynthetic activities, etc., showed that the combination of 80% red and 20% blue LED is the optimum one among those tested combinations. Key word: light-emitting diode; micro-algae; controlled ecological life support system (CELSS); space cultivation

Stabilization of flow past a rounded cylinder

NASA Astrophysics Data System (ADS)

Samtaney, Ravi; Zhang, Wei

2016-11-01

We perform global linear stability analysis on low-Re flow past a rounded cylinder. The cylinder corners are rounded with a radius R, normalized as R+ = R / D where D is the cylinder diameter, and its effect on the flow stability characteristics is investigated. We compute the critical Reynolds number (Recr) for the onset of first instability, and quantify the perturbation growth rate for the super-critical flows. It is found that the flow can be stabilized by partially rounding the cylinder. Compared with the square and circular cylinders, the partially rounded cylinder has a higher Recr , attaining a maximum at around R+ = 0 . 30 , and the perturbation growth rate of the super-critical flows is reduced for Re <= 100 . We perform sensitivity analysis to explore the source of the stabilization. The growth rate sensitivity to base flow modification has two different spatial structures: the growth rate is sensitive to the wake backflow in a large region for square-like cylinders (R+ -> 0 . 00), while only the near-wake backflow is crucial for circular-like cylinders (R+ -> 0 . 50). The stability analysis results are also verified with those of the direct simulations and very good agreement is achieved. Supported by the KAUST Office of Competitive Research Funds under Award No. URF/1/1394-01. The supercomputer Shaheen at KAUST was utilized for the simulations.

Considerations in planning vegan diets: infants.

PubMed

Mangels, A R; Messina, V

2001-06-01

Appropriately planned vegan diets can satisfy nutrient needs of infants. The American Dietetic Association and The American Academy of Pediatrics state that vegan diets can promote normal infant growth. It is important for parents to provide appropriate foods for vegan infants, using guidelines like those in this article. Key considerations when working with vegan families include composition of breast milk from vegan women, appropriate breast milk substitutes, supplements, type and amount of dietary fat, and solid food introduction. Growth of vegan infants appears adequate with post-weaning growth related to dietary adequacy. Breast milk composition is similar to that of non-vegetarians except for fat composition. For the first 4 to 6 months, breast milk should be the sole food with soy-based infant formula as an alternative. Commercial soymilk should not be the primary beverage until after age 1 year. Breastfed vegan infants may need supplements of vitamin B-12 if maternal diet is inadequate; older infants may need zinc supplements and reliable sources of iron and vitamins D and B-12. Timing of solid food introduction is similar to that recommended for non-vegetarians. Tofu, dried beans, and meat analogs are introduced as protein sources around 7-8 months. Vegan diets can be planned to be nutritionally adequate and support growth for infants.

Early growth and development impairments in patients with ganglioside GM3 synthase deficiency.

PubMed

Wang, H; Wang, A; Wang, D; Bright, A; Sency, V; Zhou, A; Xin, B

2016-05-01

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GSD) causes a complete absence of GM3 and all downstream biosynthetic derivatives. The individuals affected by this disorder manifest severe irritability, intractable seizures and profound intellectual disability. However, we have found that most newborns seem symptom-free for a period of time after birth. In order to further understand the onset of the disease, we investigated the early growth and development of patients with this condition through this study. We compared 37 affected individuals with their normal siblings and revealed that all children with GSD had relatively normal intrauterine growth and development, as their weight, length and head circumference were similar to their normal siblings at birth. However, the disease progresses quickly after birth and causes significant constitutional impairments of growth and development by 6 months of age. Neither breastfeeding nor gastrostomy tube placement made significant difference on growth and development as all groups of patients showed the similar pattern. We conclude that GSD causes significant postnatal growth and developmental impairments and the amount of gangliosides in breast milk and general nutritional intervention do not seem to alter these outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Combining ground-based measurements and satellite-based spectral vegetation indices to track biomass accumulation in post-fire chaparral

NASA Astrophysics Data System (ADS)

Uyeda, K. A.; Stow, D. A.; Roberts, D. A.; Riggan, P. J.

2015-12-01

Multi-temporal satellite imagery can provide valuable information on patterns of vegetation growth over large spatial extents and long time periods, but corresponding ground-referenced biomass information is often difficult to acquire, especially at an annual scale. In this study, I test the relationship between annual biomass estimated using shrub growth rings and metrics of seasonal growth derived from Moderate Resolution Imaging Spectroradiometer (MODIS) spectral vegetation indices (SVIs) for a small area of southern California chaparral to evaluate the potential for mapping biomass at larger spatial extents. The site had most recently burned in 2002, and annual biomass accumulation measurements were available from years 5 - 11 post-fire. I tested metrics of seasonal growth using six SVIs (Normalized Difference Vegetation Index, Enhanced Vegetation Index, Soil Adjusted Vegetation Index, Normalized Difference Water Index, Normalized Difference Infrared Index 6, and Vegetation Atmospherically Resistant Index). While additional research would be required to determine which of these metrics and SVIs are most promising over larger spatial extents, several of the seasonal growth metrics/ SVI combinations have a very strong relationship with annual biomass, and all SVIs have a strong relationship with annual biomass for at least one of the seasonal growth metrics.

GROα regulates human embryonic stem cell self-renewal or adoption of a neuronal fate

PubMed Central

Krtolica, Ana; Larocque, Nick; Genbacev, Olga; Ilic, Dusko; Coppe, Jean-Philippe; Patil, Christopher K.; Zdravkovic, Tamara; McMaster, Michael; Campisi, Judith; Fisher, Susan J.

2012-01-01

Previously we reported that feeders formed from human placental fibroblasts (hPFs) support derivation and long-term self-renewal of human embryonic stem cells (hESCs) under serum-free conditions. Here, we show, using antibody array and ELISA platforms, that hPFs secrete ~6-fold higher amounts of the CXC-type chemokine, GROα, than IMR 90, a human lung fibroblast line, which does not support hESC growth. Furthermore, immunocytochemistry and immunoblot approaches revealed that hESCs express CXCR, a GROα receptor. We used this information to develop defined culture medium for feeder-free propagation of hESCs in an undifferentiated state. Cells passaged as small aggregates and maintained in the GROα-containing medium had a normal karyotype, expressed pluripotency markers, and exhibited apical–basal polarity, i.e., had the defining features of pluripotent hESCs. They also differentiated into the three primary (embryonic) germ layers and formed teratomas in immunocompromised mice. hESCs cultured as single cells in the GROα-containing medium also had a normal karyotype, but they downregulated markers of pluripotency, lost apical–basal polarity, and expressed markers that are indicative of the early stages of neuronal differentiation—βIII tubulin, vimentin, radial glial protein, and nestin. These data support our hypothesis that establishing and maintaining cell polarity is essential for the long-term propagation of hESCs in an undifferentiated state and that disruption of cell–cell contacts can trigger adoption of a neuronal fate. PMID:21396766

Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation.

PubMed

Jansen, F A R; van Zwet, E W; Rijlaarsdam, M E B; Pajkrt, E; van Velzen, C L; Zuurveen, H R; Kragt, A; Bax, C L; Clur, S-A B; van Lith, J M M; Blom, N A; Haak, M C

2016-09-01

Congenital heart defects (CHDs) are reported to be associated with a smaller fetal head circumference (HC) and neurodevelopmental delay. Recent studies suggest that altered intrauterine brain hemodynamics may explain these findings. Our objectives were to evaluate the pattern of head growth in a large cohort of fetuses with various types of CHD, analyze these patterns according to the type of CHD and estimate the effect of cerebral hemodynamics with advancing gestation in the second and third trimesters. Singleton fetuses with an isolated CHD were selected from three fetal medicine units (n = 436). Cases with placental insufficiency or genetic syndromes were excluded. CHD types were clustered according to the flow and oxygen saturation in the aorta. Z-scores of biometric data were constructed using growth charts of a normal population. HC at different gestational ages was evaluated and univariate and multivariate mixed regression analyses were performed to examine the patterns of prenatal HC growth. Fetuses with severe and less severe types of CHD demonstrated statistically significant HC growth restriction with increasing gestational age (slope of -0.017/day); however, there was no statistically significant effect of fetal hemodynamics on HC growth. Fetuses with CHD but normal brain oxygenation and normal aortic flow showed a significant decrease in HC growth (slope of -0.024/day). Only fetuses with isolated tetralogy of Fallot demonstrated a smaller HC z-score at 20 weeks of gestation (-0.67 (95% CI, -1.16 to -0.18)). Despite the decline in head growth in fetuses with a prenatally detected isolated CHD, HC values were within the normal range, raising the question of its clinical significance. Furthermore, in contrast to other studies, this large cohort did not establish a significant correlation between aortic flow or oxygen saturation and HC growth. Factors other than altered fetal cerebral hemodynamics may contribute to HC growth restriction with increasing gestational age, such as (epi)genetic or placental factors. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Purine synthesis promotes maintenance of brain tumor initiating cells in glioma.

PubMed

Wang, Xiuxing; Yang, Kailin; Xie, Qi; Wu, Qiulian; Mack, Stephen C; Shi, Yu; Kim, Leo J Y; Prager, Briana C; Flavahan, William A; Liu, Xiaojing; Singer, Meromit; Hubert, Christopher G; Miller, Tyler E; Zhou, Wenchao; Huang, Zhi; Fang, Xiaoguang; Regev, Aviv; Suvà, Mario L; Hwang, Tae Hyun; Locasale, Jason W; Bao, Shideng; Rich, Jeremy N

2017-05-01

Brain tumor initiating cells (BTICs), also known as cancer stem cells, hijack high-affinity glucose uptake active normally in neurons to maintain energy demands. Here we link metabolic dysregulation in human BTICs to a nexus between MYC and de novo purine synthesis, mediating glucose-sustained anabolic metabolism. Inhibiting purine synthesis abrogated BTIC growth, self-renewal and in vivo tumor formation by depleting intracellular pools of purine nucleotides, supporting purine synthesis as a potential therapeutic point of fragility. In contrast, differentiated glioma cells were unaffected by the targeting of purine biosynthetic enzymes, suggesting selective dependence of BTICs. MYC coordinated the control of purine synthetic enzymes, supporting its role in metabolic reprogramming. Elevated expression of purine synthetic enzymes correlated with poor prognosis in glioblastoma patients. Collectively, our results suggest that stem-like glioma cells reprogram their metabolism to self-renew and fuel the tumor hierarchy, revealing potential BTIC cancer dependencies amenable to targeted therapy.

Analytical scalings of the linear Richtmyer-Meshkov instability

NASA Astrophysics Data System (ADS)

Cobos, Francisco; Wouchuk, Juan Gustavo

2017-11-01

In the linear Richtmyer-Meshkov instability (RMI), hydrodynamic perturbations are generated behind the transmitted and reflected rippled fronts. The contact surface reaches an asymptotic normal velocity and two different tangential velocities at each side, which are always different for moderate to strong levels of compression, depending on the amount of vorticity generated by the corrugated shocks. We show analytical scaling laws for the ripple velocity (δvi∞)in different physical limits and approximate formulas are provided, valid for arbitrary initial pre-shock parameters. An asymptotic growth for the contact surface ripple of the form ψi(t) ψ∞ + δ vi∞t is obtained. The quantity ψ∞ is in general different from the initial post-shock ripple amplitude, in agreement with the early finding of. Comparison to simulations and experimental work is shown. F.C. acknowledges support from UCLM for a predoctoral fellowship. This work has received support from MINECO, JCCM, and UCLM (Spain).

Matrix control of pancreatic cancer: New insights into fibronectin signaling.

PubMed

Topalovski, Mary; Brekken, Rolf A

2016-10-10

Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease that resists most current therapies. A defining characteristic of PDA is an intense fibrotic response that promotes tumor cell invasion and chemoresistance. Efforts to understand the complex relationship between the tumor and its extracellular network and to therapeutically perturb tumor-stroma interactions are ongoing. Fibronectin (FN), a provisional matrix protein abundant in PDA stroma but not normal tissues, supports metastatic spread and chemoresistance of this deadly disease. FN also supports angiogenesis, which is required for even hypovascular tumors such as PDA to develop and progress. Targeting components of the tumor stroma, such as FN, can effectively reduce tumor growth and spread while also enhancing delivery of chemotherapy. Here, we review the molecular mechanisms by which FN drives angiogenesis, metastasis and chemoresistance in PDA. In light of these new findings, we also discuss therapeutic strategies to inhibit FN signaling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Gastro-oesophageal reflux in infants].

PubMed

de Jong, Trudy; Kamphuis, Mascha; Kivit-Schwengle, Lilly

2014-01-01

A more prominent role for the youth healthcare physician: Youth Healthcare physicians reflect on the Dutch Paediatric Association (NVK) guideline entitled 'Gastro-oesophageal reflux (disease) in children aged 0-18 years'. This guideline states that medicinal treatment is given to these children too often. Dutch Youth Healthcare physicians see a large number of children with gastro-oesophageal reflux, with or without additional symptoms. The most common symptoms (crying and diminished weight gain) might be present even in the absence of reflux. Parents should be given advice and support when they are worried about reflux, crying or low weight gain. A lower weight gain curve on the growth chart is normal in breastfed children, and crying might be due to factors such as lack of routine or stimulus reduction. Overfeeding might also be the cause. Parents should be supported and followed up, with or without treatment, as necessary. Youth Healthcare professionals could perform this task.

Short and tall stature: a new paradigm emerges

PubMed Central

Baron, Jeffrey; Sävendahl, Lars; De Luca, Francesco; Dauber, Andrew; Phillip, Moshe; Wit, Jan M.; Nilsson, Ola

2016-01-01

In the past, the growth hormone (GH) – insulin-like growth factor-I (IGF-I) axis was thought to be the central system regulating childhood growth and therefore responsible for short stature and tall stature. However, recent findings have revealed that the GH-IGF-I axis is just one of many regulatory systems that control chondrogenesis in the growth plate, the biological process that drives height gain. Consequently, normal growth in children depends not only on GH and IGF-I but on multiple hormones, paracrine factors, extracellular matrix molecules, and intracellular proteins that regulate growth plate chondrocytes. Mutations in genes encoding many of these local proteins cause short stature or tall stature. Similarly genome-wide association studies have revealed that the normal variation in height appears to be due largely to genes outside the GH-IGF-I axis that affect growth at the growth plate through a wide variety of mechanisms. These findings point to a new conceptual framework for understanding short and tall stature, which is centered not on two particular hormones but rather on the growth plate, the structure responsible for height gain. PMID:26437621

Long Term Ex Vivo Culture and Live Imaging of Drosophila Larval Imaginal Discs.

PubMed

Tsao, Chia-Kang; Ku, Hui-Yu; Lee, Yuan-Ming; Huang, Yu-Fen; Sun, Yi Henry

Continuous imaging of live tissues provides clear temporal sequence of biological events. The Drosophila imaginal discs have been popular experimental subjects for the study of a wide variety of biological phenomena, but long term culture that allows normal development has not been satisfactory. Here we report a culture method that can sustain normal development for 18 hours and allows live imaging. The method is validated in multiple discs and for cell proliferation, differentiation and migration. However, it does not support disc growth and cannot support cell proliferation for more than 7 to 12 hr. We monitored the cellular behavior of retinal basal glia in the developing eye disc and found that distinct glia type has distinct properties of proliferation and migration. The live imaging provided direct proof that wrapping glia differentiated from existing glia after migrating to the anterior front, and unexpectedly found that they undergo endoreplication before wrapping axons, and their nuclei migrate up and down along the axons. UV-induced specific labeling of a single carpet glia also showed that the two carpet glia membrane do not overlap and suggests a tiling or repulsion mechanism between the two cells. These findings demonstrated the usefulness of an ex vivo culture method and live imaging.

Clinical outcome of nutrition-oriented intervention for primary intestinal lymphangiectasia.

PubMed

Tang, Qing-Ya; Wen, Jie; Wu, Jiang; Wang, Ying; Cai, Wei

2011-02-01

primary intestinal lymphangiectasia (PIL) is a rare digestive disease and few studies have focused on the therapeutic effect in PIL patients. This study was undertaken to evaluate nutrition-oriented intervention in children with PIL. four children with PIL were studied. Their medical records were reviewed. Anthropometric measurements and blood tests were performed during a 8-18 month follow-up. during hospitalization, the 4 patients were subjected to diet intervention. Parenteral nutrition (PN) support was also given to 3 of them. Clinical symptoms and laboratory parameters of the patients were significantly improved at discharge. After discharge, the patients continued diet control, 2 of whom received intermittent PN support. The mean follow-up duration of the 4 patients was 13 months (range, 8-18 months) and they all kept in a stable condition without symptoms relapse. Weight, height and body mass index for age were normal during the follow-up, while total protein, albumin and immunoglobulin concentrations were still slightly below normal level. nutrition therapy is effective as a valid and safe therapeutic management for PIL patients. No growth retardation was observed in the 4 children after the therapy, but they are still at risk of nutrient malabsorption. Therefore, they need long-term, regular monitoring and intensive nutritional care.

Autophagy in tumorigenesis and energy metabolism: friend by day, foe by night.

PubMed

Mathew, Robin; White, Eileen

2011-02-01

Autophagy is the mechanism by which cells consume parts of themselves to survive starvation and stress. This self-cannibalization limits cell death and tissue inflammation, recycles energy and biosynthetic substrates and removes damaged proteins and organelles, accumulation of which is toxic. In normal tissues, autophagy-mediated damage mitigation may suppress tumorigenesis, while in advanced tumors macromolecular recycling may support survival by buffering metabolic demand under stress. As a result, autophagy-activation in normal cells may suppress tumorigenesis, while autophagy inhibition may be beneficial for the therapy of established tumors. The mechanisms by which autophagy supports cancer cell metabolism are slowly emerging. As cancer is being increasingly recognized as a metabolic disease, how autophagy-mediated catabolism impacts cellular and mammalian metabolism and tumor growth is of great interest. Most cancer therapeutics induce autophagy, either directly by modulating signaling pathways that control autophagy in the case of many targeted therapies, or indirectly in the case of cytotoxic therapy. However, the functional consequence of autophagy induction in the context of cancer therapy is not yet clear. A better understanding of how autophagy modulates cell metabolism under various cellular stresses and the consequences of this on tumorigenesis will help develop better therapeutic strategies against cancer prevention and treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Management of twin pregnancy and perinatal concerns in a Beluga (Delphinapterus leucas).

PubMed

Osborn, Steven; Dalton, Les; Dold, Christopher; Robeck, Todd

2012-03-01

A 22-yr-old multiparous beluga, Delphinapterus leucas, with consistently elevated serum progesterone concentrations post-artificial insemination was diagnosed with viable twins at 149 days postconception. Twins were of similar size at least until day 264, the last point when ultrasound measurements of both twins were made. However, ultrasound was used to determine the viability of both fetuses on days 365, 393, and 400. After 90% of normal gestation, or 434 days, steroids were administered to encourage fetal lung maturation. Seven days later a 40.9-kg live female calf was delivered headfirst. A second 22.7-kg stillborn calf was delivered in fluke-first presentation 8 hr later. Immediately after birth, the live calf was administered surfactant intratracheally. The next day, it was given beluga immunoglobulin intramuscularly, and started on oral antibiotics and provided nutritional support via an oral gastric tube. The calf started nursing voluntarily on day 3. Antibiotic and nutritional support was discontinued on day 10. Bimonthly weight and length measurements demonstrated that after an initial increased growth rate, the calf has grown within normal parameters after birth. This calf represents the first known successful surviving twin of any cetacean species and sets an important precedent for treatment modalities that may be available to assist the premature cetacean neonate.

Comparison of growth and metabolic regulation between wild, domesticated and transgenic salmonids.

USDA-ARS?s Scientific Manuscript database

To gain a better understanding of the aspects underlying normal and growth hormone enhanced growth in salmonids, quantitative expression analysis was performed for a number of genes related to muscle growth, metabolism, immunology and energy regulation. This analysis was performed in liver and musc...

Staphylococci in Competition1

PubMed Central

Peterson, A. C.; Black, J. J.; Gunderson, M. F.

1964-01-01

Previous results showed definite repressive effects on the growth of staphylococci in mixed cultures due to the competitive growth of psychrophilic saprophytes. This study was continued, and the influence of other environmental factors, pH and salt, on the competition between staphylococci and saprophytes was investigated. Initial pH values varied from 5 to 9. At the extremes of the pH range, staphylococci failed to grow, while the saprophytes grew under all of the conditions tested. At pH 5, the growth curves for the saprophytes were markedly altered from those obtained at neutral pH. The lag phases were greatly lengthened at and below 20 C, but normal numbers of saprophytes were reached in the stationary phase. At pH 6 and 8, staphylococcal growth showed the same inhibition observed at pH 7, at and below 20 C; normal multiplication was observed above this temperature, but with accelerated death phases. Thus, pH did not primarily effect staphylococcal growth through its influence on saprophyte growth and competition, but rather directly affected the growth of Staphylococcus cultures. Salt concentrations from 3.5 to 9.5% were investigated for influence on staphylococcal growth in mixed populations. Above 3.5% salt, staphylococcal inhibition at and above 20 C was not as marked as in the controls, although normal numbers were never reached. The saprophytes were increasingly inhibited, and their lag phases materially lengthened as salt concentration was increased. Salt acted directly on the Staphylococcus population and also, by repressing saprophyte growth, decreased competition, which allowed the staphylococci to grow. PMID:14106943

The facts and controversies about selenium.

PubMed

Dodig, Slavica; Cepelak, Ivana

2004-12-01

Selenium is a trace element, essential in small amounts, but it can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal functioning of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. Selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation plays a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.

Downsides and benefits of unicellularity in budding yeast

NASA Astrophysics Data System (ADS)

Balazsi, Gabor; Chen, Lin; Kuzdzal-Fick, Jennie

Yeast cells that do not separate after cell division form clumps. Clumping was shown to aid utilization of certain sugars, but its effects in stressful conditions are unknown. Generally speaking, what are the costs and benefits of unicellularity versus clumping multicellularity in normal and stressful conditions? To address this question, we evolved clumping yeast towards unicellularity by continuously propagating only those cells that remain suspended in liquid culture after settling. Whole-genome sequencing indicated that mutations in the AMN1 (antagonist of mitotic exit network) gene underlie the changes from clumping to unicellular phenotypes in these evolved yeast cells. Simple models predict that clumping should hinder growth in normal conditions while being protective in stress. Accordingly, we find experimentally that yeast clumps are more resistant to freeze/thaw, hydrogen peroxide, and ethanol stressors than their unicellular counterparts. On the other hand, unicellularity seems to be advantageous in normal conditions. Overall, these results reveal the downsides and benefits of unicellularity in different environmental conditions and uncover its genetic bases in yeast. This research was supported by the NIH Director's New Innovator Award Program (1DP2 OD006481-01), by NSF/IOS 1021675 and the Laufer Center for Physical & Quantitative Biology.

Adolescent growth and pubertal progression in the Silver-Russell syndrome.

PubMed Central

Davies, P S; Valley, R; Preece, M A

1988-01-01

The pattern of growth and development of 18 adolescent children with the Silver-Russell syndrome was studied. Mature height was about -3.6 standard deviation scores in both sexes. This is comparable to the height reduction at diagnosis, which has been reported previously. The pattern of puberty and adolescent growth was essentially normal and occurred at a marginally earlier time than normal, although in this small series the differences were not significant. In the girls there was a tendency to gain subcutaneous fat after puberty. This trend was not apparent in the boys. PMID:3348659

The Arabidopsis SOS5 Locus Encodes a Putative Cell Surface Adhesion Protein and Is Required for Normal Cell Expansion

PubMed Central

Shi, Huazhong; Kim, YongSig; Guo, Yan; Stevenson, Becky; Zhu, Jian-Kang

2003-01-01

Cell surface proteoglycans have been implicated in many aspects of plant growth and development, but genetic evidence supporting their function has been lacking. Here, we report that the Salt Overly Sensitive5 (SOS5) gene encodes a putative cell surface adhesion protein and is required for normal cell expansion. The sos5 mutant was isolated in a screen for Arabidopsis salt-hypersensitive mutants. Under salt stress, the root tips of sos5 mutant plants swell and root growth is arrested. The root-swelling phenotype is caused by abnormal expansion of epidermal, cortical, and endodermal cells. The SOS5 gene was isolated through map-based cloning. The predicted SOS5 protein contains an N-terminal signal sequence for plasma membrane localization, two arabinogalactan protein–like domains, two fasciclin-like domains, and a C-terminal glycosylphosphatidylinositol lipid anchor signal sequence. The presence of fasciclin-like domains, which typically are found in animal cell adhesion proteins, suggests a role for SOS5 in cell-to-cell adhesion in plants. The SOS5 protein was present at the outer surface of the plasma membrane. The cell walls are thinner in the sos5 mutant, and those between neighboring epidermal and cortical cells in sos5 roots appear less organized. SOS5 is expressed ubiquitously in all plant organs and tissues, including guard cells in the leaf. PMID:12509519

Fetal adaptations in insulin secretion result from high catecholamines during placental insufficiency.

PubMed

Limesand, Sean W; Rozance, Paul J

2017-08-01

Placental insufficiency and intrauterine growth restriction (IUGR) of the fetus affects approximately 8% of all pregnancies and is associated with short- and long-term disturbances in metabolism. In pregnant sheep, experimental models with a small, defective placenta that restricts delivery of nutrients and oxygen to the fetus result in IUGR. Low blood oxygen concentrations increase fetal plasma catecholamine concentrations, which lower fetal insulin concentrations. All of these observations in sheep models with placental insufficiency are consistent with cases of human IUGR. We propose that sustained high catecholamine concentrations observed in the IUGR fetus produce developmental adaptations in pancreatic β-cells that impair fetal insulin secretion. Experimental evidence supporting this hypothesis shows that chronic elevation in circulating catecholamines in IUGR fetuses persistently inhibits insulin concentrations and secretion. Elevated catecholamines also allow for maintenance of a normal fetal basal metabolic rate despite low fetal insulin and glucose concentrations while suppressing fetal growth. Importantly, a compensatory augmentation in insulin secretion occurs following inhibition or cessation of catecholamine signalling in IUGR fetuses. This finding has been replicated in normally grown sheep fetuses following a 7-day noradrenaline (norepinephrine) infusion. Together, these programmed effects will potentially create an imbalance between insulin secretion and insulin-stimulated glucose utilization in the neonate which probably explains the transient hyperinsulinism and hypoglycaemia in some IUGR infants. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Foetal growth restriction is associated with poor reading and spelling skills at eight years to 10 years of age.

PubMed

Partanen, Lea; Korkalainen, Noora; Mäkikallio, Kaarin; Olsén, Päivi; Laukkanen-Nevala, Päivi; Yliherva, Anneli

2018-01-01

Foetal growth restriction (FGR) is associated with communication problems, which might lead to poor literacy skills. The reading and spelling skills of eight- to 10-year-old FGR children born at 24-40 gestational weeks were compared with those of their gestational age-matched, appropriately grown (AGA) peers. A prospectively collected cohort of 37 FGR and 31 AGA children was recruited prenatally at a Finnish tertiary care centre during 1998-2001. The children's reading and spelling skills were assessed using standardised tests for Finnish-speaking second and third graders. Significantly more children performed below the 10th percentile normal values for reading and spelling skills in the FGR group than in the AGA group. At nine years of age, the FGR children had significantly poorer performance in word reading skills and reading fluency, reading accuracy and reading comprehension than the AGA controls. No between-group differences were detected at eight years of age. FGR is associated with poor performance in reading and spelling skills. A third of the FGR children performed below the 10th percentile normal values at nine years of age. These results indicate a need to continuously evaluate linguistic and literacy skills as FGR children age to ensure optimal support. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

On the influence of altered gravity on the growth of fish inner ear otoliths

NASA Astrophysics Data System (ADS)

Beier, Marion

1999-09-01

Inner ear stones (otoliths) of developing cichlid fish ( Oreochromis mossambicus) were marked with the calcium tracer alizarin-complexone (AC) at 1g-earth gravity before and after a long-term (20 days) stay of the animals at moderate hypergravity conditions (3g; centrifuge). AC deposition at the otoliths resulted in two fluorescence bands, which enclosed the area grown during exposure to altered gravity. This area was measured with regard to size and asymmetry (size difference between the left and the right stones). Both utricular and saccular otoliths (lapilli and sagittae, respectively) were significantly smaller after hyper-g exposure as compared to parallely raised 1g-control specimens. The asymmetry concerning the lapilli was pronouncedly decreased in comparison to the 1g-controls. These findings suggest, that the growth and the development of bilateral asymmetry of otoliths is guided by the environmental gravity vector. Some of the hyper-g animals revealed a kinetotic behaviour at the transfer from hyper-g to normal 1g-earth gravity conditions, which was qualitatively similar to the behaviour observed in previous experiments at the transfer from 1g to microgravity in the course of parabolic aircraft flights. The lapillar asymmetry of kinetotic samples was found to be significantly higher than that of normally behaving experimental specimens. This result supports an earlier theoretical concept, according to which human static space sickness might be based on asymmetric utricular otoliths.

Morphometric analysis of the developing pediatric cervical spine.

PubMed

Johnson, Kyle T; Al-Holou, Wajd N; Anderson, Richard C E; Wilson, Thomas J; Karnati, Tejas; Ibrahim, Mohannad; Garton, Hugh J L; Maher, Cormac O

2016-09-01

OBJECTIVE Our understanding of pediatric cervical spine development remains incomplete. The purpose of this analysis was to quantitatively define cervical spine growth in a population of children with normal CT scans. METHODS A total of 1458 children older than 1 year and younger than 18 years of age who had undergone a cervical spine CT scan at the authors' institution were identified. Subjects were separated by sex and age (in years) into 34 groups. Following this assignment, subjects within each group were randomly selected for inclusion until a target of 15 subjects in each group had been measured. Linear measurements were performed on the midsagittal image of the cervical spine. Twenty-three unique measurements were obtained for each subject. RESULTS Data showed that normal vertical growth of the pediatric cervical spine continues up to 18 years of age in boys and 14 years of age in girls. Approximately 75% of the vertical growth occurs throughout the subaxial spine and 25% occurs across the craniovertebral region. The C-2 body is the largest single-segment contributor to vertical growth, but the subaxial vertebral bodies and disc spaces also contribute. Overall vertical growth of the cervical spine throughout childhood is dependent on individual vertebral body growth as well as vertical growth of the disc spaces. The majority of spinal canal diameter growth occurs by 4 years of age. CONCLUSIONS The authors' morphometric analyses establish parameters for normal pediatric cervical spine growth up to 18 years of age. These data should be considered when evaluating children for potential surgical intervention and provide a basis of comparison for studies investigating the effects of cervical spine instrumentation and fusion on subsequent growth.

R7 Photoreceptor Axon Growth Is Temporally Controlled by the Transcription Factor Ttk69, Which Inhibits Growth in Part by Promoting Transforming Growth Factor-β/Activin Signaling

PubMed Central

Kniss, Jonathan S.; Holbrook, Scott

2013-01-01

Work on axon growth has classically focused on understanding how extrinsic cues control growth cone dynamics independent of the cell body. However, more recently, neuron-intrinsic transcription factors have been shown to influence both normal and regenerative axon growth, suggesting that understanding their mechanism of action is of clinical importance. We are studying axon targeting in the Drosophila visual system and here show that the BTB/POZ zinc-finger transcription factor Tramtrack69 (Ttk69) plays an instructive role in inhibiting the growth of R7 photoreceptor axon terminals. Although ttk69 mutant R7 axons project to the correct medullar target layer, M6, their terminals fail to remain retinotopically restricted and instead grow laterally within M6. This overgrowth is not caused by an inability to be repelled by neighboring R7 axons or by an inability to recognize and initiate synapse formation with postsynaptic targets. The overgrowth is progressive and occurs even if contact between ttk69 mutant R7 axons and their normal target layer is disrupted. Ttk69 is first expressed in wild-type R7s after their axons have reached the medulla; ttk69 mutant R7 axon terminal overgrowth begins shortly after this time point. We find that expressing Ttk69 prematurely in R7s collapses their growth cones and disrupts axon extension, indicating that Ttk69 plays an instructive role in this process. A TGF-β/Activin pathway was shown previously to inhibit R7 axon terminal growth. We find that Ttk69 is required for normal activation of this pathway but that Ttk69 likely also inhibits R7 axon growth by a TGF-β/Activin-independent mechanism. PMID:23345225

Automatic Measurement of Fetal Brain Development from Magnetic Resonance Imaging: New Reference Data.

PubMed

Link, Daphna; Braginsky, Michael B; Joskowicz, Leo; Ben Sira, Liat; Harel, Shaul; Many, Ariel; Tarrasch, Ricardo; Malinger, Gustavo; Artzi, Moran; Kapoor, Cassandra; Miller, Elka; Ben Bashat, Dafna

2018-01-01

Accurate fetal brain volume estimation is of paramount importance in evaluating fetal development. The aim of this study was to develop an automatic method for fetal brain segmentation from magnetic resonance imaging (MRI) data, and to create for the first time a normal volumetric growth chart based on a large cohort. A semi-automatic segmentation method based on Seeded Region Growing algorithm was developed and applied to MRI data of 199 typically developed fetuses between 18 and 37 weeks' gestation. The accuracy of the algorithm was tested against a sub-cohort of ground truth manual segmentations. A quadratic regression analysis was used to create normal growth charts. The sensitivity of the method to identify developmental disorders was demonstrated on 9 fetuses with intrauterine growth restriction (IUGR). The developed method showed high correlation with manual segmentation (r2 = 0.9183, p < 0.001) as well as mean volume and volume overlap differences of 4.77 and 18.13%, respectively. New reference data on 199 normal fetuses were created, and all 9 IUGR fetuses were at or below the third percentile of the normal growth chart. The proposed method is fast, accurate, reproducible, user independent, applicable with retrospective data, and is suggested for use in routine clinical practice. © 2017 S. Karger AG, Basel.

Plant perception and response to the signal in gravity resistance

NASA Astrophysics Data System (ADS)

Hoson, Takayuki; Soga, Kouichi; Wakabayashi, Kazuyuki; Kamisaka, Seiichiro; Zhang, Yan; Otomi, Yasuhiro; Hashimoto, Takashi; Iida, Hidetoshi

2012-07-01

Gravity resistance, mechanical resistance to the gravitational force, is a principal graviresponse in plants, distinct from gravitropism. Plants increase the rigidity of their cell walls in the final step of gravity resistance. We studied cellular events leading to or related to the cell wall changes under hypergravity conditions produced by centrifugation and under microgravity conditions in space. The involvement of mechanosensitive ion channels (mechanoreceptors) in signal perception in gravity resistance has been suggested by experiments with inhibitors. As a candidate for the mechanoreceptor, we identified MCA1 and MCA2 in Arabidopsis. mca-null and MCA-overexpressing seedlings were normal in growth in the dark at 1 g. However, suppression by hypergravity of elongation growth was reduced in hypocotyls of mca-null seedlings. On the contrary, MCA-overexpressing seedlings were hypersensitive to hypergravity. These results suggest that MCAs act as the mechanoreceptor in signal perception of gravity resistance. Cortical microtubules play an essential role in maintenance of normal growth phenotype under hypergravity conditions. In Space Seed experiment in the Kibo Module (PI: S. Kamisaka), we examined the effects of microgravity on growth phenotypes of Arabidopsis tubulin mutant, tua6. Inflorescences of the mutant emerged earlier and elongated rapidly under microgravity conditions than under on-orbit or ground 1 g conditions. Also, the inflorescences grown under microgravity conditions showed higher cell wall extensibilities than the controls. The tubulin mutant thus grew and developed more or less normally under microgravity conditions, supporting the principal role of microtubules also in plant resistance to 1 g gravity. On the other hand, the cellular osmotic properties, as well as the cell wall properties, are important factors determining the rigidity of plant body. Azuki bean epicotyls were capable of maintaining osmoregulation even under hypergravity conditions for a short period. By long-term hypergravity treatment, the increase in level of total osmotic solutes was suppressed, which was accounted by suppression of translocation of organic solutes, such as sugars and amino acids, from seed to epicotyl. Nevertheless, the ATP content per epicotyl or fresh weight was kept constant even under hypergravity conditions for a long period. The maintenance of osmoregulation may contribute to plant resistance to hypergravity. Space experiments on the International Space Station will further clarify the mechanism of gravity resistance.

Normal development of spinal axons in early embryo stages and posterior locomotor function is independent of GAL-1.

PubMed

Pasquini, Juana M; Barrantes, Francisco J; Quintá, Héctor R

2017-09-01

It was recently described that Galectin-1 (Gal-1) promotes axonal growth after spinal cord injury. This effect depends on protein dimerization, since monomeric Gal-1 fails to stimulate axonal re-growth. Gal-1 is expressed in vivo at concentrations that favor the monomeric species. The aim of the present study is to investigate whether endogenous Gal-1 is required for spinal axon development and normal locomotor behavior in mice. In order to characterize axonal development, we used a novel combination of 3-DISCO technique with 1-photon microscopy and epifluorescence microscopy under high power LED illumination, followed by serial image section deconvolution and 3-D reconstruction. Cleared whole lgals-1 -/- embryos were used to analyze the 3-D cytoarchitecture of motor, commissural, and sensory axons. This approach allowed us to evaluate axonal development, including the number of fibers, fluorescence density of the fiber tracts, fiber length as well as the morphology of axonal sprouting, deep within the tissue. Gal-1 deficient embryos did not show morphological/anatomical alterations in any of the axonal populations and parameters analyzed. In addition, specific guidance receptor PlexinA4 did not change its axonal localization in the absence of Gal-1. Finally, Gal-1 deficiency did not change normal locomotor activity in post-natal animals. Taken together, our results show that development of spinal axons as well as the locomotor abilities observed in adult mice are independent of Gal-1. Supporting our previous observations, the present study further validates the use of lgals-1 -/- mice to develop spinal cord- or traumatic brain injury models for the evaluation of the regenerative action of Gal-1. © 2017 Wiley Periodicals, Inc.

GBM secretome induces transient transformation of human neural precursor cells.

PubMed

Venugopal, Chitra; Wang, X Simon; Manoranjan, Branavan; McFarlane, Nicole; Nolte, Sara; Li, Meredith; Murty, Naresh; Siu, K W Michael; Singh, Sheila K

2012-09-01

Glioblastoma (GBM) is the most aggressive primary brain tumor in humans, with a uniformly poor prognosis. The tumor microenvironment is composed of both supportive cellular substrates and exogenous factors. We hypothesize that exogenous factors secreted by brain tumor initiating cells (BTICs) could predispose normal neural precursor cells (NPCs) to transformation. When NPCs are grown in GBM-conditioned media, and designated as "tumor-conditioned NPCs" (tcNPCs), they become highly proliferative and exhibit increased stem cell self-renewal, or the unique ability of stem cells to asymmetrically generate another stem cell and a daughter cell. tcNPCs also show an increased transcript level of stem cell markers such as CD133 and ALDH and growth factor receptors such as VEGFR1, VEGFR2, EGFR and PDGFRα. Media analysis by ELISA of GBM-conditioned media reveals an elevated secretion of growth factors such as EGF, VEGF and PDGF-AA when compared to normal neural stem cell-conditioned media. We also demonstrate that tcNPCs require prolonged or continuous exposure to the GBM secretome in vitro to retain GBM BTIC characteristics. Our in vivo studies reveal that tcNPCs are unable to form tumors, confirming that irreversible transformation events may require sustained or prolonged presence of the GBM secretome. Analysis of GBM-conditioned media by mass spectrometry reveals the presence of secreted proteins Chitinase-3-like 1 (CHI3L1) and H2A histone family member H2AX. Collectively, our data suggest that GBM-secreted factors are capable of transiently altering normal NPCs, although for retention of the transformed phenotype, sustained or prolonged secretome exposure or additional transformation events are likely necessary.

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

PubMed

Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

2008-08-01

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

Effects of Ficus asperifolia on normal rat estrus cyclicity

PubMed Central

Ngadjui, Esther; Watcho, Pierre; Nguelefack, Telesphore Benoit; Kamanyi, Albert

2013-01-01

Objective To evaluate Ficus asperifolia (Moraceae) (F. asperifolia) effecting on regular estrus cycle of Wistar rats. Methods Air-dried fruits of F. asperifolia were extracted using water. Prior to the test, vaginal smear was monitored daily for a 3-week period to select females with normal (regular) estrous cycle. Those with regular estrus cycle weighing between 150–170 g were randomized into three sets of 15 animals each. Each set was then divided into three groups: Group 1 (control) was orally administered with distilled water (10 mL/kg body weight) once a day for 1 week starting from the proestrus stage. Groups 2 and 3 were respectively treated with 100 and 500 mg/kg body weight of the plant aqueous extract. The two other sets of 15 animals each were similarly treated as the first set for 3 weeks and 6 weeks respectively. Estrus cycle pattern was monitored before and during plant extract application whereas lipid profile, ovary, uterus and liver growth indices were determined at the end of each treatment. Results F. asperifolia did not disrupt (0%) the order of appearance of normal estrus cycle stages, namely, proestrus, estrus, metestrus and diestrus. Short-term treatment (1 week duration) exhibited high frequency of appearance of proestrus and estrus stages while mid- (3 weeks) and long-term (6 weeks) treatments revealed constancy in the frequency of all stages irrespective to animal groups. The plasma and organ lipid profile, as well as ovary, uterus and liver growth remained unchanged when compared to distilled water-treated animals. Following long-term administration of plant extract (6 weeks), no adverse effect was noticed. Conclusions Our data partially support the use of F. asperifolia in common medicine. PMID:23570017

Ectopic expression of ABSCISIC ACID 2/GLUCOSE INSENSITIVE 1 in Arabidopsis promotes seed dormancy and stress tolerance.

PubMed

Lin, Pei-Chi; Hwang, San-Gwang; Endo, Akira; Okamoto, Masanori; Koshiba, Tomokazu; Cheng, Wan-Hsing

2007-02-01

Abscisic acid (ABA) is an important phytohormone that plays a critical role in seed development, dormancy, and stress tolerance. 9-cis-Epoxycarotenoid dioxygenase is the key enzyme controlling ABA biosynthesis and stress tolerance. In this study, we investigated the effect of ectopic expression of another ABA biosynthesis gene, ABA2 (or GLUCOSE INSENSITIVE 1 [GIN1]) encoding a short-chain dehydrogenase/reductase in Arabidopsis (Arabidopsis thaliana). We show that ABA2-overexpressing transgenic plants with elevated ABA levels exhibited seed germination delay and more tolerance to salinity than wild type when grown on agar plates and/or in soil. However, the germination delay was abolished in transgenic plants showing ABA levels over 2-fold higher than that of wild type grown on 250 mm NaCl. The data suggest that there are distinct mechanisms underlying ABA-mediated inhibition of seed germination under diverse stress. The ABA-deficient mutant aba2, with a shorter primary root, can be restored to normal root growth by exogenous application of ABA, whereas transgenic plants overexpressing ABA2 showed normal root growth. The data reflect that the basal levels of ABA are essential for maintaining normal primary root elongation. Furthermore, analysis of ABA2 promoter activity with ABA2::beta-glucuronidase transgenic plants revealed that the promoter activity was enhanced by multiple prolonged stresses, such as drought, salinity, cold, and flooding, but not by short-term stress treatments. Coincidently, prolonged drought stress treatment led to the up-regulation of ABA biosynthetic and sugar-related genes. Thus, the data support ABA2 as a late expression gene that might have a fine-tuning function in mediating ABA biosynthesis through primary metabolic changes in response to stress.

Comparison of hair follicle histology between horses with pituitary pars intermedia dysfunction and excessive hair growth and normal aged horses.

PubMed

Innerå, Marie; Petersen, Annette D; Desjardins, Danielle R; Steficek, Barbara A; Rosser, Edmund J; Schott, Harold C

2013-02-01

Pituitary pars intermedia dysfunction (PPID) in older equids is commonly recognized by a long hair coat that fails to shed. The aim of this study was to compare hair follicle stages in PPID-affected horses with excessively long hair coats with the stages of normal aged horses (controls) and to compare hair follicle stages in PPID-affected horses after 6 months of treatment with pergolide mesylate with those of control horses. Eight PPID-affected horses and four normal, age-matched, control horses. Skin biopsies were collected from the neck and rump of PPID-affected and control horses. A diagnosis of PPID was established based on hair coat changes and supportive overnight dexamethasone suppression test results. Skin biopsies were repeated after 6 months of treatment with pergolide. The number of hair follicles in anagen (A) or telogen (T) was counted for each skin biopsy using transverse sections. Pretreatment biopsies had a greater percentage of A follicles (neck 96%, rump 95%) and a lower percentage of T follicles (neck 4%, rump 5%) in PPID-affected horses than in control horses (A, neck 15%, rump 25%; and T, neck 85%, rump 75%). After treatment with pergolide, all PPID-affected horses had improved shedding, and the percentages of A follicles (neck 69%, rump 70%) and T follicles (neck 31%, rump 30%) were not different from untreated control horses (A, neck 68%, rump 82%; and T, neck 32%, rump 18%). These findings document that excessive hair growth (hypertrichosis) in PPID-affected horses is due to persistence of hair follicles in A. Furthermore, treatment with pergolide improved shedding and reduced the percentage of A follicles in PPID-affected horses. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

The effects of extraversion, social support on the posttraumatic stress disorder and posttraumatic growth of adolescent survivors of the Wenchuan earthquake.

PubMed

Jia, Xuji; Ying, Liuhua; Zhou, Xiao; Wu, Xinchun; Lin, Chongde

2015-01-01

The aim of this study was to examine the relationships among extraversion, social support, posttraumatic stress disorder and posttraumatic growth among adolescent survivors of the Wenchuan earthquake. Six hundred thirty-eight participants were selected from the survivors of the 2008 Wenchuan earthquake. Participants completed four main questionnaires, including the Extraversion Subscale, the Social Support Scale, the Child PTSD Symptom Scale, and the Posttraumatic Growth Inventory. A bivariate correlation analysis revealed significant correlations among extraversion, social support, posttraumatic stress disorder and posttraumatic growth. Extraversion had significant indirect effects on posttraumatic stress disorder (β = -.037, p < .01) and posttraumatic growth (β = .077, p < .001) through social support. The results also indicated that extraversion had a significant direct effect on posttraumatic growth and a nonsignificant direct effect on posttraumatic stress disorder. Social support fully mediates the relationship between extraversion and posttraumatic stress disorder and partially mediates the relationship between extraversion and posttraumatic growth. Psychological interventions and care for survivors of the earthquake should include the various functions and sources of social support and how they serve to benefit individuals.

The Increasing Prevalence in Intersex Variation from Toxicological Dysregulation in Fetal Reproductive Tissue Differentiation and Development by Endocrine-Disrupting Chemicals

PubMed Central

Rich, Alisa L.; Phipps, Laura M.; Tiwari, Sweta; Rudraraju, Hemanth; Dokpesi, Philip O.

2016-01-01

An increasing number of children are born with intersex variation (IV; ambiguous genitalia/hermaphrodite, pseudohermaphroditism, etc.). Evidence shows that endocrine-disrupting chemicals (EDCs) in the environment can cause reproductive variation through dysregulation of normal reproductive tissue differentiation, growth, and maturation if the fetus is exposed to EDCs during critical developmental times in utero. Animal studies support fish and reptile embryos exhibited IV and sex reversal when exposed to EDCs. Occupational studies verified higher prevalence of offspring with IV in chemically exposed workers (male and female). Chemicals associated with endocrine-disrupting ability in humans include organochlorine pesticides, poly-chlorinated biphenyls, bisphenol A, phthalates, dioxins, and furans. Intersex individuals may have concurrent physical disorders requiring lifelong medical intervention and experience gender dysphoria. An urgent need exists to determine which chemicals possess the greatest risk for IV and the mechanisms by which these chemicals are capable of interfering with normal physiological development in children. PMID:27660460

Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress

PubMed Central

Huang, De; Li, Tingting; Wang, Lin; Zhang, Long; Yan, Ronghui; Li, Kui; Xing, Songge; Wu, Gongwei; Hu, Lan; Jia, Weidong; Lin, Sheng-Cai; Dang, Chi V; Song, Libing; Gao, Ping; Zhang, Huafeng

2016-01-01

Cancer cells are known for their capacity to rewire metabolic pathways to support survival and proliferation under various stress conditions. Ketone bodies, though produced in the liver, are not consumed in normal adult liver cells. We find here that ketone catabolism or ketolysis is re-activated in hepatocellular carcinoma (HCC) cells under nutrition deprivation conditions. Mechanistically, 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting ketolytic enzyme whose expression is suppressed in normal adult liver tissues, is re-induced by serum starvation-triggered mTORC2-AKT-SP1 signaling in HCC cells. Moreover, we observe that enhanced ketolysis in HCC is critical for repression of AMPK activation and protects HCC cells from excessive autophagy, thereby enhancing tumor growth. Importantly, analysis of clinical HCC samples reveals that increased OXCT1 expression predicts higher patient mortality. Taken together, we uncover here a novel metabolic adaptation by which nutrition-deprived HCC cells employ ketone bodies for energy supply and cancer progression. PMID:27644987

Bronchopulmonary dysplasia: improvement in lung function between 7 and 10 years of age.

PubMed

Blayney, M; Kerem, E; Whyte, H; O'Brodovich, H

1991-02-01

To evaluate the natural history of bronchopulmonary dysplasia, we studied the same 32 patients at a mean age of 7 and 10 years. The group as a whole had normal height and weight percentiles, and each child grew along his or her established somatic growth curve. Although some children had abnormal values, the group maintained a normal mean total lung capacity and functional residual capacity. The mean residual volume and the residual volume/total lung capacity ratios were elevated at both ages. At age 7 years the 19 patients (59%) who had a forced expiratory volume in 1 second (FEV1) of less than 80% had "catch up" improvement by 10 years of age (65 +/- 11% to 72 +/- 16% of predicted value; p less than 0.05). All the children who had a normal FEV1 at 7 years of age continued to have a normal FEV1 at age 10 years. Resting single-breath carbon monoxide uptake by the lung was normal when measured at age 10 years. The majority of patients had a positive methacholine challenge test result at both ages, although there was a low incidence of clinically diagnosed asthma. This study demonstrates that patients with bronchopulmonary dysplasia who have normal lung function at age 7 have had normal lung growth and that those with evidence of mild to moderate lung disease have continued lung growth or repair, or both, during their school years.

Systematic review of the effects of iodised salt and iodine supplements on prenatal and postnatal growth: study protocol.

PubMed

Farebrother, Jessica; Naude, Celeste E; Nicol, Liesl; Sang, Zhongna; Yang, Zhenyu; Andersson, Maria; Jooste, Pieter L; Zimmermann, Michael B

2015-04-23

Iodine is an essential micronutrient and component of the thyroid hormones. Sufficient ingestion of iodine is necessary for normal growth and development. If iodine requirements are not met, growth can be impaired. Salt iodisation and supplementation with iodine can prevent iodine deficiency disorders and stunted growth. No systematic review has yet collated the evidence linking iodine to growth. With an increased emphasis on stunting within the WHO Global Nutrition Targets for 2025, we propose a systematic review to address this question. We will undertake a systematic review, and if appropriate, meta-analyses, evaluating the effects of iodised salt or iodine supplements on prenatal and postnatal somatic growth, until age 18. We will search a number of databases, including MEDLINE, EMBASE, Web of Science, CINAHL, PsychINFO, the Cochrane Library, including the CENTRAL register of Controlled Trials and also the WHO library and ICTRP (International Clinical Trials Registry Platform), which includes the Clinicaltrials.gov repository. We will also search Wanfang Data and the China Knowledge Resource Integrated Database. Included studies must have compared exposure to iodised salt, iodine supplements or iodised oil, to placebo, non-iodised salt or no intervention. Primary outcomes will be continuous and categorical markers of prenatal and postnatal somatic growth. Secondary outcomes will cover further measures of growth, including growth rates and indirect markers of growth such as insulin-like growth factor-1 (IGF-1). The systematic review will be published in a peer-reviewed journal, and will be sent directly to the WHO, United Nations Children's Fund, International Council for the Control of Iodine Deficiency Disorders and other stakeholders. The results generated from this systematic review will provide evidence to support future programme recommendations regarding iodine fortification or supplementation and child growth. PROSPERO CRD42014012940. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Modified floating-zone growth of organic single crystals

NASA Astrophysics Data System (ADS)

Kou, S.; Chen, C. P.

1994-04-01

For organic materials floating-zone crystal growth is superior to other melt growth processes in two significant respects: (1) the absence of crucible-induced mechanical damage and (2) minimum heating-induced chemical degradation. Due to the rather low surface tension of organic melts, however, floating-zone crystal growth under normal gravity has not been possible so far but microgravity is ideal for such a purpose. With the help of a modified floating-zone technique, organic single crystals of small cross-sections were test grown first under normal gravity. These small crystals were round and rectangular single crystals of benzil and salol, up to about 7 cm long and 6 mm in diameter or 9 mm × 3 mm in cross-section.

Linguistic Pattern Analysis of Misspellings of Typically Developing Writers in Grades 1 to 9

PubMed Central

Bahr, Ruth Huntley; Silliman, Elaine R.; Berninger, Virginia W.; Dow, Michael

2012-01-01

Purpose A mixed methods approach, evaluating triple word form theory, was used to describe linguistic patterns of misspellings. Method Spelling errors were taken from narrative and expository writing samples provided by 888 typically developing students in grades 1–9. Errors were coded by category (phonological, orthographic, and morphological) and specific linguistic feature affected. Grade level effects were analyzed with trend analysis. Qualitative analyses determined frequent error types and how use of specific linguistic features varied across grades. Results Phonological, orthographic, and morphological errors were noted across all grades, but orthographic errors predominated. Linear trends revealed developmental shifts in error proportions for the orthographic and morphological categories between grades 4–5. Similar error types were noted across age groups but the nature of linguistic feature error changed with age. Conclusions Triple word-form theory was supported. By grade 1, orthographic errors predominated and phonological and morphological error patterns were evident. Morphological errors increased in relative frequency in older students, probably due to a combination of word-formation issues and vocabulary growth. These patterns suggest that normal spelling development reflects non-linear growth and that it takes a long time to develop a robust orthographic lexicon that coordinates phonology, orthography, and morphology and supports word-specific, conventional spelling. PMID:22473834

Loss of imprinting of IGF2 and the epigenetic progenitor model of cancer

PubMed Central

Leick, Mark B; Shoff, Christopher J; Wang, Erwin C; Congress, Jaclyn L; Gallicano, G Ian

2012-01-01

Among the hypotheses discussing cancer formation, the cancer stem cell (CSC) theory is one receiving widespread support. One version of this theory states that changes in otherwise healthy cells can cause formation of tumor- initiating cells (TICs), which have the potential to create precancerous stem cells that can lead to CSC formation. These CSCs can be rare, in contrast to their differentiated progeny, which give rise to the vast majority of the tumor mass in most cancers. Loss of imprinting (LOI) of the insulin-like growth factor-2 (IGF2) gene is one change that can produce these TICs via an epigenetic progenitor model of tumorigenesis. While IGF2 usually supports normal cellular growth, LOI of IGF2 may lead to overexpression of the gene and moreover global chromatin instability. This modification has been observed in many forms of cancer, and given the effect of LOI of IGF2 and its role in cancer, detecting a loss of imprinting in this gene could serve as a valuable diagnostic tool. Preclinical data has shown some progress in identifying therapeutic approaches seeking to exploit this relationship. Thus, further research surrounding LOI of IGF2 could lead to increased understanding of several cancer types and enhance therapies against these diseases. PMID:23671798

Evaluation of two raw diets vs a commercial cooked diet on feline growth.

PubMed

Hamper, Beth A; Bartges, Joseph W; Kirk, Claudia A

2017-04-01

Objectives The objective of this study was to determine if two raw feline diets were nutritionally adequate for kittens. Methods Twenty-four 9-week-old kittens underwent an Association of American Feed Control Officials' (AAFCO) 10 week growth feeding trial with two raw diet groups and one cooked diet group (eight kittens in each). Morphometric measurements (weight, height and length), complete blood counts, serum chemistry, whole blood taurine and fecal cultures were evaluated. Results Overall, the growth parameters were similar for all diet groups, indicating the two raw diets used in this study supported feline growth, within the limitations of an AAFCO growth feeding trial. Kittens fed the raw diets had lower albumin ( P = 0.010) and higher globulin ( P = 0.04) levels than the kittens fed the cooked diet. These lower albumin levels were not clinically significant, as all groups were still within normal age reference intervals. A red cell microcytosis ( P = 0.001) was noted in the combination raw diet group. Increases in fecal Clostridium perfringens were noted in all groups, along with positive fecal Salmonella serovar Heidelberg and Clostridium difficile toxin in the combination raw diet group. Conclusions and relevance The majority of the parameters for feline growth were similar among all groups, indicating the two raw diets studied passed an AAFCO growth trial. In theory, it is possible to pass an AAFCO growth trial but still have nutrient deficiencies in the long term due to liver and fat storage depots. Some of the raw feeders had elevated globulin and microcytosis, likely associated with known enteropathogenic exposure. Disease risks to both pets and owners are obvious. Additional research in this area is needed to investigate the impact of raw diets on the health of domestic cats.

Sex-specific effect of endothelin in the blood pressure response to acute angiotensin II in growth-restricted rats

PubMed Central

Intapad, Suttira; Ojeda, Norma B.; Varney, Elliott; Royals, Thomas P.; Alexander, Barbara T.

2015-01-01

The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhanced renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 nanogram/kilogram/minute for 30 minutes) with and without the endothelin type-A receptor antagonist, ABT 627(10 nanogram/kilogram/minute for 30 minutes), in rats pretreated with enalapril (250 milligram/Liter for one week) to normalize the endogenous renin angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II-mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline following endothelin type-A receptor blockade suggesting that factors in addition to endothelin contribute to the basic angiotensin II-induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II-mediated hemodynamic responses. Endothelin type-A receptor blockade did not reduce acute angiotensin II-mediated increases in blood pressure in female control or growth-restricted rats, intact or ovariectomized. Thus, these data suggest that endothelin type-A receptor blockade contributes to hypersensitivity to acute angiotensin II in male growth-restricted rats and further supports the sex-specific effect of endothelin on blood pressure. PMID:26459423

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas.

PubMed

Auerbach, Michael; James, Stephanie E; Nicoletti, Melissa; Lenowitz, Steven; London, Nicola; Bahrain, Huzefa F; Derman, Richard; Smith, Samuel

2017-12-01

Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P < .00001), transferrin saturations 11.7% and 22.6% (P = .0003), and ferritins 14.5 and 126.3 ng/mL, respectively (P < .000001). Six experienced minor infusion reactions. All resolved. Data for 58 infants were available; one was low on its growth charts for 11 months. The remaining 57 were normal. None were diagnosed with iron deficiency anemia. Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Life and death in the microcirculation: a role for angiotensin II

NASA Technical Reports Server (NTRS)

Greene, A. S.; Cowley, A. W. (Principal Investigator)

1998-01-01

OBJECTIVE: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high-salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats. METHODS: Immunohistochemistry, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the reninangiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture. RESULTS: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin-angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT-PCR confirm the presence of AT1 receptors, which are growth-stimulatory, and AT2 receptors, which are growth-inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rarefaction. CONCLUSIONS: Taken together, these results support the hypothesis that ANGII acting through AT1- and AT2-receptor mechanisms modulate vessel density during high-salt diet and hypertension.

High-Dose Estrogen and Clinical Selective Estrogen Receptor Modulators Induce Growth Arrest, p21, and p53 in Primate Ovarian Surface Epithelial Cells

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

Wright, Jay W.; Stouffer, Richard L.; Rodland, Karin D.

2005-06-09

Ovarian cancer is the most lethal gynecological cancer affecting women. Hormone-based therapies are variably successful in treating ovarian cancer, but the reasoning behind these therapies is paradoxical. Clinical reagents such as tamoxifen are considered to inhibit or reverse tumor growth by competitive inhibition of the estrogen receptor (ER); however high dose estrogen is as clinically effective as tamoxifen, and it is unlikely that estrogen is acting by blocking ER activity; however, it may be activating a unique function of the ER that is nonmitogenic. For poorly defined reasons, 90% of varian cancers derive from the ovarian surface epithelium (OSE). Inmore » vivo the ER-positive OSE is exposed to high estrogen levels, reaching micromolar concentrations in dominant ovarian follicles. Using cultured OSE cells in vitro, we show that these levels of estradiol (1 ug/ml; {approx}3um) block the actions of serum growth factors, activate the G1 phase retinoblastoma AQ:A checkpoint, and induce p21, an inhibitor of kinases that normally inactivate the retinoblastoma checkpoint. We also show that estradiol increases p53 levels, which may contribute to p21 induction. Supporting the hypothesis that clinical selective ER modulators activate this novel ER function, we find that micromolar doses of tamoxifen and the ''pure antiestrogen'' ICI 182,780 elicit the same effects as estradiol. We propose that, in the context of proliferation, these data clarify some paradoxical aspects of hormone-based therapy and suggest that fuller understanding of normal ER function is necessary to improve therapeutic strategies that target the ER. (J Clin Endocrinol Metab 90: 0000-0000, 2005)« less

In Vitro Evidence of the Presence of Mesenchymal Stromal Cells in Cervical Cancer and Their Role in Protecting Cancer Cells from Cytotoxic T Cell Activity

PubMed Central

Montesinos, Juan J.; Mora-García, María de L.; Mayani, Héctor; Flores-Figueroa, Eugenia; García-Rocha, Rosario; Fajardo-Orduña, Guadalupe R.; Castro-Manrreza, Marta E.; Weiss-Steider, Benny

2013-01-01

Mesenchymal stromal cells (MSCs) have been isolated from different tumors and it has been suggested that they support tumor growth through immunosuppression processes that favor tumor cell evasion from the immune system. To date, however, the presence of MSCs in cervical cancer (CeCa) and their possible role in tumor growth remains unknown. Herein we report on the presence of MSCs in cervical tissue, both in normal conditions (NCx-MSCs) and in CeCa (CeCa-MSCs), and described several biological properties of such cells. Our study showed similar patterns of cell surface antigen expression, but distinct differentiation potentials, when we compared both cervical MSC populations to MSCs from normal bone marrow (BM-MSCs, the gold standard). Interestingly, CeCa-MSCs were negative for the presence of human papiloma virus, indicating that these cells are not infected by such a viral agent. Also, interestingly, and in contrast to NCx-MSCs, CeCa-MSCs induced significant downregulation of surface HLA class I molecules (HLA-A*0201) on CaSki cells and other CeCa cell lines. We further observed that CeCa-MSCs inhibited antigen-specific T cell recognition of CaSki cells by cytotoxic T lymphocytes (CTLs). HLA class I downregulation on CeCa cells correlated with the production of IL-10 in cell cocultures. Importantly, this cytokine strongly suppressed recognition of CeCa cells by CTLs. In summary, this study demonstrates the presence of MSCs in CeCa and suggests that tumor-derived MSCs may provide immune protection to tumor cells by inducing downregulation of HLA class I molecules. This mechanism may have important implications in tumor growth. PMID:23656504

Oscillations and accelerations of ice crystal growth rates in microgravity in presence of antifreeze glycoprotein impurity in supercooled water.

PubMed

Furukawa, Yoshinori; Nagashima, Ken; Nakatsubo, Shun-Ichi; Yoshizaki, Izumi; Tamaru, Haruka; Shimaoka, Taro; Sone, Takehiko; Yokoyama, Etsuro; Zepeda, Salvador; Terasawa, Takanori; Asakawa, Harutoshi; Murata, Ken-Ichiro; Sazaki, Gen

2017-03-06

The free growth of ice crystals in supercooled bulk water containing an impurity of glycoprotein, a bio-macromolecule that functions as 'antifreeze' in living organisms in a subzero environment, was observed under microgravity conditions on the International Space Station. We observed the acceleration and oscillation of the normal growth rates as a result of the interfacial adsorption of these protein molecules, which is a newly discovered impurity effect for crystal growth. As the convection caused by gravity may mitigate or modify this effect, secure observations of this effect were first made possible by continuous measurements of normal growth rates under long-term microgravity condition realized only in the spacecraft. Our findings will lead to a better understanding of a novel kinetic process for growth oscillation in relation to growth promotion due to the adsorption of protein molecules and will shed light on the role that crystal growth kinetics has in the onset of the mysterious antifreeze effect in living organisms, namely, how this protein may prevent fish freezing.

Oscillations and accelerations of ice crystal growth rates in microgravity in presence of antifreeze glycoprotein impurity in supercooled water

PubMed Central

Furukawa, Yoshinori; Nagashima, Ken; Nakatsubo, Shun-ichi; Yoshizaki, Izumi; Tamaru, Haruka; Shimaoka, Taro; Sone, Takehiko; Yokoyama, Etsuro; Zepeda, Salvador; Terasawa, Takanori; Asakawa, Harutoshi; Murata, Ken-ichiro; Sazaki, Gen

2017-01-01

The free growth of ice crystals in supercooled bulk water containing an impurity of glycoprotein, a bio-macromolecule that functions as ‘antifreeze’ in living organisms in a subzero environment, was observed under microgravity conditions on the International Space Station. We observed the acceleration and oscillation of the normal growth rates as a result of the interfacial adsorption of these protein molecules, which is a newly discovered impurity effect for crystal growth. As the convection caused by gravity may mitigate or modify this effect, secure observations of this effect were first made possible by continuous measurements of normal growth rates under long-term microgravity condition realized only in the spacecraft. Our findings will lead to a better understanding of a novel kinetic process for growth oscillation in relation to growth promotion due to the adsorption of protein molecules and will shed light on the role that crystal growth kinetics has in the onset of the mysterious antifreeze effect in living organisms, namely, how this protein may prevent fish freezing. PMID:28262787

Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

PubMed Central

Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis

2014-01-01

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667

Desquamation takes center stage at the origin of proliferative inflammatory atrophy, epithelial-mesenchymal transition, and stromal growth in benign prostate hyperplasia.

PubMed

Ferrucci, Danilo; Biancardi, Manoel F; Nishan, Umar; Rosa-Ribeiro, Rafaela; Carvalho, Hernandes F

2017-11-01

In this commentary, we propose a relationship between desquamation, initially described as the collective detachment and deletion of epithelial cell in the prostate gland after castration, and proliferative inflammatory atrophy (PIA) and stromal growth in benign prostate hyperplasia (BPH). First, in response to diverse stimuli, including inflammatory mediators, epithelial cells desquamate and leave a large surface of the luminal side of the basement membrane (BM) exposed. Basal cells are activated into intermediate-type cells, which change morphology to cover and remodel the exposed BM (simple atrophy) to a new physiological demand (such as in the hypoandrogen environment, simulated by surgical and/or chemical castration) and/or to support re-epithelialization (under normal androgen levels). In the presence of inflammation (that might be the cause of desquamation), the intermediate-type cells proliferate and characterize PIA. Second, in other circumstances, desquamation is an early step of epithelial-to-mesenchymal transition (EMT), which contributes to stromal growth, as suggested by some experimental models of BPH. The proposed associations correlate unexplored cell behaviors and reveal the remarkable plasticity of the prostate epithelium that might be at the origin of prostate diseases. © 2017 International Federation for Cell Biology.

The antimicrobial effect of boric acid on Trichomonas vaginalis.

PubMed

Brittingham, Andrew; Wilson, Wayne A

2014-12-01

The treatment options for trichomoniasis are largely limited to nitroimidazole compounds (metronidazole and tinidazole). Few alternatives exist in cases of recalcitrant infections or in cases of nitroimidazole hypersensitivity. Recently, the intravaginal administration of boric acid has been advocated as an alternative treatment of trichomoniasis. However, no in vitro studies are available that directly assess the sensitivity of Trichomonas vaginalis to boric acid. We examined the sensitivity of common laboratory strains and recent clinical isolates of T. vaginalis to boric acid. The effect of increasing concentrations of boric acid on parasite growth and viability was determined, and a minimal lethal concentration was reported. The effect of pH on boric acid toxicity was assessed and compared with that of lactic and acetic acid. Boric acid is microbicidal to T. vaginalis, and its antitrichomonal activity is independent of environmental acidification. Unlike acetic acid and lactic acid, boric acid exposure results in growth suppression and lethality over a wide range of pH (5-7) and under conditions that are normally permissible for growth in vitro. The microbicidal effect of boric acid on T. vaginalis, coupled with its previous clinical use in treating vaginal candidiasis, supports the continued inclusion of boric acid in the therapeutic arsenal for treating trichomoniasis.

Indole-3-Acetic Acid-Producing Yeasts in the Phyllosphere of the Carnivorous Plant Drosera indica L

PubMed Central

Shin, Li-Ying; Wei, Jyuan-Yu; Fu, Shih-Feng; Chou, Jui-Yu

2014-01-01

Yeasts are widely distributed in nature and exist in association with other microorganisms as normal inhabitants of soil, vegetation, and aqueous environments. In this study, 12 yeast strains were enriched and isolated from leaf samples of the carnivorous plant Drosera indica L., which is currently threatened because of restricted habitats and use in herbal industries. According to similarities in large subunit and small subunit ribosomal RNA gene sequences, we identified 2 yeast species in 2 genera of the phylum Ascomycota, and 5 yeast species in 5 genera of the phylum Basidiomycota. All of the isolated yeasts produced indole-3-acetic acid (IAA) when cultivated in YPD broth supplemented with 0.1% L-tryptophan. Growth conditions, such as the pH and temperature of the medium, influenced yeast IAA production. Our results also suggested the existence of a tryptophan-independent IAA biosynthetic pathway. We evaluated the effects of various concentrations of exogenous IAA on yeast growth and observed that IAA produced by wild yeasts modifies auxin-inducible gene expression in Arabidopsis. Our data suggest that yeasts can promote plant growth and support ongoing prospecting of yeast strains for inclusion into biofertilizer for sustainable agriculture. PMID:25464336

Nucleation, Growth, Annealing, and Coagulation of Refractory Oxides and Metals: Recent Experimental Progress and Applications to Astrophysical Systems

NASA Technical Reports Server (NTRS)

Nuth, J. A.; Rietmeijer, F. J. M.; Hallenbeck, S. L.; Withey, P. A.

1999-01-01

Starting with cooling, refractory vapors diluted in significant quantities of H and He there are four processes that most natural systems will undergo: nucleation, growth, annealing, and coagulation. Nucleation is the processes by which the first stable refractory nuclei form in the vapor. These are the seeds onto which the remaining vapors will condense during the growth stage. Solids of any composition will try to arrange themselves into the least energetic configuration, provided that there is sufficient energy available to support such processes as diffusion and the breaking of chemical bonds. There is a significant activation energy associated with the annealing process in refractory solids due to the relatively high energy of the chemical bonds in solids. The grains formed in most cosmochemical systems are extremely small and often tightly coupled to the gas. Because of their small physical cross sections coagulation may be a very slow process unless there is another driving force involved in addition to normal Brownian motion. In what follows we will briefly cover each of these four stages for refractory oxide and metal grains, although in inverse order.

Antagonistic Effects of BACE1 and APH1B-γ-Secretase Control Axonal Guidance by Regulating Growth Cone Collapse.

PubMed

Barão, Soraia; Gärtner, Annette; Leyva-Díaz, Eduardo; Demyanenko, Galina; Munck, Sebastian; Vanhoutvin, Tine; Zhou, Lujia; Schachner, Melitta; López-Bendito, Guillermina; Maness, Patricia F; De Strooper, Bart

2015-09-01

ΒACE1 is the major drug target for Alzheimer's disease, but we know surprisingly little about its normal function in the CNS. Here, we show that this protease is critically involved in semaphorin 3A (Sema3A)-mediated axonal guidance processes in thalamic and hippocampal neurons. An active membrane-bound proteolytic CHL1 fragment is generated by BACE1 upon Sema3A binding. This fragment relays the Sema3A signal via ezrin-radixin-moesin (ERM) proteins to the neuronal cytoskeleton. APH1B-γ-secretase-mediated degradation of this fragment stops the Sema3A-induced collapse and sensitizes the growth cone for the next axonal guidance cue. Thus, we reveal a cycle of proteolytic activity underlying growth cone collapse and restoration used by axons to find their correct trajectory in the brain. Our data also suggest that BACE1 and γ-secretase inhibition have physiologically opposite effects in this process, supporting the idea that combination therapy might attenuate some of the side effects associated with these drugs. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dual inhibition of survivin and MAOA synergistically impairs growth of PTEN-negative prostate cancer.

PubMed

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

2015-07-14

Survivin and monoamine oxidase A (MAOA) levels are elevated in prostate cancer (PCa) compared to normal prostate glands. However, the relationship between survivin and MAOA in PCa is unclear. We examined MAOA expression in the prostate lobes of a conditional PTEN-deficient mouse model mirroring human PCa, with or without survivin knockout. We also silenced one gene at a time and examined the expression of the other. We further evaluated the combination of MAOA inhibitors and survivin suppressants on the growth, viability, migration and invasion of PCa cells. Survivin and MAOA levels are both increased in clinical PCa tissues and significantly associated with patients' survival. Survivin depletion delayed MAOA increase during PCa progression, and silencing MAOA decreased survivin expression. The combination of MAOA inhibitors and the survivin suppressants (YM155 and SC144) showed significant synergy on the inhibition of PCa cell growth, migration and invasion with concomitant decrease in survivin and MMP-9 levels. There is a positive feedback loop between survivin and MAOA expression in PCa. Considering that survivin suppressants and MAOA inhibitors are currently available in clinical trials and clinical use, their synergistic effects in PCa support a rapid translation of this combination to clinical practice.

Pleiotrophin is downregulated in human keloids.

PubMed

Lee, Dong Hun; Jin, Cheng Long; Kim, Yeji; Shin, Mi Hee; Kim, Ji Eun; Kim, Minji; Lee, Min Jung; Cho, Soyun

2016-10-01

Keloid is an abnormal hyperproliferative scarring process with involvement of complex genetic and triggering environmental factors. Previously published dysregulated gene expression profile of keloids includes genes involved in tumor formation. Pleiotrophin (PTN) is a secreted, heparin-binding growth factor which is involved in various biological functions such as cell growth, differentiation, and tumor progression. Although PTN expression was reported to be increased in hypertrophic scars, there is no study on PTN expression in keloids, and previous microarray results are controversial. To clarify differential expression of PTN in keloids, we investigated the expression of PTN and its interacting molecules in keloid and control fibroblasts, and performed immunohistochemical staining of PTN using tissue arrays. The expressions of PTN, its upstream regulator platelet-derived growth factor subunit B (PDGF-B) and corresponding PDGF receptors were significantly downregulated in keloid fibroblasts compared to normal human fibroblasts, and the decreased PTN protein expression was confirmed by immunohistochemistry as well as Western blot. Moreover, functional downstream receptor protein tyrosine phosphatase β/ζ was significantly upregulated in keloid fibroblasts, supporting overall downregulation of PTN signaling pathway. The lowered PTN expression in keloids suggests a different pathomechanism from that of hypertrophic scars.

Dynamics of homogeneous shear turbulence: A key role of the nonlinear transverse cascade in the bypass concept.

PubMed

Mamatsashvili, G; Khujadze, G; Chagelishvili, G; Dong, S; Jiménez, J; Foysi, H

2016-08-01

To understand the mechanism of the self-sustenance of subcritical turbulence in spectrally stable (constant) shear flows, we performed direct numerical simulations of homogeneous shear turbulence for different aspect ratios of the flow domain with subsequent analysis of the dynamical processes in spectral or Fourier space. There are no exponentially growing modes in such flows and the turbulence is energetically supported only by the linear growth of Fourier harmonics of perturbations due to the shear flow non-normality. This non-normality-induced growth, also known as nonmodal growth, is anisotropic in spectral space, which, in turn, leads to anisotropy of nonlinear processes in this space. As a result, a transverse (angular) redistribution of harmonics in Fourier space is the main nonlinear process in these flows, rather than direct or inverse cascades. We refer to this type of nonlinear redistribution as the nonlinear transverse cascade. It is demonstrated that the turbulence is sustained by a subtle interplay between the linear nonmodal growth and the nonlinear transverse cascade. This course of events reliably exemplifies a well-known bypass scenario of subcritical turbulence in spectrally stable shear flows. These two basic processes mainly operate at large length scales, comparable to the domain size. Therefore, this central, small wave number area of Fourier space is crucial in the self-sustenance; we defined its size and labeled it as the vital area of turbulence. Outside the vital area, the nonmodal growth and the transverse cascade are of secondary importance: Fourier harmonics are transferred to dissipative scales by the nonlinear direct cascade. Although the cascades and the self-sustaining process of turbulence are qualitatively the same at different aspect ratios, the number of harmonics actively participating in this process (i.e., the harmonics whose energies grow more than 10% of the maximum spectral energy at least once during evolution) varies, but always remains quite large (equal to 36, 86, and 209) in the considered here three aspect ratios. This implies that the self-sustenance of subcritical turbulence cannot be described by low-order models.

Dynamics of homogeneous shear turbulence: A key role of the nonlinear transverse cascade in the bypass concept

NASA Astrophysics Data System (ADS)

Mamatsashvili, G.; Khujadze, G.; Chagelishvili, G.; Dong, S.; Jiménez, J.; Foysi, H.

2016-08-01

To understand the mechanism of the self-sustenance of subcritical turbulence in spectrally stable (constant) shear flows, we performed direct numerical simulations of homogeneous shear turbulence for different aspect ratios of the flow domain with subsequent analysis of the dynamical processes in spectral or Fourier space. There are no exponentially growing modes in such flows and the turbulence is energetically supported only by the linear growth of Fourier harmonics of perturbations due to the shear flow non-normality. This non-normality-induced growth, also known as nonmodal growth, is anisotropic in spectral space, which, in turn, leads to anisotropy of nonlinear processes in this space. As a result, a transverse (angular) redistribution of harmonics in Fourier space is the main nonlinear process in these flows, rather than direct or inverse cascades. We refer to this type of nonlinear redistribution as the nonlinear transverse cascade. It is demonstrated that the turbulence is sustained by a subtle interplay between the linear nonmodal growth and the nonlinear transverse cascade. This course of events reliably exemplifies a well-known bypass scenario of subcritical turbulence in spectrally stable shear flows. These two basic processes mainly operate at large length scales, comparable to the domain size. Therefore, this central, small wave number area of Fourier space is crucial in the self-sustenance; we defined its size and labeled it as the vital area of turbulence. Outside the vital area, the nonmodal growth and the transverse cascade are of secondary importance: Fourier harmonics are transferred to dissipative scales by the nonlinear direct cascade. Although the cascades and the self-sustaining process of turbulence are qualitatively the same at different aspect ratios, the number of harmonics actively participating in this process (i.e., the harmonics whose energies grow more than 10% of the maximum spectral energy at least once during evolution) varies, but always remains quite large (equal to 36, 86, and 209) in the considered here three aspect ratios. This implies that the self-sustenance of subcritical turbulence cannot be described by low-order models.

[Pathologic change of elastic fibers with difference of microvessel density and expression of angiogenesis-related proteins in internal hemorrhoid tissues].

PubMed

Han, Wei; Wang, Zhen-jun; Zhao, Bo; Yang, Xin-qing; Wang, Dong; Wang, Jian-pin; Tang, Xiu-ying; Zhao, Fa; Hung, Yan-ting

2005-01-01

To investigate the pathological variations in internal hemorrhoid and evaluate the expression of nitric- oxide synthase(NOS),vascular endothelial growth factor(VEGF),matrix metalloproteinase- 2(MMP2) and MMP9. Normal anal cushion and internal hemorrhoids tissue samples were obtained from 24 patients with iii degree hemorrhoids after procedure for prolapse and hemorrhoids(PPH) procedure. The expression of NOS, VEGF, MMP2, MMP9 and CD34 were detected by immunohistochemical staining; the microvessel density (MVD) was counted by anti- CD34 antibody; the elastic fibers were detected by orcein staining. There were statistically significant differences in the expression of MVD, VEGF, MMP9 between internal hemorrhoid tissue and normal anal cushions(P< 0.05). iNOS was significantly increased in hemorrhoid tissue, but no significant difference between normal anal cushions and hemorrhoid tissue. Morphological abnormalities such as breaking, distortion, mortality, hyaline degeneration were found in elastic fibers of internal hemorrhoid tissue, but not in normal anal cushions. Angiogenesis is evident in hemorrhoid tissue, suggesting the possible mechanism in the pathogenesis of hemorrhoids. The direct degeneration effect of MMP9 on supporting structure elastic fibers in anal cushion is another important mechanism. The high expression of iNOS suggests the inflammatory factors involve in the pathogenesis of hemorrhoids, and NO may be involve in pathological effect on hemorrhoids.

Boreal forests and atmosphere - Biosphere exchange of carbon dioxide

NASA Technical Reports Server (NTRS)

D'Arrigo, Rosanne; Jacoby, Gordon C.; Fung, Inez Y.

1987-01-01

Two approaches to investigating the role of boreal forests in the global carbon cycle are presented. First, a tracer support model which incorporates the normalized-difference vegetation index obtained from advanced, very high resolution radiometer radiances was used to simulate the annual cycle of CO2 in the atmosphere. Results indicate that the seasonal growth of the combined boreal forests of North America and Eurasia accounts for about 50 percent of the mean seasonal CO2 amplitude recorded at Pt. Barrow, Alaska and about 30 percent of the more globally representative CO2 signal at Mauna Loa, Hawaii. Second, tree-ring width data from four boreal treeline sites in northern Canada were positively correlated with Pt. Barrow CO2 drawdown for the period 1971-1982. These results suggest that large-scale changes in the growth of boreal forests may be contributing to the observed increasing trend in CO2 amplitude. They further suggest that tree-ring data may be applicable as indices for CO2 uptake and remote sensing estimates of photosynthetic activity.

Biocompatibility of cluster-assembled nanostructured TiO2 with primary and cancer cells.

PubMed

Carbone, Roberta; Marangi, Ida; Zanardi, Andrea; Giorgetti, Luca; Chierici, Elisabetta; Berlanda, Giuseppe; Podestà, Alessandro; Fiorentini, Francesca; Bongiorno, Gero; Piseri, Paolo; Pelicci, Pier Giuseppe; Milani, Paolo

2006-06-01

We have characterized the biocompatibility of nanostructured TiO2 films produced by the deposition of a supersonic beam of TiOx clusters. Physical analysis shows that these films possess, at the nanoscale, a granularity and porosity mimicking those of typical extracellular matrix structures and adsorption properties that could allow surface functionalization with different macromolecules such as DNA, proteins, and peptides. To explore the biocompatibility of this novel nanostructured surface, different cancer and primary cells were analyzed in terms of morphological appearance (by bright field microscopy and immunofluorescence) and growth properties, with the aim to evaluate cluster-assembled TiO2 films as substrates for cell-based and tissue-based applications. Our results strongly suggest that this new biomaterial supports normal growth and adhesion of primary and cancer cells with no need for coating with ECM proteins; we thus propose this new material as an optimal substrate for different applications in cell-based assays, biosensors or microfabricated medical devices.

Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery.

PubMed

Dolor, Aaron; Szoka, Francis C

2018-06-04

Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies, and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion 2-10-fold. This modest improvement resulted in decreased tumor growth, but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published in vitro and in vivo benefits and limitations of collagenase treatment to improve drug delivery.

Growth and yield models for central hardwoods

Treesearch

Martin E. Dale; Donald E. Hilt

1989-01-01

Over the last 20 years computers have become an efficient tool to estimate growth and yield. Computerized yield estimates vary from simple approximation or interpolation of traditional normal yield tables to highly sophisticated programs that simulate the growth and yield of each individual tree.

Mechanisms of Integrin-Mediated Growth Control in Normal, Transformed, and Neoplastic Breast Cells

DTIC Science & Technology

1996-10-01

Takeichi ). 3. Breast Cell Isolation and Culture Normal human BC was obtained from Clonetics Corp (San Diego, CA, cat . # CC-0228) or from reduction...mammary epithelial growth medium (MEGM) from Clonetics ( cat . #CC- 3051). A number of breast carcinoma cell lines (see Table I) were obtained from the...at autophosphorylation of FAK as well as using commercially available kits for tyrosine kinases (Boehringer Mannheim cat # 1-534-505; Life

Truncated Hormone Inhibits Breast Tumor Blood Vessel Formation, Not Tumor Growth | Center for Cancer Research

Cancer.gov

The hormone prolactin (PRL) plays a critical role in normal breast development by stimulating the proliferation of mammary cells, the production of milk proteins, and the formation of new mammary blood vessels. Unfortunately, the same cell and vessel growth pathways controlled by PRL in normal cells also operate in breast cancer cells, and elevated plasma PRL is a risk factor for breast cancer, especially in post-menopausal women.

Growth Disorders

MedlinePlus

... take the missing hormone as a pill. Other Reasons Why Kids Might Not Grow Normally Hormones play ... but kids might not grow normally for other reasons, including: Chronic diseases. These include heart and kidney ...

Optimal Transient Growth of Submesoscale Baroclinic Instabilities

NASA Astrophysics Data System (ADS)

White, Brian; Zemskova, Varvara; Passaggia, Pierre-Yves

2016-11-01

Submesoscale instabilities are analyzed using a transient growth approach to determine the optimal perturbation for a rotating Boussinesq fluid subject to baroclinic instabilities. We consider a base flow with uniform shear and stratification and consider the non-normal evolution over finite-time horizons of linear perturbations in an ageostrophic, non-hydrostatic regime. Stone (1966, 1971) showed that the stability of the base flow to normal modes depends on the Rossby and Richardson numbers, with instabilities ranging from geostrophic (Ro -> 0) and ageostrophic (finite Ro) baroclinic modes to symmetric (Ri < 1 , Ro > 1) and Kelvin-Helmholtz (Ri < 1 / 4) modes. Non-normal transient growth, initiated by localized optimal wave packets, represents a faster mechanism for the growth of perturbations and may provide an energetic link between large-scale flows in geostrophic balance and dissipation scales via submesoscale instabilities. Here we consider two- and three-dimensional optimal perturbations by means of direct-adjoint iterations of the linearized Boussinesq Navier-Stokes equations to determine the form of the optimal perturbation, the optimal energy gain, and the characteristics of the most unstable perturbation.

Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression.

PubMed

Easty, D J; Guthrie, B A; Maung, K; Farr, C J; Lindberg, R A; Toso, R J; Herlyn, M; Bennett, D C

1995-06-15

Epithelial cell kinase (ECK) is a receptor protein tyrosine kinase, the role of which in melanoma biology is unclear. Here we studied the role of ECK during melanoma progression. ECK mRNA was overexpressed in virtually all melanoma lines tested, and levels were significantly higher in cell lines from distant metastases than primary melanomas; melanocytes were negative. Gene amplification was not detected in melanomas. Levels of ECK protein corresponded well with mRNA levels. B61 or LERK-1, recently identified as an ECK ligand, stimulated the growth of ECK-expressing melanoma cell lines, its first identified biological activity. Melanoma chemotaxis and chemoinvasion were not affected by B61. Growth of normal melanocytes was not affected. mRNA for B61 was detected in both melanoma cell lines and normal melanocytes. B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media. These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes.

Supporting the students most in need: academic self-efficacy and perceived teacher support in relation to within-year academic growth.

PubMed

Mercer, Sterett H; Nellis, Leah M; Martínez, Rebecca S; Kirk, Megan

2011-06-01

Academic self-efficacy and perceived teacher support in relation to academic skill growth across one academic year were examined in the study. Participants included 193 5th-grade students. Teachers collected curriculum-based measures (CBM) of reading and math on three occasions as part of routine academic benchmarks, and researchers collected student-reported measures of academic self-efficacy and perceived teacher support in the spring of the same academic year. Results indicated that academic self-efficacy was positively related to fall reading and math CBM scores and that perceived teacher support was unrelated to fall scores or growth across the academic year. Academic self-efficacy and perceived teacher support interacted in relation to math CBM growth such that low levels of perceived teacher support were related to greater growth, particularly for students with high academic self-efficacy. Follow-up analyses indicated that students with the lowest fall CBM scores and smallest growth rates reported higher levels of perceived teacher support, suggesting that teachers support the students most in need. Copyright © 2011 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Estimating differences in volumetric flat bone growth in pediatric patients by radiation treatment method

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

Hua Chiaho; Shukla, Hemant I.; Merchant, Thomas E.

2007-02-01

Purpose: To estimate potential differences in volumetric bone growth in children with sarcoma treated with intensity-modulated (IMRT) and conformal (CRT) radiation therapy using an empiric dose-effect model. Methods and Materials: A random coefficient model was used to estimate potential volumetric bone growth of 36 pelvic bones (ischiopubis and ilium) from 11 patients 4 years after radiotherapy. The model incorporated patient age, pretreatment bone volume, integral dose >35 Gy, and time since completion of radiation therapy. Three dosimetry plans were entered into the model: the actual CRT/IMRT plan, a nontreated comparable IMRT/CRT plan, and an idealized plan in which dose wasmore » delivered only to the planning target volume. The results were compared with modeled normal bone growth. Results: The model predicted that by using the idealized, IMRT, and CRT approaches, patients would maintain 93%, 87%, and 84%, respectively (p = 0.06), of their expected normal growth. Patients older than 10 years would maintain 98% of normal growth, regardless of treatment method. Those younger than 10 years would maintain 87% (idealized), 76% (IMRT), or 70% (CRT) of their expected growth (p = 0.015). Post hoc testing (Tukey) revealed that the CRT and IMRT approaches differed significantly from the idealized one but not from each other. Conclusions: Dose-effect models facilitate the comparison of treatment methods and potential interventions. Although treatment methods do not alter the growth of flat bones in older pediatric patients, they may significantly impact bone growth in children younger than age 10 years, especially as we move toward techniques with high conformity and sharper dose gradient.« less

Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

PubMed

Hasegawa, Mayumi; Cheng, Jun; Maruyama, Satoshi; Yamazaki, Manabu; Abé, Tatsuya; Babkair, Hamzah; Saito, Chikara; Saku, Takashi

2016-05-01

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Thoracic Spine Growth Revisited: How Accurate Is the Dimeglio Data?

PubMed

Dede, Ozgur; Büyükdoğan, Kadir; Demirkıran, Halil Gökhan; Akpınar, Erhan; Yazici, Muharrem

2017-06-15

Cross-sectional descriptive study. To describe the normal rate pattern of thoracic spine growth in children without any spinal deformity. The knowledge of thoracic spine growth and height is important for growing spine treatment and the decision of final fusion. Currently, pediatric spinal deformity is approached as early onset and late onset with an understanding of the fast growth during the first 5 years of life. The growth data that support this classification is often cited but has not been reconfirmed with follow-up studies. Sagittal computed tomography (CT) reformations of thoracic vertebrae were examined in children without spinal deformity. The sagittal CT cut at the widest canal diameter was identified and the measurements were performed on this image. The length of the thoracic spine was measured from the posterosuperior corner of T1 to the posteroinferior corner of the T12. One hundred forty-four thoracic CT scans satisfied the inclusion criteria. The analysis of the data identified two break points in the growth velocity; one at the end of the 4th year of life and the other at the beginning of the 12th year. Specifically, growth rate between 1 and 4 years was 1.71 cm/yr, between 4 and 8 years was 0.55 cm/yr, between 8 and 10 was 0.74 cm/yr, between 10 and 12 was 0.69 cm/yr, and between 12 and 16 was 1.61 cm/yr. The results show that in growing children the thoracic spine demonstrates two major growth spurts. The initial growth spurt is between the birth to the end of the fourth year of life and the second is between the 12 and 16 years of age. Between 4 and 12 years there is a steady but slower increase in thoracic height. The findings show that the fastest growth velocity may be limited to a younger age group than previously believed. This data will help guide growth friendly management strategies. 2.

Theory of the intermediate stage of crystal growth with applications to insulin crystallization

NASA Astrophysics Data System (ADS)

Barlow, D. A.

2017-07-01

A theory for the intermediate stage of crystal growth, where two defining equations one for population continuity and another for mass-balance, is used to study the kinetics of the supersaturation decay, the homogeneous nucleation rate, the linear growth rate and the final distribution of crystal sizes for the crystallization of bovine and porcine insulin from solution. The cited experimental reports suggest that the crystal linear growth rate is directly proportional to the square of the insulin concentration in solution for bovine insulin and to the cube of concentration for porcine. In a previous work, it was shown that the above mentioned system could be solved for the case where the growth rate is directly proportional to the normalized supersaturation. Here a more general solution is presented valid for cases where the growth rate is directly proportional to the normalized supersaturation raised to the power of any positive integer. The resulting expressions for the time dependent normalized supersaturation and crystal size distribution are compared with experimental reports for insulin crystallization. An approximation for the maximum crystal size at the end of the intermediate stage is derived. The results suggest that the largest crystal size in the distribution at the end of the intermediate stage is maximized when nucleation is restricted to be only homogeneous. Further, the largest size in the final distribution depends only weakly upon the initial supersaturation.

Effects of advanced glycation end products on ezrin-dependent functions in LLC-PK1 proximal tubule cells.

PubMed

Bach, Leon A; Gallicchio, Marisa A; McRobert, E Anne; Tikoo, Anjali; Cooper, Mark E

2005-06-01

We have recently shown that advanced glycation products (AGEs) bind to the ERM (ezrin, radixin, moesin) family of proteins. ERM proteins act as cross-linkers between cell membrane proteins and the actin cytoskeleton. They are also involved in signal transduction pathways. They therefore have a critical role in normal cell processes, including modulation of cell shape, adhesion, and motility. We postulate that AGEs may contribute to diabetic complications by disrupting ERM function. In support of this hypothesis, AGEs inhibit ezrin-dependent tubulogenesis of proximal tubule cells. Phosphorylation is an important activating mechanism for ERM proteins, and AGEs inhibit ezrin phosphorylation mediated by the epidermal growth factor receptor.

Ability of lithium to accelerate the recovery of granulopoiesis after subacute radiation injury.

PubMed

Gallicchio, V S; Chen, M G; Watts, T D

1984-01-01

Lithium stimulates granulopoietic recovery after mice are exposed to 2 Gy. By examining the hematopoietic inductive microenvironment (HIM) using the stromal colony assay, we demonstrate here that lithium, during the two weeks after irradiation, produced less stromal colony suppression than was observed from the irradiated controls. Recovery peaked by day 19 and returned to normal by day 28. This response was also observed in splenic derived stroma. Furthermore, stroma from lithium-irradiated animals supported the in vitro growth of granulocyte-macrophage colonies (CFU-GM) greater than observed from irradiated controls. These data suggest lithium accelerates granulopoietic recovery by first providing for a completely reconstituted and functional HIM.

The Effects of Extraversion, Social Support on the Posttraumatic Stress Disorder and Posttraumatic Growth of Adolescent Survivors of the Wenchuan Earthquake

PubMed Central

Jia, Xuji; Ying, Liuhua; Zhou, Xiao; Wu, Xinchun; Lin, Chongde

2015-01-01

Objective The aim of this study was to examine the relationships among extraversion, social support, posttraumatic stress disorder and posttraumatic growth among adolescent survivors of the Wenchuan earthquake. Methods Six hundred thirty-eight participants were selected from the survivors of the 2008 Wenchuan earthquake. Participants completed four main questionnaires, including the Extraversion Subscale, the Social Support Scale, the Child PTSD Symptom Scale, and the Posttraumatic Growth Inventory. Results A bivariate correlation analysis revealed significant correlations among extraversion, social support, posttraumatic stress disorder and posttraumatic growth. Extraversion had significant indirect effects on posttraumatic stress disorder (β = −.037, p < .01) and posttraumatic growth (β = .077, p < .001) through social support. The results also indicated that extraversion had a significant direct effect on posttraumatic growth and a nonsignificant direct effect on posttraumatic stress disorder. Conclusions Social support fully mediates the relationship between extraversion and posttraumatic stress disorder and partially mediates the relationship between extraversion and posttraumatic growth. Psychological interventions and care for survivors of the earthquake should include the various functions and sources of social support and how they serve to benefit individuals. PMID:25815720

Proinflammatory Cytokines as Regulators of Vaginal Microbiota.

PubMed

Kremleva, E A; Sgibnev, A V

2016-11-01

It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

Diagnostic Usefulness of Insulin-Like Growth Factor 1 and Insulin-Like Growth Factor Binding Protein 3 in Children with Suspected Pituitary Dwarfism.

PubMed

Zelazowska-Rutkowska, Beata; Trusiak, Marta; Bossowski, Artur; Cylwik, Bogdan

2018-05-01

Pituitary dwarfism (also known as short stature) is a medical condition in which the pituitary gland does not produce enough growth hormone (GH). To confirm the diagnosis of growth hormone deficiency the overnight profile of GH secretion and GH provocative tests are usually performed; however, due to wide GH fluctuations throughout the day and night and the invasiveness of stimulation tests, their clinical utility is limited. Therefore, screening for IGF-1 (insulin-like growth factor 1) and IGFBP-3 (insulin-like growth factor binding protein type 3) is proposed, suggesting that these tests provide a more accurate reflection of the mean plasma GH level, although the results of these tests are still problematic. In this context, the aim of this study was to assess the diagnostic usefulness of IGF-1 and IGFBP-3 in children with suspected pituitary dwarfism. Studies were carried out in 127 children with abnormal growth and low spontaneous 24-hour plasma GH profiles and abnormal results of GH stimulation tests. Fasting serum IGF-1 and IGFBP-3 were determined by chemiluminescent quantitative measurement using the IMMULITE 1000 IGF-1 and IGFBP-3 kits (Siemens Healthcare Diagnostics, United Kingdom) on the IMMULITE 1000 analyzer (Siemens Healthcare Diagnostics, USA). Results were compared to the normal range by children's age. Mean serum IGF-1 concentrations were within the lower normal range (41.7% cases), and 58.3% results were below the normal reference range in the study group. The average serum IGFBP-3 levels were within the lower normal range. We conclude that IGF-1 test can be a useful tool in the diagnosis of pituitary dwarfism in children suspected of this condition, but due to relatively poor sensitivity the testing cannot be performed alone, but in combination with other tests. The IGFBP-3 test is not useful for the diagnosis of this disease.

Evaluation of Delamination Growth Characterization Methods Under Mode I Fatigue Loading

NASA Technical Reports Server (NTRS)

Murri, Gretchen B.

2012-01-01

Reliable delamination characterization data for laminated composites are needed for input to analytical models of structures to predict delamination. The double-cantilevered beam (DCB) specimen is used with laminated composites to measure fracture toughness, G(sub Ic), delamination onset strain energy release rate, and growth rate data under cyclic loading. In the current study, DCB specimens of IM7/8552 graphite/epoxy supplied by two different manufacturers were tested in static and fatigue to compare the measured characterization data from the two sources, and to evaluate a proposed ASTM standard for generating Paris Law equations. Static results were used to generate compliance calibration constants for the fatigue data, and a delamination resistance curve, G(sub IR), which was used to determine the effects of fiber-bridging on delamination growth. Specimens were tested in fatigue at a cyclic G(sub Imax) level equal to 50, 40 or 30% of G(sub Ic), to determine a delamination onset curve and delamination growth rate. The delamination onset curve equations had similar exponents and the same trends. Delamination growth rate was calculated by fitting a Paris Law to the da/dN versus G(sub Imax) data. Both a 2-point and a 7-point data reduction method were used and the Paris Law equations were compared. To determine the effects of fiber-bridging, growth rate results were normalized by the delamination resistance curve for each material and compared to the non-normalized results. Paris Law exponents were found to decrease by 31% to 37% due to normalizing the growth data. Normalizing the data also greatly reduced the amount of scatter between the different specimens. Visual data records from the fatigue testing were used to calculate individual compliance calibration constants from the fatigue data for some of the specimens. The resulting da/dN versus G(sub Imax) plots showed much improved repeatability between specimens. Gretchen

Growth curves for Laron syndrome.

PubMed Central

Laron, Z; Lilos, P; Klinger, B

1993-01-01

Growth curves for children with Laron syndrome were constructed on the basis of repeated measurements made throughout infancy, childhood, and puberty in 24 (10 boys, 14 girls) of the 41 patients with this syndrome investigated in our clinic. Growth retardation was already noted at birth, the birth length ranging from 42 to 46 cm in the 12/20 available measurements. The postnatal growth curves deviated sharply from the normal from infancy on. Both sexes showed no clear pubertal spurt. Girls completed their growth between the age of 16-19 years to a final mean (SD) height of 119 (8.5) cm whereas the boys continued growing beyond the age of 20 years, achieving a final height of 124 (8.5) cm. At all ages the upper to lower body segment ratio was more than 2 SD above the normal mean. These growth curves constitute a model not only for primary, hereditary insulin-like growth factor-I (IGF-I) deficiency (Laron syndrome) but also for untreated secondary IGF-I deficiencies such as growth hormone gene deletion and idiopathic congenital isolated growth hormone deficiency. They should also be useful in the follow up of children with Laron syndrome treated with biosynthetic recombinant IGF-I. PMID:8333769

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer.

PubMed

Zammit, C; Coope, R; Gomm, J J; Shousha, S; Johnston, C L; Coombes, R C

2002-04-08

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

Antenatal glucocorticoid treatment of the growth-restricted fetus: benefit or cost?

PubMed

Morrison, Janna L; Orgeig, Sandra

2009-06-01

Women at risk of preterm labor are commonly treated with antenatal glucocorticoids to reduce neonatal complications, including respiratory distress syndrome. Despite the benefits of antenatal glucocorticoid for neonatal lung function, they are associated with negative cardiovascular outcomes. Among this population, there is a group of intrauterine growth-restricted fetuses in which substrate supply is reduced and these fetuses must undergo a range of cardiovascular adaptations to survive. Interestingly, the cardiovascular changes caused by antenatal glucocorticoid in normally grown fetuses are contrary to the cardiovascular adaptations that the intrauterine growth-restricted fetus must make to survive. Hence, the possibility exists that antenatal glucocorticoid in intrauterine growth-restricted infants may compromise cardiovascular development. This review first provides an overview of general antenatal glucocorticoid effects, before outlining the effects on cardiorespiratory development in normally grown fetuses, the cardiovascular adaptations that occur in the intrauterine growth-restricted fetus and finally integrating this with the very limited evidence for the effect of antenatal glucocorticoid in intrauterine growth-restricted infants.

SHOX triggers the lysosomal pathway of apoptosis via oxidative stress.

PubMed

Hristov, Georgi; Marttila, Tiina; Durand, Claudia; Niesler, Beate; Rappold, Gudrun A; Marchini, Antonio

2014-03-15

The SHOX gene encodes for a transcription factor important for normal bone development. Mutations in the gene are associated with idiopathic short stature and are responsible for the growth failure and skeletal defects found in the majority of patients with Léri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia. SHOX is expressed in growth plate chondrocytes where it is supposed to modulate the proliferation, differentiation and cell death of these cells. Supporting this hypothesis, in vitro studies have shown that SHOX expression induces cell cycle arrest and apoptosis in both transformed and primary cells. In this study, we further characterized the cell death mechanisms triggered by SHOX and compared them with the effects induced by one clinically relevant mutant form of SHOX, detected in LWD patients (SHOX R153L) and a SHOX C-terminally truncated version (L185X). We show that SHOX expression in U2OS osteosarcoma cells leads to oxidative stress that, in turn, induces lysosomal membrane rupture with release of active cathepsin B to the cytosol and subsequent activation of the intrinsic apoptotic pathway characterized by mitochondrial membrane permeabilization and caspase activation. Importantly, cells expressing SHOX R153L or L185X did not display any of these features. Given the fact that many of the events observed in SHOX-expressing cells also characterize the complex cell death process occurring in the growth plate during endochondral ossification, our findings further support the hypothesis that SHOX may play a central role in the regulation of the cell death pathways activated during long bone development.

Distribution of living larger benthic foraminifera in littoral environments of the United Arab Emirates

NASA Astrophysics Data System (ADS)

Fiorini, Flavia; Lokier, Stephen W.

2015-04-01

The distribution of larger benthic foraminifera in Recent littoral environment of the United Arab Emirates (Abu Dhabi and Western regions) was investigated with the aim of understanding the response of those foraminifera to an increase in water salinity. For this purpose, 100 sediment samples from nearshore shelf, beach-front, channel, lagoon, and intertidal environment were collected. Sampling was undertaken at a water depth shallower than 15 m in water with a temperature of 22 to 35˚C, a salinity ranging from 40 to 60‰ and a pH of 8. Samples were stained with rose Bengal at the moment of sample collection in order to identify living specimens. The most abundant epiphytic larger benthic foraminifera in the studied area were Peneroplis pertusus and P. planatus with less common Spirolina areatina, S. aciculate and Sorites marginalis. The living specimens of the above mentioned species with normal test growing were particularly abundant in the nearshore shelf and lagoonal samples collected on seaweed. Dead specimens were concentrated in the coarser sediments of the beach-front, probably transported from nearby environments. Shallow coastal ponds are located in the upper intertidal zone and have a maximum salinity of 60‰ and contain abundant detached seagrass. Samples collected from these ponds possess a living foraminifera assemblage dominated by Peneroplis pertusus and P. planatus. High percentages (up to 50% of the stained assemblage) of Peneroplis presented abnormality in test growth, such as the presence of multiple apertures with reduced size, deformation in the general shape of the test, irregular suture lines and abnormal coiling. The high percentage of abnormal tests reflects natural environmental stress mainly caused by high and variable salinity. The unique presence of living epiphytic species, suggests that epiphytic foraminifera may be transported into the pond together with seagrass and continued to live in the pond. This hypothesis is supported by the fact that all of the foraminifera with abnormal test growth were adults and exhibiting a normal proloculus and normal growth of the earlier chambers.

A Comprehensive Panel of Three-Dimensional Models for Studies of Prostate Cancer Growth, Invasion and Drug Responses

PubMed Central

Härmä, Ville; Virtanen, Johannes; Mäkelä, Rami; Happonen, Antti; Mpindi, John-Patrick; Knuuttila, Matias; Kohonen, Pekka; Lötjönen, Jyrki; Kallioniemi, Olli; Nees, Matthias

2010-01-01

Prostate epithelial cells from both normal and cancer tissues, grown in three-dimensional (3D) culture as spheroids, represent promising in vitro models for the study of normal and cancer-relevant patterns of epithelial differentiation. We have developed the most comprehensive panel of miniaturized prostate cell culture models in 3D to date (n = 29), including many non-transformed and most currently available classic prostate cancer (PrCa) cell lines. The purpose of this study was to analyze morphogenetic properties of PrCa models in 3D, to compare phenotypes, gene expression and metabolism between 2D and 3D cultures, and to evaluate their relevance for pre-clinical drug discovery, disease modeling and basic research. Primary and non-transformed prostate epithelial cells, but also several PrCa lines, formed well-differentiated round spheroids. These showed strong cell-cell contacts, epithelial polarization, a hollow lumen and were covered by a complete basal lamina (BL). Most PrCa lines, however, formed large, poorly differentiated spheroids, or aggressively invading structures. In PC-3 and PC-3M cells, well-differentiated spheroids formed, which were then spontaneously transformed into highly invasive cells. These cell lines may have previously undergone an epithelial-to-mesenchymal transition (EMT), which is temporarily suppressed in favor of epithelial maturation by signals from the extracellular matrix (ECM). The induction of lipid and steroid metabolism, epigenetic reprogramming, and ECM remodeling represents a general adaptation to 3D culture, regardless of transformation and phenotype. In contrast, PI3-Kinase, AKT, STAT/interferon and integrin signaling pathways were particularly activated in invasive cells. Specific small molecule inhibitors targeted against PI3-Kinase blocked invasive cell growth more effectively in 3D than in 2D monolayer culture, or the growth of normal cells. Our panel of cell models, spanning a wide spectrum of phenotypic plasticity, supports the investigation of different modes of cell migration and tumor morphologies, and will be useful for predictive testing of anti-cancer and anti-metastatic compounds. PMID:20454659

Squeezing Interval Change From Ordinal Panel Data: Latent Growth Curves With Ordinal Outcomes

ERIC Educational Resources Information Center

Mehta, Paras D.; Neale, Michael C.; Flay, Brian R.

2004-01-01

A didactic on latent growth curve modeling for ordinal outcomes is presented. The conceptual aspects of modeling growth with ordinal variables and the notion of threshold invariance are illustrated graphically using a hypothetical example. The ordinal growth model is described in terms of 3 nested models: (a) multivariate normality of the…

Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.

PubMed

Koonce, Nathan A; Griffin, Robert J; Dings, Ruud P M

2017-12-09

Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO₂) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1-e.g., by OTX008-may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.

GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

PubMed

Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

2013-01-18

Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS

PubMed Central

Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

2014-01-01

Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth. PMID:25493215

[Excessive growth and growth hormone deficiency after treatment for craniopharyngioma].

PubMed

López Siguero, J P; García García, E; Martínez-Aedo, M J; Martínez Valverde, A

2000-07-01

Some children grow normally or excessively after extirpation of a craniopharyngioma, despite growth hormone deficiency. We report a 4-year-old girl with suprasellar craniopharyngioma. Removal of the tumor resulted in panhypopituitarism. For the next 5 years growth continued at a rate of 8.4-10.6 cm/year and then decreased progressively to 1.2 cm/year. Administration of growth hormone increased growth rate to 9.3 cm/year.

Sphingosine Kinase-1 Is Central to Androgen-Regulated Prostate Cancer Growth and Survival

PubMed Central

Dayon, Audrey; Brizuela, Leyre; Martin, Claire; Mazerolles, Catherine; Pirot, Nelly; Doumerc, Nicolas; Nogueira, Leonor; Golzio, Muriel; Teissié, Justin; Serre, Guy; Rischmann, Pascal; Malavaud, Bernard; Cuvillier, Olivier

2009-01-01

Background Sphingosine kinase-1 (SphK1) is an oncogenic lipid kinase notably involved in response to anticancer therapies in prostate cancer. Androgens regulate prostate cancer cell proliferation, and androgen deprivation therapy is the standard of care in the management of patients with advanced disease. Here, we explored the role of SphK1 in the regulation of androgen-dependent prostate cancer cell growth and survival. Methodology/Principal Findings Short-term androgen removal induced a rapid and transient SphK1 inhibition associated with a reduced cell growth in vitro and in vivo, an event that was not observed in the hormono-insensitive PC-3 cells. Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease. Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT. Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype. Importantly, inhibition of the PI3K/Akt pathway—by negatively impacting SphK1 activity—could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors. Fascinatingly, the reversability of the NE phenotype by exposure to normal medium was linked with a pronounced inhibition of SphK1 activity. Conclusions/Significance We report the first evidence that androgen deprivation induces a differential effect on SphK1 activity in hormone-sensitive prostate cancer cell models. These results also suggest that SphK1 activation upon chronic androgen deprivation may serve as a compensatory mechanism allowing prostate cancer cells to survive in androgen-depleted environment, giving support to its inhibition as a potential therapeutic strategy to delay/prevent the transition to androgen-independent prostate cancer. PMID:19956567

Lymph node culture

MedlinePlus

A normal result means there was no growth of microorganisms on the lab dish. Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results.

Glucose and D-Allulose contained medium to support the growth of lactic acid bacteria

NASA Astrophysics Data System (ADS)

Al-Baarri, A. N.; Legowo, A. M.; Pramono, Y. B.; Sari, D. I.; Pangestika, W.

2018-01-01

Monosaccharide has been known as support agent for the growth of lactic acid bacteria. However the combination among monosaccharides for supporting the living of bacteria has not been understood well. This research was done for analyzing the combination glucose and D-allulose for the growth of Lactobacillus acidophilus and Streptococcus thermophillus. The NaCl medium containing glucose and D-allulose was used to analyse the growth of bacteria. The study showed that glucose and D-allulose have been detected as supportive agent to L. acidophilus and S. thermophillus specifically. As conclusion, glucose and D-allulose supported the growth of lactic acid bacteria equally. This finding might provide the beneficial information for industry to utilize D-allulose as well as glucose.

Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

PubMed Central

Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

2016-01-01

Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

Loss of the Arabidopsis thaliana P4-ATPase ALA3 Reduces Adaptability to Temperature Stresses and Impairs Vegetative, Pollen, and Ovule Development

PubMed Central

McDowell, Stephen C.; López-Marqués, Rosa L.; Poulsen, Lisbeth R.; Palmgren, Michael G.; Harper, Jeffrey F.

2013-01-01

Members of the P4 subfamily of P-type ATPases are thought to help create asymmetry in lipid bilayers by flipping specific lipids between the leaflets of a membrane. This asymmetry is believed to be central to the formation of vesicles in the secretory and endocytic pathways. In Arabidopsis thaliana, a P4-ATPase associated with the trans-Golgi network (ALA3) was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed that ala3 pollen germinated ∼2 h slower than wild-type and had approximately 2-fold reductions in both maximal growth rate and overall length. In genetic crosses under conditions of hot days and cold nights, pollen fitness was reduced by at least 90-fold; from ∼18% transmission efficiency (unstressed) to less than 0.2% (stressed). Together, these results support a model in which ALA3 functions to modify endomembranes in multiple cell types, enabling structural changes, or signaling functions that are critical in plants for normal development and adaptation to varied growth environments. PMID:23667493

Loss of the Arabidopsis thaliana P₄-ATPase ALA3 reduces adaptability to temperature stresses and impairs vegetative, pollen, and ovule development.

PubMed

McDowell, Stephen C; López-Marqués, Rosa L; Poulsen, Lisbeth R; Palmgren, Michael G; Harper, Jeffrey F

2013-01-01

Members of the P4 subfamily of P-type ATPases are thought to help create asymmetry in lipid bilayers by flipping specific lipids between the leaflets of a membrane. This asymmetry is believed to be central to the formation of vesicles in the secretory and endocytic pathways. In Arabidopsis thaliana, a P4-ATPase associated with the trans-Golgi network (ALA3) was previously reported to be important for vegetative growth and reproductive success. Here we show that multiple phenotypes for ala3 knockouts are sensitive to growth conditions. For example, ala3 rosette size was observed to be dependent upon both temperature and soil, and varied between 40% and 80% that of wild-type under different conditions. We also demonstrate that ala3 mutants have reduced fecundity resulting from a combination of decreased ovule production and pollen tube growth defects. In-vitro pollen tube growth assays showed that ala3 pollen germinated ∼2 h slower than wild-type and had approximately 2-fold reductions in both maximal growth rate and overall length. In genetic crosses under conditions of hot days and cold nights, pollen fitness was reduced by at least 90-fold; from ∼18% transmission efficiency (unstressed) to less than 0.2% (stressed). Together, these results support a model in which ALA3 functions to modify endomembranes in multiple cell types, enabling structural changes, or signaling functions that are critical in plants for normal development and adaptation to varied growth environments.

Calcium deprivation disrupts enlargement of Chara corallina cells: further evidence for the calcium pectate cycle.

PubMed

Proseus, Timothy E; Boyer, John S

2012-06-01

Pectin is a normal constituent of cell walls of green plants. When supplied externally to live cells or walls isolated from the large-celled green alga Chara corallina, pectin removes calcium from load-bearing cross-links in the wall, loosening the structure and allowing it to deform more rapidly under the action of turgor pressure. New Ca(2+) enters the vacated positions in the wall and the externally supplied pectin binds to the wall, depositing new wall material that strengthens the wall. A calcium pectate cycle has been proposed for these sub-reactions. In the present work, the cycle was tested in C. corallina by depriving the wall of external Ca(2+) while allowing the cycle to run. The prediction is that growth would eventually be disrupted by a lack of adequate deposition of new wall. The test involved adding pectate or the calcium chelator EGTA to the Ca(2+)-containing culture medium to bind the calcium while the cycle ran in live cells. After growth accelerated, turgor and growth eventually decreased, followed by an abrupt turgor loss and growth cessation. The same experiment with isolated walls suggested the walls of live cells became unable to support the plasma membrane. If instead the pectate or EGTA was replaced with fresh Ca(2+)-containing culture medium during the initial acceleration in live cells, growth was not disrupted and returned to the original rates. The operation of the cycle was thus confirmed, providing further evidence that growth rates and wall biosynthesis are controlled by these sub-reactions in plant cell walls.

The consequences of pediatric renal transplantation on bone metabolism and growth.

PubMed

Bacchetta, Justine; Ranchin, Bruno; Demède, Delphine; Allard, Lise

2013-10-01

During childhood, growth retardation, decreased final height and renal osteodystrophy are common complications of chronic kidney disease (CKD). These problems remain present in patients undergoing renal transplantation, even though steroid-sparing strategies are more widely used. In this context, achieving normal height and growth in children after transplantation is a crucial issue for both quality of life and self-esteem. The aim of this review is to provide an overview of pathophysiology of CKD-mineral bone disorder (MBD) in children undergoing renal transplantation and to propose keypoints for its daily management. In adults, calcimimetics are effective for posttransplant hyperparathyroidism, but data are missing in the pediatric population. Fibroblast growth factor 23 levels are associated with increased risk of rejection, but the underlying mechanisms remain unclear. A recent meta-analysis also demonstrated the effectiveness of rhGH therapy in short transplanted children. In 2013, the daily clinical management of CKD-MBD in transplanted children should still focus on simple objectives: to optimize renal function, to develop and promote steroid-sparing strategies, to provide optimal nutritional support to maximize final height and avoid bone deformations, to equilibrate calcium/phosphate metabolism so as to provide acceptable bone quality and cardiovascular status, to correct all metabolic and clinical abnormalities that can worsen both bone and growth (mainly metabolic acidosis, anemia and malnutrition), promote good lifestyle habits (adequate calcium intake, regular physical activity, no sodas consumption, no tobacco exposure) and eventually to correct native vitamin D deficiency (target of 25-vitamin D >75 nmol/l).

Long-acting peptidomimergic control of gigantism caused by pituitary acidophilic stem cell adenoma.

PubMed

Maheshwari, H G; Prezant, T R; Herman-Bonert, V; Shahinian, H; Kovacs, K; Melmed, S

2000-09-01

Gigantism is caused by GH hypersecretion occurring before epiphyseal long bone closure and usually is associated with pituitary adenoma. A 15-yr-old female patient presented with accelerated growth due to a large pituitary tumor that was surgically resected to relieve pressure effects. Second surgery to remove residual tumor tissue was followed by administration of octreotide LAR, a long-acting depot somatostatin analog, together with long-acting cabergoline. Height was over the 95th percentile, with evidence of a recent growth spurt. Serum GH levels were more than 60 ng/mL (normal, <10 ng/mL) with no suppression to 75 g oral glucose, and serum PRL (>8,000 ng/mL; normal, <23 ng/mL) and insulin-like growth factor I levels (845 ng/mL; age-matched normal, 242-660 ng/mL) were elevated. Histology, immunostaining, and electron microscopy demonstrated a pituitary acidophil stem cell adenoma. Tumor tissue expressed both somatostatin receptor type 2 and dopamine receptor type 2. The Gs alpha subunit, GHRH receptor, and MEN1 genes were intact, and tumor tissue abundantly expressed pituitary tumor transforming gene (PTTG). Serum GH and PRL levels were controlled after two surgeries, and with continued cabergoline and octreotide LAR GH, PRL, and insulin-like growth factor I levels were normalized. In conclusion, administration of long-acting somatostatin analog every 4 weeks in combination with a long-acting dopamine agonist biweekly controlled biochemical parameters and accelerated growth in a patient with gigantism caused by a rare pituitary acidophil stem cell adenoma.

Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

PubMed

Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

2013-09-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

Optical dynamic range maximization for humidity sensing by controlling growth of zinc oxide nanorods

NASA Astrophysics Data System (ADS)

Yusof, Haziezol Helmi Mohd; Harun, Sulaiman Wadi; Dimyati, Kaharudin; Bora, Tanujjal; Mohammed, Waleed S.; Dutta, Joydeep

2018-07-01

An experimental study of the dynamic range maximization with Zinc Oxide (ZnO) nanorods coated glass substrates for humidity and vapor sensing is reported. Growth time of the nanorods and the length of the coated segments were controlled to study the differences between a reference environmental condition (normal humidity or dry condition) and water vapor concentrations. In order to achieve long dynamic range of detection with respect to nanorods coverage, several substrates with triangular patterns of ZnO nanostructures were fabricated by selective hydrothermal growth over different durations of time (5 h, 10 h and 15 h). It was found that maximum dynamic range for the humidity sensing occurs for the combination parameters of normalized length (Z) of 0.23 and normalized scattering coefficient (ζ) of 0.3. A reduction in transmittance by 38% at humidity levels of 80% with reference point as 50% humidity was observed. The results could be correlated to a first order approximation model that assumes uniform growth and the optimum operating conditions for humidity sensing device. This study provides an option to correlate ZnO growth conditions for different vapor sensing applications which can set a platform for compact sensors where modulation of light intensity is followed.

On new non-modal hydrodynamic stability modes and resulting non-exponential growth rates - a Lie symmetry approach

NASA Astrophysics Data System (ADS)

Oberlack, Martin; Nold, Andreas; Sanjon, Cedric Wilfried; Wang, Yongqi; Hau, Jan

2016-11-01

Classical hydrodynamic stability theory for laminar shear flows, no matter if considering long-term stability or transient growth, is based on the normal-mode ansatz, or, in other words, on an exponential function in space (stream-wise direction) and time. Recently, it became clear that the normal mode ansatz and the resulting Orr-Sommerfeld equation is based on essentially three fundamental symmetries of the linearized Euler and Navier-Stokes equations: translation in space and time and scaling of the dependent variable. Further, Kelvin-mode of linear shear flows seemed to be an exception in this context as it admits a fourth symmetry resulting in the classical Kelvin mode which is rather different from normal-mode. However, very recently it was discovered that most of the classical canonical shear flows such as linear shear, Couette, plane and round Poiseuille, Taylor-Couette, Lamb-Ossen vortex or asymptotic suction boundary layer admit more symmetries. This, in turn, led to new problem specific non-modal ansatz functions. In contrast to the exponential growth rate in time of the modal-ansatz, the new non-modal ansatz functions usually lead to an algebraic growth or decay rate, while for the asymptotic suction boundary layer a double-exponential growth or decay is observed.

Regional Infant Brain Development: An MRI-Based Morphometric Analysis in 3 to 13 Month Olds

PubMed Central

Choe, Myong-sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S.; Benasich, April A.; Grant, P. Ellen

2013-01-01

Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants’ whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders. PMID:22772652

Multiplex analysis of cytokines as biomarkers that differentiate benign and malignant thyroid diseases

PubMed Central

Linkov, Faina; Ferris, Robert L.; Yurkovetsky, Zoya; Marrangoni, Adele; Velikokhatnaya, Lyudmila; Gooding, William; Nolan, Brian; Winans, Matthew; Siegel, Eric R.; Lokshin, Anna; Stack, Brendan C.

2008-01-01

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids. We hypothesized that analysis of serum growth factors would uncover diagnostically informative differences between benign and malignant thyroid conditions. Using xMAP profiling, we evaluated concentrations of 19 cytokines, chemokines, and growth factors. We used sera from 23 patients with cancer (Malignant group), 24 patients with benign nodular thyroid disease (Benign group), and 23 healthy subjects (Normal group). In univariate analysis, five factors (epithelial growth factor, hepatocyte growth factor, Interleukins-5 and -8, and regulated upon activation, normally T-expressed and presumably secreted (RANTES) distinguished subjects with thyroid disease from the Normal group. In multivariate analysis, the set {Interleukin-8, hepatocyte growth factor, monocyte-induced γ interferon, interleukin-12 p40} achieved noteworthy discrimination between Benign and Malignant groups (area under the receiver operating characteristics curve was 0.81 (95% confidence interval: 0.65–0.90)). Multiplex panels of serum biomarkers may be promising tools to diagnose cancer in patients presenting with evidence of nodular thyroid disease. PMID:19234619

A New Ghost Cell/Level Set Method for Moving Boundary Problems: Application to Tumor Growth

PubMed Central

Macklin, Paul

2011-01-01

In this paper, we present a ghost cell/level set method for the evolution of interfaces whose normal velocity depend upon the solutions of linear and nonlinear quasi-steady reaction-diffusion equations with curvature-dependent boundary conditions. Our technique includes a ghost cell method that accurately discretizes normal derivative jump boundary conditions without smearing jumps in the tangential derivative; a new iterative method for solving linear and nonlinear quasi-steady reaction-diffusion equations; an adaptive discretization to compute the curvature and normal vectors; and a new discrete approximation to the Heaviside function. We present numerical examples that demonstrate better than 1.5-order convergence for problems where traditional ghost cell methods either fail to converge or attain at best sub-linear accuracy. We apply our techniques to a model of tumor growth in complex, heterogeneous tissues that consists of a nonlinear nutrient equation and a pressure equation with geometry-dependent jump boundary conditions. We simulate the growth of glioblastoma (an aggressive brain tumor) into a large, 1 cm square of brain tissue that includes heterogeneous nutrient delivery and varied biomechanical characteristics (white matter, gray matter, cerebrospinal fluid, and bone), and we observe growth morphologies that are highly dependent upon the variations of the tissue characteristics—an effect observed in real tumor growth. PMID:21331304

Pilot study evaluating the effects of a cervical headgear on the C-axis: the growth axis of the dentomaxillary complex.

PubMed

Braun, Stanley; Bottrel, J Alexandre

2004-12-01

The C-axis, a growth vector for the dentomaxillary complex, is a means of quantifying complex maxillary growth in the sagittal plane through 3 key cephalometric measurements. This pilot study examined the effect of a cervical headgear, worn 8 to 10 hours per day, on the growth axis. The mean velocity of C-axis length increase in normally growing boys in the age range studied is 1.14 mm per year. In normally growing girls, the C-axis length increase is nonlinear, varying from a mean of 1.67 mm per year at age 9 and to 0.78 mm per year at 13.5 years of age. The cervical headgear reduced the C-axis length increases by 73.7% in boys and 61.1% in girls. The growth axis vector angle theta; was not clinically affected in either sex, but the palatal plane angle alpha became more acute in both sexes, rather than becoming more obtuse as it does in normally growing adolescents. Additional research should be undertaken to determine the effects on the C-axis by other cervical headgears having different lines of action relative to the center of resistance of the dentomaxillary complex, as well as occipital-pull and straight distal-pull headgear.

Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

PubMed

Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

2016-01-01

Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

The impact of fetal growth restriction on latency in the setting of expectant management of preeclampsia.

PubMed

McKinney, David; Boyd, Heather; Langager, Amanda; Oswald, Michael; Pfister, Abbey; Warshak, Carri R

2016-03-01

Fetal growth restriction is a common complication of preeclampsia. Expectant management for qualifying patients has been found to have acceptable maternal safety while improving neonatal outcomes. Whether fetal growth restriction influences the duration of latency during expectant management of preeclampsia is unknown. The objective of the study was to determine whether fetal growth restriction is associated with a reduced interval to delivery in women with preeclampsia being expectantly managed prior to 34 weeks. We performed a retrospective cohort of singleton, live-born, nonanomalous deliveries at the University of Cincinnati Medical Center between 2008 and 2013. Patients were included in our analysis if they were diagnosed with preeclampsia prior to 34 completed weeks and if the initial management plan was to pursue expectant management beyond administration of steroids for fetal lung maturity. Two study groups were determined based on the presence or absence of fetal growth restriction. Patients were delivered when they developed persistent neurological symptoms, severe hypertension refractory to medical therapy, renal insufficiency, nonreassuring fetal status, pulmonary edema, or hemolysis elevated liver low platelet syndrome or when they reached 37 weeks if they remained stable without any other indication for delivery. Our primary outcome was the interval from diagnosis of preeclampsia to delivery, measured in days. Secondary outcomes included indications for delivery, rates of induction and cesarean delivery, development of severe morbidities of preeclampsia, and select neonatal outcomes. We performed a multivariate logistic regression analysis comparing those with fetal growth restriction with those with normally grown fetuses to determine whether there is an association between fetal growth restriction and a shortened interval to delivery, neonatal intensive care unit admission, prolonged neonatal stay, and neonatal mortality. A total of 851 patients met the criteria for preeclampsia, of which 199 met inclusion criteria, 139 (69%) with normal growth, and 60 (31%) with fetal growth restriction. Interval to delivery was significantly shorter in women with fetal growth restriction, median (interquartile range) of 3 (1.6) days vs normal growth, 5 (2.12) days, P < .001. The association between fetal growth restriction and latency less than 7 days remained significant, even after post hoc analysis controlling for confounding variables (adjusted odds ratio, 1.66 [95% confidence interval, 1.12-2.47]). There were no differences in the development of severe disease (85.9 vs 91.7%, P = .26), need for intravenous antihypertensive medications (47.1 vs 46.7%, P = .96), and the development of severe complications of preeclampsia (51.1 vs 42.9%, P = .30) in normally grown and growth-restricted fetuses, respectively. Fewer women with fetal growth restriction attained their scheduled delivery date, 3 of 60 (5.0%), compared with normally grown fetuses,12 of 139 (15.7%), P = .03. Admission to the neonatal intensive care unit, neonatal length of stay, and neonatal mortality were higher when there was fetal growth restriction; however, after a logistic regression analysis, these associations were no longer significant. Fetal growth restriction is associated with a shortened interval to delivery in women undergoing expectant management of preeclampsia when disease is diagnosed prior to 34 weeks. These data may be helpful in counseling patients regarding the expected duration of pregnancy, guiding decision making regarding administration of steroids and determining the need for maternal transport. Copyright © 2016 Elsevier Inc. All rights reserved.

Head circumference

MedlinePlus

... a child's head circumference. Normal ranges for a child's sex and age (weeks, months), based on values that experts have obtained for normal growth rates of infants' and children's heads. Measurement of the head circumference is an ...

Non-parenchymal liver cells support the growth advantage in the first stages of hepatocarcinogenesis.

PubMed

Drucker, Claudia; Parzefall, Wolfram; Teufelhofer, Olga; Grusch, Michael; Ellinger, Adolf; Schulte-Hermann, Rolf; Grasl-Kraupp, Bettina

2006-01-01

Hepatocellular carcinoma almost always arises in chronically inflamed livers. We developed a culture model to study the role of non-parenchymal cells (NPCs) for inflammation-driven hepatocarcinogenesis. Rats were treated with the carcinogen N-nitrosomorpholine, which induced initiated hepatocytes expressing the marker placental glutathione-S-transferase (GSTp). After 21 days two preparations of hepatocytes were made: (i) conventional ones (Hep-conv) containing NPCs and (ii) hepatocytes purified of NPCs (Hep-pur). Initiated hepatocytes, being positive for GSTp (GSTp-pos) were present in both preparations and were cultured along with normal hepatocytes, being negative for GSTp (GSTp-neg). Under any culture condition DNA synthesis was approximately 4-fold higher in GSTp-pos than in GSTp-neg hepatocytes demonstrating the inherent growth advantage of the first stages of hepatocarcinogenesis. Hepatocytes showed approximately 3-fold lower rates of DNA synthesis in Hep-pur than in Hep-conv, which was elevated above Hep-conv levels by addition of NPC or NPC-supernatant. Pretreatment of NPCs with proinflammatory lipopolysaccharide (LPS) further increased DNA synthesis. Thus, NPCs release soluble growth stimulators. Next we investigated the effect of specific cytokines produced by NPCs. Tumour necrosis factor alpha and interleukin 6 barely altered DNA synthesis, whereas hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and the heparin-binding epidermal growth factor-like growth factor (HB-EGF) were potent inducers of DNA replication in both, GSTp-neg and GSTp-pos cells. In conclusion, DNA synthesis of hepatocytes is increased by factors released from NPCs, an effect augmented by LPS-stimulation. NPC-derived cytokines, such as KGF, HGF and HB-EGF, stimulate DNA synthesis preferentially in initiated hepatocytes, presumably resulting in tumour promotion. Similar mechanisms may contribute to carcinogenesis in human inflammatory liver diseases.

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

PubMed

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

2011-12-01

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

Genetics Home Reference: Jackson-Weiss syndrome

MedlinePlus

... People with Jackson-Weiss syndrome usually have normal intelligence and a normal life span. Related Information What ... called fibroblast growth factor receptor 2. Among its multiple functions, this protein signals immature cells to become ...

Delayed Puberty (For Teens)

MedlinePlus

... the chromosomes can interfere with normal growth processes. Turner syndrome is an example of a chromosome disorder. It ... production of sex hormones. Women who have untreated Turner syndrome are shorter than normal, are usually infertile, and ...

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

PubMed Central

Sande, R. D.; Alexander, J. E.; Spencer, G. R.; Padgett, G. A.; Davis, W. C.

1982-01-01

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7065114

On the generation of log-Lévy distributions and extreme randomness

NASA Astrophysics Data System (ADS)

Eliazar, Iddo; Klafter, Joseph

2011-10-01

The log-normal distribution is prevalent across the sciences, as it emerges from the combination of multiplicative processes and the central limit theorem (CLT). The CLT, beyond yielding the normal distribution, also yields the class of Lévy distributions. The log-Lévy distributions are the Lévy counterparts of the log-normal distribution, they appear in the context of ultraslow diffusion processes, and they are categorized by Mandelbrot as belonging to the class of extreme randomness. In this paper, we present a natural stochastic growth model from which both the log-normal distribution and the log-Lévy distributions emerge universally—the former in the case of deterministic underlying setting, and the latter in the case of stochastic underlying setting. In particular, we establish a stochastic growth model which universally generates Mandelbrot’s extreme randomness.

Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma

PubMed Central

Chang, Betty Y.; Kong, Sun-Young; Fulciniti, Mariateresa; Yang, Guang; Calle, Yolanda; Hu, Yiguo; Lin, Jianhong; Zhao, Jian-Jun; Cagnetta, Antonia; Cea, Michele; Sellitto, Michael A.; Zhong, Mike Y.; Wang, Qiuju; Acharya, Chirag; Carrasco, Daniel R.; Buggy, Joseph J.; Elias, Laurence; Treon, Steven P.; Matsui, William; Richardson, Paul; Munshi, Nikhil C.; Anderson, Kenneth C.

2012-01-01

Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis. Here we investigated effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multiple myeloma (MM) growth within the BM microenvironment. PCI-32765 blocked RANKL/M-CSF–induced phosphorylation of Btk and downstream PLC-γ2 in OCs, resulting in diminished TRAP5b (ED50 = 17nM) and bone resorption activity. PCI-32765 also inhibited secretion of multiple cytokines and chemokines from OC and BM stromal cell cultures from both normal donors (ED50 = 0.5nM) and MM patients. It decreased SDF-1–induced migration of MM cells, and down-regulated MIP1-α/CCL3 in MM cells. It also blocked MM cell growth and survival triggered by IL-6 or coculture with BM stromal cells or OCs in vitro. Importantly, PCI-32765 treatment significantly inhibits in vivo MM cell growth (P < .03) and MM cell–induced osteolysis of implanted human bone chips in SCID mice. Moreover, PCI-32765 prevents in vitro colony formation by stem-like cells from MM patients. Together, these results delineate functional sequelae of Btk activation mediating osteolysis and growth of MM cells, supporting evaluation of PCI-32765 as a novel therapeutic in MM. PMID:22689860

Plant adaptation to low atmospheric pressures: potential molecular responses

NASA Technical Reports Server (NTRS)

Ferl, Robert J.; Schuerger, Andrew C.; Paul, Anna-Lisa; Gurley, William B.; Corey, Kenneth; Bucklin, Ray

2002-01-01

There is an increasing realization that it may be impossible to attain Earth normal atmospheric pressures in orbital, lunar, or Martian greenhouses, simply because the construction materials do not exist to meet the extraordinary constraints imposed by balancing high engineering requirements against high lift costs. This equation essentially dictates that NASA have in place the capability to grow plants at reduced atmospheric pressure. Yet current understanding of plant growth at low pressures is limited to just a few experiments and relatively rudimentary assessments of plant vigor and growth. The tools now exist, however, to make rapid progress toward understanding the fundamental nature of plant responses and adaptations to low pressures, and to develop strategies for mitigating detrimental effects by engineering the growth conditions or by engineering the plants themselves. The genomes of rice and the model plant Arabidopsis thaliana have recently been sequenced in their entirety, and public sector and commercial DNA chips are becoming available such that thousands of genes can be assayed at once. A fundamental understanding of plant responses and adaptation to low pressures can now be approached and translated into procedures and engineering considerations to enhance plant growth at low atmospheric pressures. In anticipation of such studies, we present here the background arguments supporting these contentions, as well as informed speculation about the kinds of molecular physiological responses that might be expected of plants in low-pressure environments.

Heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by increasing protein translation of selected transcripts in cancer cells.

PubMed

Chang, Elizabeth T; Parekh, Palak R; Yang, Qingyuan; Nguyen, Duc M; Carrier, France

2016-03-01

The heterogenous ribonucleoprotein A18 (hnRNP A18) promotes tumor growth by coordinating the translation of selected transcripts associated with proliferation and survival. hnRNP A18 binds to and stabilizes the transcripts of pro-survival genes harboring its RNA signature motif in their 3'UTRs. hnRNP A18 binds to ATR, RPA, TRX, HIF-1α and several protein translation factor mRNAs on polysomes and increases de novo protein translation under cellular stress. Most importantly, down regulation of hnRNP A18 decreases proliferation, invasion and migration in addition to significantly reducing tumor growth in two mouse xenograft models, melanoma and breast cancer. Moreover, tissue microarrays performed on human melanoma, prostate, breast and colon cancer indicate that hnRNP A18 is over expressed in 40 to 60% of these malignant tissue as compared to normal adjacent tissue. Immunohistochemistry data indicate that hnRNP A18 is over expressed in the stroma and hypoxic areas of human tumors. These data thus indicate that hnRNP A18 can promote tumor growth in in vivo models by coordinating the translation of pro-survival transcripts to support the demands of proliferating cells and increase survival under cellular stress. hnRNP A18 therefore represents a new target to selectively inhibit protein translation in tumor cells.

Phorbol ester phorbol-12-myristate-13-acetate promotes anchorage-independent growth and survival of melanomas through MEK-independent activation of ERK1/2

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

Jorgensen, Kjersti; Skrede, Martina; Cruciani, Veronique

2005-04-01

The phorbol ester, phorbol-12-myristate-13-acetate (PMA), an activator of PKCs, is known to stimulate the in vitro growth of monolayer cultures of normal human melanocytes whereas it inhibits the growth of most malignant melanoma cell lines. We examined the effect of PMA on proliferation and survival of melanoma cells grown as multicellular aggregates in suspension (spheroids), and aimed to elucidate downstream targets of PKC signaling. In contrast to monolayer cultures, PMA increased cell proliferation as well as protected melanoma cells from suspension-mediated apoptosis (anoikis). Supporting the importance of PKC in anchorage-independent growth, treatment of anoikis-resistant melanoma cell lines with antisense oligonucleotidesmore » against PKC-{alpha}, or the PKC inhibitor Goe6976, strongly induced anoikis. PMA induced activation of ERK1/2, but this effect was not prevented by the MEK inhibitors PD98059 or by U0126. Whereas PD98059 treatment alone led to marked activation of the pro-apoptotic Bim and Bad proteins and significantly increased anoikis, these effects were clearly reversed by PMA. In conclusion, our results indicate that the protective effect of PMA on anchorage-independent survival of melanoma cells at least partly is mediated by MEK-independent activation of ERK1/2 and inactivation of downstream pro-apoptotic effector proteins.« less

Mechanical Stimulation Controls Canopy Architecture and Improves Volume Utilization Efficiency in Bioregenerative Life-Support Candidate Crops

NASA Technical Reports Server (NTRS)

Graham, Thomas; Wheeler, Raymond

2017-01-01

Thigmomorphogenesis can be utilized to improve volume utilization efficiency in peppers (Capsicum annum cv. California Wonder), a candidate crop for fresh food production in space. The effect occurred primarily through a reduction in average plant height. Reductions in vegetative growth metrics during the juvenile growth phase (growth leading up to and including early anthesis) were not observed during the mature or fruiting phase, with the notable exception of reduced plant height. Early flower production and fruit set was reduced under MS; however, the total edible biomass was not reduced, with MS plants producing fewer but larger fruits. The overall reduction in plant height due to MS (Mechanical Stimulation) was sufficient to realize theoretical improvements in VUE (Volume Use Efficiency) for large vertical farming systems. The reduced heights observed could improve VUE in single tier spaceflight hardware (e.g., Veggie; Massa 2016 (this issue)) in that crops that would not normally fit in these spaceflight systems may be accommodated if MS can be applied. Although the potential for using MS to induce thigmomorphogenic phenotypes has long been appreciated, it is only recently that the growth systems themselves could take advantage of the modified crop architecture associated with MS. It is with this in mind that renewed attention should be given to developing procedures for environmentally modifying crops for spaceflight applications.

Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex

PubMed Central

Thomson, Rachel E; Kind, Peter C; Graham, Nicholas A; Etherson, Michelle L; Kennedy, John; Fernandes, Ana C; Marques, Catia S; Hevner, Robert F; Iwata, Tomoko

2009-01-01

Background Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown. Results In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis. Conclusion Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex. PMID:19192266

Linking belowground and aboveground phenology in two boreal forests in Northeast China.

PubMed

Du, Enzai; Fang, Jingyun

2014-11-01

The functional equilibrium between roots and shoots suggests an intrinsic linkage between belowground and aboveground phenology. However, much less understanding of belowground phenology hinders integrating belowground and aboveground phenology. We measured root respiration (Ra) as a surrogate for root phenology and integrated it with observed leaf phenology and radial growth in a birch (Betula platyphylla)-aspen (Populus davidiana) forest and an adjacent larch (Larix gmelinii) forest in Northeast China. A log-normal model successfully described the seasonal variations of Ra and indicated the initiation, termination and peak date of root phenology. Both root phenology and leaf phenology were highly specific, with a later onset, earlier termination, and shorter period of growing season for the pioneer tree species (birch and aspen) than the dominant tree species (larch). Root phenology showed later initiation, later peak and later termination dates than leaf phenology. An asynchronous correlation of Ra and radial growth was identified with a time lag of approximately 1 month, indicating aprioritization of shoot growth. Furthermore, we found that Ra was strongly correlated with soil temperature and air temperature, while radial growth was only significantly correlated with air temperature, implying a down-regulating effect of temperature. Our results indicate different phenologies between pioneer and dominant species and support a down-regulation hypothesis of plant phenology which can be helpful in understanding forest dynamics in the context of climate change.

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

PubMed

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

2017-01-01

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

The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF.

PubMed

Odgren, P R; Popoff, S N; Safadi, F F; MacKay, C A; Mason-Savas, A; Seifert, M F; Marks, S C

1999-08-01

The osteopetrotic rat mutation toothless (tl) is characterized by little or no bone resorption, few osteoclasts and macrophages, and chondrodysplasia at the growth plates. Short-term treatment of tl rats with colony-stimulating factor-1 (CSF-1) has been shown to increase the number of osteoclasts and macrophages, producing dramatic resolution of skeletal sclerosis at some, but not all, sites. Defects in production of vitamin D-binding protein-macrophage activating factor (DBP-MAF) have been identified in two other independent osteopetrotic mutations of the rat (op and ia), and two in the mouse (op and mi), in which macrophages and osteoclasts can be activated by the administration of exogenous DBP-MAF. The present studies were undertaken to examine the histology and residual growth defects in tl rats following longer CSF-1 treatments, to investigate the possibility that exogenous DBP-MAF might act synergistically with CSF-1 to improve the tl phenotype, and to assess the integrity of the endogenous DBP-MAF pathway in this mutation. CSF-1 treatment-with or without DBP-MAF-induced resorption of metaphyseal bone to the growth plate on the marrow side, improved slightly but did not normalize long bone growth, and caused no improvement in the abnormal histology of the growth plate. Injections of lysophosphatidylcholine (lyso-Pc) to prime macrophage activation via the DBP-MAF pathway raised superoxide production to similar levels in peritoneal macrophages from both normal and mutant animals, indicating no defect in the DBP-MAF pathway in tl rats. Interestingly, pretreatments with CSF-1 alone also increased superoxide production, although the mechanism for this remains unknown. In summary, we find that, unlike other osteopetrotic mutations investigated to date, the DBP-MAF pathway does not appear to be defective in the tl rat; that additional DBP-MAF does not augment the beneficial skeletal effects seen with CSF-1 alone; and that the growth plate chondrodystrophy seen in this mutation is unaffected by either molecule. Thus, the tl mutation intercepts the function of a gene required for both normal endochondral ossification and bone resorption, thereby uncoupling the coordination of skeletal metabolism required for normal long bone growth.

Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings.

PubMed

Coutant, R; Rouleau, S; Despert, F; Magontier, N; Loisel, D; Limal, J M

2001-10-01

We analyzed the final height of 146 short children with either nonacquired GH deficiency or idiopathic short stature. Our purpose was 1) to assess growth according to the pituitary magnetic resonance imaging findings in the 63 GH-treated children with GH deficiency and 2) to compare the growth of the GH-deficient patients with normal magnetic resonance imaging (n = 48) to that of 32 treated and 51 untreated children with idiopathic short stature (GH peak to provocative tests >10 microg/liter). The mean GH dose was 0.44 IU/kg.wk (0.15 mg/kg.wk), given for a mean duration of 4.6 yr. Among the GH-deficient children, 15 had hypothalamic-pituitary abnormalities (stalk agenesis), all with total GH deficiency (GH peak <5 microg/liter). They were significantly shorter and younger at the time of diagnosis than those with normal magnetic resonance imaging, had better catch-up growth (+2.7 +/- 0.9 vs. +1.3 +/- 0.8 SD score; P < 0.01), and reached greater final height (-1.1 +/- 1.0 vs. -1.7 +/- 1.0 SD score; P < 0.05). Among patients with normal magnetic resonance imaging, there was no difference in catch-up growth and final height between partial and total GH deficiencies. GH-deficient subjects with normal magnetic resonance imaging and treated and untreated patients with idiopathic short stature had comparable auxological characteristics, age at evaluation, and target height. Although they had different catch-up growth (+1.3 +/- 0.8, +0.9 +/- 0.6, and +0.7 +/- 0.9 SD score, respectively; P < 0.01, by ANOVA), these patients reached a similar final height (-1.7 +/- 1.0, -2.1 +/- 0.8, and -2.1 +/- 1.0 SD score, respectively; P = 0.13). Pituitary magnetic resonance imaging findings show the heterogeneity within the group of nonacquired GH deficiency and help to predict the response to GH treatment in these patients. The similarities in growth between the GH-deficient children with normal magnetic resonance imaging and those with idiopathic short stature suggest that the short stature in the former subjects is at least partly due to factors other than GH deficiency.

Supporting adolescents with type 1 diabetes mellitus: a qualitative study.

PubMed

Rostami, Shahnaz; Parsa-Yekta, Zohreh; Najafi Ghezeljeh, Tahereh; Vanaki, Zohreh

2014-03-01

Without sufficient support, type 1 diabetes mellitus often disturbs patients' normal lives. This study describes and explores the support that Iranian adolescents with type 1 diabetes mellitus experienced. Semistructured interviews were conducted with ten adolescents, seven family members, one dietitian, one nurse, and one school nurse. Participants were chosen using purposive sampling from two teaching hospitals and one high school in two urban areas of Iran. Using standard procedures for content analysis, three main themes were identified: maintaining a normal life; receiving tangible, informational, and emotional support from the family and society; and advancement of life toward normalization. The cornerstone of maintaining a normal life for adolescents with type 1 diabetes mellitus is to adopt an active role in taking care of themselves within their systems of support. © 2013 Wiley Publishing Asia Pty Ltd.

Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone

PubMed Central

Ascenzi, Maria-Grazia; Du, Xia; Harding, James I; Beylerian, Emily N; de Silva, Brian M; Gross, Ben J; Kastein, Hannah K; Wang, Weiguang; Lyons, Karen M; Schaeffer, Hayden

2014-01-01

Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image’s plane of focus, and lack of cell-specific features, interfered with identification of cell. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes’ number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth. PMID:25525552

Insulin and growth hormone secretion in the nephrotic syndrome.

PubMed

Bridgman, J F; Summerskill, J; Buckler, J M; Hellman, B; Rosen, S M

1975-01-01

Carbohydrate metabolism was studied in a series of patients with the nephrotic syndrome and compared with a similar number of normal controls. The nephrotic syndrome was associated with a smaller secretion of insulin in response to intravenous glucose and tolbutamide than occurred in normals. In the syndrom fasting serum growth hormone (G.H.) concentrations were increased and did not show the characteristic suppression after glucose administration, and the disappearance rate of glucose (k value) was lower. well marked correlation existed between serum G.H. concentrations and the total urinary protein excreted. These abnormal findings returned to normal in a patient who underwent a repeat study when the nephrotic syndrome had resolved.

How Complete is Mid-Infrared Selection of Active Galactic Nuclei?

NASA Astrophysics Data System (ADS)

Grae Short, Miona; Diamond-Stanic, Aleks

2015-01-01

Essentially every galaxy hosts a supermassive black hole, and roughly 10% of those black holes are currently growing as active galactic nuclei (AGNs). Given the compelling evidence that galaxies and black holes co-evolve, there is strong motivation to study how black holes assemble their mass through cosmic time. However, this is challenging because a large fraction of black hole growth is enshrouded by gas and dust. Deep and wide surveys at X-ray and infrared wavelengths offer a powerful way to study the obscured AGN population, but an important caveat is that X-ray surveys are not complete for the most highly absorbed sources and infrared surveys are not able to distinguish low-luminosity AGNs from normal galaxies. To help address these outstanding issues and to analyze the completeness of mid-infrared AGN selection, we use Spitzer and WISE photometry to study the mid-infrared colors of a complete sample of local AGNs. The sample is drawn from the revised Shapley-Ames galaxy catalog and includes every galaxy in the sky brighter than B=13 that is known to host Seyfert activity. This sample is unique in its sensitivity to low-luminosity and highly obscured sources. Our main result is that most of these known AGNs would be classified as normal galaxies on the basis of their mid-infrared colors, implying that analogs to local Seyfert galaxies would not be identified as AGNs in existing surveys. We find that this a strong function of AGN luminosity, and we also present trends as a function of AGN obscuration, galaxy luminosity, and stellar mass. These results provide important insights into the AGN population that is missing from our census of black hole growth in the distant universe. This work was supported by the National Science Foundation's REU program through NSF Award AST-1004881. We also acknowledge support from The Grainger Foundation and from gifts made to the Department of Astronomy at UW-Madison.

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

PubMed

Koletzko, Berthold; Chourdakis, Michael; Grote, Veit; Hellmuth, Christian; Prell, Christine; Rzehak, Peter; Uhl, Olaf; Weber, Martina

2014-01-01

Growth and development are central characteristics of childhood. Deviations from normal growth can indicate serious health challenges. The adverse impact of early growth faltering and malnutrition on later health has long been known. In contrast, the impact of rapid early weight and body fat gain on programming of later disease risk have only recently received increased attention. Numerous observational studies related diet in early childhood and rapid early growth to the risk of later obesity and associated disorders. Causality was confirmed in a large, double-blind randomised trial testing the 'Early Protein Hypothesis'. In this trial we found that attenuation of protein supply in infancy normalized early growth and markedly reduced obesity prevalence in early school age. These results indicate the need to describe and analyse growth patterns and their regulation through diet in more detail and to characterize the underlying metabolic and epigenetic mechanisms, given the potential major relevance for public health and policy. Better understanding of growth patterns and their regulation could have major benefits for the promotion of public health, consumer-orientated nutrition recommendations, and the development of improved food products for specific target populations. © 2014 S. Karger AG, Basel.

Tibial dyschondroplasia associated proteomic changes in chicken growth plate cartilage

USDA-ARS?s Scientific Manuscript database

Tibial dyschondroplasia (TD) is a poultry leg problem that affects the proximal growth plate of tibia preventing its transition to bone. To understand the disease-induced proteomic changes we compared the protein extracts of cartilage from normal and TD- affected growth plates. TD was induced by fe...

In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

USDA-ARS?s Scientific Manuscript database

Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

The use of a whole animal biophotonic model as a screen for the angiogenic potential of estrogenic compounds

USDA-ARS?s Scientific Manuscript database

Vascular endothelial growth factor (VEGF) is essential for normal vascular growth and development during wound repair. VEGF is estrogen responsive and capable of regulating its own receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). Several agricultural pesticides (e.g., methoxychlor)...

Infant obesity and severe obesity growth patterns in the first two years of life.

PubMed

Gittner, Lisaann S; Ludington-Hoe, Susan M; Haller, Harold S

2014-04-01

Distinguishing an obesity growth pattern that originates during infancy is clinically important. Infancy based obesity prevention interventions may be needed while precursors of later health are forming. Infant obesity and severe obesity growth patterns in the first 2-years are described and distinguished from a normal weight growth pattern. A retrospective chart review was conducted. Body mass index (BMI) growth patterns from birth to 2-years are described for children categorized at 5-years as normal weight (n = 61), overweight (n = 47), obese (n = 41) and severely obese (n = 72) cohorts using WHO reference standards. BMI values were calculated at birth, 1-week; 2-, 4-, 6-, 9-, 12-, 15-, 18-months; and 2- and 5-years. Graphs of the longitudinal Analysis of Variance of Means of BMI values identified the earliest significant divergence of a cohort's average BMI pattern from other cohorts' patterns. ANOVA and Pearson Product Moment correlations were also performed. Statistically significant differences in BMI values and differences in growth patterns between cohorts were evident as early as 2-6 months post-birth. Children who were obese or severely obese at 5-years demonstrated a BMI pattern that differed within the first 2-years of life from that of children who were normal weight at 5-years. The earliest significant correlation between early BMI values and 5-year BMI value was at 4-months post-birth. The study fills an important gap by demonstrating early onset of an infant obesity growth pattern in full-term children who were healthy throughout their first 5 years of life.

Polyhydramnios or Excessive Fetal Growth Are Markers for Abnormal Perinatal Outcome in Euglycemic Pregnancies.

PubMed

Crimmins, Sarah; Mo, Cecilia; Nassar, Yomna; Kopelman, Jerome N; Turan, Ozhan M

2018-01-01

 This study aims to investigate the perinatal outcome of fetuses with polyhydramnios and/or accelerated growth among women with a normal oral glucose challenge test (oGCT).  Singleton, nonanomalous pregnancies with an oGCT(< 130 mg/dL) at 24 to 28 weeks, who subsequently demonstrate polyhydramnios (amniotic fluid index > 24 cm or maximum vertical pocket > 8 cm) and/or accelerated growth (abdominal circumference > 95th percentile) on two-third trimester examinations were studied. Maternal demographics, delivery, and neonatal information were recorded. Cases were compared with a reference group (normal oGCT with neither abnormal third-trimester growth nor polyhydramnios).  A total of 282 pregnancies were in the study group, and 663 were in the reference group. Deliveries in the study group were at a higher risk for birth weight (BW)% > 90%, standard deviation, and postpartum hemorrhage when compared with the reference group (adjusted odds ratio: 2.3-5.6). Pregnancies complicated by both polyhydramnios and accelerated fetal growth were significantly more likely to result in a BW% > 90% (odds ratio [OR]: 18.5; 95% confidence interval [CI]: 8.9-38.6) and PPH (OR: 4.2; 95% CI: 2.4-7.6).  Pregnancies with normal oGCT that develop polyhydramnios and accelerated growth are at higher risk for maternal and neonatal complications. Isolated polyhydramnios without accelerated growth increases the risk for delivery complications but not neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Evaluation of growth and development pattern in normal, low and very low birth weight neonates at 18 months of age.

PubMed

Abdeyazdan, Zahra; Ehsanpour, Soheila; Hemmati, Elahe

2014-01-01

Growth and development monitoring could lead to general judgment about children's health. With advances in NICUs establishment, the survival rate of very low birth weight (VLBW) neonates has increased in many countries including Iran. Because of the lack of studies about growth and development pattern of low birth weight (LBW) and VLBW neonates in Iran, the present study aimed to compare growth and development of normal, low and very low birth weight neonates at 18 months of age. In a cross- sectional descriptive study, 214 children with age 18 months were enrolled (90 LBW, 90 LBW and 34 VLBW) and their growth and development were assessed. Data gathering tool was a researcher made questionnaire including anthropometrics measures and developmental key points. Data analyzed by descriptive (mean and SD) and inferential (ANOVA) tests using SPSS version 15. There were significant differences in the mean of anthropometric indexes between three groups. Majority of subjects in three groups had normal weight growth trend. Mean scores of gross motor and fine motor development indexes had significant association with birth weight. Meanwhile, there was no significant association between mean scores of social/cognitive and also language developmental aspects and birth weight. Findings revealed that in LBW and VLBW children, growth indexes at the age of 18 months are so far from those of NBW neonates. Further nationwide prospective studies, with a longer period of time is needed to estimate when Iranian LBW children reach at the levels of NBW ones.

Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: reciprocal expression of C/EBP alpha and immediate-early growth response transcription factors.

PubMed Central

Rana, B; Mischoulon, D; Xie, Y; Bucher, N L; Farmer, S R

1994-01-01

Previous investigations have shown that culture of freshly isolated hepatocytes under conventional conditions, i.e., on dried rat tail collagen in the presence of growth factors, facilitates cell growth but also causes an extensive down-regulation of most liver-specific functions. This dedifferentiation process can be prevented if the cells are cultured on a reconstituted basement membrane gel matrix derived from the Englebreth-Holm-Swarm mouse sarcoma tumor (EHS gel). To gain insight into the mechanisms regulating this response to extracellular matrix, we are analyzing the activities of two families of transcription factors, C/EBP and AP-1, which control the transcription of hepatic and growth-responsive genes, respectively. We demonstrate that isolation of hepatocytes from the normal quiescent rat liver by collagenase perfusion activates the immediate-early growth response program, as indicated by increased expression of c-jun, junB, c-fos, and c-myc mRNAs. Adhesion of these activated cells to dried rat tail collagen augments the elevated levels of these mRNAs for the initial 1 to 2 h postplating; junB and c-myc mRNA levels then drop steeply, with junB returning to normal quiescence and the c-myc level remaining slightly elevated during the 3-day culture period. Levels of c-jun mRNA and AP-1 DNA binding activity, however, remain elevated from the outset, while C/EBP alpha mRNA expression is down-regulated, resulting in a decrease in the steady-state levels of the 42- and 30-kDa C/EBP alpha polypeptides and C/EBP alpha DNA binding activity. In contrast, C/EBP beta mRNA production remains at near-normal hepatic levels for 5 to 8 days of culture, although its DNA binding activity decreases severalfold during this time. Adhesion of hepatocytes to the EHS gel for the same period of time dramatically alters this program: it arrests growth and inhibits AP-1 DNA binding activity and the expression of c-jun, junB, and c-myc mRNAs, but, in addition, it restores C/EBP alpha mRNA and protein as well as C/EBP alpha and C/EBP beta DNA binding activities to the abundant levels present in freshly isolated hepatocytes. These changes are not due merely to growth inhibition, because suppression of hepatocyte proliferation on collagen by epidermal growth factor starvation or addition of transforming growth factor beta does not inhibit AP-1 activity or restore C/EBP alpha DNA binding activity to normal hepatic levels. These data suggest that expression of the normal hepatic phenotype requires that hepatocytes exist in a G0 state of growth arrest, facilitated here by adhesion of cells to the EHS gel, in order to express high levels of hepatic transcription factors such as C/EBP alpha. Images PMID:8065319

Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

PubMed Central

Gogtay, Nitin; Hua, Xue; Stidd, Reva; Boyle, Christina P.; Lee, Suh; Weisinger, Brian; Chavez, Alex; Giedd, Jay N.; Clasen, Liv; Toga, Arthur W.; Rapoport, Judith L.; Thompson, Paul M.

2013-01-01

Context Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. Objective To study WM growth differences in non-psychotic siblings of patients with COS. Design Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. Setting National Institutes of Health Clinical Center, Bethesda, Maryland. Participants Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1[5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9[5.3] years; 29 male, 28 female). Intervention Magnetic resonance imaging. Main Outcome Measure White matter growth rates. Results We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P =.004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. Conclusions In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM growth may also be an age-specific endophenotype that shows compensatory normalization with age. PMID:22945617

Growth of plants in solution culture containing low levels of chromium. [Tomato, lettuce, duckweed

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

Huffman, E.W.D. Jr.; Allaway, W.H.

1973-01-01

Chromium was not required for normal growth of romaine lettuce (Lactuca sativa L. subsp. longifolia), tomato (Lycopersicon esculentum Mill.), wheat (Triticum aestivum L.), or bean (Phaseolus vulgaris L.) in solution culture containing 3.8 X 10/sup -4/ ..mu..M Cr. Plants grown on this purified nutrient solution contained an average of 22 ng Cr/g dry weight. Duckweed (Lemna sp.) grew and reproduced normally on a dilute nutrient solution containing 3.8 X 20/sup -5/ ..mu..M Cr.

Contributions of muscle imbalance and impaired growth to postural and osseous shoulder deformity following brachial plexus birth palsy: a computational simulation analysis.

PubMed

Cheng, Wei; Cornwall, Roger; Crouch, Dustin L; Li, Zhongyu; Saul, Katherine R

2015-06-01

Two potential mechanisms leading to postural and osseous shoulder deformity after brachial plexus birth palsy are muscle imbalance between functioning internal rotators and paralyzed external rotators and impaired longitudinal growth of paralyzed muscles. Our goal was to evaluate the combined and isolated effects of these 2 mechanisms on transverse plane shoulder forces using a computational model of C5-6 brachial plexus injury. We modeled a C5-6 injury using a computational musculoskeletal upper limb model. Muscles expected to be denervated by C5-6 injury were classified as affected, with the remaining shoulder muscles classified as unaffected. To model muscle imbalance, affected muscles were given no resting tone whereas unaffected muscles were given resting tone at 30% of maximal activation. To model impaired growth, affected muscles were reduced in length by 30% compared with normal whereas unaffected muscles remained normal in length. Four scenarios were simulated: normal, muscle imbalance only, impaired growth only, and both muscle imbalance and impaired growth. Passive shoulder rotation range of motion and glenohumeral joint reaction forces were evaluated to assess postural and osseous deformity. All impaired scenarios exhibited restricted range of motion and increased and posteriorly directed compressive glenohumeral joint forces. Individually, impaired muscle growth caused worse restriction in range of motion and higher and more posteriorly directed glenohumeral forces than did muscle imbalance. Combined muscle imbalance and impaired growth caused the most restricted joint range of motion and the highest joint reaction force of all scenarios. Both muscle imbalance and impaired longitudinal growth contributed to range of motion and force changes consistent with clinically observed deformity, although the most substantial effects resulted from impaired muscle growth. Simulations suggest that treatment strategies emphasizing treatment of impaired longitudinal growth are warranted for reducing deformity after brachial plexus birth palsy. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Alginate foam-based three-dimensional culture to investigate drug sensitivity in primary leukaemia cells.

PubMed

Karimpoor, Mahroo; Yebra-Fernandez, Eva; Parhizkar, Maryam; Orlu, Mine; Craig, Duncan; Khorashad, Jamshid S; Edirisinghe, Mohan

2018-04-01

The development of assays for evaluating the sensitivity of leukaemia cells to anti-cancer agents is becoming an important aspect of personalized medicine. Conventional cell cultures lack the three-dimensional (3D) structure of the bone marrow (BM), the extracellular matrix and stromal components which are crucial for the growth and survival of leukaemia stem cells. To accurately predict the sensitivity of the leukaemia cells in an in vitro assay a culturing system containing the essential components of BM is required. In this study, we developed a porous calcium alginate foam-based scaffold to be used for 3D culture. The new 3D culture was shown to be cell compatible as it supported the proliferation of both normal haematopoietic and leukaemia cells. Our cell differential assay for myeloid markers showed that the porous foam-based 3D culture enhanced myeloid differentiation in both leukaemia and normal haematopoietic cells compared to two-dimensional culture. The foam-based scaffold reduced the sensitivity of the leukaemia cells to the tested antileukaemia agents in K562 and HL60 leukaemia cell line model and also primary myeloid leukaemia cells. This observation supports the application of calcium alginate foams as scaffold components of the 3D cultures for investigation of sensitivity to antileukaemia agents in primary myeloid cells. © 2018 The Author(s).

15 CFR 922.182 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... space for individual and population growth and normal behavior of humpback whales, and include sites... vegetation growth, or the upper limit of debris left by the wash of the waves. Take or taking a humpback...

15 CFR 922.182 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... space for individual and population growth and normal behavior of humpback whales, and include sites... vegetation growth, or the upper limit of debris left by the wash of the waves. Take or taking a humpback...

15 CFR 922.182 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... space for individual and population growth and normal behavior of humpback whales, and include sites... vegetation growth, or the upper limit of debris left by the wash of the waves. Take or taking a humpback...

Telogen Effluvium Hair Loss

MedlinePlus

... pillow. This is the result of the normal hair growth cycle. Hairs will grow for a few years, ... the name for the resting stage of the hair growth cycle. A telogen effluvium is when some stress ...

15 CFR 922.182 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... space for individual and population growth and normal behavior of humpback whales, and include sites... vegetation growth, or the upper limit of debris left by the wash of the waves. Take or taking a humpback...

15 CFR 922.182 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... space for individual and population growth and normal behavior of humpback whales, and include sites... vegetation growth, or the upper limit of debris left by the wash of the waves. Take or taking a humpback...

Genetic analysis of indefinite division in human cells: Evidence for a cell senescence-related gene(s) on human chromosome 4

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

Yi Ning; Ledbetter, D.H.; Smith, J.R.

1991-07-01

Earlier studies had demonstrated that fusion of normal with immortal human cells yielded hybrids having limited division potential. This indicated that the phenotype of limited proliferation (cellular senescence) is dominant and that immortal cells result from recessive changes in normal growth-regulatory genes. In additional studies, the authors exploited the fact that the immortal phenotype is recessive and, by fusing various immortal human cell lines with each other, identified four complementation groups for indefinite division. Assignment of cell lines to specific groups allowed us to take a focused approach to identify the chromosomes and genes involved in growth regulation that havemore » been modified in immortal cells. They report here that introduction of a normal human chromosome 4 into three immortal cell lines (HeLa, J82, T98G) assigned to complementation group B resulted in loss of proliferation and reversal of the immortal phenotype. No effect on the proliferation potential of cell lines representative of the other complementation groups was observed. This result suggests that a gene(s) involved in cellular senescence and normal growth regulation resides on chromosome 4.« less

Evidence for altered placental blood flow and vascularity in compromised pregnancies

PubMed Central

Reynolds, Lawrence P; Caton, Joel S; Redmer, Dale A; Grazul-Bilska, Anna T; Vonnahme, Kimberly A; Borowicz, Pawel P; Luther, Justin S; Wallace, Jacqueline M; Wu, Guoyao; Spencer, Thomas E

2006-01-01

The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can ‘rescue’ fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies. PMID:16469783

Gene expression patterns of vascular endothelial growth factor (VEGF-A) in human placenta from pregnancies with intrauterine growth restriction.

PubMed

Szentpéteri, Imre; Rab, Attila; Kornya, László; Kovács, Péter; Joó, József Gábor

2013-07-01

In this study, we describe changes in gene expression pattern of vascular endothelial growth factor (VEGF)-A in human placenta obtained from pregnancies with intrauterine growth restriction using placenta from normal pregnancies as control. We compared gene expression of VEGF-A in placental samples from Intrauterine growth restriction (IUGR) pregnancies versus placenta obtained from normal pregnancies. Among potential confounders, important clinical informations were also analyzed. In the IUGR group, the VEGF-A gene was overexpressed compared to the normal pregnancy group (Ln 2(α)β-actin: 1.32; Ln 2(α)GADPH: 1.56). There was no correlation between the degree of growth restriction and VEGF-A gene expression (Ln 2(α)(0-5)percentile: 0.58; Ln 2(α)(5-10)percentile: 0.64). Within the IUGR group, there was a trend toward a positive correlation between placental VEGF-A gene activity and gestational age at delivery (Ln 2(α)< 33 weeks: 1.09; Ln 2(α)33-37 weeks: 1.27; Ln 2(α)> 37 weeks: 1.35). Our findings suggest that the increase in placental expression of the VEGF-A gene and the resultant stimulation of angiogenesis are a response to hypoxic environment developing in the placental tissue in IUGR. Thus, it appears to be a secondary event rather than a primary factor in the development of IUGR There is a trend toward a positive correlation between gestational age and placental VEGF-A gene activity.

Underexpression of mineralocorticoid receptor in colorectal carcinomas and association with VEGFR-2 overexpression.

PubMed

Di Fabio, Francesco; Alvarado, Carlos; Majdan, Agnieszka; Gologan, Adrian; Voda, Linda; Mitmaker, Elliot; Beitel, Lenore K; Gordon, Philip H; Trifiro, Mark

2007-11-01

The human mineralocorticoid receptor (MR) is a steroid receptor widely expressed in colorectal mucosa. A significant role for the MR in the reduction of vascular endothelial growth factor receptor-2 (VEGFR-2) mRNA levels has been demonstrated in vitro. To evaluate a potential contribution of MR to colorectal carcinoma progression, we analyzed the expression of MR in relation to VEGFR-2. Fresh human colorectal cancer tissue and adjacent normal mucosa were harvested from 48 consecutive patients. MR and VEGFR-2 mRNA expression levels were determined by real-time reverse transcriptase-polymerase chain reaction and correlated with clinicopathological parameters. A decline of MR expression was observed in all carcinomas compared to normal mucosa. Expression of MR was a median of 11-fold lower in carcinoma compared to the normal mucosa, irrespective of the location, size, stage, and differentiation. MR was a median of 20-fold underexpressed in carcinomas with VEGFR-2 overexpression vs only 9-fold in carcinomas with VEGFR-2 underexpression (p = 0.035, Mann-Whitney test). These findings support the hypothesis that reduction of MR expression may be one of the early events involved in colorectal carcinoma progression. The inverse association between MR and VEGFR-2 expression in carcinoma suggests a potential tumor-suppressive function for MR.

Crop calendars for the US, USSR, and Canada in support of the early warning project

NASA Technical Reports Server (NTRS)

Hodges, T.; Sestak, M. L.; Trenchard, M. H. (Principal Investigator)

1980-01-01

New crop calendars are produced for U.S. regions where several years of periodic growth stage observations are available on a CRD basis. Preexisting crop calendars from the LACIE are also collected as are U.S. crop calendars currently being created for the Foreign Commodities Production Forecast project. For the U.S.S.R. and Canada, no new crop calendars are created because no new data are available. Instead, LACIE crop calendars are compared against simulated normal daily temperatures and against the Robertson wheat and Williams barley phenology models run on the simulated normal temperatures. Severe inconsistencies are noted and discussed. For the U.S.S.R., spring and fall planting dates can probably be estimated accurately from satellite or meteorological data. For the starter model problem, the Feyerherm spring wheat model is recommended for spring planted small grains, and the results of an analysis are presented. For fall planted small grains, use of normal planting dates supplemented by spectral observation of an early stage is recommended. The importance of nonmeteorological factors as they pertain to meteorological factors in determining fall planting is discussed. Crop calendar data available at the Johnson Space Center for the U.S., U.S.S.R., Canada, and other countries are inventoried.

A pseudospectra-based approach to non-normal stability of embedded boundary methods

NASA Astrophysics Data System (ADS)

Rapaka, Narsimha; Samtaney, Ravi

2017-11-01

We present non-normal linear stability of embedded boundary (EB) methods employing pseudospectra and resolvent norms. Stability of the discrete linear wave equation is characterized in terms of the normalized distance of the EB to the nearest ghost node (α) in one and two dimensions. An important objective is that the CFL condition based on the Cartesian grid spacing remains unaffected by the EB. We consider various discretization methods including both central and upwind-biased schemes. Stability is guaranteed when α <=αmax ranges between 0.5 and 0.77 depending on the discretization scheme. Also, the stability characteristics remain the same in both one and two dimensions. Sharper limits on the sufficient conditions for stability are obtained based on the pseudospectral radius (the Kreiss constant) than the restrictive limits based on the usual singular value decomposition analysis. We present a simple and robust reclassification scheme for the ghost cells (``hybrid ghost cells'') to ensure Lax stability of the discrete systems. This has been tested successfully for both low and high order discretization schemes with transient growth of at most O (1). Moreover, we present a stable, fourth order EB reconstruction scheme. Supported by the KAUST Office of Competitive Research Funds under Award No. URF/1/1394-01.

Hair cell regeneration in the chick inner ear following acoustic trauma: ultrastructural and immunohistochemical studies.

PubMed

Umemoto, M; Sakagami, M; Fukazawa, K; Ashida, K; Kubo, T; Senda, T; Yoneda, Y

1995-09-01

The regeneration of hair cells in the chick inner ear following acoustic trauma was examined using transmission electron microscopy. In addition, the localization of proliferation cell nuclear antigen (PCNA) and basic fibroblast growth factor (b-FGF) was demonstrated immunohistochemically. The auditory sensory epithelium of the normal chick consists of short and tall hair cells and supporting cells. Immediately after noise exposure to a 1500-Hz pure tone at a sound pressure level of 120 decibels for 48 h, all the short hair cells disappeared in the middle region of the auditory epithelium. Twelve hours to 1 day after exposure, mitotic cells, binucleate cells and PCNA-positive supporting cells were observed, and b-FGF immunoreactivity was shown in the supporting cells and glial cells near the habenula perforata. Spindle-shaped hair cells with immature stereocilia and a kinocilium appeared 3 days after exposure; these cells had synaptic connections with the newly developed nerve endings. The spindle-shaped hair cell is considered to be a transitional cell in the lineage of the supporting cell to the mature short hair cell. These results indicate that, after acoustic trauma, the supporting cells divide and differentiate into new short hair cells via spindle-shaped hair cells. Furthermore, it is suggested that b-FGF is related to the proliferation of the supporting cells and the extension of the nerve fibers.

The longitudinal sagittal growth changes of maxilla and mandible according to quantitative cervical vertebral maturation.

PubMed

Chen, Lili; Lin, Jiuxiang; Xu, Tianmin; Long, Xiaosi

2009-04-01

To investigate the longitudinal sagittal growth changes of maxilla and mandible according to the quantitative cervical vertebral maturation (QCVM) for adolescents with normal occlusion, mixed longitudinal data were used. The samples included 87 adolescents aged from 8 to 18 y old with normal occlusion (32 males, 55 females) selected from 901 candidates. Sequential lateral cephalograms and hand-wrist films were taken once a year, lasting for 6 y. The longitudinal sagittal growth changes of maxilla and mandible according to QCVM were measured. There were some significant differences between maxilla and mandible according to QCVM. The sagittal growth change of maxilla showed a trend towards high velocity-->decelerating velocity-->completing velocity from QCVM stage I to stage IV. The sagittal growth change of mandible showed a trend towards accelerating velocity-->high velocity-->decelerating velocity-->completing velocity from QCVM stage I to stage IV. With sagittal relationship, growth magnitude was almost the same between maxilla and mandible at QCVM stage I. At stage II the growth of mandible exceeded that of maxilla and growth in mandible continued at stages III and IV, while the maxilla ceased to grow. Growth magnitude was greater and the growth duration was longer with male mandible. It is concluded that the longitudinal sagittal growth changes of maxilla and mandible on the basis of QCVM is of value in the orthodontic practice.

FKBPL Is a Critical Antiangiogenic Regulator of Developmental and Pathological Angiogenesis

PubMed Central

Yakkundi, Anita; Bennett, Rachel; Hernández-Negrete, Ivette; Delalande, Jean-Marie; Hanna, Mary; Lyubomska, Oksana; Arthur, Kenneth; Short, Amy; McKeen, Hayley; Nelson, Laura; McCrudden, Cian M.; McNally, Ross; McClements, Lana; McCarthy, Helen O.; Burns, Alan J.; Bicknell, Roy; Kissenpfennig, Adrien

2015-01-01

Objective— The antitumor effects of FK506-binding protein like (FKBPL) and its extracellular role in angiogenesis are well characterized; however, its role in physiological/developmental angiogenesis and the effect of FKBPL ablation has not been evaluated. This is important as effects of some angiogenic proteins are dosage dependent. Here we evaluate the regulation of FKBPL secretion under angiogenic stimuli, as well as the effect of FKBPL ablation in angiogenesis using mouse and zebrafish models. Approach and Results— FKBPL is secreted maximally by human microvascular endothelial cells and fibroblasts, and this was specifically downregulated by proangiogenic hypoxic signals, but not by the angiogenic cytokines, VEGF or IL8. FKBPL’s critical role in angiogenesis was supported by our inability to generate an Fkbpl knockout mouse, with embryonic lethality occurring before E8.5. However, whilst Fkbpl heterozygotic embryos showed some vasculature irregularities, the mice developed normally. In murine angiogenesis models, including the ex vivo aortic ring assay, in vivo sponge assay, and tumor growth assay, Fkbpl+/− mice exhibited increased sprouting, enhanced vessel recruitment, and faster tumor growth, respectively, supporting the antiangiogenic function of FKBPL. In zebrafish, knockdown of zFkbpl using morpholinos disrupted the vasculature, and the phenotype was rescued with hFKBPL. Interestingly, this vessel disruption was ineffective when zcd44 was knocked-down, supporting the dependency of zFkbpl on zCd44 in zebrafish. Conclusions— FKBPL is an important regulator of angiogenesis, having an essential role in murine and zebrafish blood vessel development. Mouse models of angiogenesis demonstrated a proangiogenic phenotype in Fkbpl heterozygotes. PMID:25767277

Generation of fibrosarcomas in vivo by a retrovirus that expresses the normal B chain of platelet-derived growth factor and mimics the alternative splice pattern of the v-sis oncogene

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

Pech, M.; Gazit, A.; Arnstein, P.

1989-04-01

A retrovirus containing the entire human platelet-derived growth factor B-chain (PDGF-B) gene was constructed in order to investigate the in vivo biological activity of its encoded growth factor. When this virus was introduced into newborn mice, it reproducibly generated fibrosarcomas at the site of inoculation. Proviruses in each fibrosarcoma analyzed had lost 149 nucleotides downstream of the PDGF-B coding region. This deletion originated from an alternative or aberrant splice event that occurred within exon 7 of the PDGF-B gene and mimicked the v-sis oncogene. Thus, deletion of this region may be necessary for efficient retrovirus replication or for more potentmore » transforming function. Evidence that the normal growth factor coding sequence was unaltered derived from RNase protection studies and immunoprecipitation analysis. Tumors were generally polyclonal but demonstrated clonal subpopulations. Moreover, tumor-derived cell lines became monoclonal within a few tissue culture passages and rapidly formed tumors in vivo. These findings argue that overexpression of the normal human PDGF-B gene product under retrovirus control can induce the fully malignant phenotype.« less

The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

PubMed

Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R

2010-06-01

Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

EXPERIMENTAL RICKETS IN RATS

PubMed Central

Pappenheimer, A. M.; McCann, G. F.; Zucker, T. F.

1922-01-01

1. Casein phosphorus does not completely prevent the development of rickets when substituted in Diet 84 in amount equivalent to a protective dose of basic potassium phosphate. 2. The protection given by lecithin is equivalent to its phosphorus content. 3. The protection given by yeast is at least proportional to its phosphorus content. An amount carrying sufficient vitamine B to promote growth, but insufficient to provide adequate phosphorus, does not prevent rickets. 4. Vitamine A, in the form of butter or butter fat to the amount of 10 per cent of the diet, neither prevents nor cures rickets. 5. The substitution of 10 per cent of egg albumin in Diet 84 improves the nutrition, but does not prevent rickets. 6. The addition of meat to Diet 84, thereby supplying an abundance of phosphorus, promotes normal growth and normal bone formation. A diet consisting solely of meat and flour is inadequate for proper growth, and leads to changes in the bones comparable with those observed on a diet low in calcium, but rich in phosphorus. 7. A diet has been found which contains the necessary food elements for approximately normal growth, and in which the only known deficiency is phosphorus. This leads regularly to the production of rickets. PMID:19868618

Higher Leptin but Not Human Milk Macronutrient Concentration Distinguishes Normal-Weight from Obese Mothers at 1-Month Postpartum.

PubMed

De Luca, Arnaud; Frasquet-Darrieux, Marine; Gaud, Marie-Agnès; Christin, Patricia; Boquien, Clair-Yves; Millet, Christine; Herviou, Manon; Darmaun, Dominique; Robins, Richard J; Ingrand, Pierre; Hankard, Régis

2016-01-01

Exclusively breastfed infants born to obese mothers have previously been shown to gain less weight by 1-month postpartum than infants of normal-weight mothers. Our hypothesis is that human milk composition and volume may differ between obese and normal-weight mothers. To compare human milk leptin, macronutrient concentration, and volume in obese and normal-weight mothers. Mother and infant characteristics were studied as secondary aims. This cross-sectional observational study compared 50 obese mothers matched for age, parity, ethnic origin, and educational level with 50 normal-weight mothers. Leptin, macronutrient human milk concentration, and milk volume were determined at 1 month in exclusively breastfed infants. Mother characteristics and infant growth were recorded. Human milk leptin concentration was higher in obese mothers than normal-weight mothers (4.8±2.7 vs. 2.5±1.5 ng.mL-1, p<0.001). No difference was observed between obese and normal-weight mothers in protein, lipid, carbohydrate content, and volume, nor in infant weight gain. Leptin concentration was higher in the milk of obese mothers than that of normal-weight mothers, but macronutrient concentration was not. It remains to be established whether the higher leptin content impacts on infant growth beyond the 1-month of the study period.

The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador.

PubMed

Rosenbloom, A L; Guevara Aguirre, J; Rosenfeld, R G; Fielder, P J

1990-11-15

Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males.

Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

PubMed Central

2011-01-01

Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis. PMID:22136338

Normal Human Fibroblasts Are Resistant to RAS-Induced Senescence

PubMed Central

Benanti, Jennifer A.; Galloway, Denise A.

2004-01-01

Oncogenic stimuli are thought to induce senescence in normal cells in order to protect against transformation and to induce proliferation in cells with altered p53 and/or retinoblastoma (Rb) pathways. In human fibroblasts, RAS initiates senescence through upregulation of the cyclin-dependent kinase inhibitor p16INK4A. We show here that in contrast to cultured fibroblast strains, freshly isolated normal fibroblasts are resistant to RAS-induced senescence and instead show some characteristics of transformation. RAS did not induce growth arrest or expression of senescence-associated β-galactosidase, and Rb remained hyperphosphorylated despite elevated levels of p16. Instead, RAS promoted anchorage-independent growth of normal fibroblasts, although expression of hTert with RAS increased colony formation and allowed normal fibroblasts to bypass contact inhibition. To test the hypothesis that p16 levels determine how cells respond to RAS, we expressed RAS in freshly isolated fibroblasts that expressed very low levels of p16, in hTert-immortalized fibroblasts that had accumulated intermediate levels of p16, and in IMR90 fibroblasts with high levels of p16. RAS induced growth arrest in cells with higher p16 levels, and this effect was reversed by p16 knockdown in the hTert-immortalized fibroblasts. These findings indicate that culture-imposed stress sensitizes cells to RAS-induced arrest, whereas early passage cells do not arrest in response to RAS. PMID:15024073

Effects of pituitary dwarfism in the mouse on fast and slow skeletal muscles.

PubMed

Stickland, N C; Crook, A R; Sutton, C M

1994-01-01

The Snell dwarf mouse exhibits impaired growth of the anterior pituitary resulting in reduced levels of growth hormone and thyroid stimulating hormone. Ten dwarf mice and 10 phenotypically normal littermates were killed at 33 days of age. M. biceps brachii (a predominantly fast muscle) and m. soleus (a relatively slow muscle) were removed from each animal and complete frozen transverse sections obtained. Serial sections were reacted for various enzyme activities in order to identify muscle fibre types. There was no difference in the total number of muscle fibres in m. biceps brachii but a small difference in m. soleus between normal and dwarf mice. There were marked differences in the size of all fibre types between normal and dwarf mice with the largest differences in m. soleus. The percentage of slow oxidative fibres was similar (about 32%) in both groups of mice for m. soleus but there was a marked difference for this fibre type in m. biceps brachii being about 1.5% in normal mice and 8.0% in dwarf mice. This may be related to a difference in levels of thyroid hormone. Nuclear density was very significantly greater in dwarf muscles although total nuclear numbers were less than in normal muscles. These differences are most likely due to growth hormone levels. Differences in nuclear content were much greater in m. soleus than in m. biceps brachii.

ATM-dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts

PubMed Central

Zhou, Tong; Chou, Jeff; Zhou, Yingchun; Simpson, Dennis A.; Cao, Feng; Bushel, Pierre R.; Paules, Richard S.; Kaufmann, William K.

2013-01-01

The relationships between profiles of global gene expression and DNA damage checkpoint functions were studied in cells from patients with ataxia telangiectasia (AT). Three telomerase-expressing AT fibroblast lines displayed the expected hypersensitivity to ionizing radiation (IR) and defects in DNA damage checkpoints. Profiles of global gene expression in AT cells were determined at 2, 6 and 24 h after treatment with 1.5 Gy IR or sham-treatment, and were compared to those previously recognized in normal human fibroblasts. Under basal conditions 160 genes or ESTs were differentially expressed in AT and normal fibroblasts, and these were associated by gene ontology with insulin-like growth factor binding and regulation of cell growth. Upon DNA damage, 1091 gene mRNAs were changed in at least two of the three AT cell lines. When compared with the 1811 genes changed in normal human fibroblasts after the same treatment, 715 were found in both AT and normal fibroblasts, including most genes categorized by gene ontology into cell cycle, cell growth and DNA damage response pathways. However, the IR-induced changes in these 715 genes in AT cells usually were delayed or attenuated in comparison to normal cells. The reduced change in DNA-damage-response genes and the attenuated repression of cell-cycle-regulated genes may account for the defects in cell cycle checkpoint function in AT cells. PMID:17699107

Dopamine induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages in rat C6 glioma

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

Qin, Tian; Wang, Chenlong; Chen, Xuewei

Dopamine (DA), a monoamine catecholamine neurotransmitter with antiangiogenic activity, stabilizes tumor vessels in colon, prostate and ovarian cancers, thus increases chemotherapeutic efficacy. Here, in the rat C6 glioma models, we investigated the vascular normalization effects of DA and its mechanisms of action. DA (25, 50 mg/kg) inhibited tumor growth, while a precursor of DA (levodopa) prolonged the survival time of rats bearing orthotopic C6 glioma. DA improved tumor perfusion, with significant effects from day 3, and a higher level at days 5 to 7. In addition, DA decreased microvessel density and hypoxia-inducible factor-1α expression in tumor tissues, while increasing themore » coverage of pericyte. Conversely, an antagonist of dopamine receptor 2 (DR2) (eticlopride) but not DR1 (butaclamol) abrogated DA-induced tumor regression and vascular normalization. Furthermore, DA improved the delivery and efficacy of temozolomide therapy. Importantly, DA increased representative M1 markers (iNOS, CXCL9, etc.), while decreasing M2 markers (CD206, arginase-1, etc.). Depletion of macrophages by clodronate or zoledronic acid attenuated the effects of DA. Notably, DA treatment induced M2-to-M1 polarization in RAW264.7 cells and mouse peritoneal macrophages, and enhanced the migration of pericyte-like cells (10T1/2), which was reversed by eticlopride or DR2-siRNA. Such changes were accompanied by the downregulation of VEGF/VEGFR2 signaling. In summary, DA induces growth inhibition and vascular normalization through reprogramming M2-polarized macrophages. Thus, targeting the tumor microvasculature by DA represents a promising strategy for human glioma therapy. - Highlights: • Dopamine induces tumor growth inhibition and vascular normalization in rat C6 glioma. • Dopamine switches macrophage phenotype from M2 to M1. • Dopamine-induced vascular normalization is mediated by macrophage polarization. • Dopamine is a promising agent targeting the microvasculature in tumor microenvironment.« less

Fundamental mechanisms of growth failure in inflammatory bowel disease.

PubMed

Ballinger, Anne

2002-01-01

Growth failure is common in children with inflammatory bowel disease (IBD) and has been attributed chiefly to undernutrition. Liquid enteral feeding can reverse the calorie deficit and increase growth velocity. The inflammatory process per se may also directly inhibit linear growth. After institution of enteral nutrition, significant changes in serum growth factors and inflammatory indices have been observed before any changes in nutritional parameters [Bannerjee et al., Gastroenterology 2000;118:A526]. In rats with trinitrobenzenesulphonic acid (TNBS)-induced colitis, about 60% of the final growth impairment can be attributed to undernutrition, inflammation accounting for the remaining growth deficit. Young patients with Crohn's disease and growth failure have normal stimulated and spontaneous growth hormone (GH) secretion and reduced plasma concentrations of insulin-like growth factor-1 (IGF-I), suggesting a degree of GH resistance. Rats with TNBS colitis also have normal plasma GH and reduced IGF-I concentrations, mediated by a combination of undernutrition and active inflammation. Immunoneutralization of interleukin-6 (IL-6) increases hepatic IGF-I mRNA expression, plasma concentrations of IGF-I and linear growth. In contrast, administration of anti-tumour necrosis factor-alpha antibodies (TNF-ab) had no effect on IGF-I in this model. TNFab did, however, increase linear growth, suggesting inhibitory effects of TNF-alpha on the growth axis by mechanisms other than reduction in IGF-I. Preliminary data suggests that TNF-alpha inhibits maturation of growth plate chondrocytes. We have identified IL-6 receptors on growth plate chondrocytes but to date have not identified the effect, if any, of IL-6 directly at the growth plate. Copyright 2002 S. Karger AG, Basel

Characterization of crack growth under combined loading

NASA Technical Reports Server (NTRS)

Feldman, A.; Smith, F. W.; Holston, A., Jr.

1977-01-01

Room-temperature static and cyclic tests were made on 21 aluminum plates in the shape of a 91.4x91.4-cm Maltese cross with 45 deg flaws to develop crack growth and fracture toughness data under mixed-mode conditions. During cyclic testing, it was impossible to maintain a high proportion of shear-mode deformation on the crack tips. Cracks either branched or turned. Under static loading, cracks remained straight if shear stress intensity exceeded normal stress intensity. Mixed-mode crack growth rate data compared reasonably well with published single-mode data, and measured crack displacements agreed with the straight and branched crack analyses. Values of critical strain energy release rate at fracture for pure shear were approximately 50% higher than for pure normal opening, and there was a large reduction in normal stress intensity at fracture in the presence of high shear stress intensity. Net section stresses were well into the inelastic range when fracture occurred under high shear on the cracks.

THE EFFECT OF X RAYS ON THE LARVA OF THE ANFIBI ANURI. GRAFTS OF JOINTS AND ADMINISTRATION OF THYROXINE (in Italian)

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

Perri, T.

1959-11-01

The effect of x rays on the larvae of Anfibi anuri and particularly on their endocrine balunce was studied. The effect studied was the variation of the growth velocity of the joints of normal larvae transplanted onto x-irradiated larvae, either homoplastically (Bufo vulgaris and Bufo viridis) or heteroplastically (Bufo viridis and Bufo vulgaris). A joint transplant from normal larvae of Bufo vulgaris or Bufo viridis on x-irradiated larvae of Bufo vulgaris has a growth rate much less than that found in transplants on normal larvae of Bufo vulgaris. It is suggested that this results from the radiation- induced decrease ofmore » the endocrine activity of the carrier, particularly of the thyroxine activity. It is seen that in transplants from Bufo viridis on irradiated Bufo vulgaris, if the carrier larvae are treated with thyroxine, the transplants have a sharply increased growth. (J.S.R)« less

Rapamycin Inhibits Human Laryngotracheal Stenosis–derived Fibroblast Proliferation, Metabolism, and Function in Vitro

PubMed Central

Namba, Daryan R.; Ma, Garret; Samad, Idris; Ding, Dacheng; Pandian, Vinciya; Powell, Jonathan D.; Horton, Maureen R.; Hillel, Alexander T.

2015-01-01

Objective To determine if rapamycin inhibits the growth, function, and metabolism of human laryngotracheal stenosis (LTS)–derived fibroblasts. Study Design Controlled in vitro study. Setting Tertiary care hospital in a research university. Subjects and Methods Fibroblasts isolated from biopsies of 5 patients with laryngotracheal stenosis were cultured. Cell proliferation, histology, gene expression, and cellular metabolism of LTS-derived fibroblasts were assessed in 4 conditions: (1) fibroblast growth medium, (2) fibroblast growth medium with dimethylsulfoxide (DMSO), (3) fibroblast growth medium with 10−10 M (low-dose) rapamycin dissolved in DMSO, and (4) fibroblast growth medium with 10−9 M (high-dose) rapamycin dissolved in DMSO. Results The LTS fibroblast count and DNA concentration were reduced after treatment with high-dose rapamycin compared to DMSO (P = .0007) and normal (P = .0007) controls. Collagen I expression decreased after treatment with high-dose rapamycin versus control (P = .0051) and DMSO (P = .0093) controls. Maximal respiration decreased to 68.6 pMoles of oxygen/min/10 mg/protein from 96.9 for DMSO (P = .0002) and 97.0 for normal (P = .0022) controls. Adenosine triphosphate (ATP) production decreased to 66.8 pMoles from 88.1 for DMSO (P = .0006) and 83.3 for normal (P = .0003) controls. Basal respiration decreased to 78.6 pMoles from 108 for DMSO (P = .0002) and 101 for normal (P = .0014) controls. Conclusions Rapamycin demonstrated an anti-fibroblast effect by significantly reducing the proliferation, metabolism, and collagen deposition of human LTS fibroblast in vitro. Rapamycin significantly decreased oxidative phosphorylation of LTS fibroblasts, suggesting at a potential mechanism for the reduced proliferation and differentiation. Furthermore, rapamycin’s anti-fibroblast effects indicate a promising adjuvant therapy for the treatment of laryngotracheal stenosis. PMID:25754184

Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies.

PubMed

de Zegher, Francis; Reynaert, Nele; De Somer, Lien; Wouters, Carine; Roelants, Mathieu

2018-06-25

Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature. © 2018 S. Karger AG, Basel.

CLIC4 Moves Into Nucleus to Stabilize Anti-Growth Signal | Center for Cancer Research

Cancer.gov

In cancer, the delicate balance of signaling pathways that control cell growth and function is disrupted. One signaling pathway commonly altered in cancer is the TGF-beta pathway. TGF-beta significantly inhibits growth of normal cells, particularly epithelial cells. Many cancer cells have developed ways to bypass one or more steps of this pathway in order to achieve uncontrolled growth.

Reducing mortality in old-growth northern hardwoods through partial cuttings

Treesearch

F.H. Eyre; F.R. Longwood

1951-01-01

To convert uncut old-growth stands of northern hardwoods to a thrifty forest through partial cutting it is necessary both to provide growing Space for promising trees and to reduce mortality. If the mortality normal in a virgin stand is not checked through proper cutting, there may be very little net growth. How then should cutting be done to stimulate growth and at...