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Sample records for growth factor precursor

  1. Expression of transforming growth factor alpha, epidermal growth factor receptor and epidermal growth factor in precursor lesions to gastric carcinoma.

    PubMed Central

    Filipe, M. I.; Osborn, M.; Linehan, J.; Sanidas, E.; Brito, M. J.; Jankowski, J.

    1995-01-01

    Epidermal growth factor (EGF), its related peptide transforming growth factor (TGF-alpha) and their common receptor (EGFR) have been implicated in the control of cell proliferation and differentiation in the gastrointestinal epithelium and may play an important role in gastric carcinogenesis. We compared the immunohistochemical expression and topographic distribution of these peptides using Western blot analysis in gastric carcinoma precursor lesions and in non-cancer tissue. We observed: (i) increased and extended expression of TGF-alpha in normal mucosa and hyperplasia in carcinoma fields compared with non-cancer controls; (ii) increased expression of EGFR in intestinal metaplasia (IM) from carcinoma fields compared with controls; (iii) EGF expression was not detected in normal mucosa and only weakly in IM; (iv) coexpression of TGF-alpha/EGFR and EGF/EGFR was higher in intestinal metaplasia in carcinoma fields than in non-cancer controls. We conclude that altered expression of TGF-alpha/EGFR is associated with morphological changes during gastric carcinogenesis. In this regard increased expression of TGF-alpha is a very early event which is subsequently followed by up-regulation of EGFR and this has important biological and clinical implications. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:7819044

  2. The granulin-epithelin precursor/PC-cell-derived growth factor is a growth factor for epithelial ovarian cancer.

    PubMed

    Jones, Monica Brown; Michener, Chad M; Blanchette, James O; Kuznetsov, Vladimir A; Raffeld, Mark; Serrero, Ginette; Emmert-Buck, Michael R; Petricoin, Emanuel F; Krizman, David B; Liotta, Lance A; Kohn, Elise C

    2003-01-01

    The role of growth factors in ovarian cancer development and progression is complex and multifactorial. We hypothesized that new growth factors may be identified through the molecular analysis of ovarian tumors as they exist in their native environment. RNA extracted from microdissected serous low malignant potential (LMP) and invasive ovarian tumors was used to construct cDNA libraries. A total of 7300 transcripts were randomly chosen for sequencing, and those transcripts were statistically evaluated. Reverse transcription-PCR and immunohistochemistry were used to validate the findings in tumor tissue samples. Ovarian cancer cell lines were used to test gene effects on monolayer growth, proliferative capacity, and density-independent growth. Analysis of the pooled library transcripts revealed 26 genes differentially expressed between LMP and invasive ovarian cancers. The granulin-epithelin precursor [GEP/PC-cell derived growth factor (PCDGF)] was expressed only in the invasive ovarian cancer libraries (P < 0.028) and was absent in the LMP libraries (0 of 2872 clones). All of the invasive tumor epithelia, 20% of the LMP tumor epithelia, and all of the stroma from both subsets expressed GEP by reverse transcription-PCR. Immunohistochemical staining for GEP was diffuse and cytosolic in invasive ovarian cancer tumor cells compared with occasional, punctate, and apical staining in LMP tumor epithelia. Antisense transfection of GEP into ovarian cancer cell lines resulted in down-regulation of GEP production, reduction in cell growth (P < 0.002), decrease in the S-phase fraction (P < 0.04), and loss of density-independent growth potential (P < 0.01). cDNA library preparation from microdissected tumor epithelium provided a selective advantage for the identification of growth factors for epithelial ovarian cancer. Differential granulin expression in tumor samples and the antiproliferative effects of its antisense down-regulation suggest that GEP may be a new autocrine

  3. Comparison of melatonin with growth factors in promoting precursor cells proliferation in adult mouse subventricular zone

    PubMed Central

    Sotthibundhu, Areechun; Ekthuwapranee, Kasima; Govitrapong, Piyarat

    2016-01-01

    Melatonin, secreted mainly by the pineal gland, plays roles in various physiological functions including protecting cell death. We showed in previous study that the proliferation and differentiation of precursor cells from the adult mouse subventricular zone (SVZ) can be modulated by melatonin via the MT1 melatonin receptor. Since melatonin and epidermal growth factor receptor (EGFR) share some signaling pathway components, we investigated whether melatonin can promote the proliferation of precursor cells from the adult mouse SVZ via the extracellular signal-regulated protein kinase /mitogen-activated protein kinase (ERK/MAPK) pathways in comparison with epidermal growth factor (EGF). Melatonin-induced ERK/MAPK pathways compared with EGF were measured by using in vitro and vivo models. We used neurosphere proliferation assay, immunocytochemistry, and immuno-blotting to analyze significant differences between melatonin and growth factor treatment. We also used specific antagonist and inhibitors to confirm the exactly signaling pathway including luzindole and U0126. We found that significant increase in proliferation was observed when two growth factors (EGF+bFGF) and melatonin were used simultaneously compared with EGF + bFGF or compared with melatonin alone. In addition, the present result suggested the synergistic effect occurred of melatonin and growth factors on the activating the ERK/MAPK pathway. This study exhibited that melatonin could act as a trophic factor, increasing proliferation in precursor cells mediated through the melatonin receptor coupled to ERK/MAPK signaling pathways. Understanding the mechanism by which melatonin regulates precursor cells may conduct to the development of novel strategies for neurodegenerative disease therapy. PMID:28275319

  4. Increased expression of transforming growth factor α precursors in acute experimental colitis in rats

    PubMed Central

    Hoffmann, P; Zeeh, J; Lakshmanan, J; Wu, V; Procaccino, F; Reinshagen, M; McRoberts, J; Eysselein, V

    1997-01-01

    Background and aim—Epidermal growth factor (EGF) and transforming growth factor α (TGF-α), members of the EGF family of growth factors, protect rat gastric and colonic mucosa against injury. Having shown previously that exogenously applied EGF protects rat colonic mucosa against injury, the aim of the present study was to evaluate the endogenously expressed ligand mediating the protective effect of EGF/TGF-α in vivo. 
Methods—In an experimental model of trinitrobenzene sulphonic acid (TNBS)/ ethanol induced colitis in rats EGF and TGF-α expression was evaluated using a ribonuclease protection assay, northern blot analysis, western blot analysis, and immunohistochemistry. 
Results—TGF-α mRNA increased 3-4 times at 4-8 hours after induction of colitis and returned to control levels within 24 hours. TGF-α immunoreactive protein with a molecular size of about 28kDa representing TGF-α precursors increased markedly after induction of colitis with a peak at 8-12 hours. No fully processed 5.6 kDa TGF-α protein was detected in normal or inflamed colon tissue. Only a weak signal for EGF mRNA expression was detected in the rat colon and no EGF protein was observed by immunohistochemistry or western blot analysis. 
Conclusions—TGF-α precursors are the main ligands for the EGF receptor in acute colitis. It is hypothesised that TGF-α precursors convey the biological activity of endogenous TGF-α peptides during mucosal defence and repair. 

 Keywords: transforming growth factor alpha (TGF-α); epidermal growth factor (EGF); precursor molecules; colitis; rat PMID:9301498

  5. Transforming growth factor-alpha precursors in human colon carcinoma cells.

    PubMed

    Asbert, M; Montaner, B; Pérez-Tomás, R

    2001-06-01

    Among the proteins of the epidermal growth factor family, transforming growth factor-alpha (TGF-alpha) may be an especially reliable indicator of metastasis or prognosis in human colorectal carcinomas. Moreover, anomalous forms of TGF-alpha have been detected in several tissues of cancer origin, suggesting a role of these forms in the development of the disease. This study was designed to identify the presence of TGF-alpha precursors in different colon cancer cell lines by mean of immunocytochemistry and western blotting techniques. Pro-TGF-alpha was detected in all cell lines tested. Staining for pro-TGF-alpha was observed in cytoplasm. Monoclonal antibody to TGF-alpha detected two bands of 20 and 21 kDa. Polyclonal antibody to pro-TGF-alpha revealed five bands ranging from 15 to 24 kDa. All these proteins were also detected in nonmalignant cells expressing a transfected rat pro-TGF-alpha gene. In conclusions, transformation in these human colon carcinoma cells is not due to the presence of anomalous forms of TGF-alpha precursors.

  6. Epidermal growth factor precursor in mouse lactating mammary gland alveolar cells

    SciTech Connect

    Brown, C.F.; Teng, C.T.; Pentecost, B.T.; DiAugustine, R.P. )

    1989-07-01

    Previous studies have demonstrated that high levels of epidermal growth factor (EGF) occur in human and rodent milk and that oral administration of this polypeptide stimulates rodent gastrointestinal development. It is not known whether EGF in milk originates from cells of the lactating mammary gland or is sequestered from an extramammary source. In the present study, prepro-EGF mRNA (approximately 4.7 kilobases) was detected in the CD-1 mouse mammary gland throughout the period of lactation; by comparison, negligible levels of this EGF transcript were found in the gland during pregnancy. Low levels of EGF immunoreactivity (4-5 ng/g wet wt tissue) were extracted from lactating (day 18) mammary glands with dilute acetic acid. Immunolocalization was evident with antisera to either EGF or two other regions of the EGF precursor in essentially all alveolar cells of the lactating gland. The most prominent staining with antiserum to EGF was observed along the luminal borders of cells; this pattern of cellular staining required proteolytic pretreatment of tissue sections. Western blot analyses of cell membranes isolated from the day 16 lactating mammary gland revealed an EGF-immunoreactive band at about 145K, which was equivalent in size to the EGF precursor found in mouse kidney cell membranes. Despite these findings, labeling of lactating mammary gland mince with L-(35S)methionine and cysteine for up to 4 h did not reveal any specific bands in immunoprecipitates. These cumulative findings suggest that the precursor form of EGF occurs in alveolar cells of lactating mammary gland and that this protein is translocated to the cell membrane.

  7. The Role of Nerve Growth Factor (NGF) and Its Precursor Forms in Oral Wound Healing.

    PubMed

    Schenck, Karl; Schreurs, Olav; Hayashi, Katsuhiko; Helgeland, Kristen

    2017-02-11

    Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75(NTR)) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds.

  8. The Role of Nerve Growth Factor (NGF) and Its Precursor Forms in Oral Wound Healing

    PubMed Central

    Schenck, Karl; Schreurs, Olav; Hayashi, Katsuhiko; Helgeland, Kristen

    2017-01-01

    Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds. PMID:28208669

  9. Cellular processing of the nerve growth factor precursor by the mammalian pro-protein convertases.

    PubMed Central

    Seidah, N G; Benjannet, S; Pareek, S; Savaria, D; Hamelin, J; Goulet, B; Laliberte, J; Lazure, C; Chrétien, M; Murphy, R A

    1996-01-01

    In order to define the enzymes responsible for the maturation of the precursor of nerve growth factor (proNGF), its biosynthesis and intracellular processing by the pro-protein convertases furin, PC1, PC2, PACE4, PC5 and the PC5 isoform PC5/6-B were analysed using the vaccinia virus expression system in cells containing a regulated and/or a constitutive secretory pathway. Results demonstrate that in both cell types furin, and to a lesser extent PACE4 and PC5/6-B, are the best candidate proNGF convertases. Furthermore, two processed NGF forms of 16.5 and 13.5 kDa were evident in constitutively secreting cell lines such as LoVo and BSC40 cells, whereas only the 13.5 kDa form was observed in AtT20 cells, which contain secretory granules. Both forms display the same N-terminal sequence as mature NGF, and were also produced following site-directed mutagenesis of the C-terminal Arg-Arg sequence of NGF into Ala-Ala, suggesting that the difference between them is not at the C-terminus. Co-expression of proNGF with furin and either chromogranin B or secretogranin II (but not chromogranin A) in BSC40 cells eliminated the 16.5 kDa form. Data also show that N-glycosylation of the pro-segment of proNGF and trimming of the oligosaccharide chains are necessary for the exit of this precursor from the endoplasmic reticulum and its eventual processing and secretion. Sulphate labelling experiments demonstrated that proNGF is processed into mature NGF following the arrival of the precursor in the trans-Golgi network. This comparative study shows that the three candidate mammalian subtilisin/kexin-like convertases identified process proNGF into NGF and that the nature of the final processed products is dependent on the intracellular environment. PMID:8615794

  10. Neural Growth Factor Stimulates Proliferation of Spinal Cord Derived-Neural Precursor/Stem Cells

    PubMed Central

    Han, Youngmin

    2016-01-01

    Objective Recently, regenerative therapies have been used in clinical trials (heart, cartilage, skeletal). We don't make use of these treatments to spinal cord injury (SCI) patients yet, but regenerative therapies are rising interest in recent study about SCI. Neural precursor/stem cell (NPSC) proliferation is a significant event in functional recovery of the central nervous system (CNS). However, brain NPSCs and spinal cord NPSCs (SC-NPSCs) have many differences including gene expression and proliferation. The purpose of this study was to investigate the influence of neural growth factor (NGF) on the proliferation of SC-NPSCs. Methods NPSCs (2×104) were suspended in 100 µL of neurobasal medium containing NGF-7S (Sigma-Aldrich) and cultured in a 96-well plate for 12 days. NPSC proliferation was analyzed five times for either concentration of NGF (0.02 and 2 ng/mL). Sixteen rats after SCI were randomly allocated into two groups. In group 1 (SCI-vehicle group, n=8), animals received 1.0 mL of the saline vehicle solution. In group 2 (SCI-NGF group, n=8), the animals received single doses of NGF (Sigma-Aldrich). A dose of 0.02 ng/mL of NGF or normal saline as a vehicle control was intra-thecally injected daily at 24 hour intervals for 7 days. For Immunohistochemistry analysis, rats were sacrificed after one week and the spinal cords were obtained. Results The elevation of cell proliferation with 0.02 ng/mL NGF was significant (p<0.05) but was not significant for 2 ng/mL NGF. The optical density was increased in the NGF 0.02 ng/mL group compared to the control group and NGF 2 ng/mL groups. The density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group (p<0.05). High power microscopy revealed that the density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group. Conclusion SC-NPSC proliferation is an important pathway in the functional recovery of SCI. NGF enhances SC-NPSC proliferation in vitro and in

  11. Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade.

    PubMed

    Bruno, Martin A; Cuello, A Claudio

    2006-04-25

    In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation and degradation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons of the cerebral cortex and released upon neuronal stimulation. We also provide evidence that this mechanism operates in in vivo conditions, as the CNS application of inhibitors of converting and degrading enzymes lead to dramatic alterations in the tissue levels of either precursor NGF or mature NGF. Pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer's disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain.

  12. Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade

    PubMed Central

    Bruno, Martin A.; Cuello, A. Claudio

    2006-01-01

    In this report, we provide direct demonstration that the neurotrophin nerve growth factor (NGF) is released in the extracellular space in an activity-dependent manner in its precursor form (proNGF) and that it is in this compartment that its maturation and degradation takes place because of the coordinated release and the action of proenzymes and enzyme regulators. This converting protease cascade and its endogenous regulators (including tissue plasminogen activator, plasminogen, neuroserpin, precursor matrix metalloproteinase 9, and tissue inhibitor metalloproteinase 1) are colocalized in neurons of the cerebral cortex and released upon neuronal stimulation. We also provide evidence that this mechanism operates in in vivo conditions, as the CNS application of inhibitors of converting and degrading enzymes lead to dramatic alterations in the tissue levels of either precursor NGF or mature NGF. Pathological alterations of this cascade in the CNS might cause or contribute to a lack of proper neuronal trophic support in conditions such as cerebral ischemia, seizure and Alzheimer’s disease or, conversely, to excessive local production of neurotrophins as reported in inflammatory arthritis pain. PMID:16618925

  13. Insulin-Like Growth Factor Receptor Signaling is Necessary for Epidermal Growth Factor Mediated Proliferation of SVZ Neural Precursors in vitro Following Neonatal Hypoxia–Ischemia

    PubMed Central

    Alagappan, Dhivyaa; Ziegler, Amber N.; Chidambaram, Shravanthi; Min, Jungsoo; Wood, Teresa L.; Levison, Steven W.

    2014-01-01

    In this study, we assessed the importance of insulin-like growth factor (IGF) and epidermal growth factor (EGF) receptor co-signaling for rat neural precursor (NP) cell proliferation and self-renewal in the context of a developmental brain injury that is associated with cerebral palsy. Consistent with previous studies, we found that there is an increase in the in vitro growth of subventricular zone NPs isolated acutely after cerebral hypoxia–ischemia; however, when cultured in medium that is insufficient to stimulate the IGF type 1 receptor, neurosphere formation and the proliferative capacity of those NPs was severely curtailed. This reduced growth capacity could not be attributed simply to failure to survive. The growth and self-renewal of the NPs could be restored by addition of both IGF-I and IGF-II. Since the size of the neurosphere is predominantly due to cell proliferation we hypothesized that the IGFs were regulating progression through the cell cycle. Analyses of cell cycle progression revealed that IGF-1R activation together with EGFR co-signaling decreased the percentage of cells in G1 and enhanced cell progression into S and G2. This was accompanied by increases in expression of cyclin D1, phosphorylated histone 3, and phosphorylated Rb. Based on these data, we conclude that coordinate signaling between the EGF receptor and the IGF type 1 receptor is necessary for the normal proliferation of NPs as well as for their reactive expansion after injury. These data indicate that manipulations that maintain or amplify IGF signaling in the brain during recovery from developmental brain injuries will enhance the production of new brain cells to improve neurological function in children who are at risk for developing cerebral palsy. PMID:24904523

  14. The nerve growth factor administrated as eye drops activates mature and precursor cells in subventricular zone of adult rats.

    PubMed

    Tirassa, Paola

    2011-06-01

    The possibility to take advantage from the nerve growth factor (NGF) ability to induce recovery of damaged tissue has been largely explored in animal models and humans. Recently, the successful use of the ocular administration of NGF in ophthalmology, and the evidences that from the eyes NGF can access to the brain have stimulated new fields of research and open further perspectives to the clinical application of this neurotrophin. In our previous studies we have demonstrated the efficacy of NGF eye drop treatment to improved behavioural deficits and recover structural and biochemical alterations occurring follow brain lesion in animals. Since NGF exerts neuroreparative effects in brain by acting on mature neurons and neuronal precursors localised in germinal subventricular zone (SVZ), the present study has been aimed to evaluate the effects of NGF eye drop administration on the expression of the mitotic marker Ki67 in brain of adult rats. We found that a single ocular administration (10 μl) of 200 μg/mL NGF solution is sufficient to enhance the distribution of Ki67 positive cells also expressing p75 neurotrophin receptors in the proliferating layer of the SVZ. In addition, NGF treatment induces an increase of levels of brain derived neurotrophic factor (BDNF) in forebrain. This data further supports the efficacy of ocular applied NGF to affect brain activities and suggests that NGF also by inducing local factors, including BDNF, can activate the machinery regulating the proliferation and maturation of neuronal precursor in brain.

  15. Growth hormone (GH) is a survival rather than a proliferative factor for embryonic striatal neural precursor cells.

    PubMed

    Regalado-Santiago, Citlalli; López-Meraz, María Leonor; Santiago-García, Juan; Fernández-Pomares, Cynthia; Juárez-Aguilar, Enrique

    2013-10-01

    A possible role of GH during central nervous system (CNS) development has been suggested by the presence of this hormone and its receptor in brain areas before its production by the pituitary gland. Although several effects have been reported for GH, the specific role of this hormone during CNS development remains unclear. Here, we examined the effect of GH on proliferation, survival and neurosphere formation in primary cultures of striatal tissue from 14-day-old (E14) mouse embryos. GH receptor gene expression was confirmed by RT-PCR. Primary cultures of embryonic striatal cells were treated with different doses of GH in serum free media, then the number of neurospheres was determined. To examine the GH effect on proliferation and survival of the striatal primary cultures, bromodeoxyuridine (BrdU) and TUNEL immunoreactivity was conducted. In the presence of the epidermal growth factor (EGF), GH increased the formation of neurospheres, with a maximal response at 10 ng/ml, higher doses were inhibitory. In absence of EGF, GH failed to stimulate neurosphere formation. Proliferation rate in the primary striatal cultures was inhibited by 24 or 48 h incubation with GH. However, in the absence of EGF, GH increased BrdU incorporation. GH treatment decreases the rate of apoptosis of nestin and GFAP positive cells in the primary striatal cultures, enhancing neurosphere formation. Our in vitro data demonstrate that GH plays a survival role on the original population of embryonic striatal cells, improving Neural Precursor Cells (NPCs) expansion. We suggest that this GH action could be predominant during striatal neurodevelopment. © 2013.

  16. Structural characterization of the human platelet-derived growth factor A-chain cDNA and gene: Alternative exon usage predicts two different precursor proteins

    SciTech Connect

    Rorsman, F.; Bywater, M.; Knott, T.J.; Scott, J.; Betsholtz, C.

    1988-02-01

    The human platelet-derived growth factor (PDGF) A-chain locus was characterized by restriction endonuclease analysis, and the nucleotide sequence of its exons was determined. Seven exons were identified, spanning approximately 22 kilobase pairs of genomic DNA. Alternative exon usage, identified by cDNA cloning, occurs in a human glioblastoma cell line and may give rise to two types of A-chain precursors with different C termini. The exon-intron arrangement was similar to that of the PDGF B-chain/sis locus and seemed to divide the precursor proteins into functional domains. Southern blot analysis of genomic DNA showed that a single PDGF A-chain gene was present in the human genome.

  17. Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor.

    PubMed

    Arsenijevic, Y; Weiss, S

    1998-03-15

    Insulin-like growth factor-I (IGF-I) has been reported previously to promote the proliferation, survival, and maturation of sympathetic neuroblasts, the genesis of retinal neurons, and the survival of CNS projection and motor neurons. Here we asked whether IGF-I could promote the in vitro differentiation of postmitotic mammalian CNS neuronal precursors derived from multipotent epidermal growth factor (EGF)-responsive stem cells. In the absence of IGF-I, virtually no neurons were present in cultured stem cell progeny, whereas IGF-I increased neuron number by eight- to 40-fold. Brief exposures (2 hr) to IGF-I were sufficient to allow for neuronal differentiation without affecting proliferation or survival. IGF-I actions could be mimicked by insulin and IGF-II at concentrations that correspond to the pharmacology of the IGF-I receptor, the latter for which the mRNA was detected in undifferentiated stem cell progeny. Although ineffectual alone at low concentrations (10 nM) that would activate its own receptor, insulin was able to potentiate the actions of IGF-I by acting on mitotically active neural precursors. When neuronal precursor differentiation by IGF-I was examined in relation to brain-derived neurotrophic factor (BDNF), two important observations were made: (1) BDNF could potentiate the differentiating actions of IGF-I plus insulin, and (2) BDNF could act on a separate population of precursors that did not require IGF-I plus insulin for differentiation. Taken together, these results suggest that IGF-I and BDNF may act together or sequentially to promote neuronal precursor differentiation.

  18. Hydroxylation of aspartic acid in domains homologous to the epidermal growth factor precursor is catalyzed by a 2-oxoglutarate-dependent dioxygenase.

    PubMed Central

    Stenflo, J; Holme, E; Lindstedt, S; Chandramouli, N; Huang, L H; Tam, J P; Merrifield, R B

    1989-01-01

    3-Hydroxyaspartic acid and 3-hydroxyasparagine are two rare amino acids that are present in domains homologous to the epidermal growth factor precursor in vitamin K-dependent plasma proteins as well as in proteins that do not require vitamin K for normal biosynthesis. They are formed by posttranslational hydroxylation of aspartic acid and asparagine, respectively. The first epidermal growth factor-like domain in factor IX (residues 45-87) was synthesized with aspartic acid in position 64, replacing 3-hydroxyaspartic acid. It was used as substrate in a hydroxylase assay with rat liver microsomes as the source of enzyme and reaction conditions that satisfy the requirements of 2-oxoglutarate-dependent dioxygenases. The synthetic peptide stimulated the 2-oxoglutarate decarboxylation in contrast to synthetic, modified epidermal growth factor (Met-21 and His-22 deleted and Glu-24 replaced by Asp) and synthetic peptides corresponding to residues 60-71 in human factor IX. This indicates that the hydroxylase is a 2-oxoglutarate-dependent dioxygenase with a selective substrate requirement. Images PMID:2492106

  19. Basic fibroblast growth factor (bFGF) acts intracellularly to cause the transdifferentiation of avian neural crest-derived Schwann cell precursors into melanocytes.

    PubMed

    Sherman, L; Stocker, K M; Morrison, R; Ciment, G

    1993-08-01

    We previously found that cultured neural crest-derived cells from embryonic quail peripheral nerves, which consist mostly of Schwann cell precursors, gave rise to melanocytes following treatment with basic fibroblast growth factor (bFGF) or 12-O-tetradecanoyl phorbol-13-acetate (TPA). Here, we show that antisense deoxyoligonucleotides targeted against two regions of the bFGF mRNA transcript blocked this TPA-induced transdifferentiation of Schwann cell precursors. Neither sense nor scrambled antisense control oligonucleotides had any effect in this regard. TPA increased bFGF protein expression in cell lysates but not in conditioned media from these cultures, and this expression was localized to the nucleus and cytoplasm. Furthermore, bFGF-neutralizing antibodies and inositol-hexakisphosphate (InsP6) both inhibited pigmentation caused by exogenous bFGF, but had no affect on TPA-induced melanogenesis, suggesting that bFGF is not released by these cells. These data indicate that bFGF is necessary for the TPA-induced transdifferentiation of Schwann cell precursors into melanocytes and that bFGF acts via an intracrine mechanism.

  20. Expression of nerve growth factor (NGF) isoforms in the rat uterus during pregnancy: accumulation of precursor proNGF.

    PubMed

    Lobos, Edgar; Gebhardt, Claudia; Kluge, Annett; Spanel-Borowski, Katharina

    2005-04-01

    The mechanisms that promote the transient degenerative changes in the uterus innervation during pregnancy remain incompletely understood. Signaling by the nerve growth factor (NGF)-beta is important for maintaining the density of peripheral sympathetic innervation. Here, we analyzed the spatial and temporal expression of NGF isoforms in the rat uterus using RT-PCR, immunoblot analysis, and immunohistochemistry during pregnancy (d 7, 14, and 21), and postpartum (d 1, 8, and 22). Western blot analysis using antibodies to mature NGF-beta and to proNGF domain demonstrated a significant decrease in mature NGF-beta at gestational d 14 and 21 (term pregnancy) and 1 d postpartum, which paralleled a remarkable accumulation of the 26-28-, 32-, and 60-kDa proNGF forms. There were diminished ratios of mature NGF-beta to proNGF independent of uterus growth on the same gestational days. Immunohistochemistry revealed a progressive NGF-beta decline throughout pregnancy in the myometrium and a near absence at term pregnancy, which contrasted with increased NGF immunostaining in the intermyometrial connective tissue layers. More importantly, proNGF-specific antibodies identified the increased NGF immunoreactivity in the intermyometrial layers at term pregnancy as proNGF and not mature NGF-beta. Alterations in the processing of NGF and accumulation of proNGF in the intermyometrial layers, where axonal degeneration occurs, may contribute significantly to the pregnancy-related uterine denervation and to the control of myometrial activity.

  1. Skeletal myofiber vascular endothelial growth factor is required for the exercise training-induced increase in dentate gyrus neuronal precursor cells.

    PubMed

    Rich, Benjamin; Scadeng, Miriam; Yamaguchi, Masahiro; Wagner, Peter D; Breen, Ellen C

    2017-09-01

    Peripheral vascular endothelial growth factor (VEGF) is necessary for exercise to stimulate hippocampal neurogenesis. Here we report that skeletal myofiber VEGF directly or indirectly regulates exercise-signalled proliferation of neuronal precursor cells. Our results found skeletal myofiber VEGF to be necessary for maintaining blood flow through hippocampal regions independent of exercise training state. This study demonstrates that skeletal myofiber VEGF is required for the hippocampal VEGF response to acute exercise. These results help to establish the mechanisms by which exercise, through skeletal myofiber VEGF, affects the hippocampus. Exercise signals neurogenesis in the dentate gyrus of the hippocampus. This phenomenon requires vascular endothelial growth factor (VEGF) originating from outside the blood-brain barrier, but no cellular source has been identified. Thus, we hypothesized that VEGF produced by skeletal myofibers plays a role in regulating hippocampal neuronal precursor cell proliferation following exercise training. This was tested in adult conditional skeletal myofiber-specific VEGF gene-ablated mice (VEGF(HSA-/-) ) by providing VEGF(HSA-/-) and non-ablated (VEGF(f/f) ) littermates with running wheels for 14 days. Following this training period, hippocampal cerebral blood flow (CBF) was measured by functional magnetic resonance imaging (fMRI), and neuronal precursor cells (BrdU+/Nestin+) were detected by immunofluorescence. The VEGF(f/f) trained group showed improvements in both speed and endurance capacity in acute treadmill running tests (P < 0.05). The VEGF(HSA-/-) group did not. The number of proliferating neuronal precursor cells was increased with training in VEGF(f/f) (P < 0.05) but not in VEGF(HSA-/-) mice. Endothelial cell (CD31+) number did not change in this region with exercise training or skeletal myofiber VEGF gene deletion. However, resting blood flow through the hippocampal region was lower in VEGF(HSA-/-) mice, both untrained

  2. Ocular nerve growth factor administration counteracts the impairment of neural precursor cell viability and differentiation in the brain subventricular area of rats with streptozotocin-induced diabetes.

    PubMed

    Tirassa, Paola; Maccarone, Mattia; Carito, Valentina; De Nicolò, Sara; Fiore, Marco

    2015-05-01

    The ocular administration of nerve growth factor (NGF) as eye drops (oNGF) has been shown to exert protective effects in forebrain-injured animal models, including adult diabetes induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). This type 1 diabetes model was used in this study to investigate whether oNGF might extend its actions on neuronal precursors localised in the subventricular zone (SVZ). NGF or saline was administrated as eye drops twice daily for 2 weeks in rats with STZ-induced diabetes and healthy control rats. The expression of mature and precursor NGF and the NGF receptors, tropomyosin-related kinase A and neurotrophin receptor p75, and the levels of DNA fragmentation were analysed by ELISA and western blotting. Incorporation of bromodeoxyuridine was used to trace newly formed cells. Nestin, polysialylated neuronal cell adhesion molecule (PSA-NCAM), doublecortin (DCX) and glial fibrillary acidic protein antibodies were used to identify the SVZ cells by confocal microscopy. It was found that oNGF counteracts the STZ-induced cell death and the alteration of mature/pro-NGF expression in the SVZ. It also affects the survival and differentiation of SVZ progenitors. In particular, oNGF counteracts the reduction in the number of cells expressing PSA-NCAM/DCX (neuroblast type A cells) and the related reductions in the number and distribution of nestin/DCX-positive cells (C-type cells), or glia-committed cells (type B cells), observed in the SVZ of diabetic rats. These findings show that oNGF treatment counteracts the effect of type 1 diabetes on neuronal precursors in the SVZ, and further support the neuroprotective and reparative role of oNGF in the brain.

  3. Nerve Growth Factor Increases mRNA Levels for the Prion Protein and the β -amyloid Protein Precursor in Developing Hamster Brain

    NASA Astrophysics Data System (ADS)

    Mobley, William C.; Neve, Rachael L.; Prusiner, Stanley B.; McKinley, Michael P.

    1988-12-01

    Deposition of amyloid filaments serves as a pathologic hallmark for some neurodegenerative disorders. The prion protein (PrP) is found in amyloid of animals with scrapie and humans with Creutzfeldt-Jakob disease; the β protein is present in amyloid deposits in Alzheimer disease and Down syndrome patients. These two proteins are derived from precursors that in the brain are expressed primarily in neurons and are membrane bound. We found that gene expression for PrP and the β -protein precursor (β -PP) is regulated in developing hamster brain. Specific brain regions showed distinct patterns of ontogenesis for PrP and β -PP mRNAs. The increases in PrP and β -PP mRNAs in developing basal forebrain coincided with an increase in choline acetyltransferase activity, raising the possibility that these markers might be coordinately controlled in cholinergic neurons and regulated by nerve growth factor (NGF). Injections of NGF into the brains of neonatal hamsters increased both PrP and β -PP mRNA levels. Increased PrP and β -PP mRNA levels induced by NGF were confined to regions that contain NGF-responsive cholinergic neurons and were accompanied by elevations in choline acetyltransferase. It remains to be established whether or not exogenous NGF acts to increase PrP and β -PP gene expression selectively in forebrain cholinergic neurons in the developing hamster and endogenous NGF regulates expression of these genes.

  4. Evolution of insulin-like growth factor I (IGF-I): structure and expression of an IGF-I precursor from Xenopus laevis.

    PubMed

    Kajimoto, Y; Rotwein, P

    1990-02-01

    By means of a cloning strategy employing the polymerase chain reaction, we have isolated and characterized cDNAs for Xenopus laevis insulin-like growth factor I (IGF-I). These cDNAs encode a primary IGF-I translation product of 153 residues that demonstrates considerable amino acid sequence similarity with IGF-IA peptides from other species. Fifty-seven of 70 residues of the mature protein are identical among human, rat, chicken, and Xenopus IGF-I, while less amino acid conservation is found at the COOH-terminus (25/35 identities) or at the NH2-terminus (24/48 identities) of the precursor protein. Despite the lower degree of structural similarity at the NH2-terminus, in vitro studies of IGF-I biosynthesis and proteolytic processing support a conserved function for the atypically long 48 residue NH2-terminal signal sequence in directing the nascent IGF-I peptide through the secretory pathway. The 5'-untranslated region of Xenopus IGF-I mRNA matches the human, rat, and chicken sequences in greater than 90% of 279 nucleotides. IGF-I mRNAs from all four species encode a conserved upstream open reading frame of 14 amino acids starting 240-250 nucleotides 5' to the translation start site, suggesting a possible role for this region in modulating IGF-I gene expression. The X. laevis IGF-I gene is transcribed and processed into three mRNAs of 1.6, 2.1, and 3.0 kilobases in liver, and IGF-I mRNAs can be detected in liver, lung, heart, kidney, and peritoneal fat of adult animals. These studies demonstrate that both the IGF-I protein precursor and potential regulatory regions of IGF-I mRNA have been conserved during vertebrate evolution, and indicate that like several other polypeptide growth factors, IGF-I may be of fundamental importance in regulating specific aspects of growth and development in all vertebrates.

  5. Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells*

    PubMed Central

    Pituch, Katarzyna C.; Moyano, Ana L.; Lopez-Rosas, Aurora; Marottoli, Felecia M.; Li, Guannan; Hu, Chenqi; van Breemen, Richard; Månsson, Jan E.; Givogri, Maria I.

    2015-01-01

    The membrane-bound receptor for platelet-derived growth factor A (PDGFRα) is crucial for controlling the production of oligodendrocytes (OLs) for myelination, but regulation of its activity during OL differentiation is largely unknown. We have examined the effect of increased sulfated content of galactosylceramides (sulfatides) on the regulation of PDGFRα in multipotential neural precursors (NPs) that are deficient in arylsulfatase A (ASA) activity. This enzyme is responsible for the lysosomal hydrolysis of sulfatides. We show that sulfatide accumulation significantly impacts the formation of OLs via deregulation of PDGFRα function. PDGFRα is less associated with detergent-resistant membranes in ASA-deficient cells and showed a significant decrease in AKT phosphorylation. Rescue experiments with ASA showed a normalization of the ratio of long versus short sulfatides, restored PDGFRα levels, corrected its localization to detergent-resistant membranes, increased AKT phosphorylation, and normalized the production of OLs in ASA-deficient NPs. Moreover, our studies identified a novel mechanism that regulates the secretion of PDGFRα in NPs, in glial cells, and in the brain cortex via exosomal shedding. Our study provides a first step in understanding the role of sulfatides in regulating PDGFRα levels in OLs and its impact in myelination. PMID:25605750

  6. Insulin-like growth factor-1 (IGF-1)-induced processing of amyloid-beta precursor protein (APP) and APP-like protein 2 is mediated by different metalloproteinases.

    PubMed

    Jacobsen, Kristin T; Adlerz, Linda; Multhaup, Gerd; Iverfeldt, Kerstin

    2010-04-02

    alpha-Secretase cleavage of the amyloid precursor protein (APP) is of great interest because it prevents the formation of the Alzheimer-linked amyloid-beta peptide. APP belongs to a conserved gene family including the two paralogues APP-like protein (APLP) 1 and 2. Insulin-like growth factor-1 (IGF-1) stimulates the shedding of all three proteins. IGF-1-induced shedding of both APP and APLP1 is dependent on phosphatidylinositol 3-kinase (PI3-K), whereas APLP2 shedding is independent of this signaling pathway. Here, we used human neuroblastoma SH-SY5Y cells to investigate the involvement of protein kinase C (PKC) in the proteolytic processing of endogenously expressed members of the APP family. Processing was induced by IGF-1 or retinoic acid, another known stimulator of APP alpha-secretase shedding. Our results show that stimulation of APP and APLP1 processing involves multiple signaling pathways, whereas APLP2 processing is mainly dependent on PKC. Next, we wanted to investigate whether the difference in the regulation of APLP2 shedding compared with APP shedding could be due to involvement of different processing enzymes. We focused on the two major alpha-secretase candidates ADAM10 and TACE, which both are members of the ADAM (a disintegrin and metalloprotease) family. Shedding was analyzed in the presence of the ADAM10 inhibitor GI254023X, or after transfection with small interfering RNAs targeted against TACE. The results clearly demonstrate that different alpha-secretases are involved in IGF-1-induced processing. APP is mainly cleaved by ADAM10, whereas APLP2 processing is mediated by TACE. Finally, we also show that IGF-1 induces PKC-dependent phosphorylation of TACE.

  7. Insulin-like Growth Factor-1 (IGF-1)-induced Processing of Amyloid-β Precursor Protein (APP) and APP-like Protein 2 Is Mediated by Different Metalloproteinases*

    PubMed Central

    Jacobsen, Kristin T.; Adlerz, Linda; Multhaup, Gerd; Iverfeldt, Kerstin

    2010-01-01

    α-Secretase cleavage of the amyloid precursor protein (APP) is of great interest because it prevents the formation of the Alzheimer-linked amyloid-β peptide. APP belongs to a conserved gene family including the two paralogues APP-like protein (APLP) 1 and 2. Insulin-like growth factor-1 (IGF-1) stimulates the shedding of all three proteins. IGF-1-induced shedding of both APP and APLP1 is dependent on phosphatidylinositol 3-kinase (PI3-K), whereas APLP2 shedding is independent of this signaling pathway. Here, we used human neuroblastoma SH-SY5Y cells to investigate the involvement of protein kinase C (PKC) in the proteolytic processing of endogenously expressed members of the APP family. Processing was induced by IGF-1 or retinoic acid, another known stimulator of APP α-secretase shedding. Our results show that stimulation of APP and APLP1 processing involves multiple signaling pathways, whereas APLP2 processing is mainly dependent on PKC. Next, we wanted to investigate whether the difference in the regulation of APLP2 shedding compared with APP shedding could be due to involvement of different processing enzymes. We focused on the two major α-secretase candidates ADAM10 and TACE, which both are members of the ADAM (a disintegrin and metalloprotease) family. Shedding was analyzed in the presence of the ADAM10 inhibitor GI254023X, or after transfection with small interfering RNAs targeted against TACE. The results clearly demonstrate that different α-secretases are involved in IGF-1-induced processing. APP is mainly cleaved by ADAM10, whereas APLP2 processing is mediated by TACE. Finally, we also show that IGF-1 induces PKC-dependent phosphorylation of TACE. PMID:20139073

  8. Neutralizing IL-6 reduces heart injury by decreasing nerve growth factor precursor in the heart and hypothalamus during rat cardiopulmonary bypass.

    PubMed

    Cheng, Chi; Xu, Jun-Mei; Yu, Tian

    2017-06-01

    To investigate whether the expression of nerve growth factor precursor (proNGF) changes during cardiopulmonary bypass (CPB) and whether neutralizing interleukin-6 (IL-6) during CPB has cardiac benefits. Thirty patients undergoing CPB were recruited and their serum proNGF and troponin-I (TNI) were detected. In addition, rats were divided into three groups: CPB group, CPB with cardiac ischemia-reperfusion (IR) group, and a control group. The pre-CPB standard deviation of N-N intervals (SDNN) and post-CPB SDNN were compared. At the end of CPB, nerve peptide Y (NPY), acetylcholinesterase, cell apoptosis, and proNGF protein expression were measured in the heart and hypothalamus. Another rat cohort undergoing CPB was divided into two groups: an anti-IL-6 group with IL-6 antibody and a control group with phosphate buffer solution. At the end of CPB, serum hs-troponin-T and cardiac caspases 3 and 9 were detected. NPY and proNGF in the heart and hypothalamus were detected. In patients, serum proNGF increased during CPB, and the concentration was positively correlated with TNI. In rats, cardiac autonomic nervous function was disturbed during CPB. More apoptotic cells and higher levels of proNGF were found in the heart and hypothalamus in the CPB groups than in the control groups. Neutralizing IL-6 was beneficial to lower cardiac injury by decreasing proNGF and apoptosis. CPB induced changes in proNGF in the heart and hypothalamus. Suppressing inflammation attenuated myocardial apoptosis and autonomic nerve function disturbance in CPB rats, likely due in part to regulation of proNGF in the heart and hypothalamus. Copyright © 2017. Published by Elsevier Inc.

  9. Accelerated degradation of 160 kDa epidermal growth factor (EGF) receptor precursor by the tyrosine kinase inhibitor herbimycin A in the endoplasmic reticulum of A431 human epidermoid carcinoma cells.

    PubMed Central

    Murakami, Y; Mizuno, S; Uehara, Y

    1994-01-01

    The effect of herbimycin A on the biosynthesis of epidermal growth factor (EGF) receptor was examined in human epidermoid carcinoma A431 cells. Cells were pulse-labelled with [35S]methionine, and EGF receptor biosynthesis was quantified by immunoprecipitation using a monoclonal anti-(EGF receptor) antibody. In the presence of herbimycin A, an immature 160 kDa EGF receptor precursor accumulated in 1 h and disappeared completely in 4 h. Pulse-labelled 160 kDa receptor precursor in the absence of herbimycin A, however, was converted normally into a 170 kDa one by chase with herbimycin A. Herbimycin A affected neither the synthesis of the secreted form of EGF receptor devoid of cytoplasmic domain, nor that of the transferrin receptor in A431 cells. The herbimycin A-induced degradation of 160 kDa EGF receptor precursor was not inhibited by an inhibitor of lysosomal enzymes, NH4Cl. Endoglycosidase H digestion of the 160 kDa precursor converted it into the deglycosylated 130 kDa precursor peptide. These results suggested that herbimycin A selectively acted on the EGF receptor precursor during the synthesis of the 160 kDa form, probably on the cytoplasmic domain, to form an aberrant molecule which was subjected to rapid degradation in the endoplasmic reticulum. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8037692

  10. A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor

    SciTech Connect

    Mills, Philippe; Lafreniere, Jean-Francois; Benabdallah, Basma Fattouma; El Fahime, El Mostafa; Tremblay, Jacques-P. . E-mail: Jacques-P.Tremblay@crchul.ulaval.ca

    2007-02-01

    Duchenne muscular dystrophy (DMD) is an inherited disease that leads to progressive muscle wasting. Myogenic precursor cell transplantation is an approach that can introduce the normal dystrophin gene in the muscle fibers of the patients. Unfortunately, these myogenic precursor cells do not migrate well in the muscle and thus many injections have to be done to enable a good graft success. Recent reports have shown that there is extensive splicing of the IGF-1 gene in muscles. The MGF isoform contains a C-terminal 24 amino acids peptide in the E domain (MGF-Ct24E) that has intrinsic properties. It can promote the proliferation while delaying the differentiation of C{sub 2}C{sub 12} cells. Here, we demonstrated that this synthetic peptide is a motogenic factor for human precursor myogenic cells in vitro and in vivo. Indeed, MGF-Ct24E peptide can modulate members of the fibrinolytic and metalloproteinase systems, which are implicated in the migration of myogenic cells. MGF-Ct24E peptide enhances the expression of u-PA, u-PAR and MMP-7 while reducing PAI-1 activity. Moreover, it has no effect on the gelatinases MMP-2 and -9. Those combined effects can favour cell migration. Finally, we present some results suggesting that the MGF-Ct24E peptide induces these cell responses through a mechanism that does not involve the IGF-1 receptor. Thus, this MGF-Ct24E peptide has a new pro-migratory activity on human myogenic precursor cells that may be helpful in the treatment of DMD. Those results reinforce the possibility that the IGF-1Ec isoform may produce an E domain peptide that can act as a cytokine.

  11. Transition Metal Dichalcogenide Growth via Close Proximity Precursor Supply

    PubMed Central

    O'Brien, Maria; McEvoy, Niall; Hallam, Toby; Kim, Hye-Young; Berner, Nina C.; Hanlon, Damien; Lee, Kangho; Coleman, Jonathan N.; Duesberg, Georg S.

    2014-01-01

    Reliable chemical vapour deposition (CVD) of transition metal dichalcogenides (TMDs) is currently a highly pressing research field, as numerous potential applications rely on the production of high quality films on a macroscopic scale. Here, we show the use of liquid phase exfoliated nanosheets and patterned sputter deposited layers as solid precursors for chemical vapour deposition. TMD monolayers were realized using a close proximity precursor supply in a CVD microreactor setup. A model describing the growth mechanism, which is capable of producing TMD monolayers on arbitrary substrates, is presented. Raman spectroscopy, photoluminescence, X-ray photoelectron spectroscopy, atomic force microscopy, transmission electron microscopy, scanning electron microscopy and electrical transport measurements reveal the high quality of the TMD samples produced. Furthermore, through patterning of the precursor supply, we achieve patterned growth of monolayer TMDs in defined locations, which could be adapted for the facile production of electronic device components. PMID:25487822

  12. Solvothermal Molecular Precursor Routes to Semiconductor Film and Crystal Growth

    NASA Astrophysics Data System (ADS)

    Gillan, Edward G.

    2002-08-01

    This research project explored the utility of molecular precursor decomposition in superheated non-aqueous solvents directed towards semiconductor crystal growth. Reactions were run in toluene, THF, and under solvent free conditions. An in situ precursor synthesis and decomposition resulted in GaN nanoparticles from simple starting materials (GaCl(3) and NaN(3)). Particle sizes range from about 10 to hundreds of nanometers. Upon annealing to 1000 degrees C, the poorly crystalline products ordered into crystalline hexagonal GaN and luminescence. The conversion of synthesized organometallic dimeric gallium amino precursors to GaN was less successful; however they showed some utility in vapor phase film growth. Silver and silver sulfide nanoparticles were also produced in a solvothermal system via silver azide decomposition producing particles in the 100 mn to micron size regime.

  13. Meat flavor precursors and factors influencing flavor precursors--A systematic review.

    PubMed

    Khan, Muhammad Issa; Jo, Cheorun; Tariq, Muhammad Rizwan

    2015-12-01

    Flavor is the sensory impression sensed by taste and smell buds and is a leading factor determining the meat quality and purchasing decision of the consumer. Meat flavor is characteristic of volatiles produced as a result of reactions of non-volatile components that are induced thermally. The water soluble compounds having low molecular weight and meat lipids are important precursors of cooked meat flavor. The Maillard reaction, lipid oxidation, and vitamin degradation are leading reactions during cooking which develop meat flavor from uncooked meat with little aroma and bloody taste. The pre-slaughter and postmortem factors like animal breed, sex, age, feed, aging and cooking conditions contribute to flavor development of cooked meat. The objective of this review is to highlight the flavor chemistry, meat flavor precursors and factors affecting meat flavor precursors.

  14. Proinsulin: From Hormonal Precursor to Neuroprotective Factor

    PubMed Central

    de la Rosa, Enrique J.; de Pablo, Flora

    2011-01-01

    In the last decade, non-canonical functions have been described for several molecules with hormone-like activities in different stages of vertebrate development. Since its purification in the 1960s, proinsulin has been one of the best described hormonal precursors, though it has been overwhelmingly studied in the context of insulin, the mature protein secreted by the pancreas. Beginning with our discovery of the presence and precise regulation of proinsulin mRNA in early neurulation and neurogenesis, we uncovered a role for proinsulin in cell survival in the developing nervous system. We subsequently demonstrated the ability of proinsulin to prevent pathological cell death and delay photoreceptor degeneration in a mouse model of retinitis pigmentosa. In this review, we focus on the evolution of proinsulin/insulin, beginning with insulin-like peptides expressed in mainly the neurosecretory cells of some invertebrates. We summarize findings related to the regulation of proinsulin expression during development and discuss the possible effects of proinsulin in neural cells or tissue, and its potential as a neuroprotective molecule. PMID:21949502

  15. Factors affecting bone growth.

    PubMed

    Gkiatas, Ioannis; Lykissas, Marios; Kostas-Agnantis, Ioannis; Korompilias, Anastasios; Batistatou, Anna; Beris, Alexandros

    2015-02-01

    Bone growth and development are products of the complex interactions of genetic and environmental factors. Longitudinal bone growth depends on the growth plate. The growth plate has 5 different zones-each with a different functional role-and is the final target organ for longitudinal growth. Bone length is affected by several systemic, local, and mechanical factors. All these regulation systems control the final length of bones in a complicated way. Despite its significance to bone stability, bone growth in width has not been studied as extensively as longitudinal bone growth. Bone growth in width is also controlled by genetic factors, but mechanical loading regulates periosteal apposition. In this article, we review the most recent data regarding bone growth from the embryonic age and analyze the factors that control bone growth. An understanding of this complex system is important in identifying metabolic and developmental bone diseases and fracture risk.

  16. Catalytic growth of boron nitride nanotubes using gas precursors

    NASA Astrophysics Data System (ADS)

    Guo, L.; Singh, R. N.

    2009-01-01

    Hexagonal boron nitride nanotubes (BNNTs) are synthesized at low substrate temperatures on nickel (Ni)- or cobalt (Co)-coated oxidized Si (1 1 1) wafers in a microwave plasma-enhanced chemical vapor deposition (MPCVD) system by decomposition and reaction of gas mixtures consisting of B 2H 6-NH 3-H 2. The growth of one-dimensional (1-D) BN nanostructures is obtained at an optimum combination of catalyst film thickness, substrate temperature, and precursor gas flow rates. The morphology, composition and structural properties of the BNNTs are analyzed by scanning electron microscope (SEM), transmission electron microscope (TEM), energy dispersive X-ray spectroscopy (EDX), selected area diffraction (SAD), and Raman spectroscopy. The patterned growth of BNNTs is also demonstrated.

  17. Oligodendrocyte Precursor Cells Synthesize Neuromodulatory Factors

    PubMed Central

    Sakry, Dominik; Yigit, Hatice; Dimou, Leda; Trotter, Jacqueline

    2015-01-01

    NG2 protein-expressing oligodendrocyte progenitor cells (OPC) are a persisting and major glial cell population in the adult mammalian brain. Direct synaptic innervation of OPC by neurons throughout the brain together with their ability to sense neuronal network activity raises the question of additional physiological roles of OPC, supplementary to generating myelinating oligodendrocytes. In this study we investigated whether OPC express neuromodulatory factors, typically synthesized by other CNS cell types. Our results show that OPC express two well-characterized neuromodulatory proteins: Prostaglandin D2 synthase (PTGDS) and neuronal Pentraxin 2 (Nptx2/Narp). Expression levels of the enzyme PTGDS are influenced in cultured OPC by the NG2 intracellular region which can be released by cleavage and localizes to glial nuclei upon transfection. Furthermore PTGDS mRNA levels are reduced in OPC from NG2-KO mouse brain compared to WT cells after isolation by cell sorting and direct analysis. These results show that OPC can contribute to the expression of these proteins within the CNS and suggest PTGDS expression as a downstream target of NG2 signaling. PMID:25966014

  18. Growth of textured mullite fibers using polycrystalline precursors

    NASA Astrophysics Data System (ADS)

    Yoon, Wonki

    Fine ceramic oxide fibers are widely used as reinforcements in composites for high temperature applications. The primary goal of this research was to investigate the growth of textured or single crystal oxide fibers by heat treatment of polycrystalline or amorphous, extruded precursor fibers. Mullite was selected for this study due to its excellent chemical stability, creep resistance and strength at high temperatures. Micrographic analysis and in-situ synchrotron X-ray diffraction analysis have been performed on mullite systems in order to study the anisotropic grain growth and the effect of titania additions in mullite. The estimated activation energies from the SEM micrographic particle size analysis were 644.3 kJ/mol and 773.7 kJ/mol for the length and thickness, respectively. An in-situ synchrotron X-ray diffraction microstructure analysis was done with a Curved Image Plate (CIP) detector and the fiber was heat treated in a QLF. The apparent crystallite size showed anisotropy in crystallite growth. Furthermore, a higher growth rate along the [001] direction than the [110] direction was observed. Mullite whiskers were prepared by HF leaching and templated into polycrystalline mullite fibers by extrusion. Textured growth of mullite fibers with elongated grains, aligned along the long-axis of the fibers, was achieved by heat treatment. Repeated heat treatment cycles of a whisker-templated fiber showed a bamboo-like microstructure. It was confirmed by SEM, TEM and optical microscopy (OM) that the growth direction along the fiber length was the [001] direction of orthorhombic mullite.

  19. Inhibitory action of amyloid precursor protein against human Hageman factor (factor XII).

    PubMed

    Niwano, H; Embury, P B; Greenberg, B D; Ratnoff, O D

    1995-02-01

    Amyloid precursor protein forms that contain Kunitz protease inhibitor domains are released from activated platelets, T-lymphocytes, and leukocytes and inhibit trypsin, plasmin, and activated factor XI. We investigated the effects of amyloid precursor protein isoforms on activated Hageman factor (factor XII), activated factor X (Stuart factor), and thrombin. Recombinant amyloid precursor proteins with or without the Kunitz domain, 770 and 695 amino acids, respectively, were produced in insect cells by Baculovirus expression (BAC770 and BAC695). Neither BAC695 nor BAC770 inhibited human alpha-thrombin or activated factor X. The partial thromboplastin time was prolonged by both amyloid precursor proteins, only one of which, BAC770, contains the Kunitz protease inhibitor domain. Both forms of amyloid precursor proteins inhibited ellagic acid-induced activation of Hageman factor but did not inhibit activated Hageman factor. Bismuth subgallate, which is an insoluble analog of ellagic acid, lost its ability to activate Hageman factor on being exposed to BAC770. Inhibition of ellagic acid-induced activation of Hageman factor by both forms of amyloid precursor protein was enhanced by heparin. These findings suggested that the heparin-binding domain of amyloid precursor proteins is not in the Kunitz domain. This heparin-binding domain may block the activation of Hageman factor by negatively charged agents. Thus, amyloid precursor proteins may be involved in the control of hemostasis, properties not all dependent on the Kunitz domain.

  20. FGF growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY; Takahashi, Kazuyuki [Germantown, MD

    2012-07-24

    The present invention provides a fibroblast growth factor heparin-binding analog of the formula: ##STR00001## where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, X, Y and Z are as defined, pharmaceutical compositions, coating compositions and medical devices including the fibroblast growth factor heparin-binding analog of the foregoing formula, and methods and uses thereof.

  1. Growth factors for nanobacteria

    NASA Astrophysics Data System (ADS)

    Ciftcioglu, Neva; Kajander, E. Olavi

    1999-12-01

    Nanobacteria are novel microorganisms recently isolated from fetal bovine serum and blood of cows and humans. These coccoid, gram negative bacteria in alpha-2 subgroup of Proteobacteria grow slowly under mammalian cell culture conditions but not in common media for microbes. Now we have found two different kinds of culture supplement preparations that improve their growth and make them culturable in the classical sense. These are supernatant fractions of conditioned media obtained from 1 - 3 months old nanobacteria cultures and from about a 2 weeks old Bacillus species culture. Both improved multiplication and particle yields and the latter increased their resistance to gentamicin. Nanobacteria cultured with any of the methods shared similar immunological property, structure and protein pattern. The growth supporting factors were heat-stabile and nondialyzable, and dialysis improved the growth promoting action. Nanobacteria formed stony colonies in a bacteriological medium supplemented with the growth factors. This is an implication that nanobacterial growth is influenced by pre-existing bacterial flora.

  2. Peptide growth factors, part A

    SciTech Connect

    Barnes, D.; Sirbasku, D.A.

    1987-01-01

    This book contains information on the following topics: Epidermal Growth Factor;Transforming Growth Factors;Bone and Cartilage Growth Factors;Somatomedin/Insulin-Like Growth Factors;Techniques for the Study of Growth Factor Activity;Assays, Phosphorylation, and Surface Membrane Effects.

  3. New microbial growth factor.

    PubMed Central

    Bok, S H; Casida, L E

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a new microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight, and it has high specific activity. When added to the diets for a meadow vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain. PMID:327929

  4. New microbial growth factor

    NASA Technical Reports Server (NTRS)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  5. New microbial growth factor

    NASA Technical Reports Server (NTRS)

    Bok, S. H.; Casida, L. E., Jr.

    1977-01-01

    A screening procedure was used to isolate from soil a Penicillium sp., two bacterial isolates, and a Streptomyces sp. that produced a previously unknown microbial growth factor. This factor was an absolute growth requirement for three soil bacteria. The Penicillium sp. and one of the bacteria requiring the factor, an Arthrobacter sp., were selected for more extensive study concerning the production and characteristics of the growth factor. It did not seem to be related to the siderochromes. It was not present in soil extract, rumen fluid, or any other medium component tested. It appears to be a glycoprotein of high molecular weight and has high specific activity. When added to the diets for a meadow-vole mammalian test system, it caused an increased consumption of diet without a concurrent increase in rate of weight gain.

  6. [Fibroblast growth factor-2].

    PubMed

    Faitová, J

    2004-01-01

    Fibroblast growth factor-2 is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. FGF-2 occurs in several isoforms resulting from alternative initiations of traslation: an 18 kDa cytoplasmic isoform and four larger molecular weight nuclear isoforms (22, 22.5, 24 and 34 kDa). It acts mainly through a paracrine/autocrine mechanism involving high affinity transmembrane receptors and heparan sulfate proteoglycan low affinity receptors. It is expressed mostly in tissues of mesoderm and neuroectoderm origin, and plays an important role in mesoderm induction, stimulates the growth and development of the new blood vessels (angiogenesis), normal wound healing and tissue development. FGF-2 positively regulates hematopoiesis by acting on various cellular targets: stromal cells, early and committed hematopoietic progenitors and possibly some mature blood cells. FGF-2 is a potent hematopoietic growth factor that is likely to play an important role in physiological and pathological hematopoiesis.

  7. Fullerenes as precursors for diamond film growth without hydrogen or oxygen additions

    SciTech Connect

    Gruen, D.M.; Liu, S.; Krauss, A.R.; Luo, J.; Pan, X.

    1993-10-01

    Diamond films are predominantly grown using one percent or so of a hydrocarbon precursor in hydrogen gas. Hydrogen is generally believed to be necessary for the diamond thin film growth process. However, hydrogen in varying amounts is inevitably incorporated in the growing diamond lattice, leading to structural defects. The authors report here for the first time the successful growth of diamond films using fullerene precursors in an argon microwave plasma, a unique development achieved without the addition of hydrogen or oxygen. It is speculated that collisional fragmentation of C{sub 60} to give C{sub 2} could be responsible for the high growth rate of the very fine grained diamond films.

  8. Differential processing of colony-stimulating factor 1 precursors encoded by two human cDNAs.

    PubMed Central

    Rettenmier, C W; Roussel, M F

    1988-01-01

    The biosynthesis of macrophage colony-stimulating factor 1 (CSF-1) was examined in mouse NIH-3T3 fibroblasts transfected with a retroviral vector expressing the 554-amino-acid product of a human 4-kilobase (kb) CSF-1 cDNA. Similar to results previously obtained with a 1.6-kb human cDNA that codes for a 256-amino-acid CSF-1 precursor, the results of the present study showed that NIH-3T3 cells expressing the product of the 4-kb clone produced biologically active human CSF-1 and were transformed by an autocrine mechanism when cotransfected with a vector containing a human c-fms (CSF-1 receptor) cDNA. The 4-kb CSF-1 cDNA product was synthesized as an integral transmembrane glycoprotein that was assembled into disulfide-linked dimers and rapidly underwent proteolytic cleavage to generate a soluble growth factor. Although the smaller CSF-1 precursor specified by the 1.6-kb human cDNA was stably expressed as a membrane-bound glycoprotein at the cell surface and was slowly cleaved to release the extracellular growth factor, the cell-associated product of the 4-kb clone was efficiently processed to the secreted form and was not detected on the plasma membrane. Digestion with glycosidic enzymes indicated that soluble CSF-1 encoded by the 4-kb cDNA contained both asparagine(N)-linked and O-linked carbohydrate chains, whereas the product of the 1.6-kb clone had only N-linked oligosaccharides. Removal of the carbohydrate indicated that the polypeptide chain of the secreted 4-kb cDNA product was longer than that of the corresponding form encoded by the smaller clone. These differences in posttranslational processing may reflect diverse physiological roles for the products of the two CSF-1 precursors in vivo. Images PMID:3264877

  9. Growth hormone, growth factors, and acromegaly

    SciTech Connect

    Ludecke, D.K.; Tolis, G.T.

    1987-01-01

    This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.

  10. Effects of different chloride precursors on crystal growth of lead halide perovskites

    NASA Astrophysics Data System (ADS)

    Murugan, Vigneshwaran; Ogomi, Yuhei; Pandey, Shyam S.; Toyoda, Taro; Shen, Qing; Hayase, Shuzi

    2015-12-01

    The optimized quantity and nature of a chloride precursor used for the formation of large perovskite crystals with minimal disorder were explored. The effect of the alkyl chain length of an alkyl ammonium chloride precursor on the crystal growth of CH3NH3PbI3 was systematically investigated. It was found that the addition of ethyl ammonium chloride (EACl) increased the crystal size, which is almost twice (88 nm) the size of standard perovskite crystals (47 nm) having a preferential orientation towards the (110) plane. Photoacoustic studies demonstrated that the disorder in the perovskite crystals was highly reduced by the addition of the EACl precursor.

  11. The role of transforming growth factor-beta, insulin-like growth factor I, and basic fibroblast growth factor in distraction osteogenesis of the mandible.

    PubMed

    Farhadieh, R D; Dickinson, R; Yu, Y; Gianoutsos, M P; Walsh, W R

    1999-01-01

    Distraction osteogenesis is a viable method for regenerating large amounts of bone. In contrast to fracture healing, the mode of bone formation in distraction osteogenesis is primarily intramembranous ossification. The basic biology of the process is still not well understood. The growth factor cascade is likely to play an important role in distraction. This study examines the growth factor cascade in a lengthened ovine mandible model. Twenty-four animals were divided into four groups with varying rates of distraction (1, 2, 3, and 4 mm/day). A unilateral distractor at the angle of the mandible was used. The mandibles were lengthened to 24 mm and fixed for a period of 5 weeks, after which the animals were killed. The sections were probed for transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I. The growth factors studied were present in all four groups. Transforming growth factor-beta, basic fibroblast growth factor, and insulin-like growth factor I were present in both the bony matrix of the sections and the cytoplasm of the cells, osteoblasts, and a small number of mesenchymal cells. The sections obtained from groups distracted at faster rates showed stronger presence of the growth factors examined by more intense staining. In fracture healing, the localization of transforming growth factor-beta in stage I of healing corresponded with the precise region of intramembranous ossification in stage II. Diffuse presence of transforming growth factor-beta throughout the lengthened region corresponded with the process of intramembranous ossification observed in distraction. In fracture healing, insulin-like growth factor I and basic fibroblast growth factor have been shown to promote proliferation and differentiation of osteoblasts from precursor cells. The intense presence of insulin-like growth factor I and basic fibroblast growth factor in the distracted region may account for osteoblast proliferation and formation from

  12. Morphine Withdrawal Increases Brain-Derived Neurotrophic Factor Precursor.

    PubMed

    Bachis, Alessia; Campbell, Lee A; Jenkins, Kierra; Wenzel, Erin; Mocchetti, Italo

    2017-08-03

    Morphine has been shown to increase the expression of brain-derived neurotrophic factor (BDNF) in the brain. However, little is known about the effect of morphine withdrawal on BDNF and its precursor protein, or proBDNF, which induces neuronal apoptosis. In this work, we examined whether BDNF and proBDNF levels change in rats chronically injected with escalating doses of morphine and those who undergo spontaneous withdrawal for 60 h. We observed, in the frontal cortex and striatum, that the ratio of BDNF to proBDNF changed depending upon the experimental paradigm. Morphine treatment and morphine withdrawal increased both BDNF and proBDNF levels. However, the increase in proBDNF immunoreactivity in withdrawal rats was more robust than that observed in morphine-treated rats. proBDNF is processed either intracellularly by furin or extracellularly by the tissue plasminogen activator (tPA)/plasminogen system or matrix metalloproteases (MMPs). To examine the mechanisms whereby chronic morphine treatment and morphine withdrawal differentially affects BDNF/proBDNF, the levels MMP-3 and MMP-7, furin, and tPA were analyzed. We found that morphine increases tPA levels, whereas withdrawal causes a decrease. To confirm the involvement of tPA in the morphine-mediated effect on BDNF/proBDNF, we exposed cortical neurons to morphine in the presence of the tPA inhibitor plasminogen activator inhibitor-1 (PAI-1). This inhibitor reversed the morphine-mediated decrease in proBDNF, supporting the hypothesis that morphine increases the availability of BDNF by promoting the extracellular processing of proBDNF by tPA. Because proBDNF could negatively influence synaptic repair, preventing withdrawal is crucial for reducing neurotoxic mechanisms associated with opioid abuse.

  13. Molecular beam epitaxy growth of SnO{sub 2} using a tin chemical precursor

    SciTech Connect

    Wang, Tianqi; Prakash, Abhinav; Jalan, Bharat; Warner, Ellis; Gladfelter, Wayne L.

    2015-03-15

    The authors report on the development of a molecular beam epitaxy approach for atomic layer controlled growth of phase-pure, single-crystalline epitaxial SnO{sub 2} films with scalable growth rates using a highly volatile precursor (tetraethyltin) for tin and rf-oxygen plasma for oxygen. Smooth, epitaxial SnO{sub 2} (101) films on r-sapphire (101{sup ¯}2) substrates were grown as a function of tin precursor flux and substrate temperatures between 300 and 900 °C. Three distinct growth regimes were identified where SnO{sub 2} films grew in a reaction-, flux-, and desorption-limited mode, respectively, with increasing substrate temperature. In particular, with increasing tin flux, the growth rates were found to increase and then saturate indicating any excess tin precursor desorbs above a critical beam equivalent pressure of tin precursor. Important implications of growth kinetic behaviors on the self-regulating stoichiometric growth of perovskite stannates are discussed.

  14. Growth and characterization of polymer thin films grown using molecular layer deposition with heterobifunctional precursors

    NASA Astrophysics Data System (ADS)

    Gibbs, Zachary Michael Conway

    In this work, growth of thin polymer films using molecular layer deposition with heterobifunctional precursors is investigated. Several growth phenomena are observed including: loss or gain of reactive sites as a result of precursor reactivity or vapor pressure; precursor diffusion and reaction within the porous polymer film; and crosslinking. Reactions were investigated using quartz crystal microbalance, Fourier transform infrared spectroscopy, and various ex situ techniques. Reactions involving 4-azidophenylisothiocyanate and 4-aminobenzonitrile were shown to stop growth after only a few cycles which is attributed to a loss in reactive sites which was modeled by an exponentially decaying growth rate. Growth of 4-carboxyphenylisothiocyanate with TMA and water was investigated as well. Active site multiplication as a result of the trifunctionality of the TMA molecule was proposed to explain the significantly higher growth rate for TMA/CI films. TMA/H2O/CI films showed the ability to crosslink through aluminum hydroxyl condensation reactions. Upon increasing the reaction temperature, reactant diffusion was observed in the form of mass removal upon TMA exposure. This same phenomena is thought to be occurring in films grown using Diels-Alder reactions in the third section of this thesis. These films showed a strong growth rate dependence upon reactant purge time and growth temperature. FTIR seems to weakly support Diels-Alder reaction, but it appears that the primary film growth mechanism is through CVD-like diffusion and condensation reactions.

  15. Unveiling carbon dimers and their chains as precursor of graphene growth on Ru(0001)

    NASA Astrophysics Data System (ADS)

    Gao, Min; Zhang, Yan-Fang; Huang, Li; Pan, Yi; Wang, Yeliang; Ding, Feng; Lin, Yuan; Du, Shi-Xuan; Gao, Hong-Jun

    2016-09-01

    Carbon precursor that forms on the catalyst surface by the dissociation of feedstock gas plays an important role in the controllable growth of graphene on metal substrates. However, the configuration about the precursor has so far remained elusive. Here, we report the direct observation of uniformly structured precursor units and their chain formation at the nucleation stage of graphene growing on Ru(0001) substrate by using scanning tunneling microscopy. Combining this experimental information with density function theory calculations, the atomic-resolved structures of carbon precursor are characterized as adsorbed CH2 segments on the substrate. The dissociated carbon feedstock molecules or radicals further react to form nonplanar -[C2H4]- chains adsorbed on hexagonal-close-packed hollow sites of the Ru(0001) substrate before incorporating into the graphene island. These findings reveal that CH2 and nonplanar -[C2H4]- segments act as precursors in graphene growth and are helpful to improve the quality and the domain size of desired graphene by precursor or feedstock control.

  16. In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model.

    PubMed

    Tang, Haiying; Vasselli, Joseph R; Tong, Christopher; Heymsfield, Steven B; Wu, Ed X

    2009-08-01

    Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3beta 17beta-diol (4-androsdiol), 19-nor-4-androstene-3beta-17beta-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.

  17. In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

    PubMed Central

    Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

    2015-01-01

    Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

  18. Proteolytic processing of a precursor protein for a growth-promoting peptide by a subtilisin serine protease in Arabidopsis.

    PubMed

    Srivastava, Renu; Liu, Jian-Xiang; Howell, Stephen H

    2008-10-01

    Phytosulfokines (PSKs) are secreted, sulfated peptide hormones derived from larger prepropeptide precursors. Proteolytic processing of one of the precursors, AtPSK4, was demonstrated by cleavage of a preproAtPSK4-myc transgene product to AtPSK4-myc. Cleavage of proAtPSK4 was induced by placing root explants in tissue culture. The processing of proAtPSK4 was dependent on AtSBT1.1, a subtilisin-like serine protease, encoded by one of 56 subtilase genes in Arabidopsis. The gene encoding AtSBT1.1 was up-regulated following the transfer of root explants to tissue culture, suggesting that activation of the proteolytic machinery that cleaves proAtPSK4 is dependent on AtSBT1.1 expression. We also demonstrated that a fluorogenic peptide representing the putative subtilase recognition site in proAtPSK4 is cleaved in vitro by affinity-purified AtSBT1.1. An alanine scan through the recognition site peptide indicated that AtSBT1.1 is fairly specific for the AtPSK4 precursor. Thus, this peptide growth factor, which promotes callus formation in culture, is proteolytically cleaved from its precursor by a specific plant subtilase encoded by a gene that is up-regulated during the process of transferring root explants to tissue culture.

  19. Effect of growth promoters on chemistry synthesis of Cr3C2 nanowhiskers from water-soluble precursors

    NASA Astrophysics Data System (ADS)

    Yang, Ruisong; Jin, Yongzhong; Zhang, Zhengquan; Liu, Dongliang

    2017-01-01

    Cr3C2 nanowhiskers with a diameter size of 50 nm were synthesized at mild condition (800 °C for 2 h) by a new precursor method. The process has two steps in which the amorphous Cr2O3-C mixtures containing whisker growth promoters were first produced from water-soluble precursor solution by air drying and subsequent calcining at 400 °C for 1 h, and secondly carburized at 750-800 °C. Phase composition and morphology of as-prepared products were discussed by X-ray diffraction and scanning electron microscopy, respectively. Furthermore the transmission electron microscope was used to identify the fine structure of the as-prepared products. The results showed that the melting point and addition amount of the selected grow agent were two critical controlling factors during synthesizing Cr3C2 nanowhiskers, in which the addition of 4 wt% NaCl + KCl (molar ratio of 1:1) mixture with the melting point of 650 °C is optimal. Fe/Co/Ni catalysts are not suitable for the synthesis of Cr3C2 nanowhiskers as whisker growth promoters by the precursor method.

  20. Hydrothermal growth of ZnO nanowire arrays: fine tuning by precursor supersaturation

    DOE PAGES

    Yan, Danhua; Cen, Jiajie; Zhang, Wenrui; ...

    2016-12-20

    In this paper, we develop a technique that fine tunes the hydrothermal growth of ZnO nanowires to address the difficulties in controlling their growth in a conventional one-pot hydrothermal method. In our technique, precursors are separately and slowly supplied with the assistance of a syringe pump, through the entire course of the growth. Compared to the one-pot method, the significantly lowered supersaturation of precursors helps eliminating competitive homogeneous nucleation and improves the reproducibility. The supersaturation degree can be readily tuned by the precursor quantity and injection rate, thus forming ZnO nanowire arrays of various geometries and packing densities in amore » highly controllable fashion. The precise control of ZnO nanowire growth enables systematic studies on the correlation between the material's properties and its morphology. Finally, in this work, ZnO nanowire arrays of various morphologies are studied as photoelectrochemical (PEC) water splitting photoanodes, in which we establish clear correlations between the water splitting performance and the nanowires' size, shape, and packing density.« less

  1. Hydrothermal growth of ZnO nanowire arrays: fine tuning by precursor supersaturation

    SciTech Connect

    Yan, Danhua; Cen, Jiajie; Zhang, Wenrui; Orlov, Alexander; Liu, Mingzhao

    2016-12-20

    In this paper, we develop a technique that fine tunes the hydrothermal growth of ZnO nanowires to address the difficulties in controlling their growth in a conventional one-pot hydrothermal method. In our technique, precursors are separately and slowly supplied with the assistance of a syringe pump, through the entire course of the growth. Compared to the one-pot method, the significantly lowered supersaturation of precursors helps eliminating competitive homogeneous nucleation and improves the reproducibility. The supersaturation degree can be readily tuned by the precursor quantity and injection rate, thus forming ZnO nanowire arrays of various geometries and packing densities in a highly controllable fashion. The precise control of ZnO nanowire growth enables systematic studies on the correlation between the material's properties and its morphology. Finally, in this work, ZnO nanowire arrays of various morphologies are studied as photoelectrochemical (PEC) water splitting photoanodes, in which we establish clear correlations between the water splitting performance and the nanowires' size, shape, and packing density.

  2. [Stem cells and growth factors in wound healing].

    PubMed

    Pikuła, Michał; Langa, Paulina; Kosikowska, Paulina; Trzonkowski, Piotr

    2015-01-02

    Wound healing is a complex process which depends on the presence of various types of cells, growth factors, cytokines and the elements of extracellular matrix. A wound is a portal of entry for numerous pathogens, therefore during the evolution wound healing process has formed very early, being critical for the survival of every individual. Stem cells, which give rise to their early descendants progenitor cells and subsequently differentiated cells, play a specific role in the process of wound healing. Among the most important cells which take part in wound healing the following cells need to be distinguished: epidermal stem cells, dermal precursor of fibroblasts, adipose-derived stem cells as well as bone marrow cells. The activity of these cells is strictly regulated by various growth factors, inter alia epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF). Any disorders in functioning of stem cells and biological activity of growth factors may lead to the defects in wound healing, for instance delayed wound healing or creation of hypertrophic scars. Therefore, knowledge concerning the mechanisms of wound healing is extremely essential from clinical point of view. In this review the current state of the knowledge of the role of stem cells and growth factors in the process of wound healing has been presented. Moreover, some clinical aspects of wound healing as well as the possibility of the therapy based on stem cells and growth factors have included.

  3. Interstitial fibrosis and growth factors.

    PubMed Central

    Lasky, J A; Brody, A R

    2000-01-01

    Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety of inhaled agents including mineral particles, organic dusts, and oxidant gases. The disease afflicts millions of individuals worldwide, and there are no effective therapeutic approaches. A major reason for this lack of useful treatments is that few of the molecular mechanisms of disease have been defined sufficiently to design appropriate targets for therapy. Our laboratory has focused on the molecular mechanisms through which three selected peptide growth factors could play a role in the development of IPF. Hundreds of growth factors and cytokines could be involved in the complex disease process. We are studying platelet-derived growth factor because it is the most potent mesenchymal cell mitogen yet described, transforming growth factor beta because it is a powerful inducer of extracellular matrix (scar tissue) components by mesenchymal cells, and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and others have shown is essential for the development of IPF in animal models. This review describes some of the evidence from studies in humans, in animal models, and in vitro, that supports the growth factor hypothesis. The use of modern molecular and transgenic technologies could elucidate those targets that will allow effective therapeutic approaches. Images Figure 1 Figure 2 PMID:10931794

  4. Growth factors in synaptic function

    PubMed Central

    Poon, Vivian Y.; Choi, Sojoong; Park, Mikyoung

    2013-01-01

    Synapses are increasingly recognized as key structures that malfunction in disorders like schizophrenia, mental retardation, and neurodegenerative diseases. The importance and complexity of the synapse has fuelled research into the molecular mechanisms underlying synaptogenesis, synaptic transmission, and plasticity. In this regard, neurotrophic factors such as netrin, Wnt, transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and others have gained prominence for their ability to regulate synaptic function. Several of these factors were first implicated in neuroprotection, neuronal growth, and axon guidance. However, their roles in synaptic development and function have become increasingly clear, and the downstream signaling pathways employed by these factors have begun to be elucidated. In this review, we will address the role of these factors and their downstream effectors in synaptic function in vivo and in cultured neurons. PMID:24065916

  5. Novel Drosophila receptor that binds multiple growth factors

    SciTech Connect

    Rosner, M.R.; Thompson, K.L.; Garcia, V.; Decker, S.J.

    1986-05-01

    The authors have recently reported the identification of a novel growth factor receptor from Drosophila cell cultures that has dual binding specificity for both insulin and epidermal growth factor (EGF). This 100 kDa protein is also antigenically related to the cytoplasmic region of the mammalian EGF receptor-tyrosine kinase. They now report that this protein binds to mammalian nerve growth factor and human transforming growth factor alpha as well as insulin and EGF with apparent dissociation constants ranging from 10/sup -6/ to 10/sup -8/ M. The 100 kDa protein can be affinity-labeled with these /sup 125/I-labeled growth factors after immunoprecipitation with anti-EGF receptor antiserum. These four growth factors appear to share a common binding site, as evidenced by their ability to block affinity labelling by /sup 125/I-insulin. No significant binding to the 100 kDa protein was observed with platelet-derived growth factor, transforming growth factor beta, or glucagon. The 100 kDa Drosophila protein has a unique ligand-binding spectrum with no direct counterpart in mammalian cells and may represent an evolutionary precursor of the mammalian receptors for these growth factors.

  6. Phenolic acid induced growth of gold nanoshells precursor composites and their application in antioxidant capacity assay.

    PubMed

    Ma, Xiaoyuan; Qian, Weiping

    2010-11-15

    In the present work, the gold nanoshells (GNSs) precursor composites were preadsorbed onto the surface of ITO substrates. With the treatment of modified electrodes immersed in the gold nanoparticles (GNPs) growth solution containing different phenolic acids, the GNSs precursor composites were enlarged to varying degrees. Phenolic acids with one or more phenolic hydroxyl groups served as reductants for the growth of GNPs. The enlargement conditions varied with the different reducing capacity of phenolic acids, exhibiting specific morphologies differ from the complete GNSs. Consequently, the UV-vis-NIR spectra and cyclic voltammetry curves for the phenolic acid-treated ITO electrode were gradually changed. Results showed that the higher reducing capacity for phenolic acid to reduce AuCl(4)(-) to Au(0) resulted in the intensified localized surface plasmon resonance features and reduced cathodic currents. The spectral wavelength peaks red shifted hundreds of nanometers across the visible region. Moreover, the antioxidant capacity of phenolic acids correlates well with their reducing activity, both of which reflect their tendency to donate electrons. Thus, the optical and electrochemical results could be used to evaluate the antioxidant capacity of phenolic acids by utilizing GNSs precursor composites as nanoprobes. The method is simple, rapid and could be used in visual analysis to a certain extent.

  7. Gastric secretion of platelet activating factor and precursors in healthy humans: effect of pentagastrin.

    PubMed Central

    Sobhani, I; Denizot, Y; Hochlaf, S; Rigaud, D; Vatier, J; Benveniste, J; Lewin, M J; Mignon, M

    1993-01-01

    The release of platelet activating factor (PAF-ACETHER or PAF) and its precursors in the gastric lumen was assessed in 13 normal subjects in basal condition and after stimulation by gastrin. Acid, pepsin, and sialic acid outputs were determined under the same conditions. Gastric juice was collected using a nasogastric tube after overnight fast in basal condition for 60 minutes, then under pentagastrin infusion (6 micrograms/kg/hr for 60 minutes). Platelet activating factor was detected at low concentration in 4/13 subjects under basal condition (mean (SEM) 1.2 (0.6) pg/hr) while high concentrations of lyso platelet activating factor (6.1 (1.8) microgram/hr) and of alkyl-acyl-glycerophosphocholine (AAGPC) (11.5 (3) micrograms/hr) were found in 13 and 11 subjects, respectively. Platelet activating factor was not detected during pentagastrin infusion, while lyso platelet activating factor and alkyl-acyl-glycerophosphocholine were detected in 13 and in 12 subjects, respectively. Compared with the basal condition these platelet activating factor precursors increased significantly (p < 0.001) going up to fivefold baseline (31.8 (6.8) micrograms/hr and 53 (9.3) micrograms/hr respectively) in response to pentagastrin. There was a positive correlation between platelet activating factor precursors and acid or pepsin output but not between platelet activating factor precursors and sialic acid. As sialic acid may be considered an index of mucus glycoprotein degradation, it seems that gastrin stimulation of gastric epithelial cells results in a concomittant secretion of platelet activating factor precursors, acid, and pepsin irrespective of mucus glycoprotein degradation. PMID:8174952

  8. Growth and superconductivity of REBCO bulk processed by a seed/buffer layer/precursor construction

    NASA Astrophysics Data System (ADS)

    Y Li, T.; Cheng, L.; Yan, S. B.; Sun, L. J.; Yao, X.; Yoshida, Y.; Ikuta, H.

    2010-12-01

    The buffer layer has been used, for the first time, in the cold-seeding melt-growth (MG) process for REBCO superconductor bulks. In this modified method, a mini pellet was inserted between the seed and the bulk precursor. Notably, the chemical contamination, from the seed material (either REBCO films or SmBCO/NdBCO crystals), was mostly absorbed by the mini pellet. Thus a uniformly high Tc REBCO bulk was readily gained. Secondly, the higher limits of the maximum processing temperature (Tmax) were evidently raised, which is promisingly beneficial for broadening the growth window and overcoming the self-nucleation in the growth of large-sized bulk. In short, the success of this work is that it protects the bulk from seed-induced contamination, and breaks the limit of Tmax caused by the intrinsic properties of the seed material. By means of this simple seed/buffer layer/precursor construction, we successfully fabricated a large single grain of GdBCO bulk superconductor with a diameter of 56 mm.

  9. Growth behavior of titanium dioxide thin films at different precursor temperatures

    PubMed Central

    2012-01-01

    The hydrophilic TiO2 films were successfully deposited on slide glass substrates using titanium tetraisopropoxide as a single precursor without carriers or bubbling gases by a metal-organic chemical vapor deposition method. The TiO2 films were employed by scanning electron microscopy, Fourier transform infrared spectrometry, UV-Visible [UV-Vis] spectroscopy, X-ray diffraction, contact angle measurement, and atomic force microscopy. The temperature of the substrate was 500°C, and the temperatures of the precursor were kept at 75°C (sample A) and 60°C (sample B) during the TiO2 film growth. The TiO2 films were characterized by contact angle measurement and UV-Vis spectroscopy. Sample B has a very low contact angle of almost zero due to a superhydrophilic TiO2 surface, and transmittance is 76.85% at the range of 400 to 700 nm, so this condition is very optimal for hydrophilic TiO2 film deposition. However, when the temperature of the precursor is lower than 50°C or higher than 75°C, TiO2 could not be deposited on the substrate and a cloudy TiO2 film was formed due to the increase of surface roughness, respectively. PMID:22280933

  10. Interactions between fibroblast growth factors and Notch regulate neuronal differentiation.

    PubMed

    Faux, C H; Turnley, A M; Epa, R; Cappai, R; Bartlett, P F

    2001-08-01

    The differentiation of precursor cells into neurons has been shown to be influenced by both the Notch signaling pathway and growth factor stimulation. In this study, the regulation of neuronal differentiation by these mechanisms was examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By downregulating Notch1 expression and by the addition of a Delta1 fusion protein (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron differentiation in the NEP cells, in vitro. The expression of two of the Notch receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells was found to be influenced by a number of different growth factors, indicating a potential interaction between growth factors and Notch signaling. Interestingly, none of the growth factors examined promoted neuron differentiation; however, the fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1 and FGF2 upregulated the expression of Notch and decreased expression of Delta1 in the NEP cells. In addition, the inhibitory response of the cells to the FGFs could be overcome by downregulating Notch1 expression and by disrupting Notch cleavage and signaling by the ablation of the Presenilin1 gene. These results indicate that FGF1 and FGF2 act via the Notch pathway, either directly or indirectly, to inhibit differentiation. Thus, signaling through the Notch receptor may be a common regulator of neuronal differentiation within the developing forebrain.

  11. Mechanistic, surface chemistry, and growth studies of novel precursors for aluminum nitride thin films

    NASA Astrophysics Data System (ADS)

    Robinson, David Walter

    One of the primary techniques for thin film deposition used in the fabrication of microelectronic and optoelectronic devices is chemical vapor deposition (CVD). In CVD, nutrient elements for film growth are transported in the gas phase to the growth surface where a complex series of chemical reactions occurs. The selection of the chemicals and process parameters determines the properties of the film that will be obtained. Aluminum nitride (AlN) is a direct wide bandgap material with excellent physical properties making it useful for a wide variety of solid state device applications. This research focused on (1) screening novel chemicals as viable sources for vapor phase deposition of AlN by investigating their adsorption and decomposition behavior on technologically important substrates, (2) developing growth strategies from these results, (3) implementing the growth strategies, and (4) characterizing the thin films that were deposited. Surface chemistry investigations of four potential AlN CVD sources were conducted. The sources were bis[amidobis(trimethylsilyl)aluminum] (BABTMSA), 1,1-dimethylhydrazine (DMHy), ammonia (NH3), and dimethylethylamine alane (DMEAA). BABTMSA, a potential single source precursor, did not have adsorption properties that allowed for facile decomposition to AlN. DMHy, NH3, and DMEAA all showed adsorption and decomposition behavior on Si(100) under certain conditions that was promising for AIN deposition. A growth strategy was developed for the deposition of AlN thin films at low temperature with minimal impurities employing a temperature modulated atomic layer growth (ALG) process using DMHy and DMEAA precursors. The growth strategy was implemented and investigated. The deposition proceeded primarily through the dehydrogenation of AlHyNHx species where regeneration of these species occurred in each cycle. This was also found to be the primary mechanism for ALG of AlN using DMEAA and NH3 and similar processing conditions. The low

  12. NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) negatively regulates TGF-β (transforming growth factor-β) signalling by inducing ubiquitin-mediated degradation of Smad2 and TGF-β type I receptor

    PubMed Central

    2004-01-01

    Inhibitory Smad, Smad7, is a potent inhibitor of TGF-β (transforming growth factor-β) superfamily signalling. By binding to activated type I receptors, it prevents the activation of R-Smads (receptor-regulated Smads). To identify new components of the Smad pathway, we performed yeast two-hybrid screening using Smad7 as bait, and identified NEDD4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) as a direct binding partner of Smad7. NEDD4-2 is structurally similar to Smurfs (Smad ubiquitin regulatory factors) 1 and 2, which were identified previously as E3 ubiquitin ligases for R-Smads and TGF-β superfamily receptors. NEDD4-2 functions like Smurfs 1 and 2 in that it associates with TGF-β type I receptor via Smad7, and induces its ubiquitin-dependent degradation. Moreover, NEDD4-2 bound to TGF-β-specific R-Smads, Smads 2 and 3, in a ligand-dependent manner, and induced degradation of Smad2, but not Smad3. However, in contrast with Smurf2, NEDD4-2 failed to induce ubiquitination of SnoN (Ski-related novel protein N), although NEDD4-2 bound to SnoN via Smad2 more strongly than Smurf2. We showed further that overexpressed NEDD4-2 prevents transcriptional activity induced by TGF-β and BMP, whereas silencing of the NEDD4-2 gene by siRNA (small interfering RNA) resulted in enhancement of the responsiveness to TGF-β superfamily cytokines. These data suggest that NEDD4-2 is a member of the Smurf-like C2-WW-HECT (WW is Trp-Trp and HECT is homologous to the E6-accessory protein) type E3 ubiquitin ligases, which negatively regulate TGF-β superfamily signalling through similar, but not identical, mechanisms to those used by Smurfs. PMID:15496141

  13. Physiological factors influencing capillary growth.

    PubMed

    Egginton, S

    2011-07-01

    (1) Angiogenesis (growth of new capillaries from an existing capillary bed) may result from a mismatch in microvascular supply and metabolic demand (metabolic error signal). Krogh examined the distribution and number of capillaries to explore the correlation between O(2) delivery and O(2) consumption. Subsequently, the heterogeneity in angiogenic response within a muscle has been shown to reflect either differences in fibre type composition or mechanical load. However, local control leads to targetted angiogenesis in the vicinity of glycolytic fibre types following muscle stimulation, or oxidative fibres following endurance training, while heterogeneity of capillary spacing is maintained during ontogenetic growth. (2) Despite limited microscopy resolution and lack of specific markers, Krogh's interest in the structure of the capillary wall paved the way for understanding the mechanisms of capillary growth. Angiogenesis may be influenced by the response of perivascular or stromal cells (fibroblasts, macrophages and pericytes) to altered activity, likely acting as a source for chemical signals modulating capillary growth such as vascular endothelial growth factor. In addition, haemodynamic factors such as shear stress and muscle stretch play a significant role in adaptive remodelling of the microcirculation. (3) Most indices of capillarity are highly dependent on fibre size, resulting in possible bias because of scaling. To examine the consequences of capillary distribution, it is therefore helpful to quantify the area of tissue supplied by individual capillaries. This allows the spatial limitations inherent in most models of tissue oxygenation to be overcome generating an alternative approach to Krogh's tissue cylinder, the capillary domain, to improve descriptions of intracellular oxygen diffusion. © 2010 The Author. Acta Physiologica © 2010 Scandinavian Physiological Society.

  14. [Neuronal growth factors--neurotrophins].

    PubMed

    Meyer, M; Rasmussen, J Z

    1999-04-05

    Neurotrophic factors are polypeptides primarily known to regulate the survival and differentiation of nerve cells during the development of the peripheral and central nervous systems. The neurotrophic factors act via specific receptors after retrograde axonal transport from the nerve fibre target areas back to the cell bodies, and locally through autocrine and paracrine mechanisms linked to nerve cell activity. In the mature nervous system, neurotrophic factors maintain morphological and neurochemical characteristics of nerve cells and promote activity-dependent dynamic/plastic changes in the synaptic contacts between nerve cells by strengthening functionally active synaptic connections. Induction and increased production of neurotrophic factors in relation to neural injuries are thought to serve protective and reparative purposes. Specific neurotrophic factors have thus been shown to protect nerve cells in a number of experimental models for neurodegenerative diseases, such as Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis, just as specific neurotrophic factors have been shown to stimulate regenerative growth of both peripheral and central nerve fibres. Today, problems with continuous and localized delivery of specific neurotrophins or combinations thereof into the nervous system appear to be the most important obstacle for more widespread clinical application.

  15. New precursors and chemistry for the growth of transition metal films by atomic layer deposition

    NASA Astrophysics Data System (ADS)

    Knisley, Thomas Joseph

    The advancing complexity of advanced microelectronic devices is placing rigorous demands on currently used PVD and CVD deposition techniques. The ALD deposition method is proposed to meet the film thickness and conformality constraints needed by the semiconductor industry in future manufacturing processes. Unfortunately, there is a limited number of chemical precursors available that have high thermal stability, reactivity, and vapor pressure suitable for ALD film growth to occur. These properties collectively contribute to the lack of suitable transition metal precursors available for use in ALD. In this thesis, we report the discovery of a series of novel transition metal diazadienate precursors that promising properties deemed suitable for ALD. The volatility and thermal stability of the new transition metal diazadienyl compounds were studied by preparative sublimation and capillary tube melting point/decomposition experiments. Thermogravimetric analyses (TGA) demonstrate precursor residues of less than 4% at 500 °C. In addition, sublimation data, melting points, and decomposition temperatures for all complexes are presented. The manganese diazadienyl complex has the highest decomposition temperature of the series of complexes produced (325 °C). During preparative sublimations, the product recoveries of all transition metal diazadienyl complexes were greater than 92.0% with nonvolatile residues of less than 7.0%. This is an excellent indication that these complexes may be suitable candidates as metal precursors for ALD. Nickel nitride (NixN) films have been studied as an intermediate material for the formation of both nickel metal and nickel silicide using chemical vapor deposition. Herein, we describe the ALD growth of nickel nitride thin films from bis(1,4-di-tert-butyl-1,3-diazabutadiene) nickel(II) (Ni(tBu2DAD)2) and 1,1-dimethylhydrazine. An ALD window for the deposition of nickel nitride films on 500 nm thermal SiO2 substrates was observed between 225

  16. Oriented attachment growth of quantum-sized CdS nanorods by direct thermolysis of single-source precursor.

    PubMed

    Li, Zhiguo; Sui, Jiehe; Li, Xiaoli; Cai, Wei

    2011-03-15

    Quantum-sized CdS nanorods were synthesized by direct thermal decomposition of a single-source precursor in a monosurfactant system. The CdS nanorods were uniform, had high crystallinity, and exhibited strong quantum confinement effect. The nanorod growth was controlled by an oriented attachment mechanism, and the morphology was determined by the competition between dipole attraction and steric repulsion of nanodots. Increasing precursor concentration and prolonging reaction time were favorable for the formation of CdS nanorods.

  17. Recruitment of myeloid but not endothelial precursor cells facilitates tumor re-growth after local irradiation

    PubMed Central

    Kozin, Sergey V.; Kamoun, Walid S.; Huang, Yuhui; Dawson, Michelle R.; Jain, Rakesh K.; Duda, Dan G.

    2010-01-01

    Tumor neovascularization and growth may be promoted by recruitment of bone marrow-derived cells (BMDCs), which include endothelial precursor cells (EPCs) and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor re-growth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole body irradiation (WBI) of 6Gy as part of a total tumor dose of 21Gy, and compared the growth delay with the one achieved after LI of 21Gy. In both models, including WBI induced longer tumor growth delays. Moreover, including WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of SDF-1α, a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor re-growth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP-labeled BMDC population we observed an increased number of monocytes but not EPCs in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by local irradiation recruits myelomonocyte/macrophage which promote tumor re-growth. PMID:20631066

  18. Effect of Iron and Cobalt Catalysts on The Growth of Carbon Nanotubes from Palm Oil Precursor

    NASA Astrophysics Data System (ADS)

    Suriani, A. B.; Asli, N. A.; Salina, M.; Mamat, M. H.; Aziz, A. A.; Falina, A. N.; Maryam, M.; Shamsudin, M. S.; Nor, Roslan Md; Abdullah, S.; Rusop, M.

    2013-06-01

    Catalysts which are typically a transition metal is mandatory and plays an important role in the production of CNT. In this work, the effect of iron (Fe) and cobalt (Co) nitrate catalyst on the growth of carbon nanotubes (CNT) were systematically studied. Green bio-hydrocarbon precursor namely palm oil was used as a precursor. The synthesis was done using thermal chemical vapour deposition method at temperature of 750°C for 15 min synthesis time. The Fe and Co solution were spin-coated separately on silicon substrate at speed of 3000 rev.min-1. The CNT characteristics were analyzed using field emission scanning electron microscopy and micro-Raman spectroscopy. The experimental results revealed that CNT properties were strongly affected by the catalyst type. CNT catalyzed by Co yields large diameter, crooked tube and lower quality, whereas CNT produced by Fe catalyst results in the smallest diameter and reasonably good graphitization. As a conclusion, Fe was considered as the optimum catalyst for better CNT structure and crystallinity. This was due to efficient, uniform and stable Fe catalytic activity as compared to Co catalyst in producing CNT.

  19. Growth mechanism and magnetism in carbothermal synthesized Fe3O4 nanoparticles from solution combustion precursors

    NASA Astrophysics Data System (ADS)

    Wang, Xuanli; Qin, Mingli; Cao, Zhiqin; Jia, Baorui; Gu, Yueru; Qu, Xuanhui; Volinsky, Alex A.

    2016-12-01

    Magnetic Fe3O4 nanoparticles were prepared by carbothermal reduction using solution combustion synthesis precursors derived from ferric nitrate (oxidizer), glycine (fuel) and glucose (carbon source) mixed solution. In this paper, the growth mechanism and magnetism in Fe3O4 nanoparticles were investigated by adjusting the glucose content in precursor and the heat temperature in carbothermal process. The products were analyzed by X-ray diffraction, Field emission scanning electron microscopy, Infrared adsorption method and Vibrating sample magnetometry. The results revealed that the more amount of glucose, the earlier Fe3O4 phase generated as temperature increasing. Depending on glucose content and thermal temperature, the average grain size of Fe3O4 nanoparticles varied from 19.9 nm to 48 nm and saturation magnetization changed from 21.2 emu/g to 71.77 emu/g, which indicated that the saturation magnetization of Fe3O4 nanoparticles fell off as the average grain size decreasing. These results were crucial not only from the application stand-point, but more importantly leaded to a new platform for further studies of high quality magnetic Fe3O4 particles at nanoscale.

  20. Growth and growth factors in diabetes mellitus.

    PubMed Central

    Salardi, S; Tonioli, S; Tassoni, P; Tellarini, M; Mazzanti, L; Cacciari, E

    1987-01-01

    Growth of 79 children with diabetes was analysed at diagnosis and again after one to 10.7 years of treatment with insulin. Both sexes were tall at onset, whereas at the last observation boys alone showed significant growth retardation. Height standard deviation score (SDS), however, showed no significant fall either in 32 subjects reassessed after five years of disease or in 18 subjects examined at full stature. Skeletal maturity was not significantly impaired after treatment. Pubertal growth spurt was reduced, especially in girls and in subjects with onset of disease at or around puberty. We found no significant correlation between height and height velocity SDS and glycosylated haemoglobin values or secretion of growth hormone during the arginine test. Somatomedin C values were correlated with height velocity SDS in prepubertal boys. The results of this study suggest that there are interferences in the growth of children with diabetes but that they do not seem to have a significant influence on adult height. PMID:3813637

  1. Domain growth of carbon nanotubes assisted by dewetting of thin catalyst precursor films

    NASA Astrophysics Data System (ADS)

    Srivastava, Alok Kumar; Sachan, Priyanka; Samanta, Chandan; Mukhopadhyay, Kingsuk; Sharma, Ashutosh

    2014-01-01

    We explore self-organized dewetting of ultrathin films of a novel metal complex as a one step surface patterning method to create nanoislands of iron, using which spatially separated carbon nanostructures were synthesized. Dewetting of ultrathin metal complex films was induced by two different methods: liquid solvent exposure and thermal annealing to engender surface patterning. For thermal dewetting, thin films of the iron oleate complex were dewetted at high temperature. In the case of liquid solvent assisted dewetting, the metal complex, mixed with a sacrificial polymer (polystyrene) was spin coated as thin films (<40 nm) and then dewetted under an optimal solution mixture consisting of methyl ethyl ketone, acetone and water. The carrier polymer was then selectively removed to produce the iron metal islands. These metal islands were used for selective growth of discrete patches of multiwall CNTs and CNFs by a chemical vapor deposition (CVD) process. Solvent induced dewetting showed clear advantages over thermal dewetting owing to reduced size of catalyst domains formed by dewetting, an improved control over CNT growth as well as in its ability to immobilize the seed particles. The generic solution mediated dewetting and pattern generation in thin films of various catalytic precursors can thus be a powerful method for selective domain growth of a variety of functional nanomaterials.

  2. Two transcription factors can direct three photoreceptor outcomes from rod precursor cells in mouse retinal development

    PubMed Central

    Ng, Lily; Lu, Ailing; Swaroop, Alok; Sharlin, David; Swaroop, Anand; Forrest, Douglas

    2011-01-01

    The typical mammalian visual system is based upon three photoreceptor types: rods for dim light vision and two types of cones (M and S) for color vision in daylight. However, the process that generates photoreceptor diversity and the cell type in which diversity arises remain unclear. Mice deleted for thyroid hormone receptor ®2 (TR®2) and neural retina leucine zipper factor (NRL) lack M cones and rods, respectively, but gain S cones. We therefore tested the hypothesis that NRL and TR®2 direct a common precursor to a rod, M cone or S cone outcome using Nrlb2/b2 “knock-in” mice that express TR®2 instead of NRL from the endogenous Nrl gene. Nrlb2/b2 mice lacked rods and produced excess M cones in contrast to the excess S cones in Nrl−/− mice. Notably, the presence of both factors yielded rods in Nrl+/b2 mice. The results demonstrate innate plasticity in post-mitotic rod precursors that allows these cells to form three functional photoreceptor types in response to NRL or TRβ2. We also detected precursor cells in normal embryonic retina that transiently co-expressed Nrl and TRβ2, suggesting that some precursors may originate in a plastic state. The plasticity of the precursors revealed in Nrlb2/b2 mice suggests that a two-step transcriptional switch can direct three photoreceptor fates: first, rod versus cone identity dictated by NRL and secondly, if NRL fails to act, M versus S cone identity dictated by TR®2. PMID:21813673

  3. Two transcription factors can direct three photoreceptor outcomes from rod precursor cells in mouse retinal development.

    PubMed

    Ng, Lily; Lu, Ailing; Swaroop, Alok; Sharlin, David S; Swaroop, Anand; Forrest, Douglas

    2011-08-03

    The typical mammalian visual system is based upon three photoreceptor types: rods for dim light vision and two types of cones (M and S) for color vision in daylight. However, the process that generates photoreceptor diversity and the cell type in which diversity arises remain unclear. Mice deleted for thyroid hormone receptor β2 (TRβ2) and neural retina leucine zipper factor (NRL) lack M cones and rods, respectively, but gain S cones. We therefore tested the hypothesis that NRL and TRβ2 direct a common precursor to a rod, M cone, or S cone outcome using Nrl(b2/b2) "knock-in" mice that express TRβ2 instead of NRL from the endogenous Nrl gene. Nrl(b2/b2) mice lacked rods and produced excess M cones in contrast to the excess S cones in Nrl(-/-) mice. Notably, the presence of both factors yielded rods in Nrl(+/b2) mice. The results demonstrate innate plasticity in postmitotic rod precursors that allows these cells to form three functional photoreceptor types in response to NRL or TRβ2. We also detected precursor cells in normal embryonic retina that transiently coexpressed Nrl and TRβ2, suggesting that some precursors may originate in a plastic state. The plasticity of the precursors revealed in Nrl(b2/b2) mice suggests that a two-step transcriptional switch can direct three photoreceptor fates: first, rod versus cone identity dictated by NRL, and second, if NRL fails to act, M versus S cone identity dictated by TRβ2.

  4. New Chemical Precursors for the Growth of Ferroelectric and Mid-Valent Metal Oxide Films

    DTIC Science & Technology

    2014-02-20

    SECURITY CLASSIFICATION OF: This proposal seeks to prepare improved chemical vapor deposition (CVD) and atomic layer deposition (ALD) precursors to...P.O. Box 12211 Research Triangle Park, NC 27709-2211 Precursor Synthesis, Inorganic Chemistry, Chemical Vapor Deposition, Atomic Layer Deposition...chemical vapor deposition (CVD) and atomic layer deposition (ALD) precursors to materials that contain Sr, Ba, and Ti and ALD precursors for the mid

  5. Influence of layered precursor pellets on the growth and properties of Y-Ba-Cu-O bulk superconductors by top-seeded melt-textured growth

    NASA Astrophysics Data System (ADS)

    Tang, Tian-wei; Wu, Dong-jie; Xu, Ke-Xi

    2016-03-01

    It is well known that a fine and homogeneous distribution of Y2BaCuO5 (Y211) phase particles in single-grain Y-Ba-Cu-O (YBCO) bulk superconductors is essential for improving field-trapping ability. However, the size and concentration of Y211 phase particles in the fully melt-processed superconducting bulk increase significantly with the distance from the seed, which results in the accumulation of Y211 phase particles and the degradation of superconducting properties. In this paper, we report a new method of fabricating single-grain YBCO using layered precursor pellets. Using the top-seeded melt-textured growth process, single-grain YBCO bulk superconductors of about 22 mm in diameter and 9 mm in thickness were fabricated from layered precursor pellets and standard precursor pellets, respectively. The layered precursor pellets consist of precursor powders with 40 mol% Y211 at the top, 30 mol% Y211 in the middle and 20 mol% Y211 at the bottom of the whole pellets, while standard precursor pellets are prepared from precursor powders with only 40 mol% Y211. The growth morphology, microstructure and magnetic flux properties of the layered samples and standard samples were comparatively studied. The results proved that the layered precursor pellets allow a sufficient growth in the c-growth sector and a more uniform distribution of the Y211 phase in the matrix. The distribution of Y211 phase particles is qualitatively explained by the prevalent trapping/pushing theory. The trapped field at 77 K reaches 0.8 T, nearly 29% higher than the standard sample. The present results are very valuable for further improving the properties of YBCO bulk superconductors.

  6. The effect of synthesis time on graphene growth from palm oil as green carbon precursor

    NASA Astrophysics Data System (ADS)

    Salifairus, M. J.; Hamid, S. B. Abd; Alrokayan, Salman A. H.; Khan, Haseeb A.; Rusop, M.

    2016-07-01

    Graphene is the new material that arises after carbon nanotubes (CNTs) era and has extraordinary optical, electronic and mechanical properties compared to CNTs. The 2D graphene is the sp2 carbon allotropes compared to other dimensionality. It also can be in three forms that are zero-dimensional, one-dimensional or three-dimensional. The different dimensionality also called fullerenes, nanotubes and graphite. Therefore, the graphene is known as centre potential materials in expanding research area than others ever. The 2cm × 2cm silicon wafer was seeded with nickel (Ni) at different thickness by using sputter coater. The palm oil, carbon source, was placed in the precursor furnace and the silicon was placed in the second furnace (deposition furnace). The palm oil will mix with Nitrogen gas was used as carrier gas in the CVD under certain temperature and pressure to undergo pyrolysis proses. The deposition temperature was set at 1000 °C. The deposition time varied from 3 minutes, 5 minutes and 7 minutes. The graphene was growth at ambient pressure in the CVD system. Electron microscopy and Raman Spectrometer revealed the structural properties and surface morphology of the grapheme on the substrate. The D and G band appear approximately at 1350 cm-1 and 1850 cm-1. It can be concluded that the growth of graphene varies at different deposition time.

  7. The effect of synthesis time on graphene growth from palm oil as green carbon precursor

    SciTech Connect

    Salifairus, M. J.; Hamid, S. B. Abd; Alrokayan, Salman A. H.; Khan, Haseeb A.; Rusop, M.

    2016-07-06

    Graphene is the new material that arises after carbon nanotubes (CNTs) era and has extraordinary optical, electronic and mechanical properties compared to CNTs. The 2D graphene is the sp{sup 2} carbon allotropes compared to other dimensionality. It also can be in three forms that are zero-dimensional, one-dimensional or three-dimensional. The different dimensionality also called fullerenes, nanotubes and graphite. Therefore, the graphene is known as centre potential materials in expanding research area than others ever. The 2 cm × 2 cm silicon wafer was seeded with nickel (Ni) at different thickness by using sputter coater. The palm oil, carbon source, was placed in the precursor furnace and the silicon was placed in the second furnace (deposition furnace). The palm oil will mix with Nitrogen gas was used as carrier gas in the CVD under certain temperature and pressure to undergo pyrolysis proses. The deposition temperature was set at 1000 °C. The deposition time varied from 3 minutes, 5 minutes and 7 minutes. The graphene was growth at ambient pressure in the CVD system. Electron microscopy and Raman Spectrometer revealed the structural properties and surface morphology of the grapheme on the substrate. The D and G band appear approximately at 1350 cm{sup −1} and 1850 cm{sup −1}. It can be concluded that the growth of graphene varies at different deposition time.

  8. Study of CNT growth using nanocatalyst Ag precursor by HWC-VHF-PECVD

    NASA Astrophysics Data System (ADS)

    Eliyana, Ajeng; Rosikin, Ahmad; Winata, Toto

    2015-04-01

    The study of CNT growth has been done by using silver (Ag) nanocatalyst as a guide precursor on corning glass 7059 substrate. The silver catalyst was prepared by the evaporation method by varying deposition time for 50, 25, and 14 seconds. The silver films were then annealed at temperature of 400°C for 4 hours. From Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDX) results the grain sizes are 65 nm, 57 nm, and 33 nm, and also the atomic compositions are 6,06%, 4,52%, and 3,73% for 14, 25 and 50 seconds samples, respectively. The 33 nm samples were then used for CNT growth by using Hot Wire Cell (HWC) - Very High Frequency (VHF) - Plasma Enhanced Chemical Vapor Deposition (PECVD) at 275 ° C deposition temperature and pressure of 300 mTorr. The rf power was varied from 8 to 20 watts, with deposition time for 60 minutes. The methane (CH4) 99.999% was used as Carbon sources. Hydrogen gas (H2) was used to etch the oxide layer formed during the pre-deposition process. The diameter and length for the CNT are 125 nm and 1.650 to 2.989 nm respectively.

  9. Study of CNT growth using nanocatalyst Ag precursor by HWC-VHF-PECVD

    SciTech Connect

    Eliyana, Ajeng; Rosikin, Ahmad; Winata, Toto

    2015-04-16

    The study of CNT growth has been done by using silver (Ag) nanocatalyst as a guide precursor on corning glass 7059 substrate. The silver catalyst was prepared by the evaporation method by varying deposition time for 50, 25, and 14 seconds. The silver films were then annealed at temperature of 400°C for 4 hours. From Scanning Electron Microscope (SEM) and Energy Dispersive X-ray Spectroscopy (EDX) results the grain sizes are 65 nm, 57 nm, and 33 nm, and also the atomic compositions are 6,06%, 4,52%, and 3,73% for 14, 25 and 50 seconds samples, respectively. The 33 nm samples were then used for CNT growth by using Hot Wire Cell (HWC) – Very High Frequency (VHF) – Plasma Enhanced Chemical Vapor Deposition (PECVD) at 275 ° C deposition temperature and pressure of 300 mTorr. The rf power was varied from 8 to 20 watts, with deposition time for 60 minutes. The methane (CH4) 99.999% was used as Carbon sources. Hydrogen gas (H2) was used to etch the oxide layer formed during the pre-deposition process. The diameter and length for the CNT are 125 nm and 1.650 to 2.989 nm respectively.

  10. A carboxy methyl tamarind polysaccharide matrix for adhesion and growth of osteoclast-precursor cells.

    PubMed

    Sanyasi, Sridhar; Kumar, Ashutosh; Goswami, Chandan; Bandyopadhyay, Abhijit; Goswami, Luna

    2014-01-30

    Remodeling of bone by tissue engineering is a realistic option for treating several bone-related pathophysiological ailments such as osteoporosis, bone tumor, bone cancer or abnormal bone development. But, these possibilities are hindered due to lack of proper natural and biodegradable surface on which bone precursor cells can adhere efficiently and grow further. Here we describe the synthesis and characterization of a new hydrogel as an effective surface which can acts as a material for bone tissue engineering. This hydrogel has been prepared by chemically grafting a semi-synthetic polymer with a synthetic monomer, namely hydroxyethyl methacrylate (HEMA). Carboxy methyl tamarind (CMT) was selected as the semi-synthetic polymer. The hydrogel was prepared at different mole ratios and at the ratio of 1:10 (CMT:HEMA) yielded the best hydrogel as characterized by several physico-chemical analysis such as UV spectroscopy, FT-IR spectroscopy and swelling properties. We further demonstrate that this material is suitable for effective adhesion, growth and further clustering of bone precursor cells (RAW 264.7). This material is also compatible for growing other sensitive cells such as neuronal cells (Neuro2a) and human umbilical vein endothelial cells (HUVEC) demonstrating that this surface does not possess any cytotoxicity and is compatible for primary human cells too. We conclude that the hydrogel made of CMT:HEMA at a ratio of 1:10 can be suitable for bone tissue engineering and thus may have clinical as well as commercial application in future. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Heparin-binding epidermal growth factor-like growth factor regulates fibroblast growth factor-2 expression in aortic smooth muscle cells.

    PubMed

    Peifley, K A; Alberts, G F; Hsu, D K; Feng, S L; Winkles, J A

    1996-08-01

    Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a vascular smooth muscle cell (SMC) mitogen and chemotactic factor that is expressed by endothelial cells, SMCs, monocytes/macrophages, and T lymphocytes. Both the membrane-anchored HB-EGF precursor and the secreted mature HB-EGF protein are biologically active; thus, HB-EGF may stimulate SMC growth via autocrine, paracrine, and juxtacrine mechanisms. In the present study, we report that HB-EGF treatment of serum-starved at aortic SMCs can induce fibroblast growth factor (FGF)-2 (basic FGF) gene expression but not FGF-1 (acidic FGF) gene expression. Increased FGF-2 mRNA expression is first detectable at 1 hour after HB-EGF addition, and maximal FGF-2 mRNA levels, corresponding to an approximately 46-fold level of induction, are present at 4 hours. The effect of HB-EGF on FGF-2 mRNA levels appears to be mediated primarily by a transcriptional mechanism and requires de novo synthesized proteins. HB-EGF induction of FGF-2 mRNA levels can be inhibited by treating cells with the anti-inflammatory glucocorticoid dexamethasone or the glycosaminoglycan heparin. Finally, Western blot analyses indicate that HB-EGF-treated SMCs also produce an increased amount of FGF-2 protein. These results indicate that HB-EGF expressed at sites of vascular injury or inflammation in vivo may upregulate FGF-2 production by SMCs.

  12. Discovery of a SAR11 growth requirement for thiamin's pyrimidine precursor and its distribution in the Sargasso Sea.

    PubMed

    Carini, Paul; Campbell, Emily O; Morré, Jeff; Sañudo-Wilhelmy, Sergio A; Thrash, J Cameron; Bennett, Samuel E; Temperton, Ben; Begley, Tadhg; Giovannoni, Stephen J

    2014-08-01

    Vitamin traffic, the production of organic growth factors by some microbial community members and their use by other taxa, is being scrutinized as a potential explanation for the variation and highly connected behavior observed in ocean plankton by community network analysis. Thiamin (vitamin B1), a cofactor in many essential biochemical reactions that modify carbon-carbon bonds of organic compounds, is distributed in complex patterns at subpicomolar concentrations in the marine surface layer (0-300 m). Sequenced genomes from organisms belonging to the abundant and ubiquitous SAR11 clade of marine chemoheterotrophic bacteria contain genes coding for a complete thiamin biosynthetic pathway, except for thiC, encoding the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) synthase, which is required for de novo synthesis of thiamin's pyrimidine moiety. Here we demonstrate that the SAR11 isolate 'Candidatus Pelagibacter ubique', strain HTCC1062, is auxotrophic for the thiamin precursor HMP, and cannot use exogenous thiamin for growth. In culture, strain HTCC1062 required 0.7 zeptomoles per cell (ca. 400 HMP molecules per cell). Measurements of dissolved HMP in the Sargasso Sea surface layer showed that HMP ranged from undetectable (detection limit: 2.4 pM) to 35.7 pM, with maximum concentrations coincident with the deep chlorophyll maximum. In culture, some marine cyanobacteria, microalgae and bacteria exuded HMP, and in the Western Sargasso Sea, HMP profiles changed between the morning and evening, suggesting a dynamic biological flux from producers to consumers.

  13. Transforming growth factor alpha, Shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.

    PubMed

    Opgenorth, A; Nation, N; Graham, K; McFadden, G

    1993-02-01

    The epidermal growth factor (EGF) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. However, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various EGF homologues perform similar roles in viral pathogenesis remains unclear. In order to determine whether different EGF-like growth factors can perform qualitatively similar functions in the induction of myxomatosis in rabbits, we created recombinant myxoma virus variants in which the native growth factor, myxoma growth factor (MGF), was disrupted and replaced with either vaccinia virus growth factor, Shope fibroma growth factor, or rat transforming growth factor alpha. Unlike the control virus containing an inactivated MGF gene, which caused marked attenuation of the disease syndrome and substantially less proliferation of the epithelial cell layers in the conjunctiva and respiratory tract, the recombinant myxoma virus strains expressing heterologous growth factors produced infections which were both clinically and histopathologically indistinguishable from wild-type myxomatosis. We conclude that these poxviral and cellular EGF-like growth factors, which are diverse with respect to primary structure and origin, have similar biological functions in the context of myxoma virus pathogenesis and are mitogenic for the same target cells.

  14. Growth Factors in Proliferative Diabetic Retinopathy

    PubMed Central

    Khan, Zia Ali

    2003-01-01

    Many growth factors are implicated in the pathogenesis of proliferative diabetic retinopathy. Alteration of growth factors and their receptors in diabetes has been shown in both experimental and clinical studies. Sustained hyperglycemia resulting from long-standing diabetes leads to several biochemical abnormalities that consequently result in retinal hypoxia. Retinal oxygenation state regulates various growth factors that promote angiogenesis in order to meet the oxygen demands of the tissue. However, unregulated expression of these growth factors and induction of complex cascades leading to augmentation of other proangiogenic factors, which may not be regulated by tissue oxygenation, leads to uncontrolled retinal neovascularization and blindness in diabetic patients. PMID:14668050

  15. Growth factors and acute renal failure.

    PubMed

    Hirschberg, R; Ding, H

    1998-03-01

    During acute renal injury, there are alterations in the expression of several growth factors and their receptors in the kidney. The increased expression of several growth factors and/or their receptors at sites of nephron injury suggests important contributions to repair. Exogenous administration of some growth factors, such as IGF-I, EGF and HGF, accelerates recovery of renal function in experimental acute renal failure (ARF). In ARF growth factors act through several mechanisms, which may include altered cell cycle regulation and mitogenesis, differentiation of recovered cells, regulation of apoptosis, improved renal hemodynamics, and others. There is evidence for interactions of growth factors with other growth factors as well as with other genes resulting in complex orchestration of biologic events contributing to recovery from ARF.

  16. Synthetic heparin-binding growth factor analogs

    DOEpatents

    Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

    2007-01-23

    The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

  17. Gold- and Silver Nanoparticles Affect the Growth Characteristics of Human Embryonic Neural Precursor Cells

    PubMed Central

    Söderstjerna, Erika; Johansson, Fredrik; Klefbohm, Birgitta; Englund Johansson, Ulrica

    2013-01-01

    Rapid development of nanotechnologies and their applications in clinical research have raised concerns about the adverse effects of nanoparticles (NPs) on human health and environment. NPs can be directly taken up by organs exposed, but also translocated to secondary organs, such as the central nervous system (CNS) after systemic- or subcutaneous administration, or via the olfactory system. The CNS is particularly vulnerable during development and recent reports describe transport of NPs across the placenta and even into brain tissue using in vitro and in vivo experimental systems. Here, we investigated whether well-characterized commercial 20 and 80 nm Au- and AgNPs have an effect on human embryonic neural precursor cell (HNPC) growth. After two weeks of NP exposure, uptake of NPs, morphological features and the amount of viable and dead cells, proliferative cells (Ki67 immunostaining) and apoptotic cells (TUNEL assay), respectively, were studied. We demonstrate uptake of both 20 and 80 nm Au- and AgNPs respectively, by HNPCs during proliferation. A significant effect on the sphere size- and morphology was found for all cultures exposed to Au- and AgNPs. AgNPs of both sizes caused a significant increase in numbers of proliferating and apoptotic HNPCs. In contrast, only the highest dose of 20 nm AuNPs significantly affected proliferation, whereas no effect was seen on apoptotic cell death. Our data demonstrates that both Au- and AgNPs interfere with the growth profile of HNPCs, indicating the need of further detailed studies on the adverse effects of NPs on the developing CNS. PMID:23505470

  18. Growth factors, nutrient signaling, and cardiovascular aging

    PubMed Central

    Fontana, Luigi; Vinciguerra, Manlio; Longo, Valter D.

    2012-01-01

    Growth factors regulated by specific macronutrients have been shown to promote aging and accelerate mortality in the great majority of the organisms studied. In particular, the enzymes activated by growth hormone (GH), insulin and insulin-like growth factor 1 (IGF-I) in mammals and their orthologs in simple model organisms represent perhaps the best-understood proteins involved in the aging process. Dietary restriction (DR), which reduces the level of IGF-I and of other growth factors, has been associated with protection from diabetes, cancer, and cardiovascular diseases and deficiencies in GH signaling and IGF-I are strongly associated with protection from cancer and diabetes in both mice and humans, but their role in cardiac function and cardiovascular diseases is controversial. Here we review the link between growth factors, cardiac function and heart disease with focus on the cardioprotective and sensitizing effect of growth factors in both model organisms and humans. PMID:22499903

  19. Direct selective growth of ZnO nanowire arrays from inkjet-printed zinc acetate precursor on a heated substrate

    NASA Astrophysics Data System (ADS)

    Kwon, Jinhyeong; Hong, Sukjoon; Lee, Habeom; Yeo, Junyeob; Lee, Seung S.; Ko, Seung Hwan

    2013-11-01

    Inkjet printing of functional materials has drawn tremendous interest as an alternative to the conventional photolithography-based microelectronics fabrication process development. We introduce direct selective nanowire array growth by inkjet printing of Zn acetate precursor ink patterning and subsequent hydrothermal ZnO local growth without nozzle clogging problem which frequently happens in nanoparticle inkjet printing. The proposed process can directly grow ZnO nanowires in any arbitrary patterned shape, and it is basically very fast, low cost, environmentally benign, and low temperature. Therefore, Zn acetate precursor inkjet printing-based direct nanowire local growth is expected to give extremely high flexibility in nanomaterial patterning for high-performance electronics fabrication especially at the development stage. As a proof of concept of the proposed method, ZnO nanowire network-based field effect transistors and ultraviolet photo-detectors were demonstrated by direct patterned grown ZnO nanowires as active layer.

  20. Direct selective growth of ZnO nanowire arrays from inkjet-printed zinc acetate precursor on a heated substrate

    PubMed Central

    2013-01-01

    Inkjet printing of functional materials has drawn tremendous interest as an alternative to the conventional photolithography-based microelectronics fabrication process development. We introduce direct selective nanowire array growth by inkjet printing of Zn acetate precursor ink patterning and subsequent hydrothermal ZnO local growth without nozzle clogging problem which frequently happens in nanoparticle inkjet printing. The proposed process can directly grow ZnO nanowires in any arbitrary patterned shape, and it is basically very fast, low cost, environmentally benign, and low temperature. Therefore, Zn acetate precursor inkjet printing-based direct nanowire local growth is expected to give extremely high flexibility in nanomaterial patterning for high-performance electronics fabrication especially at the development stage. As a proof of concept of the proposed method, ZnO nanowire network-based field effect transistors and ultraviolet photo-detectors were demonstrated by direct patterned grown ZnO nanowires as active layer. PMID:24252130

  1. Autocrine growth factors and solid tumor malignancy.

    PubMed Central

    Walsh, J. H.; Karnes, W. E.; Cuttitta, F.; Walker, A.

    1991-01-01

    The ability of malignant cells to escape the constraint that normally regulate cell growth and differentiation has been a primary focus of attention for investigators of cancer cell biology. An outcome of this attention has been the discovery that the protein products of oncogenes play a role in the activation of growth signal pathways. A second outcome, possibly related to abnormal oncogene expression, has been the discovery that malignant cells frequently show an ability to regulate their own growth by the release of autocrine growth modulatory substances. Most important, the growth of certain malignant cell types has been shown to depend on autocrine growth circuits. A malignant tumor whose continued growth depends on the release of an autocrine growth factor may be vulnerable to treatment with specific receptor antagonists or immunoneutralizing antibodies designed to break the autocrine circuit. Information is rapidly emerging concerning autocrine growth factors in selected human solid tissue malignancy. Images PMID:1926844

  2. Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells.

    PubMed

    Cristancho, Ana G; Schupp, Michael; Lefterova, Martina I; Cao, Shengya; Cohen, Daniel M; Chen, Christopher S; Steger, David J; Lazar, Mitchell A

    2011-09-27

    The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed by adipogenic stimuli. During adipogenesis, a large number of cytostructural genes are repressed before adipocyte gene induction. Here we report that the transcriptional repressor transcription factor 7-like 1 (TCF7L1) binds and directly regulates the expression of cell structure genes. Depletion of TCF7L1 inhibits differentiation, because TCF7L1 indirectly induces the adipogenic transcription factor peroxisome proliferator-activated receptor γ in a manner that can be replaced by inhibition of myosin II activity. TCF7L1 is induced by cell contact in adipogenic cell lines, and ectopic expression of TCF7L1 alleviates the confluency requirement for adipocytic differentiation of precursor cells. In contrast, TCF7L1 is not induced during confluency of non-adipogenic fibroblasts, and, remarkably, forced expression of TCF7L1 is sufficient to commit non-adipogenic fibroblasts to an adipogenic fate. These results establish TCF7L1 as a transcriptional hub coordinating cell-cell contact with the transcriptional repression required for adipogenic competency.

  3. Repressor transcription factor 7-like 1 promotes adipogenic competency in precursor cells

    PubMed Central

    Cristancho, Ana G.; Schupp, Michael; Lefterova, Martina I.; Cao, Shengya; Cohen, Daniel M.; Chen, Christopher S.; Steger, David J.; Lazar, Mitchell A.

    2011-01-01

    The identification of factors that define adipocyte precursor potential has important implications for obesity. Preadipocytes are fibroblastoid cells committed to becoming round lipid-laden adipocytes. In vitro, this differentiation process is facilitated by confluency, followed by adipogenic stimuli. During adipogenesis, a large number of cytostructural genes are repressed before adipocyte gene induction. Here we report that the transcriptional repressor transcription factor 7-like 1 (TCF7L1) binds and directly regulates the expression of cell structure genes. Depletion of TCF7L1 inhibits differentiation, because TCF7L1 indirectly induces the adipogenic transcription factor peroxisome proliferator-activated receptor γ in a manner that can be replaced by inhibition of myosin II activity. TCF7L1 is induced by cell contact in adipogenic cell lines, and ectopic expression of TCF7L1 alleviates the confluency requirement for adipocytic differentiation of precursor cells. In contrast, TCF7L1 is not induced during confluency of non-adipogenic fibroblasts, and, remarkably, forced expression of TCF7L1 is sufficient to commit non-adipogenic fibroblasts to an adipogenic fate. These results establish TCF7L1 as a transcriptional hub coordinating cell–cell contact with the transcriptional repression required for adipogenic competency. PMID:21914845

  4. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  5. Roles for Growth Factors in Cancer Progression

    PubMed Central

    Witsch, Esther; Sela, Michael; Yarden, Yosef

    2011-01-01

    Under physiological conditions, cells receive fate-determining signals from their tissue surroundings, primarily in the form of polypeptide growth factors. Integration of these extracellular signals underlies tissue homeostasis. Although departure from homeostasis and tumor initiation are instigated by oncogenic mutations rather than by growth factors, the latter are the major regulators of all subsequent steps of tumor progression, namely clonal expansion, invasion across tissue barriers, angiogenesis, and colonization of distant niches. Here, we discuss the relevant growth factor families, their roles in tumor biology, as well as the respective downstream signaling pathways. Importantly, cancer-associated activating mutations that impinge on these pathways often relieve, in part, the reliance of tumors on growth factors. On the other hand, growth factors are frequently involved in evolvement of resistance to therapeutic regimens, which extends the roles for polypeptide factors to very late phases of tumor progression and offers opportunities for cancer therapy. PMID:20430953

  6. Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Ankylosing Spondylitis

    PubMed Central

    Caetano-Lopes, Joana; Vieira-Sousa, Elsa; Campanilho-Marques, Raquel; Ponte, Cristina; Canhão, Helena; Ainola, Mari; Fonseca, João E.

    2015-01-01

    Introduction Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic bone loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton and enthesis of AS patients. Despite reduction of inflammation and systemic bone loss, AS patients treated with TNF inhibitors (TNFi) have ongoing local bone formation. The aim of this study was to assess the effect of TNFi in the differentiation and activity of osteoclasts (OC) in AS patients. Methods 13 AS patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. 25 healthy donors were recruited as controls. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers and cytokines, in vitro OC differentiation assay and qRT-PCR for OC specific genes were performed. Results RANKL+ circulating lymphocytes (B and T cells) and IL-17A, IL-23 and TGF-β levels were decreased after TNFi treatment. We found no differences in the frequency of the different monocyte subpopulations, however, we found decreased expression of CCR2 and increased expression of CD62L after TNFi treatment. OC number was reduced in patients at baseline when compared to controls. OC specific gene expression was reduced in circulating OC precursors after TNFi treatment. However, when cultured in OC differentiating conditions, OC precursors from AS TNFi-treated patients showed increased activity as compared to baseline. Conclusion In AS patients, TNFi treatment reduces systemic pro osteoclastogenic stimuli. However, OC precursors from AS patients exposed to TNFi therapy have increased in vitro activity in response to osteoclastogenic stimuli. PMID:26674064

  7. Effect of Tumor Necrosis Factor Inhibitor Therapy on Osteoclasts Precursors in Rheumatoid Arthritis

    PubMed Central

    Rodrigues, Ana Maria; Campanilho-Marques, Raquel; Ponte, Cristina; Canhão, Helena; Ainola, Mari

    2017-01-01

    Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect of TNF inhibitors (TNFi) on the differentiation and activity of OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline and after a minimum follow-up period of 6 months. Blood samples were collected to assess receptor activator of nuclear factor kappa-B ligand (RANKL) surface expression on circulating leukocytes and frequency and phenotype of monocyte subpopulations. Quantification of serum levels of bone turnover markers, in vitro OC differentiation assays, and qRT-PCR for OC specific genes was performed. Results. After TNFi therapy, patients had reduced RANKL surface expression in B-lymphocytes and the frequency of circulating classical CD14brightCD16− monocytes was decreased. Serum levels of sRANKL, sRANKL/OPG ratio, and CTX-I were reduced in RA patients after TNFi treatment. Moreover, after exposure to TNFi, osteoclast differentiation and activity were decreased, as well as the expression of TRAF6 and cathepsin K. Conclusion. We propose that TNFi arrests bone loss and erosion, through two pathways: direct reduction of osteoclast precursor numbers and inhibition of intracellular signaling pathways acting through TRAF6. PMID:28286757

  8. Transformation of cone precursors to functional rod photoreceptors by bZIP transcription factor NRL.

    PubMed

    Oh, Edwin C T; Khan, Naheed; Novelli, Elena; Khanna, Hemant; Strettoi, Enrica; Swaroop, Anand

    2007-01-30

    Networks of transcriptional regulatory proteins dictate specification of neural lineages from multipotent retinal progenitors. Rod photoreceptor differentiation requires the basic motif-leucine zipper (bZIP) transcription factor NRL, because loss of Nrl in mice (Nrl-/-) results in complete transformation of rods to functional cones. To examine the role of NRL in cell fate determination, we generated transgenic mice that express Nrl under the control of Crx promoter in postmitotic photoreceptor precursors of WT and Nrl-/- retina. We show that NRL expression, in both genetic backgrounds, leads to a functional retina with only rod photoreceptors. The absence of cones does not alter retinal lamination, although cone synaptic circuitry is now recruited by rods. Ectopic expression of NRL in developing cones can also induce rod-like characteristics and partially suppress cone-specific gene expression. We show that NRL is associated with specific promoter sequences in Thrb (encoding TRbeta2 transcription factor required for M-cone differentiation) and S-opsin and may, therefore, directly participate in transcriptional suppression of cone development. Our studies establish that NRL is not only essential but is sufficient for rod differentiation and that postmitotic photoreceptor precursors are competent to make binary decisions during early retinogenesis.

  9. Growth factor gene therapy for Alzheimer disease.

    PubMed

    Tuszynski, Mark H; U, Hoi Sang; Alksne, John; Bakay, Roy A; Pay, Mary Margaret; Merrill, David; Thal, Leon J

    2002-11-15

    The capacity to prevent neuronal degeneration and death during the course of progressive neurological disorders such as Alzheimer disease (AD) would represent a significant advance in therapy. Nervous system growth factors are families of naturally produced proteins that, in animal models, exhibit extensive potency in preventing neuronal death due to a variety of causes, reversing age-related atrophy of neurons, and ameliorating functional deficits. The main challenge in translating growth factor therapy to the clinic has been delivery of growth factors to the brain in sufficient concentrations to influence neuronal function. One means of achieving growth factor delivery to the central nervous system in a highly targeted, effective manner may be gene therapy. In this article the authors summarize the development and implementation of nerve growth factor gene delivery as a potential means of reducing cell loss in AD.

  10. Long-term culture and differentiation of CNS precursors derived from anterior human neural rosettes following exposure to ventralizing factors

    SciTech Connect

    Colleoni, Silvia; Giannelli, Serena G.; Armentero, Marie-Therese; Blandini, Fabio; Broccoli, Vania; Lazzari, Giovanna

    2010-04-15

    In this study we demonstrated that neural rosettes derived from human ES cells can give rise either to neural crest precursors, following expansion in presence of bFGF and EGF, or to dopaminergic precursors after exposure to ventralizing factors Shh and FGF8. Both regionalised precursors are capable of extensive proliferation and differentiation towards the corresponding terminally differentiated cell types. In particular, peripheral neurons, cartilage, bone, smooth muscle cells and also pigmented cells were obtained from neural crest precursors while tyrosine hydroxylase and Nurr1 positive dopaminergic neurons were derived from FGF8 and Shh primed rosette cells. Gene expression and immunocytochemistry analyses confirmed the expression of dorsal and neural crest genes such as Sox10, Slug, p75, FoxD3, Pax7 in neural precursors from bFGF-EGF exposed rosettes. By contrast, priming of rosettes with FGF8 and Shh induced the expression of dopaminergic markers Engrailed1, Pax2, Pitx3, floor plate marker FoxA2 and radial glia markers Blbp and Glast, the latter in agreement with the origin of dopaminergic precursors from floor plate radial glia. Moreover, in vivo transplant of proliferating Shh/FGF8 primed precursors in parkinsonian rats demonstrated engraftment and terminal dopaminergic differentiation. In conclusion, we demonstrated the derivation of long-term self-renewing precursors of selected regional identity as potential cell reservoirs for cell therapy applications, such as CNS degenerative diseases, or for the development of toxicological tests.

  11. Factors that influence particle formation during pulsed electron deposition of YBCO precursors

    NASA Astrophysics Data System (ADS)

    Mathis, John E.; Christen, Hans M.

    2007-08-01

    Pulsed electron deposition (PED) is an attractive alternative to pulsed laser deposition (PLD) for growing thin films because of PED’s relatively low cost. A potential problem with PED, however, is the generation of particulates that interfere with film growth. The influence of ambient pressure and accelerating potential on the number of and size of particulates appearing on the surface of films was investigated for the barium fluoride-based YBCO precursor process. It was found that the size of the particulates varies exponentially with accelerating voltage. The size of the particulates can be reduced to less than 100 nm by increasing the ambient pressure beyond that required for optimum deposition rate. The ability to control the size of particulates could make PED useful for technical applications where the generation of sub-micron sized materials is desired.

  12. Discovery of a SAR11 growth requirement for thiamin's pyrimidine precursor and its distribution in the Sargasso Sea

    PubMed Central

    Carini, Paul; Campbell, Emily O; Morré, Jeff; Sañudo-Wilhelmy, Sergio A; Cameron Thrash, J; Bennett, Samuel E; Temperton, Ben; Begley, Tadhg; Giovannoni, Stephen J

    2014-01-01

    Vitamin traffic, the production of organic growth factors by some microbial community members and their use by other taxa, is being scrutinized as a potential explanation for the variation and highly connected behavior observed in ocean plankton by community network analysis. Thiamin (vitamin B1), a cofactor in many essential biochemical reactions that modify carbon–carbon bonds of organic compounds, is distributed in complex patterns at subpicomolar concentrations in the marine surface layer (0–300 m). Sequenced genomes from organisms belonging to the abundant and ubiquitous SAR11 clade of marine chemoheterotrophic bacteria contain genes coding for a complete thiamin biosynthetic pathway, except for thiC, encoding the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) synthase, which is required for de novo synthesis of thiamin's pyrimidine moiety. Here we demonstrate that the SAR11 isolate ‘Candidatus Pelagibacter ubique', strain HTCC1062, is auxotrophic for the thiamin precursor HMP, and cannot use exogenous thiamin for growth. In culture, strain HTCC1062 required 0.7 zeptomoles per cell (ca. 400 HMP molecules per cell). Measurements of dissolved HMP in the Sargasso Sea surface layer showed that HMP ranged from undetectable (detection limit: 2.4 pM) to 35.7 pM, with maximum concentrations coincident with the deep chlorophyll maximum. In culture, some marine cyanobacteria, microalgae and bacteria exuded HMP, and in the Western Sargasso Sea, HMP profiles changed between the morning and evening, suggesting a dynamic biological flux from producers to consumers. PMID:24781899

  13. Growth factors from genes to clinical application

    SciTech Connect

    Sara, V.R. ); Hall, K.; Low, H. )

    1990-01-01

    The last decade has witnessed an explosion in the identification of growth factors and their receptors. This has been greatly facilitated by recombinant DNA technology, which has provided the tools not only to identify these proteins at the gene level but also to produce recombinant proteins for evaluating their biological activities. With the help of such techniques, we are moving toward an understanding of the biosynthesis of growth factors and their receptors, structure-function relationships, as well as mechanisms for intracellular signal transmission. The possibility of modifying these factors has opened new fields of clinical application. In this paper, four major areas of growth factor research are presented: the characterization of growth factor genes and their protein products, growth factor receptors and signal transduction by the receptors to mediate biological action, the biological actions of the various growth factors, and the role of growth factors in health and disease and their possible clinical application. Some of the topics covered include: structure of the IGFs and their variants; isoforms of PDGF receptor types; tyrosine kinase activation; structure of G-proteins in biological membranes; possible therapeutic application of NGF in the treatment of Parkinson's and Alzheimer's diseases; PDGF's possible role in the development of several fibroproliferative diseases and its therapeutic application in wound healing; and the possible use of angiogenic inhibitors in tumor treatment.

  14. [Transforming growth factor of beta-type].

    PubMed

    Stoĭka, R S

    1988-01-01

    Recent data about the structure and properties of the beta-type transforming growth factor as well as evidence about its influence on different target cells are presented. The regulatory action of the factor is shown to depend mainly on the type of tested cells, conditions of their culturing and the presence of other bioregulators of cell proliferation in the medium. The prospects of the beta-type transforming growth factor use in practice are considered.

  15. Growth factors for the treatment of ischemic brain injury (growth factor treatment).

    PubMed

    Larpthaveesarp, Amara; Ferriero, Donna M; Gonzalez, Fernando F

    2015-04-30

    In recent years, growth factor therapy has emerged as a potential treatment for ischemic brain injury. The efficacy of therapies that either directly introduce or stimulate local production of growth factors and their receptors in damaged brain tissue has been tested in a multitude of models for different Central Nervous System (CNS) diseases. These growth factors include erythropoietin (EPO), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and insulin-like growth factor (IGF-1), among others. Despite the promise shown in animal models, the particular growth factors that should be used to maximize both brain protection and repair, and the therapeutic critical period, are not well defined. We will review current pre-clinical and clinical evidence for growth factor therapies in treating different causes of brain injury, as well as issues to be addressed prior to application in humans.

  16. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, H. H.

    1987-01-01

    Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

  17. Contribution of granulocyte colony-stimulating factor to the acute mobilization of endothelial precursor cells by vascular disrupting agents.

    PubMed

    Shaked, Yuval; Tang, Terence; Woloszynek, Jill; Daenen, Laura G; Man, Shan; Xu, Ping; Cai, Shi-Rong; Arbeit, Jeffrey M; Voest, Emile E; Chaplin, David J; Smythe, Jon; Harris, Adrian; Nathan, Paul; Judson, Ian; Rustin, Gordon; Bertolini, Francesco; Link, Daniel C; Kerbel, Robert S

    2009-10-01

    Vascular disrupting agents (VDA) cause acute shutdown of abnormal established tumor vasculature, followed by massive intratumoral hypoxia and necrosis. However, a viable rim of tumor tissue invariably remains from which tumor regrowth rapidly resumes. We have recently shown that an acute systemic mobilization and homing of bone marrow-derived circulating endothelial precursor (CEP) cells could promote tumor regrowth following treatment with either a VDA or certain chemotherapy drugs. The molecular mediators of this systemic reactive host process are unknown. Here, we show that following treatment of mice with OXi-4503, a second-generation potent prodrug derivative of combretastatin-A4 phosphate, rapid increases in circulating plasma vascular endothelial growth factor, stromal derived factor-1 (SDF-1), and granulocyte colony-stimulating factor (G-CSF) levels are detected. With the aim of determining whether G-CSF is involved in VDA-induced CEP mobilization, mutant G-CSF-R(-/-) mice were treated with OXi-4503. We found that as opposed to wild-type controls, G-CSF-R(-/-) mice failed to mobilize CEPs or show induction of SDF-1 plasma levels. Furthermore, Lewis lung carcinomas grown in such mice treated with OXi-4503 showed greater levels of necrosis compared with tumors treated in wild-type mice. Evidence for rapid elevations in circulating plasma G-CSF, vascular endothelial growth factor, and SDF-1 were also observed in patients with VDA (combretastatin-A4 phosphate)-treated cancer. These results highlight the possible effect of drug-induced G-CSF on tumor regrowth following certain cytotoxic drug therapies, in this case using a VDA, and hence G-CSF as a possible therapeutic target.

  18. Angiogenic growth factors in preinvasive breast disease.

    PubMed

    Heffelfinger, S C; Miller, M A; Yassin, R; Gear, R

    1999-10-01

    Recently, we showed that preinvasive breast pathologies, such as usual hyperplasia, atypical hyperplasia, and carcinoma in situ, have an increased vascularity when compared with normal breast tissue (S. C. Heffelfinger et al., Clinical Cancer Res., 2: 1873-1878, 1996). To understand the mechanism of this increased vascularity, we examined by immunohistochemistry each of these pathological lesions for the expression of angiogenic growth factors. These studies showed that normal breast tissue contains numerous angiogenic agents, particularly vascular endothelial cell growth factor and basic fibroblast growth factor. At the transition from normal epithelium to proliferative breast disease, insulin-like growth factor (IGF) II expression was increased, primarily in the stroma and infiltrating leukocytes. However, among proliferative tissues, IGF I decreased with increasing vascularity. Finally, both epithelial vascular endothelial growth factor and epithelial and leukocytic platelet-derived endothelial cell growth factor increased at the transition to carcinoma in situ, whereas stromal and leukocytic basic fibroblast growth factor were elevated only in invasive carcinoma. Therefore, during histological progression there is also a complex progression of angiogenic growth factors. For CIS, two forms of vascularity are found: stromal microvascular density (MVD), and vascularity associated with the epithelial basement membrane (vascular score). There was 35% discordance between these two measurement systems. Among carcinoma in situ cases, decreases in stromal IGF II were associated with increasing vascular scores but not MVD, and increases in platelet-derived endothelial cell growth factor were associated with increasing MVD but not the vascular score. The presence of discordance and differential association with specific angiogenic agents suggests that these two forms of vascularity may be differentially regulated.

  19. Vascular growth factors and receptors in capillary hemangioblastomas and hemangiopericytomas.

    PubMed Central

    Hatva, E.; Böhling, T.; Jääskeläinen, J.; Persico, M. G.; Haltia, M.; Alitalo, K.

    1996-01-01

    Capillary hemangioblastomas and hemangiopericytomas are highly vascular central nervous system tumors of controversial origin. Of interest in their pathogenesis are mechanisms regulating endothelial cell growth. The endothelial cell mitogen vascular endothelial growth factor (VEGF) stimulates angiogenesis, and together with its two receptor tyrosine kinases VEGFR-1(FLT1) and VEGFR-2(KDR), is up-regulated during the malignant progression of gliomas. We have analyzed the expression of VEGF and its receptors, the related placental growth factor (PlGF) and the endothelial receptors FLT4 and Tie by in situ hybridization in capillary hemangioblastomas and hemangiopericytomas. VEGF mRNA was up-regulated in all of the hemangiopericytomas studied and highly expressed in the stromal cells of hemangioblastomas. In addition, some hemangioblastoma tumor cells expressed high levels of PlGF. Significantly elevated levels of Tie mRNA, Tie protein, VEGFR-1, and VEGFR-2 but not FLT4 mRNAs were observed in the endothelia of both tumor types. In hemangioblastomas, however, the receptors were also highly expressed by a subpopulation of stromal cells. Consistent results were obtained for a human hemangioblastoma cell line in culture. Up-regulation of the endothelial growth factors and receptors may result in autocrine or paracrine stimulation of endothelial cells and their precursors involved in the genesis of these two vascular tumors. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8774132

  20. Platelet Activating Factor: A Growth Factor for Breast Cancer

    DTIC Science & Technology

    2006-09-01

    Factor for Breast Cancer PRINCIPAL INVESTIGATOR: Larry W. Daniel, Ph.D. CONTRACTING ORGANIZATION: Wake Forest University...A Growth Factor for Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-04-1-0682 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Larry W...Relevance: If PAF is found to be a growth and angiogenic factor for breast cancer cells, these studies can be followed up by in vivo studies in nude

  1. Ion-assisted precursor dissociation and surface diffusion: Enabling rapid, low-temperature growth of carbon nanofibers

    NASA Astrophysics Data System (ADS)

    Denysenko, I.; Ostrikov, K.

    2007-06-01

    Growth kinetics of carbon nanofibers in a hydrocarbon plasma is studied. In addition to gas-phase and surface processes common to chemical vapor deposition, the model includes (unique to plasma-exposed catalyst surfaces) ion-induced dissociation of hydrocarbons, interaction of adsorbed species with incoming hydrogen atoms, and dissociation of hydrocarbon ions. It is shown that at low, nanodevice-friendly process temperatures the nanofibers grow via surface diffusion of carbon adatoms produced on the catalyst particle via ion-induced dissociation of a hydrocarbon precursor. These results explain a lower activation energy of nanofiber growth in a plasma and can be used for the synthesis of other nanoassemblies.

  2. Improved quality of graphene in the absence of hydrogen in a low-temperature growth process using an alcohol precursor

    NASA Astrophysics Data System (ADS)

    Choi, Kyeonggon; Lee, Kiyeol; Jeong, Jaehoon; Ye, Jongpil

    2017-03-01

    We present the results of low-temperature growth of graphene on polycrystalline copper foil surfaces at 800 °C by using low-pressure chemical-vapor deposition of alcohol precursors. The structural quality of the graphene sample was found to depend significantly on the ambient conditions during the annealing and the growth processes. The improved quality of graphene grown in an oxidizing environment was found to be associated with a lower nucleation density, suggesting that chemisorbed oxygen atoms play a critical role in determining the quality of graphene.

  3. Nickelocene-Precursor-Facilitated Fast Growth of Graphene/h-BN Vertical Heterostructures and Its Applications in OLEDs.

    PubMed

    Li, Qiucheng; Zhao, Zifeng; Yan, Baoming; Song, Xiuju; Zhang, Zhepeng; Li, Jia; Wu, Xiaosong; Bian, Zuqiang; Zou, Xiaolong; Zhang, Yanfeng; Liu, Zhongfan

    2017-08-01

    The direct growth of high-quality, large-area, uniform, vertically stacked Gr/h-BN heterostructures is of vital importance for applications in electronics and optoelectronics. However, the main challenge lies in the catalytically inert nature of the hexagonal boron nitride (h-BN) substrates, which usually afford a rather low decomposition rate of carbon precursors, and thus relatively low growth rate of graphene. Herein, a nickelocene-precursor-facilitated route is developed for the fast growth of Gr/h-BN vertical heterostructures on Cu foils, which shows much improved synthesis efficiency (8-10 times faster) and crystalline quality of graphene (large single-crystalline domain up to ≈20 µm). The key advantage of our synthetic route is the utilization of nickel atoms that are decomposed from nickelocene molecules as the gaseous catalyst, which can decrease the energy barrier for graphene growth and facilitate the decomposition of carbon sources, according to our density functional theory calculations. The high-quality Gr/h-BN stacks are proved to be perfect anode/protecting layers for high-performance organic light-emitting diode devices. In this regard, this work offers a brand-new route for the fast growth of Gr/h-BN heterostructures with practical scalability and high crystalline quality, thus should propel its wide applications in transparent electrodes, high-performance electronic devices, and energy harvesting/transition directions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. [Prokaryotic expression and activity identification of gene recombinant protein of brain-derivedneurotrophic factor precursor].

    PubMed

    Chen, Jia; Liang, Xiaomin; Xu, Zhiqiang

    2014-08-19

    To generate the gene recombinant protein of brain-derived neurotrophic factor precursor (proBDNF) in prokaryotic cells and investigate its biological activity. Rat-derived cDNA of proBDNF with point mutation was amplified by polymerase chain reaction (PCR) and cloned into plasmid pET-28a for expression in E. coli BL21. Western blot was used to identify the product and DAPI performed to test its effect on apoptosis of PC12 cells. PCR product of recombinant gene was successfully expressed in E. coli. And the product agreed with the target protein in molecular weight and showed reactivity with its specific antibody. Apoptosis of PC12 cells was induced by a certain concentration of recombinant proBDNF. The prokaryotic expression vector has been successfully constructed for recombinant gene of proBDNF. And the product has biological toxicity and it may induce the apoptosis of PC12 cells.

  5. Psychopathy and sexual assault: static risk factors, emotional precursors, and rapist subtypes.

    PubMed

    Brown, S L; Forth, A E

    1997-10-01

    This study compared psychopathic and nonpsychopathic rapists on static risk factors and on emotional and motivational precursors. Sixty incarcerated rapists were assessed for psychopathy with the Psychopathy Checklist--Revised (R. D. Hare, 1991), and they were classified according to the Massachusetts Treatment Center: Revised Rapist Typology, Version 3 (R. A. Knight & R. A. Prentky, 1990b). Psychopathy was positively associated with past nonsexual offenses and negatively associated with age onset for criminal offending, number of sexual victims, and the intensity of negative emotions experienced before sexual offending. However, psychopathy was not related to sexual offense history, age of onset for sexual offending, or victim harm. Last, psychopaths were most likely to be classified as opportunistic and pervasively angry rapists. The findings indicate that psychopathy should be considered when developing intervention strategies for rapists.

  6. The role of fibroblast growth factors in tumor growth.

    PubMed

    Korc, M; Friesel, R E

    2009-08-01

    Biological processes that drive cell growth are exciting targets for cancer therapy. The fibroblast growth factor (FGF) signaling network plays a ubiquitous role in normal cell growth, survival, differentiation, and angiogenesis, but has also been implicated in tumor development. Elucidation of the roles and relationships within the diverse FGF family and of their links to tumor growth and progression will be critical in designing new drug therapies to target FGF receptor (FGFR) pathways. Recent studies have shown that FGF can act synergistically with vascular endothelial growth factor (VEGF) to amplify tumor angiogenesis, highlighting that targeting of both the FGF and VEGF pathways may be more efficient in suppressing tumor growth and angiogenesis than targeting either factor alone. In addition, through inducing tumor cell survival, FGF has the potential to overcome chemotherapy resistance highlighting that chemotherapy may be more effective when used in combination with FGF inhibitor therapy. Furthermore, FGFRs have variable activity in promoting angiogenesis, with the FGFR-1 subgroup being associated with tumor progression and the FGFR-2 subgroup being associated with either early tumor development or decreased tumor progression. This review highlights the growing knowledge of FGFs in tumor cell growth and survival, including an overview of FGF intracellular signaling pathways, the role of FGFs in angiogenesis, patterns of FGF and FGFR expression in various tumor types, and the role of FGFs in tumor progression.

  7. Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells.

    PubMed

    Listerman, Imke; Sapra, Aparna K; Neugebauer, Karla M

    2006-09-01

    Coupling between transcription and RNA processing is a key gene regulatory mechanism. Here we use chromatin immunoprecipitation to detect transcription-dependent accumulation of the precursor mRNA (pre-mRNA) splicing factors hnRNP A1, U2AF65 and U1 and U5 snRNPs on the intron-containing human FOS gene. These factors were poorly detected on intronless heat-shock and histone genes, a result that opposes direct recruitment by RNA polymerase II (Pol II) or the cap-binding complex in vivo. However, an observed RNA-dependent interaction between U2AF65 and active forms of Pol II may stabilize U2AF65 binding to intron-containing nascent RNA. We establish chromatin-RNA immunoprecipitation and show that FOS pre-mRNA is cotranscriptionally spliced. Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis.

  8. Metal-organic chemical vapor deposition of cadmium oxide-based transparent conductors: Precursor design, film growth, and film characterization

    NASA Astrophysics Data System (ADS)

    Metz, Andrew William

    2003-07-01

    The growing importance of cadmium containing thin films and the desire for their efficient deposition has necessitated the development of high performance MOCVD precursors. To this end, a series of low-melting, and thermally-stable cadmium MOCVD precursors has been synthesized, characterized, and implemented in the growth of highly conductive and transparent CdO-based thin films. One member of the series, bis(1,1,1,5,5,5-hexafluoro-2,4-pentanedionato)(N,N-diethyl-N ', N'-dimethyl-ethylenediamine)cadmium(II), Cd(hfa)2(N,N-DE-N' ,N'-DMEDA), represents a particularly significant improvement over previously available Cd precursors owing to its low melting point, and robust thermal stability. This precursor will allow careful control of composition and growth rates in complex cadmium-containing oxide systems owing to the elimination of sintering effects detrimental to reproducible growth with solid precursors. Materials with high electrical conductivity and optical transparency are needed for future flat panel display, solar energy, and other opto-electronic technologies. High quality Cd1-xInxO films with been deposited utilizing our new class of MOCVD precursors. The x = 0.05 film, with conductivity of 17,000 S/cm, carrier mobility of 70 cm2/V·s, and wide visible region optical transparency window considerably exceed the corresponding parameters for commercial indium-tin oxide (ITO). A detailed understanding of the fundamental aspects of charge transport in degenerate semiconductors is of great interest. In order to elucidate the importance of individual scattering mechanisms in TCO materials, high-quality CdO films were grown by MOCVD in parallel on glass and single-crystal MgO (100) between 300°C and 412°C. Enhanced mobilities observed for highly biaxially textured films grown on MgO (100) vs. glass are attributed, on the basis of DC charge transport measurements and microstructure analysis, to a reduction in neutral impurity scattering and/or to a more densely

  9. An unnatural PIP simulates growth factor signaling.

    PubMed

    Swan, Laura

    2009-11-25

    In this issue of Chemistry & Biology, Laketa et al. describe the synthesis of a membrane permeant phosphoinositide lipid that acts to stimulate PI(3,4,5)P(3)-dependent signaling without the need of growth factor stimulation.

  10. New Clue Found to Growth Factor Action.

    ERIC Educational Resources Information Center

    Hoffman, Michelle

    1991-01-01

    Discussed is the discovery which may help to explain epidermal growth factor effects on the cell skeleton. The role of a protein called profilin in the regulation of the microfilament system is described. (CW)

  11. New Clue Found to Growth Factor Action.

    ERIC Educational Resources Information Center

    Hoffman, Michelle

    1991-01-01

    Discussed is the discovery which may help to explain epidermal growth factor effects on the cell skeleton. The role of a protein called profilin in the regulation of the microfilament system is described. (CW)

  12. The function of vascular endothelial growth factor.

    PubMed

    Nieves, Bonnie J; D'Amore, Patricia A; Bryan, Brad A

    2009-01-01

    Vascular endothelial growth factor (VEGF) is considered the master regulator of angiogenesis during growth and development, as well as in disease states such as cancer, diabetes, and macular degeneration. This review details our current understanding of VEGF signaling and discusses the benefits and unexpected side effects of promising anti-angiogenic therapeutics that are currently being used to inhibit neovacularization in tumors.

  13. Confirmatory Factor Analysis of the Trinity Inventory of Precursors to Suicide (TIPS) and Its Relationship to Hopelessness and Depression

    ERIC Educational Resources Information Center

    Smyth, Caroline L.; MacLachlan, Malcolm

    2005-01-01

    Numerous existing measures assess attitudes toward suicide yet fail to account for contextual factors. The Trinity Inventory of Precursors to Suicide (TIPS) is presented as an alternative, with implications for the development of prevention programs. Having previously reported exploratory analysis of the TIPS; confirmatory factor analysis and…

  14. Placental growth factor and vascular endothelial growth factor receptor-2 in human lung development.

    PubMed

    Janér, Joakim; Andersson, Sture; Haglund, Caj; Karikoski, Riitta; Lassus, Patrik

    2008-08-01

    We examined the pulmonary expression of 2 proangiogenic factors, namely, placental growth factor and vascular endothelial growth factor receptor-2, during lung development and acute and chronic lung injury in newborn infants. Six groups were included in an immunohistochemical study of placental growth factor and vascular endothelial growth factor receptor-2, that is, 9 fetuses, 4 preterm and 8 term infants without lung injury who died soon after birth, 5 preterm infants with respiratory distress syndrome of <2 days and 7 with respiratory distress syndrome of >10 days, and 6 with bronchopulmonary dysplasia. Placental growth factor concentrations in tracheal aspirate fluid were measured in 70 samples from 20 preterm infants during the first postnatal week. In immunohistochemical analyses, placental growth factor staining was seen in bronchial epithelium and macrophages in all groups. Distal airway epithelium positivity was observed mostly in fetuses and in preterm infants who died soon after birth. Vascular endothelial growth factor receptor-2 staining was seen in vascular endothelium in all groups and also in lymphatic endothelium in fetuses. Vascular endothelial growth factor receptor-2 staining in arterial endothelium was associated with higher and staining in venous endothelium with lower gestational age. In capillaries, less vascular endothelial growth factor receptor-2 staining was seen in bronchopulmonary dysplasia. The mean placental growth factor protein concentration in tracheal aspirate fluid during the first postnatal week was 0.64 +/- 0.42 pg/mL per IgA-secretory component unit. Concentrations during the first postnatal week were stable. Lower placental growth factor concentrations correlated with chorioamnionitis and lactosyl ceramide positivity. The vascular endothelial growth factor receptor-2 staining pattern seems to reflect ongoing differentiation and activity of different endothelia. Lower vascular endothelial growth factor receptor-2 expression

  15. Cancer cells. 3: Growth factors and transformation

    SciTech Connect

    Feramisco, J.; Ozanne, B.; Stiles, C.

    1985-01-01

    This book contains over 50 papers. Some of the titles are: Structure of Human Epidermal Growth Factor and Expression of Normal and Variant mRNAs in Epdermoid Carcinoma Cells; Tyrosine Kinase Activity Associated with the v-erb-B Gene Product; Cloning and Characterization of Human Epidermal Growth Factor-Receptor Gene Sequences in A431 Carcinoma Cells; Anti-oncogenes and the Suppression of Tumor Formation; and Normal Human sis/PDGF-2 Gene Expression Induces Cellular Transformation.

  16. Growth factors and growth factor receptors in the hippocampus. Role in plasticity and response to injury.

    PubMed

    Nieto-Sampedro, M; Bovolenta, P

    1990-01-01

    Various growth factors are present in the hippocampal formation and appear responsible for the prominent plasticity of this brain area. Although hormone-like growth-promoting polypeptides are the best known, recent studies emphasize the importance in the growth response of molecules such as laminin proteoglycans, neurotransmitters and growth inhibitors. The progress and problems in the study of these substances are reviewed.

  17. Extensive Ex Vivo Expansion of Functional Human Erythroid Precursors Established From Umbilical Cord Blood Cells by Defined Factors

    PubMed Central

    Huang, Xiaosong; Shah, Siddharth; Wang, Jing; Ye, Zhaohui; Dowey, Sarah N; Tsang, Kit Man; Mendelsohn, Laurel G; Kato, Gregory J; Kickler, Thomas S; Cheng, Linzhao

    2014-01-01

    There is a constant shortage of red blood cells (RBCs) from sufficiently matched donors for patients who need chronic transfusion. Ex vivo expansion and maturation of human erythroid precursors (erythroblasts) from the patients or optimally matched donors could represent a potential solution. Proliferating erythroblasts can be expanded from umbilical cord blood mononuclear cells (CB MNCs) ex vivo for 106–107-fold (in ~50 days) before proliferation arrest and reaching sufficient number for broad application. Here, we report that ectopic expression of three genetic factors (Sox2, c-Myc, and an shRNA against TP53 gene) associated with iPSC derivation enables CB-derived erythroblasts to undergo extended expansion (~1068-fold in ~12 months) in a serum-free culture condition without change of cell identity or function. These expanding erythroblasts maintain immature erythroblast phenotypes and morphology, a normal diploid karyotype and dependence on a specific combination of growth factors for proliferation throughout expansion period. When being switched to a terminal differentiation condition, these immortalized erythroblasts gradually exit cell cycle, decrease cell size, accumulate hemoglobin, condense nuclei and eventually give rise to enucleated hemoglobin-containing erythrocytes that can bind and release oxygen. Our result may ultimately lead to an alternative approach to generate unlimited numbers of RBCs for personalized transfusion medicine. PMID:24002691

  18. Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma

    PubMed Central

    Zhu, Shuang; Zhang, Baole; Qin, Yuxia; Yao, Ruiqin; Zhou, Hao; Gao, Dian Shuai

    2017-01-01

    As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion. We hypothesize that proN-cadherin might cause homotypic adhesion loss within neighboring cells and at the same time promote heterotypic adhesion within the extracellular matrix (ECM) through a certain mechanism. This study also demonstrates that the interaction between GDNF and proN-cadherin activates specific intracellular signaling pathways; furthermore, GDNF promoted the secretion of matrix metalloproteinase-9 (MMP-9), which degrades the ECM via proN-cadherin. To reach the future goal of developing novel therapies of glioma, this study, reveals a unique mechanism of glioma cell migration and invasion. PMID:28212546

  19. Precursor N-cadherin mediates glial cell line-derived neurotrophic factor-promoted human malignant glioma.

    PubMed

    Xiong, Ye; Liu, Liyun; Zhu, Shuang; Zhang, Baole; Qin, Yuxia; Yao, Ruiqin; Zhou, Hao; Gao, Dian Shuai

    2017-02-12

    As the most prevalent primary brain tumor, gliomas are highly metastatic, invasive and are characteristic of high levels of glial cell-line derived neurotrophic factor (GDNF). GDNF is an important factor for invasive glioma cell growth; however, the underlying mechanism involved is unclear. In this study, we affirm a significantly higher expression of the precursor of N-cadherin (proN-cadherin) in most gliomas compared with normal brain tissues. Our findings reveal that GDNF interacts with the extracellular domain of proN-cadherin, which suggests that proN-cadherin mediates GDNF-induced glioma cell migration and invasion. We hypothesize that proN-cadherin might cause homotypic adhesion loss within neighboring cells and at the same time promote heterotypic adhesion within the extracellular matrix (ECM) through a certain mechanism. This study also demonstrates that the interaction between GDNF and proN-cadherin activates specific intracellular signaling pathways; furthermore, GDNF promoted the secretion of matrix metalloproteinase-9 (MMP-9), which degrades the ECM via proN-cadherin. To reach the future goal of developing novel therapies of glioma, this study, reveals a unique mechanism of glioma cell migration and invasion.

  20. Insulin-like growth factor 1 and hair growth.

    PubMed

    Su, H Y; Hickford, J G; Bickerstaffe, R; Palmer, B R

    1999-11-01

    Insulin-like growth factor 1 (IGF-1) has been identified as an important growth factor in many biological systems.[1] It shares considerable structural homology with insulin and exerts insulin-like effects on food intake and glucose metabolism. Recently it has been suggested to play a role in regulating cellular proliferation and migration during the development of hair follicles. [2,3] To exert its biological effects, the IGF-1 is required to activate cells by binding to specific cell-surface receptors. The type I IGF receptor (IGF-1R) is the only IGF receptor to have IGF-mediated signaling functions.[1] In circulation, this growth factor mediates endocrine action of growth hormone (GH) on somatic growth and is bound to specific binding proteins (BPs). The latter control IGF transport, efflux from vascular compartments and association with cell surface receptors.[4] In tissues, IGF-1 is produced by mesenchymal type cells and acts in a paracrine and autocrine fashion by binding to the IGF-1R. This binding activates the receptor tyrosine kinase (RTK) that triggers the downstream responses and finally stimulates cell division.[5] IGF-1 may therefore be able to stimulate the proliferation of hair follicle cells through cellular signaling pathways of its receptors. Local infusion of IGF-1 into sheep has been reported to be capable of stimulating protein synthesis in the skin.[6] It may also increase the production of wool keratin. Recently, transgenic mice overexpressing IGF-1 in the skin have been shown to have earlier hair follicle development than controls.[7] In addition, this growth factor plays an important role in many cell types as a survival factor to prevent cell death.[8] This anti-apoptotic function of IGF-1 may be important to the development of follicle cells as follicles undergo a growth cycle where the regressive, catagen phase is apoptosis driven. In this review, the effects of IGF-1 on follicle cell proliferation and differentiation are discussed. In

  1. Effects of phorbol esters and site-directed mutations on proteolytic processing of a cell surface precursor to human macrophage colony-stimulating factor (M-CSF, CSF-1)

    SciTech Connect

    Rettenmier, C.W.; Stein, J. Children's Hospital, Los Angeles, CA Case Western Reserve Univ., Cleveland, OH )

    1991-03-11

    Soluble forms of DSF-1 are generated by proteolytic cleavage of membrane-bound glycoprotein precursors. In eukaryotic expression systems, a 4 kilobase (kb) human cDNA encodes a 522 amino acid DSF-1 precursor which is rapidly processed within the cell to yield an efficiently secreted form of the growth factor. By contrast, an alternatively spliced 1.6 kb cDNA encodes a 224 amino acid precursor stably expressed on the cell surface where it is slowly and inefficiently cleaved to release soluble human CSF-1; this plasma membrane-bound precursor is biologically active for stimulating CSF-1-dependent cells. Treatment with phorbol ester (PMA) accelerated proteolytic processing of the cell surface CSF-1 precursor, resulting in a 30-fold increase in the recovery of soluble growth factor within 60 min. This enhanced cleavage was mediated by a cellular protease which is possibly the same enzyme responsible for the normally slow rate of processing and whose activity is stimulated by PMA activation of protein kinase C. Two mutations were introduced near the proteolytic cleavage site of the precursor. Substitution of the only basic amino acid in the vicinity had no effect on processing. However, deletion of a 6 amino acid segment in the region reduced the rate of cleavage about six-fold in the absence or presence of PMA.

  2. Rhomboid Enhancer Activity Defines a Subset of Drosophila Neural Precursors Required for Proper Feeding, Growth and Viability

    PubMed Central

    Gresser, Amy L.; Gutzwiller, Lisa M.; Gauck, Mackenzie K.; Hartenstein, Volker; Cook, Tiffany A.; Gebelein, Brian

    2015-01-01

    Organismal growth regulation requires the interaction of multiple metabolic, hormonal and neuronal pathways. While the molecular basis for many of these are well characterized, less is known about the developmental origins of growth regulatory structures and the mechanisms governing control of feeding and satiety. For these reasons, new tools and approaches are needed to link the specification and maturation of discrete cell populations with their subsequent regulatory roles. In this study, we characterize a rhomboid enhancer element that selectively labels four Drosophila embryonic neural precursors. These precursors give rise to the hypopharyngeal sensory organ of the peripheral nervous system and a subset of neurons in the deutocerebral region of the embryonic central nervous system. Post embryogenesis, the rhomboid enhancer is active in a subset of cells within the larval pharyngeal epithelium. Enhancer-targeted toxin expression alters the morphology of the sense organ and results in impaired larval growth, developmental delay, defective anterior spiracle eversion and lethality. Limiting the duration of toxin expression reveals differences in the critical periods for these effects. Embryonic expression causes developmental defects and partially penetrant pre-pupal lethality. Survivors of embryonic expression, however, ultimately become viable adults. In contrast, post-embryonic toxin expression results in fully penetrant lethality. To better define the larval growth defect, we used a variety of assays to demonstrate that toxin-targeted larvae are capable of locating, ingesting and clearing food and they exhibit normal food search behaviors. Strikingly, however, following food exposure these larvae show a rapid decrease in consumption suggesting a satiety-like phenomenon that correlates with the period of impaired larval growth. Together, these data suggest a critical role for these enhancer-defined lineages in regulating feeding, growth and viability. PMID

  3. Rhomboid Enhancer Activity Defines a Subset of Drosophila Neural Precursors Required for Proper Feeding, Growth and Viability.

    PubMed

    Gresser, Amy L; Gutzwiller, Lisa M; Gauck, Mackenzie K; Hartenstein, Volker; Cook, Tiffany A; Gebelein, Brian

    2015-01-01

    Organismal growth regulation requires the interaction of multiple metabolic, hormonal and neuronal pathways. While the molecular basis for many of these are well characterized, less is known about the developmental origins of growth regulatory structures and the mechanisms governing control of feeding and satiety. For these reasons, new tools and approaches are needed to link the specification and maturation of discrete cell populations with their subsequent regulatory roles. In this study, we characterize a rhomboid enhancer element that selectively labels four Drosophila embryonic neural precursors. These precursors give rise to the hypopharyngeal sensory organ of the peripheral nervous system and a subset of neurons in the deutocerebral region of the embryonic central nervous system. Post embryogenesis, the rhomboid enhancer is active in a subset of cells within the larval pharyngeal epithelium. Enhancer-targeted toxin expression alters the morphology of the sense organ and results in impaired larval growth, developmental delay, defective anterior spiracle eversion and lethality. Limiting the duration of toxin expression reveals differences in the critical periods for these effects. Embryonic expression causes developmental defects and partially penetrant pre-pupal lethality. Survivors of embryonic expression, however, ultimately become viable adults. In contrast, post-embryonic toxin expression results in fully penetrant lethality. To better define the larval growth defect, we used a variety of assays to demonstrate that toxin-targeted larvae are capable of locating, ingesting and clearing food and they exhibit normal food search behaviors. Strikingly, however, following food exposure these larvae show a rapid decrease in consumption suggesting a satiety-like phenomenon that correlates with the period of impaired larval growth. Together, these data suggest a critical role for these enhancer-defined lineages in regulating feeding, growth and viability.

  4. Engineering growth factors for regenerative medicine applications.

    SciTech Connect

    Mitchell, Aaron C.; Briquez, Priscilla S.; Hubbell, Jeffrey A.; Cochran, Jennifer R.

    2016-01-15

    Growth factors are important morphogenetic proteins that instruct cell behavior and guide tissue repair and renewal. Although their therapeutic potential holds great promise in regenerative medicine applications, translation of growth factors into clinical treatments has been hindered by limitations including poor protein stability, low recombinant expression yield, and suboptimal efficacy. This review highlights current tools, technologies, and approaches to design integrated and effective growth factor-based therapies for regenerative medicine applications. The first section describes rational and combinatorial protein engineering approaches that have been utilized to improve growth factor stability, expression yield, biodistribution, and serum half-life, or alter their cell trafficking behavior or receptor binding affinity. The second section highlights elegant biomaterial-based systems, inspired by the natural extracellular matrix milieu, that have been developed for effective spatial and temporal delivery of growth factors to cell surface receptors. Although appearing distinct, these two approaches are highly complementary and involve principles of molecular design and engineering to be considered in parallel when developing optimal materials for clinical applications.

  5. Placenta Growth Factor in Diabetic Wound Healing

    PubMed Central

    Cianfarani, Francesca; Zambruno, Giovanna; Brogelli, Laura; Sera, Francesco; Lacal, Pedro Miguel; Pesce, Maurizio; Capogrossi, Maurizio C.; Failla, Cristina Maria; Napolitano, Monica; Odorisio, Teresa

    2006-01-01

    Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process. PMID:17003476

  6. Hafnium carbamates and ureates: new class of precursors for low-temperature growth of HfO2 thin films.

    PubMed

    Pothiraja, Ramasamy; Milanov, Andrian P; Barreca, Davide; Gasparotto, Alberto; Becker, Hans-Werner; Winter, Manuela; Fischer, Roland A; Devi, Anjana

    2009-04-21

    Novel volatile compounds of hafnium, namely tetrakis-N,O-dialkylcarbamato hafnium(iv) [Hf((i)PrNC(O)O(i)Pr)(4)] () and tetrakis-N,N,N'-trialkylureato hafnium(iv) [Hf((i)PrNC(O)N-(Me)Et)(4)] (), have been synthesized through the simple insertion reaction of isopropyl isocyanate into hafnium isopropoxide and hafnium ethylmethylamide, respectively; based on the promising thermal properties, compound has been evaluated as a precursor for metalorganic chemical vapor deposition (MOCVD) of HfO(2) thin films, which resulted in the growth of stoichiometric and crystalline layers with a uniform morphology at temperature as low as 250 degrees C.

  7. Metabolism of the phospholipid precursor inositol and its relationship to growth and viability in the natural auxotroph Schizosaccharomyces pombe.

    PubMed Central

    Fernandez, S; Homann, M J; Henry, S A; Carman, G M

    1986-01-01

    Phospholipid metabolism in the fission yeast Schizosaccharomyces pombe was examined. Three enzymes of phospholipid biosynthesis, cytidine diphosphate diacylglycerol synthase (CDP-DG), phosphatidylinositol (PI) synthase, and phosphatidylserine (PS) synthase, were characterized in extracts of S. pombe cells. Contrary to an earlier report, we were able to demonstrate that CDP-DG served as a precursor for PI and PS biosynthesis in S. pombe. S. pombe is naturally auxotrophic for the phospholipid precursor inositol. We found that S. pombe was much more resistant to loss of viability during inositol starvation than artificially generated inositol auxotrophs of Saccharomyces cerevisiae. The phospholipid composition of S. pombe cells grown in inositol-rich medium (50 microM) was similar to that of S. cerevisiae cells grown under similar conditions. However, growth of S. pombe at low inositol concentrations (below 30 microM) affected the ratio of the anionic phospholipids PI and PS, while the relative proportions of other glycerophospholipids remained unchanged. During inositol starvation, the rate of PI synthesis decreased rapidly, and there was a concomitant increase in the rate of PS synthesis. Phosphatidic acid and CDP-DG, which are precursors to these phospholipids, also increased when PI synthesis was blocked by lack of exogenous inositol. The major product of turnover of inositol-containing phospholipids in S. pombe was found to be free inositol, which accumulated in the medium and could be reused by the cell. Images PMID:3011744

  8. Aging Precursor Solution in High Humidity Remarkably Promoted Grain Growth in Cu₂ZnSnS₄ Films.

    PubMed

    Guan, Zhongjie; Luo, Wenjun; Xu, Yao; Tao, Qiuchen; Wen, Xin; Zou, Zhigang

    2016-03-02

    Earth-abundant Cu2ZnSnS4 (CZTS) is a promising material for thin film solar cells or solar water splitting cells. Generally, large grain size and vertical penetration are highly desirable microstructures to high-efficiency solar conversion devices. Up to date, some kinds of vacuum methods have been used to prepare large grain-sized CZTS, which are expensive and limit their applications on a large scale. It is still a key challenge to prepare large-grained and vertical-penetration CZTS by a low-cost solution method. In this study, we obtained vertical-penetration CZTS thin film with 1.3 μm grain sizes by a faclie solution method. Different from previous studies, precursor solution was aged in high-humidity air before it was used to prepare CZTS films. The grain size prepared with aging precursor solution was one of the largest among the samples prepared by a solution method after sulfurizing. Moreover, the large-grained CZTS films were used as photocathodes for solar water splitting, which exhibited a much higher photocurrent than those of the samples without aging. To the best of our knowledge, this is the first demonstration to promote grain growth in CZTS by aging precursor solution in high-humidity air. This aging method can offer a reference to prepare other high-performance films.

  9. In situ growth of ZnO nanoparticles in precursor-insensitive water-in-oil microemulsion as soft nanoreactors.

    PubMed

    Bumajdad, Ali; Madkour, Metwally

    2015-01-01

    Zinc oxide (ZnO) nanostructures of uniform shapes and sizes (spherical, needle-like, and acicular) were directly synthesized using a relatively precursor-insensitive water-in-n-heptane microemulsion system stabilized by a mixture of cationic and non-ionic surfactants. With this colloidal system, the synthesized ZnO possesses the highest reported surface area (76 m(2) g(-1)) among the published reports utilizing other microemulsion systems. Such precursor insensitivity allowed studying the effect of Zn precursor:precipitating agent molar ratio (as high as 1:8) on the particle size, specific surface area, porosity, and morphology of the synthesized nanoparticles. The interaction of the cationic surfactant head groups and their Br(-) counter ions with Zn(2+) and OH(-) ions is believed to play a major role in controlling the ZnO characteristics. Due to such interactions, it is believed that the nucleation processes are retarded while the growth is more dominating if compared with other microemulsion systems.

  10. Layered Seed-Growth of AgGe Football-like Microspheres via Precursor-Free Picosecond Laser Synthesis in Water

    NASA Astrophysics Data System (ADS)

    Zhang, Dongshi; Gökce, Bilal; Notthoff, Christian; Barcikowski, Stephan

    2015-09-01

    Hybrid particles are of great significance in terms of their adjustable optical, electronic, magnetic, thermal and mechanical properties. As a novel technique, laser ablation in liquids (LAL) is famous for its precursor-free, “clean” synthesis of hybrid particles with various materials. Till now, almost all the LAL-generated particles originate from the nucleation-growth mechanism. Seed-growth of particles similar to chemical methods seems difficult to be achieved by LAL. Here, we not only present novel patch-joint football-like AgGe microspheres with a diameter in the range of 1 ~ 7 μm achievable by laser ablation in distilled water but also find direct evidences of their layered seed growth mechanism. Many critical factors contribute to the formation of AgGe microspheres: fast laser-generated plasma process provide an excellent condition for generating large amount of Ge and Ag ions/atoms, their initial nucleation and galvanic replacement reaction, while cavitation bubble confinement plays an important role for the increase of AgGe nuclei and subsequent layered growth in water after bubble collapse. Driven by work function difference, Ge acts as nucleation agent for silver during alloy formation. This new seed-growth mechanism for LAL technique opens new opportunities to develop a large variety of novel hybrid materials with controllable properties.

  11. Layered Seed-Growth of AgGe Football-like Microspheres via Precursor-Free Picosecond Laser Synthesis in Water

    PubMed Central

    Zhang, Dongshi; Gökce, Bilal; Notthoff, Christian; Barcikowski, Stephan

    2015-01-01

    Hybrid particles are of great significance in terms of their adjustable optical, electronic, magnetic, thermal and mechanical properties. As a novel technique, laser ablation in liquids (LAL) is famous for its precursor-free, “clean” synthesis of hybrid particles with various materials. Till now, almost all the LAL-generated particles originate from the nucleation-growth mechanism. Seed-growth of particles similar to chemical methods seems difficult to be achieved by LAL. Here, we not only present novel patch-joint football-like AgGe microspheres with a diameter in the range of 1 ~ 7 μm achievable by laser ablation in distilled water but also find direct evidences of their layered seed growth mechanism. Many critical factors contribute to the formation of AgGe microspheres: fast laser-generated plasma process provide an excellent condition for generating large amount of Ge and Ag ions/atoms, their initial nucleation and galvanic replacement reaction, while cavitation bubble confinement plays an important role for the increase of AgGe nuclei and subsequent layered growth in water after bubble collapse. Driven by work function difference, Ge acts as nucleation agent for silver during alloy formation. This new seed-growth mechanism for LAL technique opens new opportunities to develop a large variety of novel hybrid materials with controllable properties. PMID:26334136

  12. Heterogeneous Pyrolysis: A Route for Epitaxial Growth of hBN Atomic Layers on Copper Using Separate Boron and Nitrogen Precursors.

    PubMed

    Siegel, Gene; Ciobanu, Cristian V; Narayanan, Badri; Snure, Michael; Badescu, Stefan C

    2017-04-12

    Growth of hBN on metal substrates is often performed via chemical vapor deposition from a single precursor (e.g., borazine) and results in hBN monolayers limited by the substrates catalyzing effect. Departing from this paradigm, we demonstrate close control over the growth of mono-, bi-, and trilayers of hBN on copper using triethylborane and ammonia as independent sources of boron and nitrogen. Using density functional theory (DFT) calculations and reactive force field molecular dynamics, we show that the key factor enabling the growth beyond the first layer is the activation of ammonia through heterogeneous pyrolysis with boron-based radicals at the surface. The hBN layers grown are in registry with each other and assume a perfect or near perfect epitaxial relation with the substrate. From atomic force microscopy (AFM) characterization, we observe a moiré superstructure in the first hBN layer with an apparent height modulation and lateral periodicity of ∼10 nm. While this is unexpected given that the moiré pattern of hBN/Cu(111) does not have a significant morphological corrugation, our DFT calculations reveal a spatially modulated interface dipole layer which determines the unusual AFM response. These findings have improved our understanding of the mechanisms involved in growth of hBN and may help generate new growth methods for applications in which control over the number of layers and their alignment is crucial (such as tunneling barriers, ultrathin capacitors, and graphene-based devices).

  13. FACTORS WHICH CONTROL MAXIMAL GROWTH OF BACTERIA

    PubMed Central

    Sinclair, N. A.; Stokes, J. L.

    1962-01-01

    Sinclair, N. A. (Washington State University, Pullman) and J. L. Stokes. Factors which control maximal growth of bacteria. J. Bacteriol. 83:1147–1154. 1962.—In a chemically defined medium containing 1% glucose and 0.1% (NH4)2SO4, both of these compounds are virtually exhausted by the growth of Pseudomonas fluorescens. If these carbon, energy, and nitrogen sources are added back to the culture filtrate, maximal growth to the level of the original culture is obtained. This process can be repeated several times with the same results. Eventually, however, the supply of minerals in the culture limits growth. When the nutrient levels are raised to 3% glucose and 0.3% (NH4)2SO4, lack of oxygen and low pH limit growth before the supply of nutrients is exhausted. There is no evidence that specific autoinhibitory substances are produced either in chemically defined or complex nitrogenous media or that physical crowding of the cells limits growth. The results with Escherichia coli are similar to those with P. fluorescens. However, after a few growth cycles aerobically and after only one growth cycle anaerobically, inhibitory substances, probably organic acids, accumulate and limit growth. PMID:13913264

  14. Role of fibroblast growth factor receptor signaling in kidney development.

    PubMed

    Bates, Carlton M

    2011-08-01

    Fibroblast growth factor receptors (Fgfrs) consist of four signaling family members and one nonsignaling "decoy" receptor, Fgfr-like 1 (Fgfrl1), all of which are expressed in the developing kidney. Several studies have shown that exogenous fibroblast growth factors (Fgfs) affect growth and maturation of the metanephric mesenchyme (MM) and ureteric bud (UB) in cultured tissues. Transgenic and conditional knockout approaches in whole animals have shown that Fgfr1 and Fgfr2 (predominantly the IIIc isoform) in kidney mesenchyme are critical for early MM and UB formation. Conditional deletion of the ligand, Fgf8, in nephron precursors or global deletion of Fgfrl1 interrupts nephron formation. Fgfr2 (likely the IIIb isoform signaling downstream of Fgf7 and Fgf10) is critical for ureteric morphogenesis. Moreover, Fgfr2 appears to act independently of Frs2α (the major signaling adapter for Fgfrs) in regulating UB branching. Loss of Fgfr2 in the MM leads to many kidney and urinary tract anomalies, including vesicoureteral reflux. Thus Fgfr signaling is critical for patterning of virtually all renal lineages at early and later stages of development.

  15. PROSPECT - GROWTH FACTOR CONTROL OF BONE MASS

    PubMed Central

    Canalis, Ernesto

    2010-01-01

    Bone formation is determined by the number and function of osteoblasts. Cell number is governed by factors that regulate the replication and differentiation of pre-osteoblasts and factors that regulate osteoblastic cell death. Cell function is controlled by signals acting on the mature osteoblast. Platelet derived and fibroblast growth factors are bone cell mitogens. Bone morphogenetic proteins (BMP) and Wnt induce the differentiation of mesenchymal cells toward osteoblasts, and insulin-like growth factor (IGF)-I stimulates the function of mature osteoblasts and prevents their death. The activity of BMP, Wnt and IGF-I is modulated by extracellular antagonists or binding proteins. Changes in growth factor synthesis and activity may play a role in the pathogenesis of selected forms of osteoporosis, and alterations in the expression or binding of the extracellular antagonists can be associated with changes in bone mass. Current approaches to bone anabolic therapies for osteoporosis include the administration of a growth factor, such as IGF-I, or the neutralization of an antagonist. Ideally, the targeting of an anabolic agent should be specific to bone to preclude non-skeletal unwanted side effects. Clinical trials are needed to determine the long-term effectiveness and safety of novel anabolic agents for the management of osteoporosis. PMID:19718659

  16. Depression is a risk factor for coronary artery disease in men: the precursors study.

    PubMed

    Ford, D E; Mead, L A; Chang, P P; Cooper-Patrick, L; Wang, N Y; Klag, M J

    1998-07-13

    Several studies have found that depression is an independent predictor of poor outcome after the onset of clinical coronary artery disease. There are few data concerning depression as a risk factor for the development of coronary artery disease. To determine if clinical depression is an independent risk factor for incident coronary artery disease. The Johns Hopkins Precursors Study is a prospective, observational study of 1190 male medical students who were enrolled between 1948 and 1964 and who continued to be followed up. In medical school and through the follow-up period, information was collected on family history, health behaviors, and clinical depression. Cardiovascular disease end points have been assessed with reviews of annual questionnaires, National Death Index searches, medical records, death certificates, and autopsy reports. The cumulative incidence of clinical depression in the medical students at 40 years of follow-up was 12%. Men who developed clinical depression drank more coffee than those who did not but did not differ in terms of baseline blood pressure, serum cholesterol levels, smoking status, physical activity, obesity, or family history of coronary artery disease. In multivariate analysis, the men who reported clinical depression were at significantly greater risk for subsequent coronary heart disease (relative risk [RR], 2.12; 95% confidence interval [CI], 1.24-3.63) and myocardial infarction (RR, 2.12; 95% CI, 1.11-4.06). The increased risk associated with clinical depression was present even for myocardial infarctions occurring 10 years after the onset of the first depressive episode (RR, 2.1; 95% CI, 1.1-4.0). Clinical depression appears to be an independent risk factor for incident coronary artery disease for several decades after the onset of the clinical depression.

  17. gone early, a novel germline factor, ensures the proper size of the stem cell precursor pool in the Drosophila ovary.

    PubMed

    Matsuoka, Shinya; Gupta, Swati; Suzuki, Emiko; Hiromi, Yasushi; Asaoka, Miho

    2014-01-01

    In order to sustain lifelong production of gametes, many animals have evolved a stem cell-based gametogenic program. In the Drosophila ovary, germline stem cells (GSCs) arise from a pool of primordial germ cells (PGCs) that remain undifferentiated even after gametogenesis has initiated. The decision of PGCs to differentiate or remain undifferentiated is regulated by somatic stromal cells: specifically, epidermal growth factor receptor (EGFR) signaling activated in the stromal cells determines the fraction of germ cells that remain undifferentiated by shaping a Decapentaplegic (Dpp) gradient that represses PGC differentiation. However, little is known about the contribution of germ cells to this process. Here we show that a novel germline factor, Gone early (Goe), limits the fraction of PGCs that initiate gametogenesis. goe encodes a non-peptidase homologue of the Neprilysin family metalloendopeptidases. At the onset of gametogenesis, Goe was localized on the germ cell membrane in the ovary, suggesting that it functions in a peptidase-independent manner in cell-cell communication at the cell surface. Overexpression of Goe in the germline decreased the number of PGCs that enter the gametogenic pathway, thereby increasing the proportion of undifferentiated PGCs. Inversely, depletion of Goe increased the number of PGCs initiating differentiation. Excess PGC differentiation in the goe mutant was augmented by halving the dose of argos, a somatically expressed inhibitor of EGFR signaling. This increase in PGC differentiation resulted in a massive decrease in the number of undifferentiated PGCs, and ultimately led to insufficient formation of GSCs. Thus, acting cooperatively with a somatic regulator of EGFR signaling, the germline factor goe plays a critical role in securing the proper size of the GSC precursor pool. Because goe can suppress EGFR signaling activity and is expressed in EGF-producing cells in various tissues, goe may function by attenuating EGFR signaling

  18. gone early, a Novel Germline Factor, Ensures the Proper Size of the Stem Cell Precursor Pool in the Drosophila Ovary

    PubMed Central

    Matsuoka, Shinya; Gupta, Swati; Suzuki, Emiko; Hiromi, Yasushi; Asaoka, Miho

    2014-01-01

    In order to sustain lifelong production of gametes, many animals have evolved a stem cell–based gametogenic program. In the Drosophila ovary, germline stem cells (GSCs) arise from a pool of primordial germ cells (PGCs) that remain undifferentiated even after gametogenesis has initiated. The decision of PGCs to differentiate or remain undifferentiated is regulated by somatic stromal cells: specifically, epidermal growth factor receptor (EGFR) signaling activated in the stromal cells determines the fraction of germ cells that remain undifferentiated by shaping a Decapentaplegic (Dpp) gradient that represses PGC differentiation. However, little is known about the contribution of germ cells to this process. Here we show that a novel germline factor, Gone early (Goe), limits the fraction of PGCs that initiate gametogenesis. goe encodes a non-peptidase homologue of the Neprilysin family metalloendopeptidases. At the onset of gametogenesis, Goe was localized on the germ cell membrane in the ovary, suggesting that it functions in a peptidase-independent manner in cell–cell communication at the cell surface. Overexpression of Goe in the germline decreased the number of PGCs that enter the gametogenic pathway, thereby increasing the proportion of undifferentiated PGCs. Inversely, depletion of Goe increased the number of PGCs initiating differentiation. Excess PGC differentiation in the goe mutant was augmented by halving the dose of argos, a somatically expressed inhibitor of EGFR signaling. This increase in PGC differentiation resulted in a massive decrease in the number of undifferentiated PGCs, and ultimately led to insufficient formation of GSCs. Thus, acting cooperatively with a somatic regulator of EGFR signaling, the germline factor goe plays a critical role in securing the proper size of the GSC precursor pool. Because goe can suppress EGFR signaling activity and is expressed in EGF-producing cells in various tissues, goe may function by attenuating EGFR

  19. Controlled Isotropic and Anisotropic Shell Growth in β-NaLnF4 Nanocrystals Induced by Precursor Injection Rate.

    PubMed

    Fischer, Stefan; Swabeck, Joseph K; Alivisatos, A Paul

    2017-09-06

    Precise morphology and composition control is vital for designing multifunctional lanthanide-doped core/shell nanocrystals. Herein, we report controlled isotropic and anisotropic shell growth techniques in hexagonal sodium rare-earth tetrafluoride (β-NaLnF4) nanocrystals by exploiting the kinetics of the shell growth. A drastic change of the shell morphology was observed by changing the injection rate of the shell precursors while keeping all other reaction conditions constant. We obtained isotropic shell growth for fast sequential injection and a preferred growth of the shell layers along the crystal's c-axis [001] for slow dropwise injection. Using this slow shell growth technique, we have grown rod-like shells around different almost spherical core nanocrystals. Bright and efficient upconversion was measured for both isotropic and rod-like shells around β-NaYF4 nanocrystals doped with Yb(3+)/Er(3+) and Yb(3+)/Tm(3+). Photoluminescence upconversion quantum yield and lifetime measurements reveal the high quality of the core/shell nanocrystal. Furthermore, multishell rod-like nanostructures have been prepared with optically active cores and tips separated by an inert intermediate shell layer. The controlled anisotropic shell growth allows the design of new core/multishell nanostructures and enables independent investigations of the chemistry and physics of different nanocrystal facets.

  20. Sequential and γ-secretase-dependent processing of the betacellulin precursor generates a palmitoylated intracellular-domain fragment that inhibits cell growth

    PubMed Central

    Stoeck, Alexander; Shang, Li; Dempsey, Peter J.

    2010-01-01

    Betacellulin (BTC) belongs to the family of epidermal growth factor (EGF)-like growth factors that are expressed as transmembrane precursors and undergo proteolytic ectodomain shedding to release soluble mature ligands. BTC is a dual-specificity ligand for ErbB1 and ErbB4 receptors, and can activate unique signal-transduction pathways that are beneficial for the function, survival and regeneration of pancreatic β-cells. We have previously shown that BTC precursor (proBTC) is cleaved by ADAM10 to generate soluble ligand and a stable, transmembrane remnant (BTC-CTF). In this study, we analyzed the fate of the BTC-CTF in greater detail. We demonstrated that proBTC is cleaved by ADAM10 to produce BTC-CTF, which then undergoes intramembrane processing by presenilin-1- and/or presenilin-2-dependent γ-secretase to generate an intracellular-domain fragment (BTC-ICD). We found that the proBTC cytoplasmic domain is palmitoylated and that palmitoylation is not required for ADAM10-dependent cleavage but is necessary for the stability and γ-secretase-dependent processing of BTC-CTF to generate BTC-ICD. Additionally, palmitoylation is required for nuclear-membrane localization of BTC-ICD, as demonstrated by the redistribution of non-palmitoylated BTC-ICD mutant to the nucleoplasm. Importantly, a novel receptor-independent role for BTC-ICD signaling is suggested by the ability of BTC-ICD to inhibit cell growth in vitro. PMID:20530572

  1. Peripheral Brain Derived Neurotrophic Factor Precursor Regulates Pain as an Inflammatory Mediator

    PubMed Central

    Luo, Cong; Zhong, Xiao-Lin; Zhou, Fiona H.; Li, Jia-yi; Zhou, Pei; Xu, Jun-Mei; Song, Bo; Li, Chang-Qi; Zhou, Xin-Fu; Dai, Ru-Ping

    2016-01-01

    The precursor of brain derived neurotrophic factor (proBDNF), the unprocessed BDNF gene product, binds to its receptors and exerts the opposing biologic functions of mature BDNF. proBDNF is expressed in the peripheral tissues but the functions of peripheral proBDNF remain elusive. Here we showed that proBDNF and its predominant receptor, p75 pan-neurotrophin receptor were upregulated in the nerve fibers and inflammatory cells in the local tissue in inflammatory pain. Neutralization of proBDNF by polyclonal antibody attenuated pain in different models of inflammatory pain. Unilateral intra-plantar supplementation of proBDNF by injecting exogenous proBDNF or ectopic overexpression resulted in pain hypersensitivity and induced spinal phosphorylated extracellular signal-regulated kinase activation. Exogenous proBDNF injection induced the infiltration of inflammatory cells and the activation of proinflammatory cytokines, suggesting that inflammatory reaction contributed to the pro-algesic effect of proBDNF. Finally, we generated monoclonal anti-proBDNF antibody that could biologically block proBDNF. Administration of monoclonal Ab-proBDNF attenuated various types of inflammatory pain and surgical pain. Thus, peripheral proBDNF is a potential pain mediator and anti-proBDNF pretreatment may alleviate the development of inflammatory pain. PMID:27251195

  2. Patterned growth of p-type MoS2 atomic layers using sol-gel as precursor

    SciTech Connect

    Zheng, Wei; Lin, Junhao; Feng, Wei; Xiao, Kai; Qiu, Yunfeng; Chen, XiaoShuang; Liu, Guangbo; Cao, Wenwu; Pantelides, Sokrates T.; Zhou, Wu; Hu, PingAn

    2016-07-19

    2D layered MoS2 has drawn intense attention for its applications in flexible electronic, optoelectronic, and spintronic devices. Most of the MoS2 atomic layers grown by conventional chemical vapor deposition techniques are n-type due to the abundant sulfur vacancies. Facile production of MoS2 atomic layers with p-type behavior, however, remains challenging. Here, a novel one-step growth has been developed to attain p-type MoS2 layers in large scale by using Mo-containing sol–gel, including 1% tungsten (W). Atomic-resolution electron microscopy characterization reveals that small tungsten oxide clusters are commonly present on the as-grown MoS2 film due to the incomplete reduction of W precursor at the reaction temperature. These omnipresent small tungsten oxide clusters contribute to the p-type behavior, as verified by density functional theory calculations, while preserving the crystallinity of the MoS2 atomic layers. The Mo containing sol–gel precursor is compatible with the soft-lithography techniques, which enables patterned growth of p-type MoS2 atomic layers into regular arrays with different shapes, holding great promise for highly integrated device applications. Lastly, an atomically thin p–n junction is fabricated by the as-prepared MoS2, which shows strong rectifying behavior.

  3. Patterned growth of p-type MoS2 atomic layers using sol-gel as precursor

    SciTech Connect

    Zheng, Wei; Lin, Junhao; Feng, Wei; Xiao, Kai; Qiu, Yunfeng; Chen, XiaoShuang; Liu, Guangbo; Cao, Wenwu; Pantelides, Sokrates T.; Zhou, Wu; Hu, PingAn

    2016-07-19

    2D layered MoS2 has drawn intense attention for its applications in flexible electronic, optoelectronic, and spintronic devices. Most of the MoS2 atomic layers grown by conventional chemical vapor deposition techniques are n-type due to the abundant sulfur vacancies. Facile production of MoS2 atomic layers with p-type behavior, however, remains challenging. Here, a novel one-step growth has been developed to attain p-type MoS2 layers in large scale by using Mo-containing sol–gel, including 1% tungsten (W). Atomic-resolution electron microscopy characterization reveals that small tungsten oxide clusters are commonly present on the as-grown MoS2 film due to the incomplete reduction of W precursor at the reaction temperature. These omnipresent small tungsten oxide clusters contribute to the p-type behavior, as verified by density functional theory calculations, while preserving the crystallinity of the MoS2 atomic layers. The Mo containing sol–gel precursor is compatible with the soft-lithography techniques, which enables patterned growth of p-type MoS2 atomic layers into regular arrays with different shapes, holding great promise for highly integrated device applications. Lastly, an atomically thin p–n junction is fabricated by the as-prepared MoS2, which shows strong rectifying behavior.

  4. Effect of precursor on growth and morphology of MoS2 monolayer and multilayer

    NASA Astrophysics Data System (ADS)

    Ganorkar, Shraddha; Kim, Jungyoon; Kim, Young-Hwan; Kim, Seong-II

    2015-12-01

    The rise of two-dimensional (2D) material is one of the results of successful efforts of researchers which laid the path to the new era of electronics. One of the most exciting materials is MoS2. Synthesis has been always a major issue as electronic devices need reproducibility along with similar properties for mass productions. Chemical vapor deposition (CVD) is one of the successful methods for 2D materials including graphene. Furthermore, the choice of starting materials for Mo and S source is crucial. The different source has different effects on the layers and morphology of MoS2 films. In this work, we have extensively studied the CVD technique to grow few layers of MoS2 with two precursors MoO3 and MoCl5, show remarkable changes. The MoO3 source gives a triangular shaped MoS2 monolayer while that of MoCl5 can achieve uniform MoS2 without triangle. The absence of geometric shapes with MoCl5 is poorly understood. We tried to explain with MoCl5 precursor, the formation of continuous monolayer of MoS2 without any triangle on the basis of chemical reaction formalism mostly due to one step reaction process and formation of MoS2 from gas phase to the solid phase. The film synthesized by MoCl5 is more continuous and it would be a good choice for device applications.

  5. The role of floodplain width and alluvial bar growth as a precursor for the formation of anabranching rivers

    NASA Astrophysics Data System (ADS)

    Morón, S.; Edmonds, D. A.; Amos, K.

    2017-02-01

    Anabranching rivers are defined as a system of multiple channels separated by stable alluvial islands. While substantial progress has been made in developing a physics-based understanding of what drives the differences between meandering and braided river channels, anabranching rivers have not been well-integrated into these models. Here, we propose that alluvial bar growth on the floodplain may be a precursor for the formation of anabranching rivers. Alluvial bar growth strongly depends on the aspect ratio of the flow (width divided by depth) and rivers with wide floodplains have flows with a large aspect ratio. Consistent with this idea, remotely sensed measurements of floodplain width of four rivers from different climatic and tectonic settings show that anabranching river patterns are often associated with relatively wide floodplains. To explore the physics behind that empirical relationship we carried out two sets of morphodynamic numerical simulations using boundary conditions from field-scale modern anabranching rivers spanning different climatic and geologic settings as well as hypothetical floodplain widths. Results from the simulations show that, for a given flood discharge, widening the floodplain changes the river pattern from single channel to multi-threaded with mobile bars to multi-channeled with immobile islands. Multi-channeled patterns arise because the emergence of bars causes flow bifurcation. Subsequent bifurcation instability leads to the emergence of multiple stable channels. As the channels increase their cross-sectional area, shields stresses on intervening bars are reduced until the bars stabilize into islands. We suggest that the presence of stable islands allows vegetation to grow or cohesive sediment to accumulate leading to enhanced channel bank strength and a stable anabranching pattern. Our results suggest that alluvial bar growth can be a precursor to formation of anabranching rivers. Compared with field measurements our simulations

  6. Transforming growth factor beta1 regulates melanocyte proliferation and differentiation in mouse neural crest cells via stem cell factor/KIT signaling.

    PubMed

    Kawakami, Tamihiro; Soma, Yoshinao; Kawa, Yoko; Ito, Masaru; Yamasaki, Emiko; Watabe, Hidenori; Hosaka, Eri; Yajima, Kenji; Ohsumi, Kayoko; Mizoguchi, Masako

    2002-03-01

    Stem cell factor is essential to the migration and differentiation of melanocytes during embryogenesis based on the observation that mutations in either the stem cell factor gene, or its ligand, KIT, result in defects in coat pigmentation in mice. Stem cell factor is also required for the survival of melanocyte precursors while they are migrating towards the skin. Transforming growth factor beta1 has been implicated in the regulation of both cellular proliferation and differentiation. NCC-melb4, an immortal cloned cell line, was cloned from a mouse neural crest cell. NCC-melb4 cells provide a model to study the specific stage of differentiation and proliferation of melanocytes. They also express KIT as a melanoblast marker. Using the NCC-melb4 cell line, we investigated the effect of transforming growth factor beta1 on the differentiation and proliferation of immature melanocyte precursors. Immunohistochemically, NCC-melb4 cells showed transforming growth factor beta1 expression. The anti-transforming growth factor beta1 antibody inhibited the cell growth, and downregulated the KIT protein and mRNA expression. To investigate further the activation of autocrine transforming growth factor beta1, NCC-melb4 cells were incubated in nonexogenous transforming growth factor beta1 culture medium. KIT protein decreased with anti-transforming growth factor beta1 antibody concentration in a concentration-dependent manner. We concluded that in NCC-melb4 cells, transforming growth factor beta1 promotes melanocyte precursor proliferation in autocrine and/or paracrine regulation. We further investigated the influence of transforming growth factor beta1 in vitro using a neural crest cell primary culture system from wild-type mice. Anti-transforming growth factor beta1 antibody decreased the number of KIT positive neural crest cell. In addition, the anti-transforming growth factor beta1 antibody supplied within the wild-type neural crest explants abolished the growth of the neural

  7. Growth factors and hormones pro-peptides: the unexpected adventures of the BDNF prodomain.

    PubMed

    Zanin, Juan Pablo; Unsain, Nicolás; Anastasia, Agustin

    2017-05-01

    Most growth factors and hormones are synthesized as pre-pro-proteins which are processed to the biologically active mature protein. The pre- and prodomains are cleaved from the precursor protein in the secretory pathway or, in some cases, extracellularly. The canonical functions of these prodomains are to assist in folding and stabilization of the mature domain, to direct intra and extracellular localization, to facilitate storage, and to regulate bioavailability of their mature counterpart. Recently, exciting evidence has revealed that prodomains of certain growth factors, after cleaved from the precursor pro-protein, can act as independent active signaling molecules. In this review, we discuss the various classical functions of prodomains, and the biological consequences of these pro-peptides acting as ligands. We will focus our attention on the brain-derived neurotrophic factor prodomain (pBDNF), which has been recently described as a novel secreted ligand influencing neuronal morphology and physiology. © 2017 International Society for Neurochemistry.

  8. Epidermal Growth Factor and Intestinal Barrier Function

    PubMed Central

    Liu, Hu; Yang, Shufen; Li, Zuohua; Zhong, Jinfeng

    2016-01-01

    Epidermal growth factor (EGF) is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health. PMID:27524860

  9. Role of hematopoietic growth factors in angiogenesis.

    PubMed

    Ribatti, D; Vacca, A; De Falco, G; Ria, R; Roncali, L; Dammacco, F

    2001-01-01

    In early ontogeny, hematopoiesis is closely associated with angiogenesis. This article reviews recent studies of the effect of hematopoietic growth factors on several endothelial cell functions together with recent findings about angiogenesis and antiangiogenic therapies in hematopoietic malignancies such as leukemia, lymphoma and myeloma. Copyright 2001 S. Karger AG, Basel

  10. The amplitude reduction factor and the cumulant expansion method: crucial factors in the structural analysis of alkoxide precursors in solution.

    PubMed

    Bauer, Matthias; Bertagnolli, Helmut

    2007-12-13

    The transition-metal alkoxide yttrium 2-methoxyethoxide Y(OEtOMe)(3) in solution is studied as a model system of the large class of alkoxide precursors used in the sol-gel process by means of EXAFS spectroscopy. The discussion is focused on the amplitude reduction factor S (2)(0) and the cumulant expansion method. If asymmetry is present in the radial distribution function, the determination of the correct structural model can only be achieved by balancing multiple Gaussian shell fits against only one shell fit with a third cumulant C3. A method to identify the best model, based on statistical parameters of the EXAFS fit, is proposed and checked with two well-known reference compounds, Y(5)O(O(i)Pr)(13) and Y(acac)(3).3H(2)O, and applied to the structurally unknown solution of Y(OEtOMe)(3) in 2-methoxyethanol. The two references are also used to discuss the transferability of S(2)(0) values, determined from reference compounds to unknown samples. A model-free procedure to identify the correct amplitude reduction factor S(2)(0) by making use of fits with different k-weighting schemes is critically investigated. This procedure, which does not require any crystallographic data, is used for the case of Y(OEtOMe)(3) in solution, where significant differences of the amplitude reducing factor of both the oxygen and yttrium shell in comparison to the reference Y(5)O(O(i)Pr)(13) were found. With such a detailed analysis of EXAFS data, a reliable characterization of Y(OEtOMe)3 in 2-methoxyethanol by means of EXAFS spectroscopy is possible. The decameric structure unit found in solid Y(OEtOMe)(3) is not preserved, but rather, a pentameric framework similar to that in Y5O(O(i)Pr)(13) is formed.

  11. Nerve Growth Factor and Diabetic Neuropathy

    PubMed Central

    Vinik, Aaron

    2003-01-01

    Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50–90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium. PMID:14668049

  12. Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor.

    PubMed Central

    Mellon, J. K.; Cook, S.; Chambers, P.; Neal, D. E.

    1996-01-01

    We have examined levels of epidermal growth factor (EGF) and transforming growth factor alpha (TGF-alpha) in neoplastic and non-neoplastic bladder tissue using a standard radioimmunoassay technique. Tumour samples had much higher TGF-alpha levels compared with EGF and TGF-alpha levels in malignant tissue were significantly higher than in benign bladder samples. There was, in addition, a difference in mean EGF levels from 'normal' bladder samples from non-tumour bearing areas of bladder in patients with bladder cancer compared with 'normal' bladder tissue obtained at the time of organ retrieval surgery. Levels of EGF and TGF-alpha did not correlate with levels of EGF receptor (EGFR) as determined by a radioligand binding method but levels of TGF-alpha > 10 ng gm-1 of tumour tissue did correlate with EGFR positivity defined using immunohistochemistry. These data suggest that TGF-alpha is the likely ligand for EGFR in bladder tumours. PMID:8605103

  13. Precursor dependent nucleation and growth of ruthenium films during chemical vapor deposition

    SciTech Connect

    Liao, Wen; Ekerdt, John G.

    2016-07-15

    Nucleation and film growth characteristics are reported during chemical vapor deposition of Ru on SiO{sub 2} using triruthenium dodecacarbonyl [Ru{sub 3}(CO){sub 12}] and ruthenium bis(di-t-butylacetamidinate) dicarbonyl [Ru({sup t}Bu-Me-amd){sub 2}(CO){sub 2}]. Films grown from Ru{sub 3}(CO){sub 12} follow the three dimensional (3D) Volmer–Weber growth mode. In contrast, films grown from Ru({sup t}Bu-Me-amd){sub 2}(CO){sub 2} follow the pseudo-layer-by-layer growth mode with two dimensional wetting layer islands forming before 3D particle growth is observed on the islands. A relationship between free isolated hydroxyl [(Si-OH){sub i}] group density and Ru nucleation density is found for Ru{sub 3}(CO){sub 12} and is associated with (Si-OH){sub i} acting as the reaction sites for activation of Ru{sub 3}(CO){sub 12} and in turn generating an adjustable adatom concentration. Carbon monoxide and ammonia addition to the gas phase during film growth from Ru({sup t}Bu-Me-amd){sub 2}(CO){sub 2} lead to smoother films by inducing surface reconstructions during the 3D phase of pseudo-layer-by-layer growth; these gases also lead to films with lower resistivity and lower crystalline character.

  14. Apical Epidermal Growth Factor Receptor Signaling: Regulation of Stretch-dependent Exocytosis in Bladder Umbrella Cells

    PubMed Central

    Balestreire, Elena M.

    2007-01-01

    The apical surface of polarized epithelial cells receives input from mediators, growth factors, and mechanical stimuli. How these stimuli are coordinated to regulate complex cellular functions such as polarized membrane traffic is not understood. We analyzed the requirement for growth factor signaling and mechanical stimuli in umbrella cells, which line the mucosal surface of the bladder and dynamically insert and remove apical membrane in response to stretch. We observed that stretch-stimulated exocytosis required apical epidermal growth factor (EGF) receptor activation and that activation occurred in an autocrine manner downstream of heparin-binding EGF-like growth factor precursor cleavage. Long-term changes in apical exocytosis depended on protein synthesis, which occurred upon EGF receptor-dependent activation of mitogen-activated protein kinase signaling. Our results indicate a novel physiological role for the EGF receptor that couples upstream mechanical stimuli to downstream apical EGF receptor activation that may regulate apical surface area changes during bladder filling. PMID:17287395

  15. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

    PubMed

    Gaviglio, Angela L; Knelson, Erik H; Blobe, Gerard C

    2017-02-07

    High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low Schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble factors that promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent prodifferentiating factor in neuroblastoma. HBEGF mRNA expression is decreased in human neuroblastoma tumors compared with benign tumors, with loss correlating with decreased survival. HBEGF protein is expressed only in stromal compartments of human neuroblastoma specimens, with tissue from high-stage disease containing very little stroma or HBEGF expression. In 3 human neuroblastoma cell lines (SK-N-AS, SK-N-BE2, and SH-SY5Y), soluble HBEGF is sufficient to promote neuroblast differentiation and decrease proliferation. Heparan sulfate proteoglycans and heparin derivatives further enhance HBEGF-induced differentiation by forming a complex with the epidermal growth factor receptor, leading to activation of the ERK1/2 and STAT3 pathways and up-regulation of the inhibitor of DNA binding transcription factor. These data support a role for loss of HBEGF in the neuroblastoma tumor microenvironment in neuroblastoma pathogenesis.-Gaviglio, A. L., Knelson, E. H., Blobe, G. C. Heparin-binding epidermal growth factor-like growth factor promotes neuroblastoma differentiation.

  16. Growth Factors and Tension-Induced Skeletal Muscle Growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  17. Growth factor expression in degenerated intervertebral disc tissue. An immunohistochemical analysis of transforming growth factor beta, fibroblast growth factor and platelet-derived growth factor.

    PubMed

    Tolonen, Jukka; Grönblad, Mats; Vanharanta, Heikki; Virri, Johanna; Guyer, Richard D; Rytömaa, Tapio; Karaharju, Erkki O

    2006-05-01

    Degenerated intervertebral disc has lost its normal architecture, and there are changes both in the nuclear and annular parts of the disc. Changes in cell shape, especially in the annulus fibrosus, have been reported. During degeneration the cells become more rounded, chondrocyte-like, whereas in the normal condition annular cells are more spindle shaped. These chondrocyte-like cells, often forming clusters, affect extracellular matrix turnover. In previous studies transforming growth factor beta (TGFbeta) -1 and -2, basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been highlighted in herniated intervertebral disc tissue. In the present study the same growth factors are analysed immunohistochemically in degenerated intervertebral disc tissue. Disc material was obtained from 16 discs operated for painful degenerative disc disease. Discs were classified according to the Dallas Discogram Description. Different disc regions were analysed in parallel. As normal control disc tissue material from eight organ donors was used. Polyclonal antibodies against different growth factors and TGFbeta receptor type II were used, and the immunoreaction was detected by the avidin biotin complex method. All studied degenerated discs showed immunoreactivity for TGFbeta receptor type II and bFGF. Fifteen of 16 discs were immunopositive for TGFbeta-1 and -2, respectively, and none showed immunoreaction for PDGF. Immunopositivity was located in blood vessels and in disc cells. In the nucleus pulposus the immunoreaction was located almost exclusively in chondrocyte-like disc cells, whereas in the annular region this reaction was either in chondrocyte-like disc cells, often forming clusters, or in fibroblast-like disc cells. Chondrocyte-like disc cells were especially prevalent in the posterior disrupted area. In the anterior area of the annulus fibrosus the distribution was more even between these two cell types. bFGF was expressed in the anterior annulus

  18. Macrophage Migration Inhibitory Factor (MIF) Supports Homing of Osteoclast Precursors to Peripheral Osteolytic Lesions.

    PubMed

    Movila, Alexandru; Ishii, Takenobu; Albassam, Abdullah; Wisitrasameewong, Wichaya; Howait, Mohammed; Yamaguchi, Tsuguno; Ruiz-Torruella, Montserrat; Bahammam, Laila; Nishimura, Kazuaki; Van Dyke, Thomas; Kawai, Toshihisa

    2016-09-01

    By binding to its chemokine receptor CXCR4 on osteoclast precursor cells (OCPs), it is well known that stromal cell-derived factor-1 (SDF-1) promotes the chemotactic recruitment of circulating OCPs to the homeostatic bone remodeling site. However, the engagement of circulating OCPs in pathogenic bone resorption remains to be elucidated. The present study investigated a possible chemoattractant role of macrophage migration inhibitory factor (MIF), another ligand for C-X-C chemokine receptor type 4 (CXCR4), in the recruitment of circulating OCPs to the bone lytic lesion. To accomplish this, we used Csf1r-eGFP-knock-in (KI) mice to establish an animal model of polymethylmethacrylate (PMMA) particle-induced calvarial osteolysis. In the circulating Csf1r-eGFP+ cells of healthy Csf1r-eGFP-KI mice, Csf1r+/CD11b+ cells showed a greater degree of RANKL-induced osteoclastogenesis compared to a subset of Csf1r+/RANK+ cells in vitro. Therefore, Csf1r-eGFP+/CD11b+ cells were targeted as functionally relevant OCPs in the present study. Although expression of the two cognate receptors for MIF, CXCR2 and CXCR4, was elevated on Csf1r+/CD11b+ cells, transmigration of OCPs toward recombinant MIF in vitro was facilitated by ligation with CXCR4, but not CXCR2. Meanwhile, the level of PMMA-induced bone resorption in calvaria was markedly greater in wild-type (WT) mice compared to that detected in MIF-knockout (KO) mice. Interestingly, in contrast to the elevated MIF, diminished SDF-1 was detected in a particle-induced bone lytic lesion of WT mice in conjunction with an increased number of infiltrating CXCR4+ OCPs. However, such diminished SDF-1 was not found in the PMMA-injected calvaria of MIF-KO mice. Furthermore, stimulation of osteoblasts with MIF in vitro suppressed their production of SDF-1, suggesting that MIF can downmodulate SDF-1 production in bone tissue. Systemically administered anti-MIF neutralizing monoclonal antibody (mAb) inhibited the homing of CXCR4+ OCPs, as well as

  19. Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap

    PubMed Central

    Raiesdana, Azad; Kundu, Ramendra; Miller, Clint L.; Kim, Juyong B.; Arora, Komal; Carcamo-Oribe, Ivan; Xiong, Yiqin; Tellakula, Nikhil; Nanda, Vivek; Murthy, Nikitha; Boisvert, William A.; Hedin, Ulf; Perisic, Ljubica; Aldi, Silvia; Maegdefessel, Lars; Pjanic, Milos; Owens, Gary K.; Tallquist, Michelle D.; Quertermous, Thomas

    2015-01-01

    Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including “vascular disease,” “disorder of artery,” and “occlusion of artery,” as well as disease-related cellular functions including “cellular movement” and “cellular growth and proliferation.” In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide

  20. Nerve growth factor promotes human hemopoietic colony growth and differentiation.

    PubMed Central

    Matsuda, H; Coughlin, M D; Bienenstock, J; Denburg, J A

    1988-01-01

    Nerve growth factor (NGF) is a neurotropic polypeptide necessary for the survival and growth of some central neurons, as well as sensory afferent and sympathetic neurons. Much is now known of the structural and functional characteristics of NGF, whose gene has recently been cloned. Since it is synthesized in largest amounts by the male mouse submandibular gland, its role exclusively in nerve growth is questionable. NGF also causes histamine release from rat peritoneal mast cells in vitro, and we have shown elsewhere that it causes significant, dose-dependent, generalized mast cell proliferation in the rat in vivo when administered neonatally. Our experiments now indicate that NGF causes a significant stimulation of granulocyte colonies grown from human peripheral blood in standard hemopoietic methylcellulose assays. Further, NGF appears to act in a relatively selective fashion to induce the differentiation of eosinophils and basophils/mast cells. Depletion experiments show that the NGF effect may be T-cell dependent and that NGF augments the colony-stimulating effect of supernatants from the leukemic T-cell (Mo) line. The hemopoietic activity of NGF is blocked by polyclonal and monoclonal antibodies to NGF. We conclude that NGF may indirectly act as a local growth factor in tissues other than those of the nervous system by causing T cells to synthesize or secrete molecules with colony-stimulating activity. In view of the synthesis of NGF in tissue injury, the involvement of basophils/mast cells and eosinophils in allergic and other inflammatory processes, and the association of mast cells with fibrosis and tissue repair, we postulate that NGF plays an important biological role in a variety of repair processes. PMID:3413109

  1. Effects of Escherichia coli on Mixotrophic Growth of Chlorella minutissima and Production of Biofuel Precursors

    PubMed Central

    Higgins, Brendan T.; VanderGheynst, Jean S.

    2014-01-01

    Chlorella minutissima was co-cultured with Escherichia coli in airlift reactors under mixotrophic conditions (glucose, glycerol, and acetate substrates) to determine possible effects of bacterial contamination on algal biofuel production. It was hypothesized that E. coli would compete with C. minutissima for nutrients, displacing algal biomass. However, C. minutissima grew more rapidly and to higher densities in the presence of E. coli, suggesting a symbiotic relationship between the organisms. At an initial 1% substrate concentration, the co-culture produced 200-587% more algal biomass than the axenic C. minutissima cultures. Co-cultures grown on 1% substrate consumed 23–737% more of the available carbon substrate than the sum of substrate consumed by E. coli and C. minutissima alone. At 1% substrate, total lipid and starch productivity were elevated in co-cultures compared to axenic cultures indicating that bacterial contamination was not detrimental to the production of biofuel precursors in this specific case. Bio-fouling of the reactors observed in co-cultures and acid formation in all mixotrophic cultures, however, could present challenges for scale-up. PMID:24805253

  2. MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells.

    PubMed

    Modzelewska, Katarzyna; Boer, Elena F; Mosbruger, Timothy L; Picard, Daniel; Anderson, Daniela; Miles, Rodney R; Kroll, Mitchell; Oslund, William; Pysher, Theodore J; Schiffman, Joshua D; Jensen, Randy; Jette, Cicely A; Huang, Annie; Stewart, Rodney A

    2016-10-25

    Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway. Modeling NRAS activation in embryonic OPCs generated malignant brain tumors in zebrafish that closely mimic the human oligoneural/NB-FOXR2 CNS-PNET subgroup by histology and comparative oncogenomics. The zebrafish CNS-PNET model was used to show that MEK inhibitors selectively eliminate Olig2(+)/Sox10(+) CNS-PNET tumors in vivo without impacting normal brain development. Thus, MEK inhibitors represent a promising rationally designed therapy for children afflicted with oligoneural/NB-FOXR2 CNS-PNETs.

  3. Growth factor and co-receptor release by structural regulation of substrate metalloprotease accessibility

    PubMed Central

    Parra, Liseth M.; Hartmann, Monika; Schubach, Salome; Ma, Junzhi; Herrlich, Peter; Herrlich, Andreas

    2016-01-01

    Release of cytokines, growth factors and other life-essential molecules from precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high substrate-specificity. We hypothesized that this is achieved by cleavage-regulatory intracellular-domain (ICD)-modifications of the precursors. We show here that cleavage-stimuli-induced specific ICD-modifications cause structural substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1; epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to chymotrypsin/trypsin or soluble ADAM. This inside-out signal transfer required substrate homodimerization and was prevented by cleavage-inhibitory ICD-mutations. In chimeras, regulation could be conferred to a foreign ectodomain, suggesting a common higher-order structure. We predict that substrate-specific protease-accessibility-regulation controls release of numerous ADAM substrates. PMID:27876763

  4. Epidermal growth factor receptor signaling in tissue

    SciTech Connect

    Shvartsman, Stanislav; Wiley, H. S.; Lauffenburger, Douglas A.

    2004-08-01

    Abstract: A peptide purified from the salivary gland of a mouse was shown few years ago to accelerate incisor eruption and eyelid opening in newborn mice, and was named epidermal growth factor (EGF). The members of this family of peptide growth factors had been identified in numerous physiological and pathological contexts. EGF binds to a cell surface EGF receptor, which induces a biochemical modification (phosphorylation) of the receptor's cytoplasmic tail. There is a growing consensus in the research community that, in addition to cellular and molecular studies, the dynamics of the EGFR network and its operation must be examined in tissues. A key challenge is to integrate the existing molecular and cellular information into a system-level description of the EGFR network at the tissue and organism level. In this paper, the two examples of EGFR signaling in tissues are described, and the recent efforts to model EGFR autocrine loops, which is a predominant mode of EGFR activation in vivo, are summarized.

  5. Association of the macrophage activating factor (MAF) precursor activity with polymorphism in vitamin D-binding protein.

    PubMed

    Nagasawa, Hideko; Sasaki, Hideyuki; Uto, Yoshihiro; Kubo, Shinichi; Hori, Hitoshi

    2004-01-01

    Serum vitamin D-binding protein (Gc protein or DBP) is a highly expressed polymorphic protein, which is a precursor of the inflammation-primed macrophage activating factor, GcMAF, by a cascade of carbohydrate processing reactions. In order to elucidate the relationship between Gc polymorphism and GcMAF precursor activity, we estimated the phagocytic ability of three homotypes of Gc protein, Gc1F-1F, Gc1S-1S and Gc2-2, through processing of their carbohydrate moiety. We performed Gc typing of human serum samples by isoelectric focusing (IEF). Gc protein from human serum was purified by affinity chromatography with 25-hydroxyvitamin D3-sepharose. A phagocytosis assay of Gc proteins, modified using beta-glycosidase and sialidase, was carried out. The Gc1F-1F phenotype was revealed to possess Galbeta1-4GalNAc linkage by the analysis of GcMAF precursor activity using beta1-4 linkage-specific galactosidase from jack bean. The GcMAF precursor activity of the Gc1F-1F phenotype was highest among three Gc homotypes. The Gc polymorphism and carbohydrate diversity of Gc protein are significant for its pleiotropic effects.

  6. A mathematical model for crystal growth by aggregation of precursor metastable nanoparticles.

    PubMed

    Drews, Timothy O; Katsoulakis, Markos A; Tsapatsis, Michael

    2005-12-22

    A mathematical model is developed to describe aggregative crystal growth, including oriented aggregation, from evolving pre-existing primary nanoparticles with composition and structure that are different from that of the final crystalline aggregate. The basic assumptions of the model are based on the ideas introduced in an earlier published report [Buyanov and Krivoruchko, Kinet. Katal. 1976, 17, 666-675] to describe the growth of low-solubility metal hydroxides (e.g., iron oxides) by oriented aggregation. It is assumed that primary particles can be described as pseudo-species A, B, and C, which have the following properties: (1) fresh primary particles (colloidally stable inert nanoparticles, denoted as A), (2) mature primary particles (partially transformed nanoparticles at an optimum stage of development for attachment to a growing crystal, denoted as B), and (3) nucleated primary particles (denoted as C1). The evolution of primary particles, A --> B --> C1, is treated as two first-order consecutive reactions. Crystal growth via crystal-crystal aggregation (Ci +) is described using the Smoluchowski equation. The new element of this model is the inclusion of an additional crystal growth mechanism via the addition of primary particles (B) to crystals (Ci): (B + ). Two distinct, but constant, kernels (K not equal K') are used. It is shown that, when K' = 0, a steplike crystal size distribution (CSD) is obtained. Within a range of K'/K values (e.g., K'/K = 10(3)), CSD with multiple peaks are obtained. Comparison with predictions of models that do not include the intermediate stage of primary particles (B) indicates pronounced differences. Despite its simplicity, the model is able to capture the qualitative features of CSD evolution that have been obtained from crystal growth experiments in hematite, which is a system that is believed to undergo oriented aggregation.

  7. Simplifying the growth of hybrid single-crystals by using nanoparticle precursors: the case of AgI

    NASA Astrophysics Data System (ADS)

    Xu, Biao; Wang, Ruji; Wang, Xun

    2012-03-01

    We report the synthesis of a series of AAgmIn single-crystals within 24 h, at room temperature, utilizing AgI nanoparticles (NPs) as the precursor. The AgI NPs impart high reactivity under mild conditions and favor the growth kinetics. 0D, 1D and 2D iodoargentate crystals can be obtained. This work represents the first application of NPs in the field of organo-metal-halide crystals and will inspire the design of other AMmXn crystals.We report the synthesis of a series of AAgmIn single-crystals within 24 h, at room temperature, utilizing AgI nanoparticles (NPs) as the precursor. The AgI NPs impart high reactivity under mild conditions and favor the growth kinetics. 0D, 1D and 2D iodoargentate crystals can be obtained. This work represents the first application of NPs in the field of organo-metal-halide crystals and will inspire the design of other AMmXn crystals. Electronic supplementary information (ESI) available: XPS spectra of AgI NPs, schematic representation of the formation process of [Ag4I8]4- in 2, UV-Vis spectra of the DTMA-Ag-I clusters, analysis of force balance of a crystal at the interface between H2O and CH2Cl2 and crystal structure depiction of 1-4. CIF files of 1-4 are also provided. CCDC reference numbers 863848, 863849, 863850 and 863851. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2nr30139c

  8. Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors

    PubMed Central

    Bortvedt, Sarah F.; Lund, P. Kay

    2013-01-01

    Purpose of review To summarize recent evidence that IGF1 mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent findings Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogues in short bowel syndrome and Crohn’s disease. This review highlights evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn’s disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that SOCS protein induction by GH or GLP2 in normal or inflamed intestine, may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. Summary IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed. PMID:22241077

  9. Proteolytic Processing Regulates Placental Growth Factor Activities*

    PubMed Central

    Hoffmann, Daniel C.; Willenborg, Sebastian; Koch, Manuel; Zwolanek, Daniela; Müller, Stefan; Becker, Ann-Kathrin A.; Metzger, Stephanie; Ehrbar, Martin; Kurschat, Peter; Hellmich, Martin; Hubbell, Jeffrey A.; Eming, Sabine A.

    2013-01-01

    Placental growth factor (PlGF) is a critical mediator of blood vessel formation, yet mechanisms of its action and regulation are incompletely understood. Here we demonstrate that proteolytic processing regulates the biological activity of PlGF. Specifically, we show that plasmin processing of PlGF-2 yields a protease-resistant core fragment comprising the vascular endothelial growth factor receptor-1 binding site but lacking the carboxyl-terminal domain encoding the heparin-binding domain and an 8-amino acid peptide encoded by exon 7. We have identified plasmin cleavage sites, generated a truncated PlGF118 isoform mimicking plasmin-processed PlGF, and explored its biological function in comparison with that of PlGF-1 and -2. The angiogenic responses induced by the diverse PlGF forms were distinct. Whereas PlGF-2 increased endothelial cell chemotaxis, vascular sprouting, and granulation tissue formation upon skin injury, these activities were abrogated following plasmin digestion. Investigation of PlGF/Neuropilin-1 binding and function suggests a critical role for heparin-binding domain/Neuropilin-1 interaction and its regulation by plasmin processing. Collectively, here we provide new mechanistic insights into the regulation of PlGF-2/Neuropilin-1-mediated tissue vascularization and growth. PMID:23645683

  10. Patterned growth of p-type MoS2 atomic layers using sol-gel as precursor

    DOE PAGES

    Zheng, Wei; Lin, Junhao; Feng, Wei; ...

    2016-07-19

    2D layered MoS2 has drawn intense attention for its applications in flexible electronic, optoelectronic, and spintronic devices. Most of the MoS2 atomic layers grown by conventional chemical vapor deposition techniques are n-type due to the abundant sulfur vacancies. Facile production of MoS2 atomic layers with p-type behavior, however, remains challenging. Here, a novel one-step growth has been developed to attain p-type MoS2 layers in large scale by using Mo-containing sol–gel, including 1% tungsten (W). Atomic-resolution electron microscopy characterization reveals that small tungsten oxide clusters are commonly present on the as-grown MoS2 film due to the incomplete reduction of W precursormore » at the reaction temperature. These omnipresent small tungsten oxide clusters contribute to the p-type behavior, as verified by density functional theory calculations, while preserving the crystallinity of the MoS2 atomic layers. The Mo containing sol–gel precursor is compatible with the soft-lithography techniques, which enables patterned growth of p-type MoS2 atomic layers into regular arrays with different shapes, holding great promise for highly integrated device applications. Lastly, an atomically thin p–n junction is fabricated by the as-prepared MoS2, which shows strong rectifying behavior.« less

  11. Growth and structure of microscale fibers as precursors of alumina nanofibers

    NASA Astrophysics Data System (ADS)

    Krivoshapkin, Pavel V.; Krivoshapkina, Elena F.; Dudkin, Boris N.

    2013-07-01

    There is a new proposed technique for obtaining two types of nanoscale aluminum oxide fibers using a sol-gel method. At the surface of hydrated aluminum oxide gels a spontaneous fiber structure formation takes place, where crystalline ammonium chloride acts as the basic component. These synthesized fibers have been studied by SEM, ТEM, XRPD and DTA methods, and by FTIR spectroscopy. Nanoscale fibers are generated by thermal treatment of fiber structures. Organic components being present in the system, the alumina fiber diameter is 100-150 nm, while in their absence the diameter varies from 50 to 90 nm. Mechanisms of the fiber growth and nanoscale aluminum oxide fiber formation in the process of thermal treatment are proposed .

  12. Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors.

    PubMed

    Venturelli, Sascha; Belz, Regina G; Kämper, Andreas; Berger, Alexander; von Horn, Kyra; Wegner, André; Böcker, Alexander; Zabulon, Gérald; Langenecker, Tobias; Kohlbacher, Oliver; Barneche, Fredy; Weigel, Detlef; Lauer, Ulrich M; Bitzer, Michael; Becker, Claude

    2015-11-01

    To secure their access to water, light, and nutrients, many plant species have developed allelopathic strategies to suppress competitors. To this end, they release into the rhizosphere phytotoxic substances that inhibit the germination and growth of neighbors. Despite the importance of allelopathy in shaping natural plant communities and for agricultural production, the underlying molecular mechanisms are largely unknown. Here, we report that allelochemicals derived from the common class of cyclic hydroxamic acid root exudates directly affect the chromatin-modifying machinery in Arabidopsis thaliana. These allelochemicals inhibit histone deacetylases both in vitro and in vivo and exert their activity through locus-specific alterations of histone acetylation and associated gene expression. Our multilevel analysis collectively shows how plant-plant interactions interfere with a fundamental cellular process, histone acetylation, by targeting an evolutionarily highly conserved class of enzymes. © 2015 American Society of Plant Biologists. All rights reserved.

  13. Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors[OPEN

    PubMed Central

    Venturelli, Sascha; Belz, Regina G.; Kämper, Andreas; Berger, Alexander; von Horn, Kyra; Wegner, André; Böcker, Alexander; Zabulon, Gérald; Barneche, Fredy; Lauer, Ulrich M.; Bitzer, Michael

    2015-01-01

    To secure their access to water, light, and nutrients, many plant species have developed allelopathic strategies to suppress competitors. To this end, they release into the rhizosphere phytotoxic substances that inhibit the germination and growth of neighbors. Despite the importance of allelopathy in shaping natural plant communities and for agricultural production, the underlying molecular mechanisms are largely unknown. Here, we report that allelochemicals derived from the common class of cyclic hydroxamic acid root exudates directly affect the chromatin-modifying machinery in Arabidopsis thaliana. These allelochemicals inhibit histone deacetylases both in vitro and in vivo and exert their activity through locus-specific alterations of histone acetylation and associated gene expression. Our multilevel analysis collectively shows how plant-plant interactions interfere with a fundamental cellular process, histone acetylation, by targeting an evolutionarily highly conserved class of enzymes. PMID:26530086

  14. Growth History of Kaena Volcano, the Isolated, Dominantly Submarine, Precursor Volcano to Oahu, Hawaii

    NASA Astrophysics Data System (ADS)

    Sinton, J. M.; Eason, D. E.

    2014-12-01

    The construction of O'ahu began with the recently recognized, ~3.5-4.9 Ma Ka'ena Volcano, as an isolated edifice in the Kaua'i Channel. Ka'ena remained submarine until, near the end of its lifetime as magma supply waned and the volcano transitioned to a late-shield stage of activity, it emerged to reach a maximum elevation of ~1000 m above sea level. We estimate that Ka'ena was emergent only for the last 15-25% of its lifespan, and that subaerial lavas make up < 5% of the total volume (20-27 x 103 km3). O'ahu's other volcanoes, Wai'anae (~3.9-2.85 Ma) and Ko'olau (~3.0-1.9 Ma), were built at least partly on the flanks of earlier edifices and both were active subaerial volcanoes for at least 1 Ma. The constructional history of Ka'ena contrasts with that of Wai'anae, Ko'olau, and many other Hawaiian volcanoes, which likely emerge within a few hundred kyr after inception, and with subaerial lavas comprising up to 35 volume % of the volcano. These relations suggest that volcano growth history and morphology are critically dependent on whether volcanic initiation and growth occur in the deep ocean floor (isolated), or on the flanks of pre-existing edifices. Two other volcanoes that likely formed in isolation are West Moloka'i and Kohala, both of which have long submarine rift zones, and neither attained great heights above sea level despite having substantial volume. The partitioning of volcanism between submarine and subaerial volcanism depends on the distance between volcanic centers, whether new volcanoes initiate on the flanks of earlier ones, and the time over which neighboring volcanoes are concurrently active. Ka'ena might represent an end-member in this spectrum, having initiated far from its next oldest neighbor and completed much of its evolution in isolation.

  15. Transforming growth factor beta in Alzheimer's disease.

    PubMed Central

    Chao, C C; Hu, S; Frey, W H; Ala, T A; Tourtellotte, W W; Peterson, P K

    1994-01-01

    Alzheimer's disease (AD) has been hypothesized to be an inflammatory condition. We hypothesized that anti-inflammatory cytokines, such as transforming growth factor beta (TGF-beta), counteract the inflammatory process. In the present study, we found that TGF-beta levels were elevated in both cerebrospinal fluid and serum samples obtained from AD patients < 6 h after death. Serum TGF-beta levels were also markedly elevated before death. These results suggest that elevated TGF-beta levels in AD may represent a protective host response to immunologically mediated neuronal injury. PMID:7496909

  16. UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels1[OPEN

    PubMed Central

    Fina, Julieta; AbdElgawad, Hamada; Prinsen, Els

    2017-01-01

    Ultraviolet-B (UV-B) radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibit maize (Zea mays) leaf growth without causing any other visible stress symptoms, including the accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth in UV-B-irradiated leaves is a consequence of a reduction in cell production and a shortened growth zone (GZ). To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B-exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including growth-regulating factors (GRFs) and transcripts for proteins participating in different hormone pathways. Interestingly, the decrease in the GZ size correlates with a decrease in the concentration of GA19, the immediate precursor of the active gibberellin, GA1, by UV-B in this zone, which is regulated, at least in part, by the expression of GRF1 and possibly other transcription factors of the GRF family. PMID:28400494

  17. Plant-Produced Human Recombinant Erythropoietic Growth Factors Support Erythroid Differentiation In Vitro

    PubMed Central

    Musiychuk, Konstantin; Sivalenka, Rajarajeswari; Jaje, Jennifer; Bi, Hong; Flores, Rosemary; Shaw, Brenden; Jones, R. Mark; Golovina, Tatiana; Schnipper, Jacob; Khandker, Luipa; Sun, Ruiqiang; Li, Chang; Kang, Lin; Voskinarian-Berse, Vanessa; Zhang, Xiaokui; Streatfield, Stephen; Hambor, John; Abbot, Stewart

    2013-01-01

    Clinically available red blood cells (RBCs) for transfusions are at high demand, but in vitro generation of RBCs from hematopoietic stem cells requires significant quantities of growth factors. Here, we describe the production of four human growth factors: erythropoietin (EPO), stem cell factor (SCF), interleukin 3 (IL-3), and insulin-like growth factor-1 (IGF-1), either as non-fused proteins or as fusions with a carrier molecule (lichenase), in plants, using a Tobacco mosaic virus vector-based transient expression system. All growth factors were purified and their identity was confirmed by western blotting and peptide mapping. The potency of these plant-produced cytokines was assessed using TF1 cell (responsive to EPO, IL-3 and SCF) or MCF-7 cell (responsive to IGF-1) proliferation assays. The biological activity estimated here for the cytokines produced in plants was slightly lower or within the range cited in commercial sources and published literature. By comparing EC50 values of plant-produced cytokines with standards, we have demonstrated that all four plant-produced growth factors stimulated the expansion of umbilical cord blood-derived CD34+ cells and their differentiation toward erythropoietic precursors with the same potency as commercially available growth factors. To the best of our knowledge, this is the first report on the generation of all key bioactive cytokines required for the erythroid development in a cost-effective manner using a plant-based expression system. PMID:23517237

  18. Growth factor-binding proteases in the murine submaxillary gland: isolation of a cDNA clone.

    PubMed Central

    Ronne, H; Lundgren, S; Severinsson, L; Rask, L; Peterson, P A

    1983-01-01

    The submaxillary gland of the adult male mouse contains a number of serine proteases, several of which are involved in the proteolytic processing of precursors to growth factors and other biologically active polypeptides. Here we report the isolation and identification of a cDNA clone corresponding to one of the proteases, the type B of the epidermal growth factor-binding protein. A pronounced sequence homology was found between the predicted activation peptide of this protease and the NH2-terminal extension of the nerve growth factor alpha subunit, suggesting that the latter protein has an uncleaved activation peptide attached to its NH2 terminus. Images Fig. 1. PMID:11892812

  19. A free energy study of carbon clusters on Ir(111): Precursors to graphene growth

    NASA Astrophysics Data System (ADS)

    Tetlow, H.; Ford, I. J.; Kantorovich, L.

    2017-01-01

    It is widely accepted that the nucleation of graphene on transition metals is related to the formation of carbon clusters of various sizes and shapes on the surface. Assuming a low concentration of carbon atoms on a crystal surface, we derive a thermodynamic expression for the grand potential of the cluster of N carbon atoms, relative to a single carbon atom on the surface (the cluster work of formation). This is derived taking into account both the energetic and entropic contributions, including structural and rotational components, and is explicitly dependent on the temperature. Then, using ab initio density functional theory, we calculate the work of formation of carbon clusters CN on the Ir(111) surface as a function of temperature considering clusters with up to N = 16 C atoms. We consider five types of clusters (chains, rings, arches, top-hollow, and domes), and find, in agreement with previous zero temperature studies, that at elevated temperatures the structure most favoured depends on N, with chains and arches being the most likely at N <10 and the hexagonal domes becoming the most favourable at all temperatures for N >10 . Our calculations reveal the work of formation to have a much more complex character as a function of the cluster size than one would expect from classical nucleation theory: for typical conditions, the work of formation displays not one but two nucleation barriers, at around N = 4-5 and N = 9-11. This suggests, in agreement with existing LEEM data, that five atom carbon clusters, along with C monomers, must play a pivotal role in the nucleation and growth of graphene sheets, whereby the formation of large clusters is achieved from the coalescence of smaller clusters (Smoluchowski ripening). Although the main emphasis of our study is on thermodynamic aspects of nucleation, the pivotal role of kinetics of transitions between different cluster types during the nucleation process is also discussed for a few cases as illustrative examples.

  20. Water Activity Limits the Hygroscopic Growth Factor of Organic Aerosols

    NASA Astrophysics Data System (ADS)

    Rodriguez, L. I.; Cabrera, J. A.; Golden, D.; Tabazadeh, A.

    2007-12-01

    In this work we study the hygroscopic behavior of organic aerosols, which has important implications for Earth's climate. The hygroscopic growth factor (HGF) is defined as the ratio of the diameter of a spherical particle when it is exposed to dry conditions to that at humid conditions. We present a new formulation to express the HGF of an aerosol particle as a function of water activity (aw) in the aqueous phase. This new formulation matches reported HGFs for common inorganic salts and water-miscible organic particles that are known to deliquesce into aqueous drops at high relative humidities (RH). Many studies use tandem differential mobility analyzers (TDMA) to determine the HGF of organic aerosols. For example, Brooks et al. used a TDMA to measure a HGF of 1.2 for 2 μm phthalic acid (PA) particles at 90% RH (aw= 0.9). However, water activity limits the growth of a particle that can be attributed to water uptake. We have assembled a vapor pressure apparatus to measure aw of aqueous solutions at room temperature. Measured water activities for PA, used in our growth formulation, yield a HGF of ~ 1.0005 for 2 μm PA particles at 90% RH. Comparing our results against Brooks et al. suggests that TDMA experiments may grossly overestimate the HGF of PA particles since water activity limits this growth to below 1.0005. Alternatively, we suggest that the adsorption of a negligible mass of water by a highly porous PA particle can lead to an apparent growth in particle size by changing its morphology. Other studies also use TDMAs to measure HGFs of secondary organic aerosols (SOAs). HGFs reported for SOAs are very similar to PA, suggesting that the observed growth may be due to morphological changes in particle size rather than water uptake as commonly assumed. We built a smog chamber where an organic precursor, such as d-limonene, reacts with nitrogen oxides under UV radiation to produce SOAs. We compare the HGFs for SOAs obtained with our method to those obtained with

  1. Vapor-liquid-solid epitaxial growth of Si1-xGex alloy nanowires. Composition dependence on precursor reactivity and morphology control for vertical forests

    DOE PAGES

    Choi, S. G.; Manandhar, P.; Picraux, S. T.

    2015-07-07

    The growth of high-density group IV alloy nanowire forests is critical for exploiting their unique functionalities in many applications. Here, the compositional dependence on precursor reactivity and optimized conditions for vertical growth are studied for Si1- x Ge x alloy nanowires grown by the vapor-liquid-solid method. The nanowire composition versus gas partial-pressure ratio for germane-silane and germane-disilane precursor combinations is obtained at 350°C over a wide composition range (0.05 ≤ x ≤ 0.98) and a generalized model to predict composition for alloy nanowires is developed based on the relative precursor partial pressures and reactivity ratio. In combination with germane, silanemore » provides more precise compositional control at high Ge concentrations (x > 0.7), whereas disilane greatly increases the Si concentration for a given gas ratio and enables more precise alloy compositional control at small Ge concentrations (x < 0.3). Vertically oriented, non-kinking nanowire forest growth on Si (111) substrates is then discussed for silane/germane over a wide range of compositions, with temperature and precursor partial pressure optimized by monitoring the nanowire growth front using in-situ optical reflectance. For high Ge compositions (x ≈ 0.9), a “two-step” growth approach with nucleation at higher temperatures results in nanowires with high-density and uniform vertical orientation. Furthermore, increasing Si content (x ≈ 0.8), the optimal growth window is shifted to higher temperatures, which minimizes nanowire kinking morphologies. For Si-rich Si1- x Ge x alloys (x ≈ 0.25), vertical nanowire growth is enhanced by single-step, higher-temperature growth at reduced pressures.« less

  2. Autologous Growth Factor Injections in Chronic Tendinopathy

    PubMed Central

    Sandrey, Michelle A.

    2014-01-01

    Reference: de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63–77. Clinical Question: The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich–plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? Data Sources: The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Study Selection: Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). Data Extraction: All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of

  3. Autologous growth factor injections in chronic tendinopathy.

    PubMed

    Sandrey, Michelle A

    2014-01-01

    de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63-77. The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich-plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of each article to determine if it met the inclusion criteria. If opinions differed on

  4. Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

    PubMed Central

    Grubeck-Loebenstein, B; Buchan, G; Sadeghi, R; Kissonerghis, M; Londei, M; Turner, M; Pirich, K; Roka, R; Niederle, B; Kassal, H

    1989-01-01

    The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter. Images PMID:2921318

  5. Shear-Induced Precursor Relaxation-Dependent Growth Dynamics and Lamellar Orientation of β-Crystals in β-Nucleated Isotactic Polypropylene.

    PubMed

    Chen, Yan-Hui; Fang, Du-Fei; Lei, Jun; Li, Liang-Bin; Hsiao, Benjamin S; Li, Zhong-Ming

    2015-04-30

    Although a shear flow field and β-nucleating agents (β-NAs) can separately induce the formation of β-crystals in isotactic polypropylene (iPP) in an efficient manner, we previously encountered difficulty in obtaining abundant β-crystals when these two factors were applied due to the competitive growth of α- and β-crystals. In the current study, to induce the formation of a high fraction of β-crystals, a strategy that introduces a relaxation process after applying a shear flow field but before cooling to crystallize β-nucleated iPP was proposed. Depending on the relaxation state of the shear-induced oriented precursors, abundant β-crystals with a refined orientation morphology were indeed formed. The key to producing these crystals lay in the partially dissolved shear-induced oriented precursors as a result of the relaxation process's ability to generate β-crystals by inducing the formation of needlelike β-NAs. Therefore, the content of β-crystals gradually increased with relaxation time, whereas the overall crystallization kinetics progressively decreased. Moreover, more time was required for the content of the β-phase to increase to the (maximum) value observed in quiescent crystallization than for the effect of flow on crystallization kinetics to be completely eliminated. The c-axis of the oriented β-lamellae was observed to be perpendicular, rather than parallel, to the fiber axis of the needlelike β-NAs, as first evidenced by the unique small-angle X-ray scattering patterns obtained. The significance of the relaxation process was manifested in regulating the content and morphology of oriented β-crystals in sheared, β-nucleated iPP and thus in the structure and property manipulation of iPP.

  6. Lactoferrin – A Novel Bone Growth Factor

    PubMed Central

    Naot, Dorit; Grey, Andrew; Reid, Ian R; Cornish, Jillian

    2005-01-01

    Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2–7 x 10−6 g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis. PMID:16012127

  7. Effects of meteorological conditions and plant growth stage on the accumulation of carvacrol and its precursors in Thymus pulegioides.

    PubMed

    Vaičiulytė, Vaida; Butkienė, Rita; Ložienė, Kristina

    2016-08-01

    The effects of meteorological conditions (temperature, rainfall, photosynthetically active solar radiation (PAR) and sunshine duration) and plant growth stages on the quantitative composition of a secondary metabolite - essential oil and its main compounds, in the carvacrol chemotype of Thymus pulegioides L. (Lamiaceae) cultivated in open ground were studied under the same micro-edaphoclimatic environmental conditions for six years. The essential oil was isolated by hydrodistillation, the analysis of monoterpenic phenol carvacrol and the biogenetic precursors (monoterpene hydrocarbons p-cymene and γ-terpinene) were carried out annually using GC-FID and GC-MS. In the carvacrol chemotype investigated in this study, the yield of essential oil varied from 0.72% to 0.98% (CV = 12%) at full flowering stage. Regression analysis showed a significant negative relationship between the amount of essential oil and both temperature and rainfall during T. pulegioides flowering (July) and the period from April (beginning of vegetation) to July, but a strong positive relationship with photosynthetically active solar radiation during April-July (beta = 0.658, p < 0.05). The percentage of carvacrol, p-cymene and γ-terpinene ranged between 16.88 and 29.29% (CV = 18%), 5.54-11.33% (CV = 23%) and 20.60-24.43% (CV = 6%) respectively. Regression analysis showed the significant positive relationship between the percentage of carvacrol and sunshine duration at the flowering stage (in July) (beta = 0.699, p < 0.05); while the negative relationship was established between the percentages of precursors of carvacrol and photosynthetically active solar radiation and sunshine duration. The accumulation of p-cymene, the percentage of which varied most strongly from all investigated chemical compounds, showed significant positive relationships with temperature and rainfall during the period April-July and temperature in July (beta = 0.617, beta = 0.439 and beta = 0

  8. [Growth Hormone-Insulin Growth Factor I (GH-IGF-I) axis and growth].

    PubMed

    Castell, A-L; Sadoul, J-L; Bouvattier, C

    2013-10-01

    Normal human linear growth results from an evolutionary process expressing the sum effect of multiple genes. The growth hormone (GH) - insulin like growth factor (IGF)-I axis is one of the main actors in the growth process. Defects in this axis can be responsible for short or tall stature. Short stature is defined as smaller than - 2 standard deviations (SD). It is a very common reason for consultation in pediatrics; indeed, 2.5 % of children are concerned. Multiple causes make diagnosis difficult. In this article, we detail the most common constitutional causes of small size, including those related to a defect in the GH-IGF-I axis. Then, we report, the first results of the clinical and genetic study conducted on 213 patients with gigantism. Tall stature is defined by a height superior to 2 SD. Finally, recent work linking epigenetics and growth - via signaling pathways of GH-IGF-I axis - will be presented.

  9. Insulin-like growth factor and epidermal growth factor signaling in breast cancer cell growth: focus on endocrine resistant disease.

    PubMed

    Voudouri, Kallirroi; Berdiaki, Aikaterini; Tzardi, Maria; Tzanakakis, George N; Nikitovic, Dragana

    2015-01-01

    Breast cancer is the most common type of cancer for women worldwide with a lifetime risk amounting to a staggering total of 10%. It is well established that the endogenous synthesis of insulin-like growth factor (IGF) and epidermal growth factor (EGF) polypeptide growth factors are closely correlated to malignant transformation and all the steps of the breast cancer metastatic cascade. Numerous studies have demonstrated that both estrogens and growth factors stimulate the proliferation of steroid-dependent tumor cells, and that the interaction between these signaling pathways occurs at several levels. Importantly, the majority of breast cancer cases are estrogen receptor- (ER-) positive which have a more favorable prognosis and pattern of recurrence with endocrine therapy being the backbone of treatment. Unfortunately, the majority of patients progress to endocrine therapy resistant disease (acquired resistance) whereas a proportion of patients may fail to respond to initial therapy (de novo resistance). The IGF-I and EGF downstream signaling pathways are closely involved in the process of progression to therapy resistant disease. Modifications in the bioavailability of these growth factors contribute critically to disease progression. In the present review therefore, we will discuss in depth how IGF and EGF signaling participate in breast cancer pathogenesis and progression to endocrine resistant disease.

  10. Secreted Human Amyloid Precursor Protein Binds Semaphorin 3a and Prevents Semaphorin-Induced Growth Cone Collapse

    PubMed Central

    Guerreiro, Luiz H.; Beltrão, Paulo José I.; Carvalho, Milena M. V. F.; da S. Santos, Luís Eduardo; de Mello, Fernando G.; Reis, Ricardo A. M.; Ferreira, Sérgio T.

    2011-01-01

    The amyloid precursor protein (APP) is well known for giving rise to the amyloid-β peptide and for its role in Alzheimer's disease. Much less is known, however, on the physiological roles of APP in the development and plasticity of the central nervous system. We have used phage display of a peptide library to identify high-affinity ligands of purified recombinant human sAPPα695 (the soluble, secreted ectodomain from the main neuronal APP isoform). Two peptides thus selected exhibited significant homologies with the conserved extracellular domain of several members of the semaphorin (Sema) family of axon guidance proteins. We show that sAPPα695 binds both purified recombinant Sema3A and Sema3A secreted by transfected HEK293 cells. Interestingly, sAPPα695 inhibited the collapse of embryonic chicken (Gallus gallus domesticus) dorsal root ganglia growth cones promoted by Sema3A (Kd≤8·10−9 M). Two Sema3A-derived peptides homologous to the peptides isolated by phage display blocked sAPPα binding and its inhibitory action on Sema3A function. These two peptides are comprised within a domain previously shown to be involved in binding of Sema3A to its cellular receptor, suggesting a competitive mechanism by which sAPPα modulates the biological action of semaphorins. PMID:21829538

  11. Nanofibers Support Oligodendrocyte Precursor Cell Growth and Function as a Neuron-Free Model for Myelination Study

    PubMed Central

    Li, Yongchao; Ceylan, Muhammet; Shrestha, Bikesh; Wang, Haibo; Lu, Q.Richard; Asmatulu, Ramazan; Yao, Li

    2014-01-01

    Nanofiber-based scaffolds may simultaneously provide immediate contact guidance for neural regeneration and act as a vehicle for therapeutic cell delivery to enhance axonal myelination. Additionally, nanofibers can serve as a neuron-free model to study myelination of oligodendrocytes. In this study, we fabricated nanofibers using a polycaprolactone and gelatin co-polymer. The ratio of the gelatin component in the fibers was confirmed by energy dispersive x-ray spectroscopy. The addition of gelatin to the polycaprolactone (PCL) for nanofiber fabrication decreased the contact angle of the electrospun fibers. We showed that both polycaprolactone nanofibers as well as polycaprolactone and gelatin co-polymer nanofibers can support oligodendrocyte precursor cell (OPC) growth and differentiation. OPCs maintained their phenotype and viability on nanofibers and were induced to differentiate into oligodendrocytes. The differentiated oligodendrocytes extend their processes along the nanofibers and ensheathed the nanofibers. Oligodendrocytes formed significantly more myelinated segments on the PCL and gelatin co3polymer nanofibers than those on PCL nanofibers alone. PMID:24304204

  12. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia.

    PubMed

    Danis, Etienne; Yamauchi, Taylor; Echanique, Kristen; Zhang, Xi; Haladyna, Jessica N; Riedel, Simone S; Zhu, Nan; Xie, Huafeng; Orkin, Stuart H; Armstrong, Scott A; Bernt, Kathrin M; Neff, Tobias

    2016-03-01

    Early T cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Growth factor control of epidermal growth factor receptor kinase activity via an intramolecular mechanism.

    PubMed

    Koland, J G; Cerione, R A

    1988-02-15

    The mechanism by which the protein kinase activity of the epidermal growth factor (EGF) receptor is activated by binding of growth factor was investigated. Detergent-solubilized receptor in monomeric form was isolated by sucrose density gradient centrifugation and both its kinase and autophosphorylation activities monitored. In a low ionic strength medium and with MnCl2 as an activator, the activity of the monomeric receptor was EGF-independent. However, with 0.25 M ammonium sulfate present, the MnCl2-stimulated kinase activity was strikingly EGF-dependent. In contrast, the kinase activity expressed in the presence of MgCl2 showed growth factor control in the absence of added salt. Under the conditions of these experiments there was apparently little tendency for growth factor to induce aggregation of the receptor, indicating that the allosteric activation of the receptor kinase by EGF occurred via an intramolecular mechanism. Whereas detergent-solubilized receptor was the subject of these studies, the kinase activity of cell surface receptors might also be controlled by an intramolecular mechanism. These results indicate that an individual receptor molecule has the potential to function as a transmembrane signal transducer.

  14. Effect of Group-III precursors on unintentional gallium incorporation during epitaxial growth of InAlN layers by metalorganic chemical vapor deposition

    SciTech Connect

    Kim, Jeomoh Ji, Mi-Hee; Detchprohm, Theeradetch; Dupuis, Russell D.; Fischer, Alec M.; Ponce, Fernando A.; Ryou, Jae-Hyun

    2015-09-28

    Unintentional incorporation of gallium (Ga) in InAlN layers grown with different molar flow rates of Group-III precursors by metalorganic chemical vapor deposition has been experimentally investigated. The Ga mole fraction in the InAl(Ga)N layer was increased significantly with the trimethylindium (TMIn) flow rate, while the trimethylaluminum flow rate controls the Al mole fraction. The evaporation of metallic Ga from the liquid phase eutectic system between the pyrolized In from injected TMIn and pre-deposited metallic Ga was responsible for the Ga auto-incorporation into the InAl(Ga)N layer. The theoretical calculation on the equilibrium vapor pressure of liquid phase Ga and the effective partial pressure of Group-III precursors based on growth parameters used in this study confirms the influence of Group-III precursors on Ga auto-incorporation. More Ga atoms can be evaporated from the liquid phase Ga on the surrounding surfaces in the growth chamber and then significant Ga auto-incorporation can occur due to the high equilibrium vapor pressure of Ga comparable to effective partial pressure of input Group-III precursors during the growth of InAl(Ga)N layer.

  15. Nerve growth factor: neurotrophin or cytokine?

    PubMed

    Bonini, S; Rasi, G; Bracci-Laudiero, M L; Procoli, A; Aloe, L

    2003-06-01

    Nerve growth factor (NGF) is a neutrophin exerting an important role in the development and functions of the central and peripheral nervous system. However, it has recently been documented that several immune cells - such as mast cells, lymphocytes and eosinophils - produce, store and release NGF. Moreover, NGF high and low affinity receptors are widely expressed in the immune system, thus indicating the potential of responding to this neurotrophin through an autocrine mechanism. In fact, NGF influences development differentiation, chemotaxis and mediator release of inflammatory cells as well as fibroblast activation through a complex network influenced by other pro-inflammatory cytokines. Finally, NGF is increased in biological fluids of several allergic, immune and inflammatory diseases. Data reviewed suggest, therefore, that NGF might also be viewed as a (Th2?) cytokine with a modulatory role in allergic inflammation and tissue remodeling. Copyright 2003 S. Karger AG, Basel

  16. The Fibroblast Growth Factor signaling pathway

    PubMed Central

    Ornitz, David M; Itoh, Nobuyuki

    2015-01-01

    The signaling component of the mammalian Fibroblast Growth Factor (FGF) family is comprised of eighteen secreted proteins that interact with four signaling tyrosine kinase FGF receptors (FGFRs). Interaction of FGF ligands with their signaling receptors is regulated by protein or proteoglycan cofactors and by extracellular binding proteins. Activated FGFRs phosphorylate specific tyrosine residues that mediate interaction with cytosolic adaptor proteins and the RAS-MAPK, PI3K-AKT, PLCγ, and STAT intracellular signaling pathways. Four structurally related intracellular non-signaling FGFs interact with and regulate the family of voltage gated sodium channels. Members of the FGF family function in the earliest stages of embryonic development and during organogenesis to maintain progenitor cells and mediate their growth, differentiation, survival, and patterning. FGFs also have roles in adult tissues where they mediate metabolic functions, tissue repair, and regeneration, often by reactivating developmental signaling pathways. Consistent with the presence of FGFs in almost all tissues and organs, aberrant activity of the pathway is associated with developmental defects that disrupt organogenesis, impair the response to injury, and result in metabolic disorders, and cancer. © 2015 Wiley Periodicals, Inc. PMID:25772309

  17. Neuropeptides as lung cancer growth factors.

    PubMed

    Moody, Terry W; Moreno, Paola; Jensen, Robert T

    2015-10-01

    This manuscript is written in honor of the Festschrift for Abba Kastin. I met Abba at a Society for Neuroscience meeting and learned that he was Editor-in-Chief of the Journal Peptides. I submitted manuscripts to the journal on "Neuropeptides as Growth Factors in Cancer" and subsequently was named to the Editorial Advisory Board. Over the past 30 years I have published dozens of manuscripts in Peptides and reviewed hundreds of submitted manuscripts. It was always rewarding to interact with Abba, a consummate professional. When I attended meetings in New Orleans I would sometimes go out to dinner with him at the restaurant "Commanders Palace". When I chaired the Summer Neuropeptide Conference we were honored to have him receive the Fleur Strand Award one year in Israel. I think that his biggest editorial contribution has been the "Handbook of Biologically Active Peptides." I served as a Section Editor on "Cancer/Anticancer Peptides" and again found that it was a pleasure working with him. This review focuses on the mechanisms by which bombesin-like peptides, neurotensin and vasoactive intestinal peptide regulate the growth of lung cancer. Published by Elsevier Inc.

  18. Temperature-dependent modification of muscle precursor cell behaviour is an underlying reason for lasting effects on muscle cellularity and body growth of teleost fish.

    PubMed

    Steinbacher, Peter; Marschallinger, Julia; Obermayer, Astrid; Neuhofer, Alois; Sänger, Alexandra M; Stoiber, Walter

    2011-06-01

    Temperature is an important factor influencing teleost muscle growth, including a lasting ('imprinted') influence of embryonic thermal experience throughout all further life. However, little is known about the cellular processes behind this phenomenon. The study reported here used digital morphometry and immunolabelling for Pax7, myogenin and H3P to quantitatively examine the effects of thermal history on muscle precursor cell (MPC) behaviour and muscle growth in pearlfish (Rutilus meidingeri) until the adult stage. Fish were reared at three different temperatures (8.5, 13 and 16°C) until hatching and subsequently kept under the same (ambient) thermal conditions. Cellularity data were combined with a quantitative analysis of Pax7+ MPCs including those that were mitotically active (Pax7+/H3P+) or had entered differentiation (Pax7+/myogenin+). The results demonstrate that at hatching, body lengths, fast and slow muscle cross-sectional areas and fast fibre numbers are lower in fish reared at 8.5 and 13°C than at 16°C. During the larval period, this situation changes in the 13°C-fish, so that these fish are finally the largest. The observed effects can be related to divergent cellular mechanisms at the MPC level that are initiated in the embryo during the imprinting period. Embryos of 16°C-fish have reduced MPC proliferation but increased differentiation, and thus give rise to larger hatchlings. However, their limited MPC reserves finally lead to smaller adults. By contrast, embryos of 13°C-fish and, to a lesser extent, 8.5°-fish, show enhanced MPC proliferation but reduced differentiation, thus leading to smaller hatchlings but allowing for a larger MPC pool that can be used for enhanced post-hatching growth, finally resulting in larger adults.

  19. Growth factors and cytokines in acute renal failure.

    PubMed

    Harris, R C

    1997-04-01

    The mammalian kidney is susceptible to injury by ischemia/reperfusion and toxins, and regeneration after injury is characterized by hyperplasia and recovery of the damaged epithelial cells that line the tubules. Locally produced growth factors may serve as mediators of nephrogenesis and differentiation during renal development and of renal regeneration after acute injury. In cultured cells, administration of one or a mixture of growth factors to quiescent cells will initiate progression through the cell cycle and cell division. In the adult kidney, cell division normally is very low, but will increase up to 10-fold after acute injury. In addition to proliferation after lethal injury, there also is cellular repair in cells that have undergone sublethal injury. Recent studies indicate that growth factors inhibit programmed cell death in response to acute injury. Growth factors also may initiate or promote protein and lipid biosynthesis and provide an intracellular milieu that promotes cellular repair. In addition to cellular repair, growth factors also may be involved in the re-establishment of cell-extracellular matrix and cell-cell integrity. Finally, growth factors may limit injury by decreasing the factors that induce damage. Increased local renal expression of growth factors in response to acute injury include heparin binding epidermal growth factor (HB-EGF), hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I), transforming growth factor-beta, parathyroid hormone-related peptide, and acidic fibroblast growth factor. In a number of experimental models of acute renal injury, administration of exogenous growth factors has been shown to accelerate both structural and functional recovery. Specifically, EGF, IGF-1, and HGF all have been shown to be effective in this regard. These studies are reviewed and potential therapeutic uses of growth factors and cytokines will be discussed.

  20. [Regulation of uterine cellular proliferation with estrogens and growth factors].

    PubMed

    Alvarez-Rodríguez, C; Baiza-Guzmán, L A

    1996-09-01

    In this paper the role of estrogen and growth factors in the uterine cellular proliferation is analyzed. The evidences indicate that the estradiol-stimulate cell division is associated with the induction of expression of a variety of growth factors from the all major uterine cell types (epithelia, stroma and myometrium). These growth factors amplify the estrogen proliferation signal in autocrine and/or paracrin fashion. The best-studied growth factors in the uterine response to estradiol are epidermal growth factor (EGF) and insulin-like growth factor (IGF-1). Uterine cell proliferation is a complex process that involves interactions of several growth factors, ovarian steroids hormones action and cell to cell signaling.

  1. Hepatocyte growth factor, vascular endothelial growth factor, glial cell-derived neurotrophic factor and nerve growth factor are differentially affected by early chronic ethanol or red wine intake.

    PubMed

    Fiore, Marco; Mancinelli, Rosanna; Aloe, Luigi; Laviola, Giovanni; Sornelli, Federica; Vitali, Mario; Ceccanti, Mauro

    2009-08-10

    Ethanol intake during pregnancy and lactation induces severe changes in brain and liver throughout mechanisms involving growth factors. These are signaling molecules regulating survival, differentiation, maintenance and connectivity of brain and liver cells. Ethanol is an element of red wine which contains also compounds with antioxidant properties. Aim of the study was to investigate differences in hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in brain areas and liver by ELISA of 1-month-old male mice exposed perinatally to ethanol at 11 vol.% or to red wine at same ethanol concentration. Ethanol was administered before and during pregnancy up to pups' weaning. Ethanol per se elevated HGF in liver and cortex, potentiated liver VEGF, reduced GDNF in the liver and decreased NGF content in hippocampus and cortex in the offspring. We did not find changes in HGF or NGF due to red wine exposure. However, we revealed elevation in VEGF levels in liver and reduced GDNF in the cortex of animals exposed to red wine but the VEGF liver increase was more marked in animals exposed to ethanol only compared to the red wine group. In conclusion the present findings in the mouse show differences in ethanol-induced toxicity when ethanol is administered alone or in red wine that may be related to compounds with antioxidant properties present in the red wine.

  2. The {beta}-chemokines CCL2 and CCL7 are two novel differentiation factors for midbrain dopaminergic precursors and neurons

    SciTech Connect

    Edman, Linda C.; Mira, Helena; Arenas, Ernest

    2008-06-10

    {beta}-chemokines are secreted factors that regulate diverse functions in the adult brain, such as neuro-immune responses and neurotransmission, but their function in the developing brain is largely unknown. We recently found that the orphan nuclear receptor, Nurr1, up regulates CCL2 and CCL7 in neural stem cells, suggesting a possible function of {beta}-chemokines in midbrain development. Here we report that two {beta}-chemokines, CCL2 and CCL7, and two of their receptors, CCR1 and CCR2, are expressed and developmentally regulated in the ventral midbrain (VM). Moreover, we found that the expression of CCL7 was down regulated in the Nurr1 knockout mice, linking CCL7 to dopamine (DA) neuron development. When the function of CCL2 and CCL7 was examined, we found that they selectively enhanced the differentiation of Nurr1+ precursors into DA neurons, but not their survival or progenitor proliferation in primary precursor cultures. Moreover, both CCL2 and CCL7 promoted neuritogenesis in midbrain DA neuron cultures. Thus, our results show for the first time a function of {beta}-chemokines in the developing brain and identify {beta}-chemokines as novel class of pro-differentiation factors for midbrain DA neurons. These data also suggest that {beta}-chemokines may become useful tools to enhance the differentiation of DA cell preparations for cell replacement therapy and drug discovery in Parkinson's disease (PD)

  3. Design of Growth Factor Sequestering Biomaterials

    PubMed Central

    Belair, David G.; Le, Ngoc Nhi; Murphy, William L.

    2014-01-01

    Growth factors (GFs) are major regulatory proteins that can govern cell fate, migration, and organization. Numerous aspects of the cell milieu can modulate cell responses to GFs, and GF regulation is often achieved by the native extracellular matrix (ECM). For example, the ECM can sequester GFs and thereby control GF bioavailability. In addition, GFs can exert distinct effects depending on whether they are sequestered in solution, at two-dimensional interfaces, or within three-dimensional matrices. Understanding how the context of GF sequestering impacts cell function in the native ECM can instruct the design of soluble or insoluble GF sequestering moieties, which can then be used in a variety of bioengineering applications. This Feature Article provides an overview of the natural mechanisms of GF sequestering in the cell milieu, and reviews the recent bioengineering approaches that have sequestered GFs to modulate cell function. Results to date demonstrate that the cell response to GF sequestering depends on the affinity of the sequestering interaction, the spatial proximity of sequestering in relation to cells, the source of the GF (supplemented or endogenous), and the phase of the sequestering moiety (soluble or insoluble). We highlight the importance of context for the future design of biomaterials that can leverage endogenous molecules in the cell milieu and mitigate the need for supplemented factors. PMID:25182455

  4. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by beta3 integrin.

    PubMed

    Faccio, Roberta; Novack, Deborah V; Zallone, Alberta; Ross, F Patrick; Teitelbaum, Steven L

    2003-08-04

    The beta3 integrin cytoplasmic domain, and specifically S752, is critical for integrin localization and osteoclast (OC) function. Because growth factors such as macrophage colony-stimulating factor and hepatocyte growth factor affect integrin activation and function via inside-out signaling, a process requiring the beta integrin cytoplasmic tail, we examined the effect of these growth factors on OC precursors. To this end, we retrovirally expressed various beta3 integrins with cytoplasmic tail mutations in beta3-deficient OC precursors. We find that S752 in the beta3 cytoplasmic tail is required for growth factor-induced integrin activation, cytoskeletal reorganization, and membrane protrusion, thereby affecting OC adhesion, migration, and bone resorption. The small GTPases Rho and Rac mediate cytoskeletal reorganization, and activation of each is defective in OC precursors lacking a functional beta3 subunit. Activation of the upstream mediators c-Src and c-Cbl is also dependent on beta3. Interestingly, although the FAK-related kinase Pyk2 interacts with c-Src and c-Cbl, its activation is not disrupted in the absence of functional beta3. Instead, its activation is dependent upon intracellular calcium, and on the beta2 integrin. Thus, the beta3 cytoplasmic domain is responsible for activation of specific intracellular signals leading to cytoskeletal reorganization critical for OC function.

  5. Neurobiological actions by three distinct subtypes of brain-derived neurotrophic factor: Multi-ligand model of growth factor signaling.

    PubMed

    Mizui, Toshiyuki; Ishikawa, Yasuyuki; Kumanogoh, Haruko; Kojima, Masami

    2016-03-01

    Brain-derived neurotrophic factor (BDNF) is one of the most active members of the neurotrophin family. BDNF not only regulates neuronal survival and differentiation, but also functions in activity-dependent plasticity processes such as long-term potentiation (LTP), long-term depression (LTD), learning, and memory. Like other growth factors, BDNF is produced by molecular and cellular mechanisms including transcription and translation, and functions as a bioactive molecule in the nervous system. Among these mechanisms, a particular post-translational mechanism, namely the conversion of precursor BDNF into mature BDNF by proteolytic cleavage, was not fully understood. In this review, we discuss the manner through which this post-translational mechanism alters the biological actions of BDNF protein. In addition to the initially elucidated findings on BDNF, the biological roles of precursor BDNF and the BDNF pro-peptide, especially synaptic plasticity, will be extensively discussed. Recent findings on the BDNF pro-peptide will provide new insights for understanding the mechanisms of action of the pro-peptides of growth factors.

  6. Growth factor involvement in tension-induced skeletal muscle growth

    NASA Technical Reports Server (NTRS)

    Vandenburgh, Herman W.

    1987-01-01

    New muscle tissue culture techniques were developed to grow embryonic skeletal myofibers which are able to differentiate into more adultlike myofibers. Studies on mechanical simulation of cultured muscle cell growth will now be more directly applicable to mechanically-induced growth in adult muscle, and lead to better models for understanding muscle tissue atrophy caused by disuse in the microgravity of space.

  7. In vivo injection of fibroblast growth factor-2 into the cisterna magna induces glypican-6 expression in mouse brain tissue.

    PubMed

    Salehi, Zivar

    2009-05-01

    The proteoglycans (PGs) are multifunctional macromolecules composed of a core polypeptide and a variable number of glycosaminoglycan chains. In the nervous system, PGs regulate the structural organization of the extracellular matrix (ECM) and modulate growth factor activities and cell proliferation and migration. Most cortical neurons are generated from neural precursor cells that reside in the ventricular zone of the embryonic brain. The proliferation and differentiation of neural precursor cells are regulated by various growth and neurotrophic factors. Fibroblast growth factor-2 (FGF-2) is an important mitogen for cortical neural precursor cells, and glypicans regulate the action of FGF-2 on neural precursor cells. Glypican-6 is one of the most abundant ECM molecules in the brain. In this study the effects of FGF-2 on glypican-6 expression in brain tissue have been investigated. FGF-2 was injected into the cerebrospinal fluid (CSF) through the cisterna magna of mouse pups. Using Western blotting, it was shown that the expression of glypican-6 is increased in response to infusion of FGF-2 into the CSF. The injection of anti-FGF-2 antibody into the cisterna magna decreased glypican-6 expression in brain tissue. The results from this study suggest that glypican-6 is important in regulating FGF-2 activity during cerebral cortical development.

  8. Growth factors and their relationship to neoplastic and paraneoplastic disease.

    PubMed

    Badawi, R A; Birns, J; Watson, T; Kalra, L

    2005-04-01

    Growth factors are extracellular signaling molecules that act in an autocrine and paracrine fashion to regulate growth, proliferation, differentiation, and survival of cells. Dysregulation of the growth factor networks is intimately related to the molecular pathogenesis of neoplastic and paraneoplastic disease. Increasing knowledge of the molecular mechanisms underlying growth factors and their actions on cell cycling, cell division, and cell death is shedding light on new therapeutic avenues for molecular targeting of tumors. Epidermal growth factor and vascular endothelial growth factor both offer examples of how growth factor biology and its relationship to cancer can be harnessed to create effective clinical therapeutic tools such as monoclonal antibodies. This approach heralds a future in which rational molecular oncological therapy may increasingly become the norm.

  9. Kinetics of epidermal growth factor in saliva.

    PubMed

    Ino, M; Ushiro, K; Ino, C; Yamashita, T; Kumazawa, T

    1993-01-01

    Human epidermal growth factor (hEGF) stimulates the growth and differentiation of various tissues. We measured EGF levels in saliva (n = 128), urine (n = 94), and serum (n = 99) with radioimmunoassay in order to study the kinetics of hEGF in saliva of normal subjects and patients with oral disease. Salivary EGF levels showed an apparent diurnal rhythm related to the taking of meals. Urinary and serum EGF levels showed no obvious diurnal rhythm. There was no significant correlation between salivary and urinary EGF levels, nor between salivary and serum EGF levels. Salivary EGF levels were significantly lower in the younger group (0-9 years old, 3.06 +/- 0.32 ng/ml, p < 0.05) than in the elder group (10-79 years old, 4.78 +/- 3.5 ng/ml), but did not correlate with age in the elder group. There was no significant difference between males and females between EGF levels in saliva, urine or serum. The relative proportion of EGF levels in submandibular gland saliva, parotid saliva, and whole saliva was 1:6:4. The positive rate of immunohistochemical EGF showed no significant differences between submandibular gland, parotid gland, sublingual gland or minor salivary gland. Salivary EGF levels were markedly low in patients with oral inflammations (stomatitis aphthosa, or peritonsillar abscess) or head and neck tumors (squamous cell carcinoma of the tongue, oral cavity, hypopharynx or larynx). These findings may be significant pathophysiologically. Low salivary EGF levels may reduce the capacity of oral mucosal defense mechanisms to fight against injury by physiochemical agents.

  10. Endorsement of Growth Factors in Experiential Training Groups

    ERIC Educational Resources Information Center

    Kiweewa, John; Gilbride, Dennis; Luke, Melissa; Seward, Derek

    2013-01-01

    The purpose of this study was to identify student growth factors during a semester long Master's level group counseling class. Results indicated that 12 growth factors accounted for 86% of the total number of critical incidents that participants reported as influencing their personal growth and awareness during the group experience. Two other…

  11. Endorsement of Growth Factors in Experiential Training Groups

    ERIC Educational Resources Information Center

    Kiweewa, John; Gilbride, Dennis; Luke, Melissa; Seward, Derek

    2013-01-01

    The purpose of this study was to identify student growth factors during a semester long Master's level group counseling class. Results indicated that 12 growth factors accounted for 86% of the total number of critical incidents that participants reported as influencing their personal growth and awareness during the group experience. Two other…

  12. Coupled incremental precursor and co-factor supply improves 3-hydroxypropionic acid production in Saccharomyces cerevisiae.

    PubMed

    Chen, Yun; Bao, Jichen; Kim, Il-Kwon; Siewers, Verena; Nielsen, Jens

    2014-03-01

    3-Hydroxypropionic acid (3-HP) is an attractive platform chemical, which can be used to produce a variety of commodity chemicals, such as acrylic acid and acrylamide. For enabling a sustainable alternative to petrochemicals as the feedstock for these commercially important chemicals, fermentative production of 3-HP is widely investigated and is centered on bacterial systems in most cases. However, bacteria present certain drawbacks for large-scale organic acid production. In this study, we have evaluated the production of 3-HP in the budding yeast Saccharomyces cerevisiae through a route from malonyl-CoA, because this allows performing the fermentation at low pH thus making the overall process cheaper. We have further engineered the host strain by increasing availability of the precursor malonyl-CoA and by coupling the production with increased NADPH supply we were able to substantially improve 3-HP production by five-fold, up to a final titer of 463 mg l⁻¹. Our work thus led to a demonstration of 3-HP production in yeast via the malonyl-CoA pathway, and this opens for the use of yeast as a cell factory for production of bio-based 3-HP and derived acrylates in the future. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  13. Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia.

    PubMed Central

    Bajaj-Elliott, M; Poulsom, R; Pender, S L; Wathen, N C; MacDonald, T T

    1998-01-01

    Immune reactions in the gut are associated with increased epithelial cell proliferation. Here we have studied the role of keratinocyte growth factor (KGF; FGF7) and transforming growth factor-alpha (TGF-alpha) in the epithelial cell hyperplasia seen in explants of fetal human small intestine after activation of lamina propria T cells with the superantigen Staphylococcus aureus enterotoxin B (SEB). After the addition of SEB to the explants there is a 10-fold increase in KGF mRNA by 72 h of culture. KGF transcripts were abundant in the lamina propria using in situ hybridization and the culture supernatants contained elevated amounts of KGF protein. SEB had no direct effect on KGF mRNA and protein production by cultured lamina propria mesenchymal cells, but both were upregulated by TNF-alpha. Accompanying the increase in KGF there was also an increase in TGF-alpha precursor proteins in the culture supernatants and the phosphorylated form of the EGFR receptor was also detected in the tissue. Increased TGF-alpha precursor proteins were also detected in the supernatants of control explants stimulated with KGF alone. The direct addition of KGF and TGF-alpha enhanced epithelial cell proliferation and antibodies against KGF and TGF-alpha partially inhibited SEB-induced crypt hyperplasia. These results suggest molecular cross-talk between the KGF/KGFR and the TGF-alpha/EGFR in immune-mediated crypt cell hyperplasia. PMID:9788959

  14. Gene expression of growth factors and growth factor receptors for potential targeted therapy of canine hepatocellular carcinoma.

    PubMed

    Iida, Gentoku; Asano, Kazushi; Seki, Mamiko; Sakai, Manabu; Kutara, Kenji; Ishigaki, Kumiko; Kagawa, Yumiko; Yoshida, Orie; Teshima, Kenji; Edamura, Kazuya; Watari, Toshihiro

    2014-03-01

    The purpose of this study was to evaluate the gene expression of growth factors and growth factor receptors of primary hepatic masses, including hepatocellular carcinoma (HCC) and nodular hyperplasia (NH), in dogs. Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to measure the expression of 18 genes in 18 HCCs, 10 NHs, 11 surrounding non-cancerous liver tissues and 4 healthy control liver tissues. Platelet-derived growth factor-B (PDGF-B), transforming growth factor-α, epidermal growth factor receptor, epidermal growth factor and hepatocyte growth factor were found to be differentially expressed in HCC compared with NH and the surrounding non-cancerous and healthy control liver tissues. PDGF-B is suggested to have the potential to become a valuable ancillary target for the treatment of canine HCC.

  15. Step dynamics in the homoepitaxial growth of 6H-SiC by chemical vapor deposition on 1° offcut substrate using dichlorosilane as Si precursor

    NASA Astrophysics Data System (ADS)

    Omar, Sabih U.; Chandrashekhar, M. V. S.; Chowdhury, Iftekhar A.; Rana, Tawhid A.; Sudarshan, Tangali S.

    2013-05-01

    Step flow epitaxial growth was achieved on 1° offcut 6H-SiC substrate using dichlorosilane (DCS) as the Si precursor. High crystal quality and polytype uniformity were verified by XRD and Raman spectroscopy. Mirror-like surfaces with very few triangular and carrot defects were obtained over a wide range of C/Si ratios. Surface step bunching and step crossover were observed and rms roughness values were measured to be 2-4 nm. N-type doping was achieved by site-competition epitaxy at low C/Si ratios. Growth rates of 0.5-4 μm/h was obtained over a temperature range of 1470-1550 °C. The surface diffusion length of the adatoms on the step terraces was calculated using a model based on the Burton-Cabrera-Frank theory of epigrowth on stepped surfaces. In the experimental temperature range, the surface diffusion length varied from 5 to 13 nm, which is significantly shorter than those reported in literature for epigrowth using the conventional silane precursor. The short diffusion lengths for DCS imply a strong desorption process at the growth front, which is ideal for polytype-matched step-flow growth on low offcut substrates. The understanding of these step dynamics issues is critical for crystal growers using chlorinated gas precursors.

  16. Influence of Fatty Acid Precursors, Including Food Preservatives, on the Growth and Fatty Acid Composition of Listeria monocytogenes at 37 and 10°C ▿

    PubMed Central

    Julotok, Mudcharee; Singh, Atul K.; Gatto, Craig; Wilkinson, Brian J.

    2010-01-01

    Listeria monocytogenes is a food-borne pathogen that grows at refrigeration temperatures and increases its content of anteiso-C15:0 fatty acid, which is believed to be a homeoviscous adaptation to ensure membrane fluidity, at these temperatures. As a possible novel approach for control of the growth of the organism, the influences of various fatty acid precursors, including branched-chain amino acids and branched- and straight-chain carboxylic acids, some of which are also well-established food preservatives, on the growth and fatty acid composition of the organism at 37°C and 10°C were studied in order to investigate whether the organism could be made to synthesize fatty acids that would result in impaired growth at low temperatures. The results indicate that the fatty acid composition of L. monocytogenes could be modulated by the feeding of branched-chain amino acid, C4, C5, and C6 branched-chain carboxylic acid, and C3 and C4 straight-chain carboxylic acid fatty acid precursors, but the growth-inhibitory effects of several preservatives were independent of effects on fatty acid composition, which were minor in the case of preservatives metabolized via acetyl coenzyme A. The ability of a precursor to modify fatty acid composition was probably a reflection of the substrate specificities of the first enzyme, FabH, in the condensation of primers of fatty acid biosynthesis with malonyl acyl carrier protein. PMID:20048057

  17. Transforming growth factor alpha and epidermal growth factor levels in normal human gastrointestinal mucosa.

    PubMed Central

    Cartlidge, S. A.; Elder, J. B.

    1989-01-01

    Acid soluble proteins from 23 samples of normal human gastrointestinal mucosa derived from four normal adult organ donors were extracted and subjected to specific radiommunoassays for transforming growth factor alpha (TGF alpha) and urogastrone epidermal growth factor (URO-EGF). All tissues were found to contain immunoreactive TGF alpha and levels ranged from 57 to 4,776 pg-1 wet weight of tissue. Although levels varied between tissue donors, the distribution of TGF alpha throughout the gastrointestinal tract appeared similar in all cases. URO-EGF levels were much lower (0-216 pg g-1 wet weight). TGF alpha levels in extracts of gastrointestinal mucosa from a 7-year-old female donor were higher and the observed distribution was markedly different from adult levels. URO-EGF was not detected in mucosal or submucosal tissue extracts from this patient. Further studies in juveniles are indicated. PMID:2803941

  18. Direct binding of hepatocyte growth factor and vascular endothelial growth factor to CD44v6.

    PubMed

    Volz, Yvonne; Koschut, David; Matzke-Ogi, Alexandra; Dietz, Marina S; Karathanasis, Christos; Richert, Ludovic; Wagner, Moritz G; Mély, Yves; Heilemann, Mike; Niemann, Hartmut H; Orian-Rousseau, Véronique

    2015-06-29

    CD44v6, a member of the CD44 family of transmembrane glycoproteins is a co-receptor for two receptor tyrosine kinases (RTKs), Met and VEGFR-2 (vascular endothelial growth factor receptor 2). CD44v6 is not only required for the activation of these RTKs but also for signalling. In order to understand the role of CD44v6 in Met and VEGFR-2 activation and signalling we tested whether CD44v6 binds to their ligands, HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor), respectively. FACS analysis and cellular ELISA showed binding of HGF and VEGF only to cells expressing CD44v6. Direct binding of CD44v6 to HGF and VEGF was demonstrated in pull-down assays and the binding affinities were determined using MicroScale Thermophoresis, fluorescence correlation spectroscopy and fluorescence anisotropy. The binding affinity of CD44v6 to HGF is in the micromolar range in contrast with the high-affinity binding measured in the case of VEGF and CD44v6, which is in the nanomolar range. These data reveal a heparan sulfate-independent direct binding of CD44v6 to the ligands of Met and VEGFR-2 and suggest different roles of CD44v6 for these RTKs.

  19. Brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) in genetically defined fear-induced aggression.

    PubMed

    Ilchibaeva, Tatiana V; Kondaurova, Elena M; Tsybko, Anton S; Kozhemyakina, Rimma V; Popova, Nina K; Naumenko, Vladimir S

    2015-09-01

    The brain-derived neurotrophic factor (BDNF), its precursor (proBDNF) and BDNF mRNA levels were studied in the brain of wild rats selectively bred for more than 70 generations for either high level or for the lack of affective aggressiveness towards man. Significant increase of BDNF mRNA level in the frontal cortex and increase of BDNF level in the hippocampus of aggressive rats was revealed. In the midbrain and hippocampus of aggressive rats proBDNF level was increased, whereas BDNF/proBDNF ratio was reduced suggesting the prevalence and increased influence of proBDNF in highly aggressive rats. In the frontal cortex, proBDNF level in aggressive rats was decreased. Thus, considerable structure-specific differences in BDNF and proBDNF levels as well as in BDNF gene expression between highly aggressive and nonaggressive rats were shown. The data suggested the implication of BDNF and its precursor proBDNF in the mechanism of aggressiveness and in the creation of either aggressive or nonaggressive phenotype.

  20. Riluzole enhances expression of brain-derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus.

    PubMed

    Katoh-Semba, Ritsuko; Asano, Tomiko; Ueda, Hiroshi; Morishita, Rika; Takeuchi, Ikuo K; Inaguma, Yutaka; Kato, Kanefusa

    2002-08-01

    The dentate gyrus of the hippocampus, generating new cells throughout life, is essential for normal recognition memory performance. Reduction of brain-derived neurotrophic factor (BDNF) in this structure impairs its functions. To elucidate the association between BDNF levels and hippocampal neurogenesis, we first conducted a search for compounds that stimulate endogenous BDNF production in hippocampal granule neurons. Among ion channel modulators tested, riluzole, a neuroprotective agent with anticonvulsant properties that is approved for treatment of amyotrophic lateral sclerosis, was highly effective as a single dose by an intraperitoneal injection, causing a rise in BDNF localized in dentate granule neurons, the hilus, and the stratum radiatum of the CA3 region. Repeated, but not single, injections resulted in prolonged elevation of hippocampal BDNF and were associated with increased numbers of newly generated cells in the granule cell layer. This appeared due to promoted proliferation rather than survival of precursor cells, many of which differentiated into neurons. Intraventricular administration of BDNF-specific antibodies blocked such riluzole effects, suggesting that BDNF increase is necessary for the promotion of precursor proliferation. Our results suggest the basis for a new strategy for treatment of memory dysfunction.

  1. [Growth factors in human tooth development].

    PubMed

    Bellone, C; Barni, T; Pagni, L; Balboni, G C; Vannelli, G B

    1990-03-01

    Our research concerns the immunohistochemical localization of EGF and IGF-I receptors in the tooth germ, using monoclonal antibodies. The results show that in the early phases of human tooth development EGF and IGF-I receptors are present. At bud stage both receptors are localized at dental laminae level, in some epithelial cells of the tooth bud and in some mesenchymal cells. At cap stage the receptors are present in the outer and inner enamel epithelium, and in some cells of stellate reticulum. As far as concerns the mesenchymal cells, some cells of dental papilla in contact with enamel organ, are intensely positive. The immunopositivity is present also in some mesenchymal cells at follicular level. At late cap stage and at early bell stage receptors are not present at inner enamel epithelium level but they can be detectable in the mesenchyma of dental papilla and in some cells of the follicle. On the basis of these results it may be hypothesized that EGF and IGF-I can act as growth factors in the modulation of cellular proliferation and differentiation during the human tooth morphogenesis. Moreover, it is possible that these substances can play a role in the mesenchymal-epithelial interaction in the developing human tooth.

  2. Transforming growth factor beta1 and aldosterone

    PubMed Central

    Matsuki, Kota; Hathaway, Catherine K.; Chang, Albert S.; Smithies, Oliver; Kakoki, Masao

    2016-01-01

    Purpose of review It is well established that blocking renin-angiotensin II-aldosterone system (RAAS) is effective for the treatment of cardiovascular and renal complications in hypertension and diabetes mellitus. Although the induction of transforming growth factor beta1 (TGFbeta1) by components of RAAS mediates the hypertrophic and fibrogenic changes in cardiovascular-renal complications, it is still controversial as to whether TGFbeta1 can be a target to prevent such complications. Here we review recent findings on the role of TGFbeta1 in fluid homeostasis, focusing on the relationship with aldosterone. Recent findings TGFbeta1 suppresses adrenal production of aldosterone and renal tubular sodium reabsorption. We have generated mice with TGFbeta1 mRNA expression graded in five steps from 10% to 300% normal, and found that blood pressure and plasma volume are negatively regulated by TGFbeta1. Notably, the 10 % hypomorph exhibits primary aldosteronism and sodium and water retention due to markedly impaired urinary excretion of water and electrolytes. Summary These results identify TGFbeta signaling as an important counterregulatory system against aldosterone. Understanding the molecular mechanisms for the suppressive effects of TGFbeta1 on adrenocortical and renal function may further our understanding of primary aldosteronism as well as assist in the development of novel therapeutic strategies for hypertension. PMID:25587902

  3. Vascular Endothelial Growth Factor in Eye Disease

    PubMed Central

    Penn, J.S.; Madan, A.; Caldwell, R.B.; Bartoli, M.; Caldwell, R.W.; Hartnett, M.E.

    2012-01-01

    Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis. PMID:18653375

  4. Nerve growth factor actions on the brain

    SciTech Connect

    Martinez, H.J.

    1989-01-01

    We examined the effect of the trophic protein, nerve growth factor (NGF), on cultures of fetal rat neostriatum and basal forebrain-medial septal area (BF-MS) to define its role in brain development. Treatment of cultures with NGF resulted in an increase in the specific activity of the cholinergic enzyme choline acetyltransferase (CAT) in both brain areas. CAT was immunocytochemically localized to neurons. In the BF-MS, NGF treatment elicited a marked increase in staining intensity and an apparent increase in the number of CAT-positive neurons. Moreover, treatment of BF-MS cultures with NGF increased the activity of acetylcholinesterase, suggesting that the cholinergic neuron as a whole was affected. To begin defining mechanisms of action of NGF in the BF-MS, we detected NGF receptors by two independent methods. Receptors were localized to two different cellular populations: neuron-like cells, and non-neuron-like cells. Dissociation studies with ({sup 125}I)NGF suggested that high affinity receptors were localized to the neuron-like population. Only low-affinity receptors were localized to the non-neuron-like cells. Moreover, employing combined immunocytochemistry and ({sup 125}I)NGF autoradiography, we detected a subpopulation of CAT-containing neutrons that exhibited high-affinity binding. Unexpectedly, a gamma-aminobutyric acid (GABA)-containing cell group also expressed high affinity binding. However, only subsets of cholinergic or GABA neurons expressed high-affinity biding, suggesting that these transmitter populations are composed of differentially response subpopulations.

  5. Nerve growth factor enhances sleep in rabbits.

    PubMed

    Takahashi, S; Krueger, J M

    1999-04-02

    Nerve growth factor (NGF) elicits rapid-eye-movement sleep (REMS) in cats. Removal of NGF receptor-positive cholinergic basal forebrain neurons inhibits REMS in rats. The aim of the present study was to determine the effects of NGF on sleep and brain temperature (Tbr) in rabbits. Male rabbits were implanted with electroencephalograph (EEG) electrodes, a brain thermistor and an intraventricular (i.c.v.) guide cannula. Rabbits received human beta-NGF i.c.v. (0.01, 0.1, 1.0 or 10 microg] and on a separate day, 25 microl pyrogen-free saline i.c.v. as control. EEG and Tbr were recorded for 23 h after injections. The highest two doses of NGF increased both non-REMS and REMS across the 23-h recording period. REMS was enhanced dose-dependently. Tbr was not affected by any dose of NGF. These results suggest that NGF is involved in both REMS and non-REMS regulation.

  6. [Epidermal growth factor, innovation and safety].

    PubMed

    Esquirol Caussa, Jordi; Herrero Vila, Elisabeth

    2015-10-05

    Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations.

  7. 'Mature' nerve growth factor is a minor species in most peripheral tissues.

    PubMed

    Bierl, Michael A; Jones, Elizabeth E; Crutcher, Keith A; Isaacson, Lori G

    The classic neurotrophin hypothesis is based on the idea that innervating neurons derive 'mature' neurotrophin provided by the target for their survival. Yet large precursor forms of the neurotrophin nerve growth factor (NGF) have been reported in both central and peripheral tissues. In the present study, immunoblotting was used to survey peripheral tissues containing NGF-responsive neurons and to characterize various NGF species. These results demonstrate that 'mature' forms of NGF, i.e., the 13 and 16kDa species, are rare in sympathetic and sensory ganglia and in their peripheral targets, and that large molecular weight NGF precursors are abundant. In addition, certain NGF forms predominate in a given tissue, with each tissue exhibiting a characteristic NGF expression pattern. These findings suggest that NGF processing in peripheral tissues and in NGF-responsive ganglia may involve a variety of NGF species.

  8. Impact of nanoscale surface heterogeneity on precursor film growth and macroscopic spreading of [Rmim][NTf2] ionic liquids on mica.

    PubMed

    Wang, Zhantao; Priest, Craig

    2013-09-10

    The connection between the interfacial properties of ionic liquids and their wetting behavior has been studied very little to date and not at all on heterogeneous surfaces. Therefore, we have investigated the static and dynamic wetting for a family of ionic liquids, 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, [Rmim][NTf2], on mica, where R represents an ethyl, butyl, or hexyl alkyl chain on the imidazolium ring. Spreading is impacted greatly by a precursor film that forms on both homogeneous and heterogeneous mica surfaces. Macroscopically, the initial viscous spreading of the ionic liquid droplet on bare mica occurs within seconds but is then followed by a very slow relaxation that can be closely correlated with the typical time-scales of the precursor film growth. The contact angle for [emim][NTf2] and [bmim][NTf2] relaxes from about 40° to 23° over 30 and 90 min, respectively. For [hmim][NTf2], the process takes approximately 24 h and approaches complete wetting. The thickness of the precursor films for [emim][NTf2], [bmim][NTf2], and [hmim][NTf2] were 0.53, 0.65, and 1.0 nm, respectively, according to atomic force microscopy (AFM). These values are consistent with a monolayer of ionic liquid cations on mica, rather than ion pairs. A monolayer of octadecylphosphonic acid (OPA) on mica prevents both the formation of a precursor film and the relaxation of the contact angle. However, only a partial surface coverage of ~60% OPA is required to have the same effect. Quenching of precursor film formation (and associated contact angle relaxation) is due to an increasingly connected network of OPA regions that closes the nanoscale paths of bare mica on which the precursor film can develop via surface diffusion.

  9. Growth behavior and properties of atomic layer deposited tin oxide on silicon from novel tin(II)acetylacetonate precursor and ozone

    SciTech Connect

    Kannan Selvaraj, Sathees; Feinerman, Alan; Takoudis, Christos G.

    2014-01-15

    In this work, a novel liquid tin(II) precursor, tin(II)acetylacetonate [Sn(acac){sub 2}], was used to deposit tin oxide films on Si(100) substrate, using a custom-built hot wall atomic layer deposition (ALD) reactor. Three different oxidizers, water, oxygen, and ozone, were tried. Resulting growth rates were studied as a function of precursor dosage, oxidizer dosage, reactor temperature, and number of ALD cycles. The film growth rate was found to be 0.1 ± 0.01 nm/cycle within the wide ALD temperature window of 175–300 °C using ozone; no film growth was observed with water or oxygen. Characterization methods were used to study the composition, interface quality, crystallinity, microstructure, refractive index, surface morphology, and resistivity of the resulting films. X-ray photoelectron spectra showed the formation of a clean SnO{sub x}–Si interface. The resistivity of the SnO{sub x} films was calculated to be 0.3 Ω cm. Results of this work demonstrate the possibility of introducing Sn(acac){sub 2} as tin precursor to deposit conducting ALD SnO{sub x} thin films on a silicon surface, with clean interface and no formation of undesired SiO{sub 2} or other interfacial reaction products, for transparent conducting oxide applications.

  10. [Periodontal regeneration: the use of polypeptide growth factors].

    PubMed

    Di Genio, M; Barone, A; Ramaglia, L; Sbordone, L

    1994-10-01

    Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration and metabolism. Periodontal regeneration is thought to require the migration and proliferation of periodontal ligament cells on the root surface. In fact, repopulation of the detached root surface by cells from periodontal ligament (PDL) is a prerequisite for new attachment formation. Many studies suggested that Polypeptide Growth Factors (PGF) such as Insulin-like Growth Factor I (IGF-I), Platelet Derived Growth Factor (PDGF), Transforming Growth Factor B (TGF-B), Epidermal Growth Factor (EGF), are important mediators of cellular events in wound healing. Studies in vitro analysed the mitogenic effects determined on periodontal ligament cells by growth factors using (3H) Thymidine incorporation during DNA synthesis. The results suggested that recombinant human PDGF and IGF-I stimulate the proliferation of PDL fibroblastic cells and the combination of these growth factors showed a synergistic effect revealing the highest mitogenic effect among all individual growth factors as well as any combination of the growth factors tested. Furthermore these studies demonstrated that rh-PDGF and IGF-I stimulate chemotaxis of PDL fibroblastic cells, and supported a role for TGF-B as a regulator of the mitogenic response to PDGF in these cells. Other studies in vivo showed periodontal tissues regeneration introducing mixtures of recombinant human platelet derived growth factor and insulin-like growth factor into lesions of experimentally induced periodontitis in beagle dogs and monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Mast cell diversion of T-lineage precursor cells by the essential T-lineage transcription factor GATA-3

    PubMed Central

    Taghon, Tom; Yui, Mary A.; Rothenberg, Ellen V.

    2011-01-01

    GATA-3 is essential for T cell development from the earliest stages. However, highly abundant GATA-3 can drive T-lineage precursors to a non-T fate, depending on Notch signaling and developmental stage. GATA-3 overexpression blocked pro-T cell survival when Notch-Delta signals were present, but enhanced viability in their absence. In double-negative (DN1) and DN2 but not DN3 fetal thymocytes, GATA-3 overexpression rapidly induced mast cell lineage respecification with high frequency by direct transcriptional reprogramming. Normal DN2 thymocytes also displayed mast cell potential, when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro-T and mast cell programs and a new role for Notch in T-lineage fidelity. PMID:17603486

  12. Genetics of ischemic stroke, stroke-related risk factors, stroke precursors and treatments.

    PubMed

    Della-Morte, David; Guadagni, Fiorella; Palmirotta, Raffaele; Testa, Gianluca; Caso, Valeria; Paciaroni, Maurizio; Abete, Pasquale; Rengo, Franco; Ferroni, Patrizia; Sacco, Ralph L; Rundek, Tatjana

    2012-04-01

    Stroke remains a leading cause of death worldwide and the first cause of disability in the western world. Ischemic stroke (IS) accounts for almost 80% of the total cases of strokes and is a complex and multifactorial disease caused by the combination of vascular risk factors, environment and genetic factors. Investigations of the genetics of atherosclerosis and IS has greatly enhanced our knowledge of this complex multifactorial disease. In this article we sought to review common single-gene disorders relevant to IS, summarize candidate gene and genome-wide studies aimed at discovering genetic stroke risk factors and subclinical phenotypes, and to briefly discuss pharmacogenetics related to stroke treatments. Genetics of IS is, in fact, one of the most promising research frontiers and genetic testing may be helpful for novel drug discoveries as well as for appropriate drug and dose selection for treatment of patients with cerebrovascular disease.

  13. Nerve growth factor gene therapy in Alzheimer disease.

    PubMed

    Tuszynski, Mark H

    2007-01-01

    Nervous system growth factors potently stimulate cell function and prevent neuronal death. These broad effects on survival and function arise from direct downstream activation of antiapoptotic pathways, inhibition of proapoptotic pathways, and stimulation of functionally important cellular mechanisms including ERK/MAP kinase and CREB. Thus, as a class, growth factors offer the potential to treat neurodegenerative disorders for the first time by preventing neuronal degeneration rather than compensating for cell loss after it has occurred. Different growth factors affect distinct and specific populations of neurons: the first nervous system growth factor identified, nerve growth factor, potentially stimulates the survival and function of basal forebrain cholinergic neurons, suggesting that nerve growth factor could be a means for reducing the cholinergic component of cell degeneration in Alzheimer disease. This review will discuss the transition of growth factors from preclinical studies to human clinical trials in Alzheimer disease. The implementation of clinical testing of growth factor therapy for neurologic disease has been constrained by the dual need to achieve adequate concentrations of these proteins in specific brain regions containing degenerating neurons, and preventing growth factor spread to nontargeted regions to avoid adverse effects. Gene therapy is one of a limited number of potential methods for achieving these requirements.

  14. Role of tissue growth factors in aqueous humor homeostasis.

    PubMed

    Welge-Lüssen, U; May, C A; Neubauer, A S; Priglinger, S

    2001-04-01

    The aqueous humor supplies nutrients to the nonvascularized cornea, lens, and trabecular meshwork. A number of tissue growth factors have been detected in this fluid. The composition of these proteins changes dramatically with different ocular conditions, such as inflammation and glaucoma. In this review, an overview of new findings regarding effects of aqueous humor growth factors is given. Our main emphasis is on the regulation of the avascular anterior eye compartment, the possible role of growth factors in the pathogenesis of glaucoma, and the importance of growth factors for the special immunosuppressive status of the anterior chamber.

  15. Insulin-Like Growth Factor-Independent Effects of Growth Hormone on Growth Plate Chondrogenesis and Longitudinal Bone Growth.

    PubMed

    Wu, Shufang; Yang, Wei; De Luca, Francesco

    2015-07-01

    GH stimulates growth plate chondrogenesis and longitudinal bone growth directly at the growth plate. However, it is not clear yet whether these effects are entirely mediated by the local expression and action of IGF-1 and IGF-2. To determine whether GH has any IGF-independent growth-promoting effects, we generated (TamCart)Igf1r(flox/flox) mice. The systemic injection of tamoxifen in these mice postnatally resulted in the excision of the IGF-1 receptor (Igf1r) gene exclusively in the growth plate. (TamCart)Igf1r(flox/flox) tamoxifen-treated mice [knockout (KO) mice] and their Igf1r(flox/flox) control littermates (C mice) were injected for 4 weeks with GH. At the end of the 4-week period, the tibial growth and growth plate height of GH-treated KO mice were greater than those of untreated C or untreated KO mice. The systemic injection of GH increased the phosphorylation of Janus kinase 2 and signal transducer and activator of transcription 5B in the tibial growth plate of the C and KO mice. In addition, GH increased the mRNA expression of bone morphogenetic protein-2 and the mRNA expression and protein phosphorylation of nuclear factor-κB p65 in both C and KO mice. In cultured chondrocytes transfected with Igf1r small interfering RNA, the addition of GH in the culture medium significantly induced thymidine incorporation and collagen X mRNA expression. In conclusion, our findings demonstrate that GH can promote growth plate chondrogenesis and longitudinal bone growth directly at the growth plate, even when the local effects of IGF-1 and IGF-2 are prevented. Further studies are warranted to elucidate the intracellular molecular mechanisms mediating the IGF-independent, growth-promoting GH effects.

  16. Efficient synthesis of human type alpha transforming growth factor: its physical and biological characterization.

    PubMed Central

    Tam, J P; Sheikh, M A; Solomon, D S; Ossowski, L

    1986-01-01

    Human transforming growth factor type alpha (TGF-alpha) was synthesized by a stepwise solid-phase method with an overall yield of 26%. Synthetic TGF-alpha, consisting of 50 amino acid residues deduced from a cDNA precursor sequence, was purified in a single HPLC step. The homogeneity and primary structure were confirmed by several criteria including Edman degradation and mass spectrometry. Synthetic TGF-alpha was as active as murine epidermal growth factor in binding to the epidermal growth factor receptor and in stimulation of anchorage-dependent and of anchorage-independent growth of normal indicator cells in culture. Synthetic TGF-alpha stimulated plasminogen activator production in A 431 and HeLa cells; the stimulation was similar to that induced by epidermal growth factor. Furthermore, synthetic human TGF-alpha showed similar immunoreactivity when compared with rat TGF-alpha. Thus, the 50-amino acid TGF-alpha is likely to be the bioactive principle produced and secreted by tumor cell lines. PMID:3490662

  17. Transforming growth factor-β and Smads.

    PubMed

    Lan, Hui Yao; Chung, Arthur C K

    2011-01-01

    Diabetic nephropathy (DN) is a major diabetic complication. Transforming growth factor-β(TGF-β) is a key mediator in the development of diabetic complications. It is well known that TGF-β exerts its biological effects by activating downstream mediators, called Smad2and Smad3, which is negatively regulated by an inhibitory Smad7. Recent studies also demonstrated that under disease conditions Smads act as signal integrators and interact with other signaling pathways such as the MAPK and NF-κB pathways. In addition, Smad2and Smad3 can reciprocally regulate target genes of TGF-β signaling. Novel research into microRNA has revealed the complexity of TGF-β signaling during DN. It has been found that TGF-β and elevated glucose concentration can positively regulate miR-192 and miR-377, but negatively regulate miR-29a in a diabetic milieu. These microRNAs are found to contribute to DN. Although targeting TGF-β may exert adverse effects on immune system, therapeutic approach against TGF-β signaling during DN still draws much attention. Blocking TGF-β signaling by neutralizing antibody, anti-sense oligonucleotides, and soluble receptors have been tested, but effects are limited. Gene transfer of Smad7 into diseased kidneys demonstrates a prominent inhibition on renal fibrosis and amelioration of renal impairment. Alteration of TGF-β-regulated microRNA expression in diseased kidneys may provide an alternative therapeutic approach against DN. In conclusion, TGF-β/Smad signaling plays a critical role in DN. A better understanding of the role of TGF-β/Smad signaling in the development of DN should provide an effective therapeutic strategy to combat DN.

  18. Fibroblast Growth Factor Signaling in Metabolic Regulation

    PubMed Central

    Nies, Vera J. M.; Sancar, Gencer; Liu, Weilin; van Zutphen, Tim; Struik, Dicky; Yu, Ruth T.; Atkins, Annette R.; Evans, Ronald M.; Jonker, Johan W.; Downes, Michael Robert

    2016-01-01

    The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions. PMID:26834701

  19. Characterization of Single-Nucleotide Polymorphisms in the Tumor Necrosis Factor α Promoter Region and in Lymphotoxin α in Squamous Intraepithelial Lesions, Precursors of Cervical Cancer1

    PubMed Central

    Nieves-Ramirez, Miriam Enriqueta; Partida-Rodriguez, Oswaldo; Alegre-Crespo, Pedro Eduardo; Tapia-Lugo, Maria del Carmen; Perez-Rodriguez, Martha Esthela

    2011-01-01

    Development of cervical cancer is a long process of abnormal cancerous cell growth in the cervix and is primarily the result of infection with specific high-risk types of human papillomavirus (HPV). The cytokines tumor necrosis factor α (TNFα) and lymphotoxin α (LTA) have an important role in all stages of cervical cancer and have the ability to induce the regression or promote the development of human tumors. Biologically important single-nucleotide polymorphisms (SNPs) occur within the TNFα and LTA genes. Therefore, the purpose of this study was to investigate the SNPs in the TNFα promoter region (-163, -238, -244, -308, -376, -857, -863, and -1031) and in the first intron of LTA (+252) in women with precursor lesions of cervical cancer. Overall, we studied 396 women from Mexico City. A total of 191 patients with HPV infection and precursor cervical lesions were subdivided in two groups: those with low-grade squamous intraepithelial lesions (n = 132) and those with high-grade squamous intraepithelial lesions (n = 59). Women (n = 205) negative for HPV and without cervical lesions were also included in the study. DNA was extracted from peripheral white blood cells and from cervical samples, and detection of biallelic polymorphisms of TNFα and LTA was performed using the polymerase chain reaction-sequence-specific oligonucleotide probe and restriction fragment length polymorphism techniques, respectively. We demonstrated that risk is associated with the genotype G/A (odds ratio = 2.48) and that protection is associated with the genotype G/G of SNP TNFα -376 (odds ratio = 0.37). PMID:22190997

  20. In vivo growth of a bioengineered internal anal sphincter: comparison of growth factors for optimization of growth and survival.

    PubMed

    Miyasaka, Eiichi A; Raghavan, Shreya; Gilmont, Robert R; Mittal, Krittika; Somara, Sita; Bitar, Khalil N; Teitelbaum, Daniel H

    2011-02-01

    Our laboratory has developed and implanted a novel bioengineered internal anal sphincter (IAS) to treat anal incontinence. Fibroblast growth factor-2 (FGF-2) has been used in mice; however, the optimal growth factor for successful IAS implantation is unclear. This study compares several growth factors in order to optimize IAS viability and functionality. Bioengineered IAS rings were implanted subcutaneously into the dorsum of wildtype C57Bl/6 mice, with an osmotic pump dispensing FGF-2, vascular endothelial growth factor (VEGF), or platelet-derived growth factor (PDGF) (n = 4 per group). Control mice received IAS implants but no growth factor. The IAS was harvested approximately 25 days post-implantation. Tissue was subjected to physiologic testing, then histologically analyzed. Muscle phenotype was confirmed by immunofluorescence. All implants supplemented with growth factors maintained smooth muscle phenotype. Histological scores, blood vessel density and muscle fiber thickness were all markedly better with growth factors. Neovascularization was comparable between the three growth factors. Basal tonic force of the constructs was highest with VEGF or PDGF. All growth factors demonstrated excellent performance. As our ultimate goal is clinical implantation, our strong results with PDGF, a drug approved for use in the United States and the European Union, pave the way for translating bioengineered IAS implantation to the clinical realm.

  1. Growth of highly oriented LiNbO 3 thin films through structure controlled metal alkoxide precursor solution

    NASA Astrophysics Data System (ADS)

    Hirano, Shin-ichi; Takeichi, Yoshikuni; Sakamoto, Wataru; Yogo, Toshinobu

    2002-04-01

    Highly oriented LiNbO 3 thin films have been successfully synthesized by chemical solution deposition through a structure controlled metal-organic precursor. The homogeneous LiNbO 3 precursor solution was prepared by controlling the reaction of metal alkoxides and selecting the ligand for modification. LiNbO 3 thin films with c-axis preferred orientation were directly crystallized on sapphire C substrates from chemical solutions synthesized in this study. The epitaxial relation of LiNbO 3 film to sapphire substrate was found to depend strongly upon the precursor structure modified with β-diketone. 1-Phenyl-1,3-butanedione (PBD) was found to be superior to acetylacetone (acacH) and dibenzoylmethane (DBM) for the crystallization of epitaxial LiNbO 3 films. The results suggested that the existence of a benzene ring in the ligand strongly influenced the degree of orientation of synthesized films.

  2. Expression of growth factors and growth factor receptors in human cleft-affected tissue.

    PubMed

    Krivicka, Benita; Pilmane, Mara; Akota, Ilze

    2013-01-01

    OBJECTIVE. To investigate cleft disordered tissue in children with cleft palate and cleft lip with or without alveolar clefting for detection of local tissue growth factors and growth factor receptors and compare findings. Design. Morphological analysis of human tissue. Patients. Three groups were studied: 14 patients with cleft palate at the age from eight months to 18 years and two months, 12 patients with cleft lip with or without alveolar clefting in the age from four months to 15 years and four months and 11 control patients. RESULTS. In general, cleft palate disordered tissue showed more prominent expression of BMP2/4 (z=3.574; p=0.0004) and TGFβ (z=2.127; p=0.033), while expression of TGFBR3 significantly higher was only in connective tissue (z=3.822; p=0.0001). Cleft lip affected tissue showed significantly pronounced expression of FGFR1 in general as well as separately in epithelium. CONCLUSIONS. The marked and statistically significant expression of BMP 2/4 in cleft palate disordered soft tissue probably is delayed, but still proliferation and differentiation as well as tissue, especially, bone remodeling contributing signal. Cleft palate affected tissue show more prominent expression of TGFβ, still the weak regional expression of TGFβ type III receptors prove the disordered tissue growth and changed TGFβ signalling pathway in postnatal pathogenesis. In general, expression of TGFβ, BMP 2/4 and FGFR1 is significantly different, giving evidence to the involvement of these mentioned factors in the cleft severity morphopathogenesis.

  3. Clinical Application of Growth Factors and Cytokines in Wound Healing

    PubMed Central

    Barrientos, Stephan; Brem, Harold; Stojadinovic, Olivera; Tomic-Canic, Marjana

    2016-01-01

    Wound healing is a complex and dynamic biological process that involves the coordinated efforts of multiple cell types and is executed and regulated by numerous growth factors and cytokines. There has been a drive in the past two decades to study the therapeutic effects of various growth factors in the clinical management of non-healing wounds (e.g. pressure ulcers, chronic venous ulcers, diabetic foot ulcers). For this review, we conducted a nonline search of Medline and Pub Medical and critically analyzed the literature regarding the role of growth factors and cytokines in the management of these wounds. We focused on currently approved therapies, emerging therapies and future research possibilities. In this review we discuss four growth factors and cytokines currently being used on and off label for the healing of wounds. These include: granulocyte-macrophage colony stimulating factor (GM-CSF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). While the clinical results of using growth factors and cytokines are encouraging, many studies involved a small sample size and are disparate in measured endpoints. Therefore, further research is required to provide definitive evidence of efficacy. PMID:24942811

  4. An Exploratory Study of Factors Differentiating Freshmen Educational Growth.

    ERIC Educational Resources Information Center

    Lenning, Oscar T.

    The present study was an exploratory investigation of factors that differentiate students who exhibit "negative educational growth" from a group of equally able students who exhibit marked "positive educational growth." Educational growth was operationally defined as estimated true test-retest change on American College Tests (ACT) composite…

  5. Co-operative signalling mechanisms required for erythroid precursor expansion in response to erythropoietin and stem cell factor.

    PubMed

    Arcasoy, Murat O; Jiang, Xiaohong

    2005-07-01

    The regeneration of circulating red blood cells in response to anaemia associated with blood loss or haemolysis involves an increased rate of erythropoiesis and expansion of proerythroblasts, the bone marrow precursor cells that terminally differentiate into mature erythrocytes. This study investigated the mechanisms by which erythropoietin (Epo) and stem cell factor (Scf) modulate the expansion of proerythroblasts. Homogenous populations of primary human proerythroblasts were generated in liquid cultures of CD34(+) cells. In serum-free cultures, proerythroblasts failed to survive in the presence of Epo or Scf alone, but exhibited synergistic proliferation in response to combined Epo and Scf treatment, exhibiting one-log expansion in 5 d. Intracellular signal transduction in response to Epo and Scf revealed that tyrosine phosphorylation of signal transducers and activators of transcription (Stat) 5, a downstream target for the non-receptor tyrosine kinase, Janus kinase 2 (Jak2), was mediated by Epo but not Scf. The mitogen-activated protein kinases (MAPKs) extracellular regulated kinase (Erk) 1-2 were phosphorylated in response to either Epo or Scf. Phosphorylation of Akt, a signalling molecule downstream of phosphatidylinositol 3-kinase (PI3K), was observed following Scf but not Epo treatment. To determine the contribution of specific signalling pathways to synergistic expansion of proerythroblasts in response to co-operative effects of Epo and Scf, cells were treated with kinase inhibitors targeting Jak2, PI3K and MAPK kinase. There was a significant, dose-dependent inhibition of proerythroblast expansion in response to all three kinase inhibitors. In conclusion, Epo- and Scf-mediated co-operative, synergistic expansion of primary erythroid precursors requires selective activation of multiple signalling pathways, including the Jak-Stat, PI3K and MAPK pathways.

  6. Brain-derived neurotrophic factor promotes vasculature-associated migration of neuronal precursors toward the ischemic striatum.

    PubMed

    Grade, Sofia; Weng, Yuan C; Snapyan, Marina; Kriz, Jasna; Malva, João O; Saghatelyan, Armen

    2013-01-01

    Stroke induces the recruitment of neuronal precursors from the subventricular zone (SVZ) into the ischemic striatum. In injured areas, de-routed neuroblasts use blood vessels as a physical scaffold to their migration, in a process that resembles the constitutive migration seen in the rostral migratory stream (RMS). The molecular mechanism underlying injury-induced vasculature-mediated migration of neuroblasts in the post-stroke striatum remains, however, elusive. Using adult mice we now demonstrate that endothelial cells in the ischemic striatum produce brain-derived neurotrophic factor (BDNF), a neurotrophin that promotes the vasculature-mediated migration of neuronal precursors in the RMS, and that recruited neuroblasts maintain expression of p75NTR, a low-affinity receptor for BDNF. Reactive astrocytes, which are widespread throughout the damaged area, ensheath blood vessels and express TrkB, a high-affinity receptor for BDNF. Despite the absence of BDNF mRNA, we observed strong BDNF immunolabeling in astrocytes, suggesting that these glial cells trap extracellular BDNF. Importantly, this pattern of expression is reminiscent of the adult RMS, where TrkB-expressing astrocytes bind and sequester vasculature-derived BDNF, leading to the entry of migrating cells into the stationary phase. Real-time imaging of cell migration in acute brain slices revealed a direct role for BDNF in promoting the migration of neuroblasts to ischemic areas. We also demonstrated that cells migrating in the ischemic striatum display higher exploratory behavior and longer stationary periods than cells migrating in the RMS. Our findings suggest that the mechanisms involved in the injury-induced vasculature-mediated migration of neuroblasts recapitulate, at least partially, those observed during constitutive migration in the RMS.

  7. Radar Interferometric Applications for a Better Understanding of the Distribution, Controlling Factors, and Precursors of Large Earthquakes in Turkey

    NASA Astrophysics Data System (ADS)

    Emil, M.; Sultan, M.; Fawzy, D. E.; Ahmed, M. E.; Chouinard, K.

    2012-12-01

    We are analyzing ERS-1 and ERS-2 and ENVISAT data to measure the spatial and temporal variations in three tectonically active areas near Izmit, Duzce and Van provinces in Turkey. We are using ERS-1 and ERS-2 data sets, which provide a longer time period of coverage (1992 to 2001). In addition, we will extend this forward to the present with ENVISAT radar data. The proposed activities can potentially provide predictive tools that can identify precursors to earthquakes and hence develop procedures to identify areas at risk. We are using radar interferometric techniques that have the ability of detecting deformation on the order of millimeters in scale over relatively large areas. We are applying the persistent scatterer and the small baseline subset (SBAS) techniques. A four fold exercise is being conducted: (1) extraction of land deformation rates and patterns from radar interferometry, (2) comparison and calibration of extracted rates to those extracted from existing geodetic ground stations, (3) identification of the natural factors (e.g., displacement along one or more faults) that are largely responsible for the observed deformation patterns, (4) utilizing the extracted deformation rates and/or patterns to identify areas prone to earthquake development in the near future, and (5) utilizing the extracted deformation rates or patterns to identify the areal extent of the domains affected by the earthquakes and the magnitude of the deformation following the earthquakes. The conditions in Turkey are typical of many of the world's areas that are witnessing continent to continent collisions. To date, applications similar to those advocated here for the assessment of ongoing land deformation in such areas and for identifying and characterizing land deformation as potential precursors to earthquakes have not been fully explored. Thus, the broader impact of this work lies in a successful demonstration of the advocated procedures in the study area which will invite similar

  8. Extracellular matrix and growth factors in branching morphogenesis

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1993-01-01

    The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

  9. Extracellular matrix and growth factors in branching morphogenesis

    NASA Technical Reports Server (NTRS)

    Hardman, P.; Spooner, B. S.

    1993-01-01

    The unifying hypothesis of the NSCORT in gravitational biology postulates that the ECM and growth factors are key interrelated components of a macromolecular regulatory system. The ECM is known to be important in growth and branching morphogenesis of embryonic organs. Growth factors have been detected in the developing embryo, and often the pattern of localization is associated with areas undergoing epithelial-mesenchymal interactions. Causal relationships between these components may be of fundamental importance in control of branching morphogenesis.

  10. Expression of vascular endothelial growth factor and basic fibroblast growth factor in extramammary Paget disease.

    PubMed

    Xu, Xiaoyun; Shao, Ning; Qiao, Di; Wang, Zengjun; Song, Ningjing; Song, Ninghong

    2015-01-01

    Extramammary Paget's disease (EMPD) is a special type of cancers. The etiology of the disease is still unclear. We aimed to study the expression differences of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in EMPD tissues and corresponding adjacent normal tissues. The mRNA expression was detected by RT-PCR and the protein expression was explored by immunohistochemistry. Higher immunostaining signal scores of bFGF and VEGF in EMPD tissues had been found (z=-3.827, P<0.001, z=-3.729, P<0.001, respectively). In addition, the mRNA expression of bFGF and VEGF was higher in EMPD tissues, which had been validated by RT-PCR (t=5.771, P<0.001, t=3.304, P=0.004, respectively). The VEGF and bFGF might be the key signaling proteins in angiogenesis of EMPD. How to block the VEGF and bFGF in EMPD and to destroy the blood supply of the tumor cells becomes the focus of our future research.

  11. Nerve growth factor-mediated vascular endothelial growth factor expression of astrocyte in retinal vascular development.

    PubMed

    Kim, You Sun; Jo, Dong Hyun; Lee, Hanjae; Kim, Jin Hyoung; Kim, Kyu-Won; Kim, Jeong Hun

    2013-02-22

    The angiogenic aspect of neurotrophins and their receptors rather than the neuroscientific aspect has been focused. However, their role in retinal vascular development is underdiscovered. The purpose of this study is to understand the role of neurotrophin receptors in retinal vascular development and the mechanisms of their action. To identify the expression of tropomyosin receptor kinase receptor (Trk) in developing retina, tissues of 4, 8, 12, 16 and 26 day-old mice were prepared for experiments. Immunohistochemistry and immunofluorescence double staining against glial fibrillary acidic protein and type IV collagen were performed. TrkA was expressed mainly along the vessel structure in inner part of retina, especially in retinal astrocyte. In cultured primary astrocyte, recombinant nerve growth factor (NGF) was used to activate TrkA. NGF induced the phosphorylation of TrkA, and it also enhanced the level of activated Akt and vascular endothelial growth factor (VEGF) mRNA. Inhibition of phosphoinositide 3-kinase (PI3K) reversed the NGF-induced activation of these two molecules. This study demonstrated that TrkA activation on NGF leads to VEGF elevation by PI3K-Akt pathway and therefore suggested that TrkA could be a stimulator of retinal vascular development. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Epidermal growth factor receptor mutation enhances expression of vascular endothelial growth factor in lung cancer.

    PubMed

    Hung, Ming-Szu; Chen, I-Chuan; Lin, Paul-Yann; Lung, Jr-Hau; Li, Ya-Chin; Lin, Yu-Ching; Yang, Cheng-Ta; Tsai, Ying-Huang

    2016-12-01

    Epidermal growth factor receptor (EGFR) activation has been demonstrated to have a critical role in tumor angiogenesis. In the present study, the correlation between EGFR mutations and vascular endothelial growth factor (VEGF) was investigated in lung cancer cell lines and non-small-cell lung cancer (NSCLC) tumor tissues. VEGF levels were significantly increased in culture medium of lung cancer cells and NSCLC tissues with EGFR mutations (H1650 vs. A549, P=0.0399; H1975 vs. A549, P<0.0001). Stable lung cancer cell lines expressing mutant (exon 19 deletion, E746-A750; exon 21 missense mutation, L858R) and wild-type EGFR genes were established. Significantly increased expression of VEGF and stronger inhibitory effects of gefitinib to VEGF expression were observed in exon 19 deletion stable lung cancer cells (exon 19 deletion vs. wild-type EGFR, P=0.0005). The results of the present study may provide an insight into the association of mutant EGFR and VEGF expression in lung cancer, and may assist with further development of targeted therapy for NSCLC in the future.

  13. Epicardium and Myocardium Separate From a Common Precursor Pool by Crosstalk Between Bone Morphogenetic Protein– and Fibroblast Growth Factor–Signaling Pathways

    PubMed Central

    van Wijk, Bram; van den Berg, Gert; Abu-Issa, Radwan; Barnett, Phil; van der Velden, Saskia; Schmidt, Martina; Ruijter, Jan M.; Kirby, Margaret L.; Moorman, Antoon F.M.; van den Hoff, Maurice J.B.

    2010-01-01

    Rationale The epicardium contributes to the majority of nonmyocardial cells in the adult heart. Recent studies have reported that the epicardium is derived from Nkx2.5-positive progenitors and can differentiate into cardiomyocytes. Not much is known about the relation between the myocardial and epicardial lineage during development, whereas insights into these embryonic mechanisms could facilitate the design of future regenerative strategies. Objective Acquiring insight into the signaling pathways involved in the lineage separation leading to the differentiation of myocardial and (pro)epicardial cells at the inflow of the developing heart. Methods and Results We made 3D reconstructions of Tbx18 gene expression patterns to give insight into the developing epicardium in relation to the developing myocardium. Next, using DiI tracing, we show that the (pro)epicardium separates from the same precursor pool as the inflow myocardium. In vitro, we show that this lineage separation is regulated by a crosstalk between bone morphogenetic protein (BMP) signaling and fibroblast growth factor (FGF) signaling. BMP signaling via Smad drives differentiation toward the myocardial lineage, which is inhibited by FGF signaling via mitogen-activated protein kinase kinase (Mek)1/2. Embryos exposed to recombinant FGF2 in vivo show enhanced epicardium formation, whereas a misbalance between FGF and BMP by Mek1/2 inhibition and BMP stimulation causes a developmental arrest of the epicardium and enhances myocardium formation at the inflow of the heart. Conclusion Our data show that FGF signaling via Mek1/2 is dominant over BMP signaling via Smad and is required to separate the epicardial lineage from precardiac mesoderm. Consequently, myocardial differentiation requires BMP signaling via Smad and inhibition of FGF signaling at the level of Mek1/2. These findings are of clinical interest for the development of regeneration-based therapies for heart disease. PMID:19628790

  14. Lack of neurogenesis in the adult rat cerebellum after Purkinje cell degeneration and growth factor infusion.

    PubMed

    Grimaldi, Piercesare; Rossi, Ferdinando

    2006-05-01

    Although constitutive neurogenesis exclusively occurs in restricted regions of the adult mammalian brain, resident progenitors can be isolated from many different CNS sites, and neuronal neogeneration can be stimulated in vivo by injury or infusion of growth factors. To ask whether latent compensatory mechanisms, which may be exploited to promote repair processes, are present throughout the CNS, we examined the neurogenic potentialities of the adult rat cerebellum in normal conditions, following injury, and after infusion of growth factors. Degeneration of Purkinje cells was induced by intracerebroventricular administration of the toxin saporin, conjugated to anti-p75 antibodies. In addition, epidermal growth factor and basic fibroblast growth factor, or FGF8, were infused for 2 weeks to either intact or injured animals. In all conditions, proliferating cells were identified from bromodeoxyuridine (BrdU) incorporation. In the unmanipulated cerebellum there were rare dividing cells, mainly represented by NG2-positive presumptive oligodendrocyte precursors. Mitotic activity was strongly enhanced in cortical areas with Purkinje cell degeneration, being mostly sustained by microglia, plus minor fractions of NG2-expressing cells, astrocytes and oligodendrocytes. In contrast, growth factor infusion had a weak effect on both intact and injured cerebella. In all experimental conditions, we never found any BrdU-positive cells coexpressing distinctive markers for immature or differentiated cerebellar neurons. Therefore, although some progenitor cells reside in the adult cerebellum, the local environment, either intact or injured, does not provide efficient cues to direct their differentiation towards neuronal phenotypes. In addition, neurogenic potentialities cannot be induced or boosted by the application of growth factors which are effective in other CNS regions.

  15. Material factors influencing metallic whisker growth

    NASA Astrophysics Data System (ADS)

    Rodekohr, Chad L.

    Whiskering refers to the formation of slender, long, metallic filaments, much thinner than a human hair, that grow on a metallic thin film surface. They are readily observed for pure and alloyed zinc (Zn), silver (Ag), cadmium (Cd), indium (In), and tin (Sn) surfaces. The longest reported whisker length is 4.5 mm long but most high-aspect ratio whiskers range from 1-500 mum. The focus of this research is upon Sn whiskers. Sn whiskers pose serious reliability problems for the electronics industry and are known to be the source of failure in a wide range of electronic devices, such as nuclear power facilities, heart pacemakers, commercial satellites, aviation radar, telecommunication equipment, and desktop computers. The problem with whiskering has been recently exacerbated by the worldwide shift to lead (Pb) free electronics and the continuing reduction in electrical contact pitches. A thorough understanding of the growth mechanism of Sn whiskers is urgently needed. Currently, there is no universally accepted model that explains the broad range of observations on whiskering. The goals of this research are: (1) to develop a more detailed understanding of the physical mechanisms leading to the initiation and growth of Sn whiskers and (2) to outline reasonable mitigation strategies that could be followed to reduce or eliminate the problem of Sn whiskers. The major contributions of this work are: (1) A reliable method for growing Sn whiskers with predictable incubation times has been developed and tested. (2) A surface oxide is not necessary for whisker growth. (3) Intermetallic compounds (IMC) are not necessary for whisker growth. (4) Smoother, not rougher, substrate surfaces promote whisker growth. (5) Whiskers grow under both compressive and tensile thin film stress states. (6) Whisker growth increases with externally applied compression and tension forces. (7) Sn whiskers are composed of pure Sn except for the expected thin, native Sn oxide on their surface. (8) For

  16. Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells.

    PubMed Central

    Gutacker, C; Klock, G; Diel, P; Koch-Brandt, C

    1999-01-01

    Clusterin (apolipoprotein J) is an extracellular glycoprotein that might exert functions in development, cell death and lipid transport. Clusterin gene expression is elevated at sites of tissue remodelling, such as differentiation and apoptosis; however, the signals responsible for this regulation have not been identified. We use here the clusterin gene as a model system to examine expression in PC12 cells under the control of differentiation and proliferation signals produced by nerve growth factor (NGF) and by epidermal growth factor (EGF) respectively. NGF induced clusterin mRNA, which preceded neurite outgrowth typical of neuronal differentiation. EGF also activated the clusterin mRNA, demonstrating that both proliferation and differentiation signals regulate the gene. To localize NGF- and EGF-responsive elements we isolated the clusterin promoter and tested it in PC12 cell transfections. A 2.5 kb promoter fragment and two 1.5 and 0.3 kb deletion mutants were inducible by NGF and EGF. The contribution to this response of a conserved activator protein 1 (AP-1) motif located in the 0.3 kb fragment was analysed by mutagenesis. The mutant promoter was not inducible by NGF or EGF, which identifies the AP-1 motif as an element responding to both factors. Binding studies with PC12 nuclear extracts showed that AP-1 binds to this sequence in the clusterin promoter. These findings suggest that NGF and EGF, which give differential gene regulation in PC12 cells, resulting in neuronal differentiation and proliferation respectively, use the common Ras/extracellular signal-regulated kinase/AP-1 signalling pathway to activate clusterin expression. PMID:10215617

  17. Heparin-binding epidermal growth factor-like growth factor and hepatocyte growth factor inhibit cholestatic liver injury in mice through different mechanisms

    PubMed Central

    Sakamoto, Kouichi; Khai, Ngin Cin; Wang, Yuqing; Irie, Rie; Takamatsu, Hideo; Matsufuji, Hiroshi; Kosai, Ken-Ichiro

    2016-01-01

    In contrast to hepatocyte growth factor (HGF), the therapeutic potential and pathophysiologic roles of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver diseases remain relatively unknown. To address the lack of effective pharmacologic treatments for cholestatic liver injuries, as well as to clarify the biologic features of these growth factors, we explored the effects of HB-EGF and HGF in mice with cholestatic liver injury induced by bile duct ligation (BDL). The mice were assessed 3, 5 and/or 14 days after BDL (acute, subacute and/or chronic phases, respectively) and intravenous injection of adenoviral vector expressing LacZ (control), HB-EGF, HGF, or HB-EGF and HGF. HB-EGF, HGF, or a combination of the growth factors exerted potent antioncotic (antinecrotic), antiapoptotic, anticholestatic, and regenerative effects on hepatocytes in vivo, whereas no robust antiapoptotic or regenerative effects were detected in interlobular bile ducts. Based on serum transaminase levels, the acute protective effects of HB-EGF on hepatocytes were greater than those of HGF. On the other hand, liver fibrosis and cholestasis during the chronic phase were more potently inhibited by HGF compared with HB-EGF. Compared with either growth factor alone, combining HB-EGF and HGF produced greater anticholestatic and regenerative effects during the chronic phase. Taken together, these findings suggest that HB-EGF and HGF inhibited BDL-induced cholestatic liver injury, predominantly by exerting acute cytoprotective and chronic antifibrotic effects, respectively; combining the growth factors enhanced the anticholestatic effects and liver regeneration during the chronic phase. Our results contribute to a better understanding of the pathophysiologic roles of HB-EGF and HGF, as well as to the development of novel effective therapies for cholestatic liver injuries. PMID:27779646

  18. Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas.

    PubMed Central

    Olivero, M.; Rizzo, M.; Madeddu, R.; Casadio, C.; Pennacchietti, S.; Nicotra, M. R.; Prat, M.; Maggi, G.; Arena, N.; Natali, P. G.; Comoglio, P. M.; Di Renzo, M. F.

    1996-01-01

    Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8980383

  19. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    EPA Science Inventory

    TITLE:
    TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  20. The discovery of basic fibroblast growth factor/fibroblast growth factor-2 and its role in haematological malignancies.

    PubMed

    Ribatti, Domenico; Vacca, Angelo; Rusnati, Marco; Presta, Marco

    2007-01-01

    Basic fibroblast growth factor/fibroblast growth factor-2 is one of the best characterized of the pro-angiogenic cytokines. This review describes its history, as well as its role in tumor angiogenesis associated with haematological malignancies, as traced by the main contributions to the international medical literature.

  1. TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF)

    EPA Science Inventory

    TITLE:
    TERATOGENIC RESPONSES ARE MODULATED IN MICE LACKING EXPRESSION OF EPIDERMAL GROWTH FACTOR (EGF) AND TRANSFORMING GROWTH FACTOR-ALPHA (TGF). AUTHORS (ALL): Abbott, Barbara D.1; Best, Deborah S.1; Narotsky, Michael G.1. SPONSOR NAME: None INSTITUTIONS (ALL): 1. Repro Tox ...

  2. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    PubMed Central

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  3. A Prodomain Fragment from the Proteolytic Activation of Growth Differentiation Factor 11 Remains Associated with the Mature Growth Factor and Keeps It Soluble.

    PubMed

    Pepinsky, Blake; Gong, Bang-Jian; Gao, Yan; Lehmann, Andreas; Ferrant, Janine; Amatucci, Joseph; Sun, Yaping; Bush, Martin; Walz, Thomas; Pederson, Nels; Cameron, Thomas; Wen, Dingyi

    2017-08-22

    Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β (TGF-β) family, plays diverse roles in mammalian development. It is synthesized as a large, inactive precursor protein containing a prodomain, pro-GDF11, and exists as a homodimer. Activation requires two proteolytic processing steps that release the prodomains and transform latent pro-GDF11 into active mature GDF11. In studying proteolytic activation in vitro, we discovered that a 6-kDa prodomain peptide containing residues 60-114, PDP60-114, remained associated with the mature growth factor. Whereas the full-length prodomain of GDF11 is a functional antagonist, PDP60-114 had no impact on activity. The specific activity of the GDF11/PDP60-114 complex (EC50 = 1 nM) in a SMAD2/3 reporter assay was identical to that of mature GDF11 alone. PDP60-114 improved the solubility of mature GDF11 at neutral pH. As the growth factor normally aggregates/precipitates at neutral pH, PDP60-114 can be used as a solubility-enhancing formulation. Expression of two engineered constructs with PDP60-114 genetically fused to the mature domain of GDF11 through a 2x or 3x G4S linker produced soluble monomeric products that could be dimerized through redox reactions. The construct with a 3x G4S linker retained 10% activity (EC50 = 10 nM), whereas the construct connected with a 2x G4S linker could only be activated (EC50 = 2 nM) by protease treatment. Complex formation with PDP60-114 represents a new strategy for stabilizing GDF11 in an active state that may translate to other members of the TGF-β family that form latent pro/mature domain complexes.

  4. Growth of II-VI thin-films from single-source precursors based on sterically encumbered sitel ligands

    SciTech Connect

    Arnold, J.; Seligson, A.L.; Walker, J.M.; Bourret, E.D.; Bonasia, P.J.

    1992-04-01

    We have developed a new route to MOCVD of II-VI compounds based on the use of novel single-source precursors in which the II-VI elements are combined at the molecular level in a single covalent compound. We have prepared and fully characterized a number of new derivatives of zinc, cadmium and mercury incorporating large, sterically demanding tellurolate ligands of general formula: M(sitel){sub 2} where sitel = -TeSi(SiMe{sub 3}){sub 3}. The crystalline compounds are relatively volatile and are easily manipulated under nitrogen. Several of these compounds have been tested for their suitability as precursors in the MOCVD process. Clean pyrolysis reactions and deposition of thin films were achieved. The stoichiometry of the pyrolysis reaction has been determined by analysis of the reaction by-products.

  5. Growth of II-VI thin-films from single-source precursors based on sterically encumbered sitel ligands

    SciTech Connect

    Arnold, J.; Seligson, A.L.; Walker, J.M.; Bourret, E.D.; Bonasia, P.J.

    1992-04-01

    We have developed a new route to MOCVD of II-VI compounds based on the use of novel single-source precursors in which the II-VI elements are combined at the molecular level in a single covalent compound. We have prepared and fully characterized a number of new derivatives of zinc, cadmium and mercury incorporating large, sterically demanding tellurolate ligands of general formula: M(sitel){sub 2} where sitel = -TeSi(SiMe{sub 3}){sub 3}. The crystalline compounds are relatively volatile and are easily manipulated under nitrogen. Several of these compounds have been tested for their suitability as precursors in the MOCVD process. Clean pyrolysis reactions and deposition of thin films were achieved. The stoichiometry of the pyrolysis reaction has been determined by analysis of the reaction by-products.

  6. Regulation of transferrin receptor expression at the cell surface by insulin-like growth factors, epidermal growth factor and platelet-derived growth factor

    SciTech Connect

    Davis, R.J.; Kuck, L.; Faucher, M.; Czech, M.P.

    1986-05-01

    Addition of platelet-derived growth factor (PDGF), recombinant insulin-like growth factor I (rIGF-I) or epidermal growth factor (EGF) to BALB/c 3T3 fibroblasts causes a marked increase in the binding of (/sup 125/I) diferric transferrin to cell surface receptors. This effect is very rapid and is complete within 5 minutes. The effect is transient with (/sup 125/I) diferric transferrin binding returning to control values within 25 minutes. In contrast, PDGF and rIGF-I cause a prolonged stimulation of (/sup 125/I) diferric transferrin binding that could be observed up to 2 hours. The increase in the binding of (/sup 125/I) diferric transferrin caused by growth factors was investigated by analysis of the binding isotherm. EGF, PDGF and rIGF-I were found to increase the cell surface expression of transferrin receptors rather than to alter the affinity of the transferrin receptors. Furthermore, PDGF and rIGF-I stimulated the sustained uptake of (/sup 59/Fe) diferric transferrin by BALB/c 3T3 fibroblasts. Thus, the effect of these growth factors to increase the cell surface expression of the transferrin receptor appears to have an important physiological consequence.

  7. Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF).

    PubMed

    Rittchen, Sonja; Boyd, Amanda; Burns, Alasdair; Park, Jason; Fahmy, Tarek M; Metcalfe, Su; Williams, Anna

    2015-07-01

    Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LIF), a cytokine known to play a key regulatory role in self-tolerant immunity and recently identified as a pro-myelination factor. In this study, we tested a nanoparticle-based strategy for targeted delivery of LIF to oligodendrocyte precursor cells (OPC) to promote their differentiation into mature oligodendrocytes able to repair myelin. Poly(lactic-co-glycolic acid)-based nanoparticles of ∼120 nm diameter were constructed with LIF as cargo (LIF-NP) with surface antibodies against NG-2 chondroitin sulfate proteoglycan, expressed on OPC. In vitro, NG2-targeted LIF-NP bound to OPCs, activated pSTAT-3 signalling and induced OPC differentiation into mature oligodendrocytes. In vivo, using a model of focal CNS demyelination, we show that NG2-targeted LIF-NP increased myelin repair, both at the level of increased number of myelinated axons, and increased thickness of myelin per axon. Potency was high: a single NP dose delivering picomolar quantities of LIF is sufficient to increase remyelination. Impact statement Nanotherapy-based delivery of leukaemia inhibitory factor (LIF) directly to OPCs proved to be highly potent in promoting myelin repair in vivo: this delivery strategy introduces a novel approach to delivering drugs or biologics targeted to myelin repair in diseases such as MS.

  8. High-growth-factor implosions (HEP4)

    SciTech Connect

    Landen, O.L.; Keane, C.J.; Hammel, B.A.

    1996-06-01

    In inertial confinement fusion (ICF), the kinetic energy of an ablating, inward-driven, solid spherical shell is used to compressionally heat the low-density fuel inside. For a given drive, the maximum achievable compressed fuel density and temperature - and hence the maximum neutron production rate depend on the degree of shell isentropy and integrity maintained during the compression. Shell integrity will be degraded by hydrodynamic instability growth of areal density imperfections in the capsule. Surface imperfections on the shell grow as a result of the Richtmyer-Meshkov and Rayleigh-Taylor (RT) instabilities when the shell is accelerated by the ablating lower-density plasma. Perturbations at the outer capsule surface are transferred hydrodynamically to the inner surface, where deceleration of the shell by the lower-density fuel gives rise to further RT growth at the pusher-fuel interface.

  9. Cobalt (II) β-diketonate adducts as new precursors for the growth of cobalt oxide films by liquid injection MOCVD

    NASA Astrophysics Data System (ADS)

    Pasko, S.; Abrutis, A.; Hubert-Pfalzgraf, L. G.; Kubilius, V.

    2004-02-01

    New metalorganic compounds—adducts of cobalt(II) acetylacetonate (acac) and cobalt(II) 2,2,6,6-tetramethyl-3,5-heptanedionate (thd) with N,N,N',N'-tetramethyl-1,2-diaminoethane have been synthesized and studied as potential precursors for liquid injection metalorganic chemical vapor deposition of Co 3O 4 films. The properties of the films were compared with those deposited using standard [Co(acac) 2] 4 and Co(thd) 2 precursors. Depositions were carried out at 350-600°C on LaAlO 3 (1 0 0), sapphire (R-plane), MgO (1 0 0) and Si (1 0 0) substrates. The films were characterized by X-ray diffraction, X-ray photoelectron spectroscopy and atomic force microscopy. Depending on substrate material, highly (1 1 0) or (1 0 0) textured Co 3O 4 films have been deposited; moreover, films exhibited preferential in-plane orientation. No significant difference has been found in the quality of Co 3O 4 films deposited from different precursors.

  10. Colloidal Precursor-Induced Growth of Ultra-Even CH3NH3PbI3 for High-Performance Paintable Carbon-Based Perovskite Solar Cells.

    PubMed

    Chang, Xiaowen; Li, Weiping; Chen, Haining; Zhu, Liqun; Liu, Huicong; Geng, Huifang; Xiang, Sisi; Liu, Jiaming; Zheng, Xiaoli; Yang, Yinglong; Yang, Shihe

    2016-11-09

    Carbon-based hole transport material (HTM)-free perovskite solar cells (PSCs) have attracted intense attention due to their relatively high stability. However, their power conversion efficiency (PCE) is still low, especially for the simplest paintable carbon-based PSCs (C-PSCs), whose performance is greatly limited by poor contact at the perovskite/carbon interface. To enhance interface contact, it is important to fabricate an even-surface perovskite layer in a porous scaffold, which is not usually feasible due to roughness of the crystal precursor. Herein, colloidal engineering is applied to replace the traditional crystal precursor with a colloidal precursor, in which a small amount of dimethyl sulfoxide (DMSO) is added into the conventional PbI2 dimethylformamide (DMF) solution. After deposition, PbI2(DMSO) adduct colloids (which are approximately tens of nanometers in size) are stabilized and dispersed in DMF to form a colloidal film. Compared with PbI2 and PbI2(DMSO) adduct crystal precursors deposited from pure DMF and DMSO solvents, respectively, the PbI2(DMSO) adduct colloidal precursor is highly mobile and flexible, allowing an ultra-even surface to be obtained in a TiO2 porous scaffold. Furthermore, this ultra-even surface is well-maintained after chemical conversion to CH3NH3PbI3 in a CH3NH3I solution. As a result, the contact at the CH3NH3PbI3/carbon interface is significantly enhanced, which largely boosts the fill factor and PCE of C-PSCs. Impressively, the achieved champion PCE of 14.58% is among the highest reported for C-PSCs.

  11. Efficacy of glial growth factor and nerve growth factor on the recovery of traumatic facial paralysis.

    PubMed

    Yildiz, Mucahit; Karlidag, Turgut; Yalcin, Sinasi; Ozogul, Candan; Keles, Erol; Alpay, Hayrettin Cengiz; Yanilmaz, Muhammed

    2011-08-01

    The aim of this study was to assess the effects of Glial growth factor (GGF) and nerve growth factor (NGF) on nerve regeneration in facial nerve anastomosis. In this study, approximately a 1-mm segment was resected from the facial nerve and the free ends were anastomosed. All animals underwent the same surgical procedure and 30 rabbits were grouped randomly in three groups. Control group, the group without any medications; NGF group, the group receiving 250 ng/0.1 ml NGF in the epineurium at the site of anastomosis; GBF group, the group receiving 500 ng/0.1 ml GGF in the epineurium at the site of anastomosis. Medications were given at the time of surgery, and at 24 and 48 h postoperatively. After 2 months, the sites of anastomosis were excised and examined using the electron microscope. It was found that the best regeneration was in the group receiving GGF as compared to the control group in terms of nerve regeneration. Schwann cell and glial cell proliferation were found to be significantly higher in the group receiving GGF as compared to the group receiving NGF. Besides, the number of myelin debris, an indicator of degeneration, was significantly lower in the group with GGF as compared to NGF and control groups (p < 0.005). Using GGF and NGF in order to increase regeneration after nerve anastomosis in experimental traumatic facial nerve paralysis may be a hopeful alternative treatment option in the future. However, further studies on human studies are required to support these results.

  12. Maternal growth factor regulation of human placental development and fetal growth.

    PubMed

    Forbes, Karen; Westwood, Melissa

    2010-10-01

    Normal development and function of the placenta is critical to achieving a successful pregnancy, as normal fetal growth depends directly on the transfer of nutrients from mother to fetus via this organ. Recently, it has become apparent from both animal and human studies that growth factors within the maternal circulation, for example the IGFs, are important regulators of placental development and function. Although these factors act via distinct receptors to exert their effects, the downstream molecules activated upon ligand/receptor interaction are common to many growth factors. The expression of numerous signaling molecules is altered in the placentas from pregnancies affected by the fetal growth complications, fetal growth restriction, and macrosomia. Thus, targeting these molecules may lead to more effective treatments for complications of pregnancy associated with altered placental development. Here, we review the maternal growth factors required for placental development and discuss their mechanism of action.

  13. Guanine is a growth factor for Legionella species.

    PubMed Central

    Pine, L; Franzus, M J; Malcolm, G B

    1986-01-01

    Evaluation of previously described chemically defined media for the growth of Legionella pneumophila showed that these media supported poor growth of several strains of L. pneumophila and did not support growth of certain of the Legionella species described later. Growth was stimulated by the dialysate from yeast extract but not by the nondialyzable fraction. Further investigations indicated that the active factors from the yeast extract dialysate were purine or pyrimidine derivatives, and certain known purines and pyrimidines were found to stimulate growth. Of these, guanine universally stimulated growth of all Legionella strains and was a growth requirement for several of the species tested. A balanced, N-(2-acetamido)-2-aminoethanesulfonic acid-buffered, chemically defined medium having guanine or a purine-pyrimidine mix is presented for the general growth of Legionella species. PMID:3700600

  14. Platelet-rich growth factor in oral and maxillofacial surgery

    PubMed Central

    Pal, Uma Shanker; Mohammad, Shadab; Singh, Rakesh K.; Das, Somdipto; Singh, Nimisha; Singh, Mayank

    2012-01-01

    Platelet-rich growth factor is an innovative regenerative therapy used to promote hard and soft tissue healing. It involves the application of autologous platelet-leukocyte-rich plasma containing growth factors and thrombin directly to the site of treatment. It is the intrinsic growth factors released by activated platelets which are concentrated in a topical gel formula. Clinically, it is an affordable treatment with potentially broad spectrum of applications in maxillofacial surgery especially in the treatment of complex or refractory wounds. The present article reviews its various applications not only in the specialization of oral and maxillofacial surgery but also in regenerative medicine. PMID:23833484

  15. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

    2012-04-24

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  16. Dual chain synthetic heparin-binding growth factor analogs

    DOEpatents

    Zamora, Paul O [Gaithersburg, MD; Pena, Louis A [Poquott, NY; Lin, Xinhua [Plainview, NY

    2009-10-06

    The invention provides synthetic heparin-binding growth factor analogs having two peptide chains each branched from a branch moiety, such as trifunctional amino acid residues, the branch moieties separated by a first linker of from 3 to about 20 backbone atoms, which peptide chains bind a heparin-binding growth factor receptor and are covalently bound to a non-signaling peptide that includes a heparin-binding domain, preferably by a second linker, which may be a hydrophobic second linker. The synthetic heparin-binding growth factor analogs are useful as pharmaceutical agents, soluble biologics or as surface coatings for medical devices.

  17. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    PubMed Central

    Irving, Julie A. E.; Enshaei, Amir; Parker, Catriona A.; Sutton, Rosemary; Kuiper, Roland P.; Erhorn, Amy; Minto, Lynne; Venn, Nicola C.; Law, Tamara; Yu, Jiangyan; Schwab, Claire; Davies, Rosanna; Matheson, Elizabeth; Davies, Alysia; Sonneveld, Edwin; den Boer, Monique L.; Love, Sharon B.; Harrison, Christine J.; Hoogerbrugge, Peter M.; Revesz, Tamas; Saha, Vaskar

    2016-01-01

    Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < .001). TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P < .001) and 2.15 (1.32-3.48, P = .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P = .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at www.clinicaltrials.org as #ISCRTN45724312. PMID:27229005

  18. Tumour necrosis factor-alpha impairs neuronal differentiation but not proliferation of hippocampal neural precursor cells: Role of Hes1.

    PubMed

    Keohane, Aoife; Ryan, Sinead; Maloney, Eimer; Sullivan, Aideen M; Nolan, Yvonne M

    2010-01-01

    Tumour necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine, which influences neuronal survival and function yet there is limited information available on its effects on hippocampal neural precursor cells (NPCs). We show that TNFalpha treatment during proliferation had no effect on the percentage of proliferating cells prepared from embryonic rat hippocampal neurosphere cultures, nor did it affect cell fate towards either an astrocytic or neuronal lineage when cells were then allowed to differentiate. However, when cells were differentiated in the presence of TNFalpha, significantly reduced percentages of newly born and post-mitotic neurons, significantly increased percentages of astrocytes and increased expression of TNFalpha receptors, TNF-R1 and TNF-R2, as well as expression of the anti-neurogenic Hes1 gene, were observed. These data indicate that exposure of hippocampal NPCs to TNFalpha when they are undergoing differentiation but not proliferation has a detrimental effect on their neuronal lineage fate, which may be mediated through increased expression of Hes1.

  19. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  20. Relationships among growth mechanism, structure and morphology of PEALD TiO2 films: the influence of O2 plasma power, precursor chemistry and plasma exposure mode.

    PubMed

    Chiappim, W; Testoni, G E; Doria, A C O C; Pessoa, R S; Fraga, M A; Galvão, N K A M; Grigorov, K G; Vieira, L; Maciel, H S

    2016-07-29

    Titanium dioxide (TiO2) thin films have generated considerable interest over recent years, because they are functional materials suitable for a wide range of applications. The efficient use of the outstanding functional properties of these films relies strongly on their basic characteristics, such as structure and morphology, which are affected by deposition parameters. Here, we report on the influence of plasma power and precursor chemistry on the growth kinetics, structure and morphology of TiO2 thin films grown on Si(100) by plasma-enhanced atomic layer deposition (PEALD). For this, remote capacitively coupled 13.56 MHz oxygen plasma was used to act as a co-reactant during the ALD process using two different metal precursors: titanium tetrachloride (TiCl4) and titanium tetraisopropoxide (TTIP). Furthermore, we investigate the effect of direct plasma exposure during the co-reactant pulse on the aforementioned material properties. The extensive characterization of TiO2 films using Rutherford backscattering spectroscopy, ellipsometry, x-ray diffraction (XRD), field-emission scanning electron microscopy, and atomic force microscopy (AFM) have revealed how the investigated process parameters affect their growth per cycle (GPC), crystallization and morphology. The GPC tends to increase with plasma power for both precursors, however, for the TTIP precursor, it starts decreasing when the plasma power is greater than 100 W. From XRD analysis, we found a good correlation between film crystallinity and GPC behavior, mainly for the TTIP process. The AFM images indicated the formation of films with grain size higher than film thickness (grain size/film thickness ratio ≈20) for both precursors, and plasma power analysis allows us to infer that this phenomenon can be directly related to the increase of the flux of energetic oxygen species on the substrate/growing film surface. Finally, the effect of direct plasma exposure on film structure and morphology was evidenced

  1. Relationships among growth mechanism, structure and morphology of PEALD TiO2 films: the influence of O2 plasma power, precursor chemistry and plasma exposure mode

    NASA Astrophysics Data System (ADS)

    Chiappim, W.; Testoni, G. E.; Doria, A. C. O. C.; Pessoa, R. S.; Fraga, M. A.; Galvão, N. K. A. M.; Grigorov, K. G.; Vieira, L.; Maciel, H. S.

    2016-07-01

    Titanium dioxide (TiO2) thin films have generated considerable interest over recent years, because they are functional materials suitable for a wide range of applications. The efficient use of the outstanding functional properties of these films relies strongly on their basic characteristics, such as structure and morphology, which are affected by deposition parameters. Here, we report on the influence of plasma power and precursor chemistry on the growth kinetics, structure and morphology of TiO2 thin films grown on Si(100) by plasma-enhanced atomic layer deposition (PEALD). For this, remote capacitively coupled 13.56 MHz oxygen plasma was used to act as a co-reactant during the ALD process using two different metal precursors: titanium tetrachloride (TiCl4) and titanium tetraisopropoxide (TTIP). Furthermore, we investigate the effect of direct plasma exposure during the co-reactant pulse on the aforementioned material properties. The extensive characterization of TiO2 films using Rutherford backscattering spectroscopy, ellipsometry, x-ray diffraction (XRD), field-emission scanning electron microscopy, and atomic force microscopy (AFM) have revealed how the investigated process parameters affect their growth per cycle (GPC), crystallization and morphology. The GPC tends to increase with plasma power for both precursors, however, for the TTIP precursor, it starts decreasing when the plasma power is greater than 100 W. From XRD analysis, we found a good correlation between film crystallinity and GPC behavior, mainly for the TTIP process. The AFM images indicated the formation of films with grain size higher than film thickness (grain size/film thickness ratio ≈20) for both precursors, and plasma power analysis allows us to infer that this phenomenon can be directly related to the increase of the flux of energetic oxygen species on the substrate/growing film surface. Finally, the effect of direct plasma exposure on film structure and morphology was evidenced

  2. Body size regulation and insulin-like growth factor signaling.

    PubMed

    Hyun, Seogang

    2013-07-01

    How animals achieve their specific body size is a fundamental, but still largely unresolved, biological question. Over the past decades, studies on the insect model system have provided some important insights into the process of body size determination and highlighted the importance of insulin/insulin-like growth factor signaling. Fat body, the Drosophila counterpart of liver and adipose tissue, senses nutrient availability and controls larval growth rate by modulating peripheral insulin signaling. Similarly, insulin-like growth factor I produced from liver and muscle promotes postnatal body growth in mammals. Organismal growth is tightly coupled with the process of sexual maturation wherein the sex steroid hormone attenuates body growth. This review summarizes some important findings from Drosophila and mammalian studies that shed light on the general mechanism of animal size determination.

  3. Dual control of cell growth by somatomedins and platelet-derived growth factor.

    PubMed Central

    Stiles, C D; Capone, G T; Scher, C D; Antoniades, H N; Van Wyk, J J; Pledger, W J

    1979-01-01

    Quiescent BALB/c 3T3 cells exposed briefly to a platelet-derived growth factor (PDGF) become "competent" to replicate their DNA but do not "progress" into S phase unless incubated with growth factors contained in platelet-poor plasma. Plasma from hypophysectomized rats is deficient in progression activity; it does not stimulate PDGF-treated competent cells to synthesize DNA, demonstrating that somatomedin C is required for progression. Various growth factors were tested for progression activity and competence activity by using BALB/c 3T3 tissue culture assays. Multiplication stimulating activity and other members of the somatomedin family of growth factors are (like somatomedin C) potent mediators of progression. Other mitogenic agents, such as fibroblast growth factor, are (like PDGF) potent inducers of competence. Growth factors with potent progression activity have little or no competence activity and vice versa. In contrast, simian virus 40 provides both competence and progression activity. Coordinate control of BALB/c 3T3 cell growth in vitro by competence factors and somatomedins may be a specific example of a common pattern of growth regulation in animal tissues. PMID:312500

  4. Insulin-like growth factor-I gene expression in three models of accelerated lung growth.

    PubMed

    Nobuhara, K K; DiFiore, J W; Ibla, J C; Siddiqui, A M; Ferretti, M L; Fauza, D O; Schnitzer, J J; Wilson, J M

    1998-07-01

    We have learned previously that in utero tracheal ligation reverses the structural and physiological effects of surgically created congenital diaphragmatic hernia. In addition, we have discovered that postnatal lung growth similarly can be accelerated using liquid-based airway distension with perfluorocarbon. Another model of accelerated lung growth is that of compensatory growth seen after neonatal pneumonectomy. In all of these models, growth has occurred because of an increase in alveolar number rather than enlargement of preexisting alveoli. However, the molecular mechanisms underlying these processes remain unknown. The purpose of this study was to determine if gene expression could be altered by changes in physical forces in the prenatal and postnatal lung. The three models of accelerated lung growth studied were the following: (1) The prenatal group, consisted of fetal lambs (n = 12) that underwent the surgical creation of a left diaphragmatic hernia at 90 days' gestation. Six of these animals also underwent simultaneous tracheal ligation. (2) The PFC group consisted of five neonatal animals that underwent isolation of the superior segment of the right upper lobe, with intrabronchial distension with perfluorocarbon to 7 to 10 mm Hg pressure for a 3-week period. (3) The postpneumonectomy group consisted of four neonatal animals that underwent left pneumonectomy. In the fetal study, lungs were retrieved at term (130 days), and in the postnatal study, lungs were retrieved 3 weeks after initial intervention. In all cases, RNA was extracted from snap-frozen lung samples and Northern blot analysis performed. Insulinlike growth factor-I, insulinlike growth factor-II, and vascular endothelial growth factor gene expression were analyzed by densitometry. Insulinlike growth factor-I gene expression was found to be decreased in association with experimental diaphragmatic hernia (P = .005), but restored to normal with tracheal ligation. Insulinlike growth factor-I gene

  5. Release kinetics of platelet-derived and plasma-derived growth factors from autologous plasma rich in growth factors.

    PubMed

    Anitua, Eduardo; Zalduendo, Mari Mar; Alkhraisat, Mohammad Hamdan; Orive, Gorka

    2013-10-01

    Many studies have evaluated the biological effects of platelet rich plasma reporting the final outcomes on cell and tissues. However, few studies have dealt with the kinetics of growth factor delivery by plasma rich in growth factors. Venous blood was obtained from three healthy volunteers and processed with PRGF-Endoret technology to prepare autologous plasma rich in growth factors. The gel-like fibrin scaffolds were then incubated in triplicate, in a cell culture medium to monitor the release of PDGF-AB, VEGF, HGF and IGF-I during 8 days of incubation. A leukocyte-platelet rich plasma was prepared employing the same technology and the concentrations of growth factors and interleukin-1β were determined after 24h of incubation. After each period, the medium was collected, fibrin clot was destroyed and the supernatants were stored at -80°C until analysis. The growth factor delivery is diffusion controlled with a rapid initial release by 30% of the bioactive content after 1h of incubation and a steady state release when almost 70% of the growth factor content has been delivered. Autologous fibrin matrix retained almost 30% of the amount of the growth factors after 8 days of incubation. The addition of leukocytes to the formula of platelet rich plasma did not increase the concentration of the growth factors, while it drastically increased the presence of pro-inflammatory IL-1β. Further studies employing an in vitro inflammatory model would be interesting to study the difference in growth factors and pro-inflammatory cytokines between leukocyte-free and leukocyte-rich platelet rich plasma.

  6. Cardiac Regeneration using Growth Factors: Advances and Challenges

    PubMed Central

    Rebouças, Juliana de Souza; Santos-Magalhães, Nereide Stela; Formiga, Fabio Rocha

    2016-01-01

    Myocardial infarction is the most significant manifestation of ischemic heart disease and is associated with high morbidity and mortality. Novel strategies targeting at regenerating the injured myocardium have been investigated, including gene therapy, cell therapy, and the use of growth factors. Growth factor therapy has aroused interest in cardiovascular medicine because of the regeneration mechanisms induced by these biomolecules, including angiogenesis, extracellular matrix remodeling, cardiomyocyte proliferation, stem-cell recruitment, and others. Together, these mechanisms promote myocardial repair and improvement of the cardiac function. This review aims to address the strategic role of growth factor therapy in cardiac regeneration, considering its innovative and multifactorial character in myocardial repair after ischemic injury. Different issues will be discussed, with emphasis on the regeneration mechanisms as a potential therapeutic resource mediated by growth factors, and the challenges to make these proteins therapeutically viable in the field of cardiology and regenerative medicine. PMID:27355588

  7. Polyamines: essential factors for growth and survival.

    PubMed

    Kusano, T; Berberich, T; Tateda, C; Takahashi, Y

    2008-08-01

    Polyamines are low molecular weight, aliphatic polycations found in the cells of all living organisms. Due to their positive charges, polyamines bind to macromolecules such as DNA, RNA, and proteins. They are involved in diverse processes, including regulation of gene expression, translation, cell proliferation, modulation of cell signalling, and membrane stabilization. They also modulate the activities of certain sets of ion channels. Because of these multifaceted functions, the homeostasis of polyamines is crucial and is ensured through regulation of biosynthesis, catabolism, and transport. Through isolation of the genes involved in plant polyamine biosynthesis and loss-of-function experiments on the corresponding genes, their essentiality for growth is reconfirmed. Polyamines are also involved in stress responses and diseases in plants, indicating their importance for plant survival. This review summarizes the recent advances in polyamine research in the field of plant science compared with the knowledge obtained in microorganisms and animal systems.

  8. Actions of activin A, connective tissue growth factor, hepatocyte growth factor and teratocarcinoma-derived growth factor 1 on the development of the bovine preimplantation embryo.

    PubMed

    Kannampuzha-Francis, Jasmine; Tribulo, Paula; Hansen, Peter J

    2016-05-17

    The reproductive tract secretes bioactive molecules collectively known as embryokines that can regulate embryonic growth and development. In the present study we tested four growth factors expressed in the endometrium for their ability to modify the development of the bovine embryo to the blastocyst stage and alter the expression of genes found to be upregulated (bone morphogenetic protein 15 (BMP15) and keratin 8, type II (KRT8)) or downregulated (NADH dehydrogenase 1 (ND1) and S100 calcium binding protein A10 (S100A10)) in embryos competent to develop to term. Zygotes were treated at Day 5 with 0.01, 0.1 or 1.0 nM growth factor. The highest concentration of activin A increased the percentage of putative zygotes that developed to the blastocyst stage. Connective tissue growth factor (CTGF) increased the number of cells in the inner cell mass (ICM), decreased the trophectoderm : ICM ratio and increased blastocyst expression of KRT8 and ND1. The lowest concentration of hepatocyte growth factor (HGF) reduced the percentage of putative zygotes becoming blastocysts. Teratocarcinoma-derived growth factor 1 increased total cell number at 0.01 nM and expression of S100A10 at 1.0 nM, but otherwise had no effects. Results confirm the prodevelopmental actions of activin A and indicate that CTGF may also function as an embryokine by regulating the number of ICM cells in the blastocyst and altering gene expression. Low concentrations of HGF were inhibitory to development.

  9. Effect of sericin on diabetic hippocampal growth hormone/insulin-like growth factor 1 axis

    PubMed Central

    Chen, Zhihong; Yang, Songhe; He, Yaqiang; Song, Chengjun; Liu, Yongping

    2013-01-01

    Previous studies have shown that sericin extracted from silk cocoon significantly reduces blood glucose levels and protects the nervous system against diabetes mellitus. In this study, a rat type 2 diabetes mellitus model was established by intraperitoneal injection of 25 mg/kg streptozotocin for 3 successive days, following which the rats were treated with sericin for 35 days. After treatment, the blood glucose levels of the diabetic rats decreased significantly, the growth hormone level in serum and its expression in the hippocampus decreased significantly, while the insulin-like growth factor-1 level in serum and insulin-like growth factor-1 and growth hormone receptor expression in the hippocampus increased significantly. The experimental findings indicate that sericin improves disorders of the growth hormone/insulin-like growth factor 1 axis to alleviate hippocampal damage in diabetic rats. PMID:25206472

  10. Metallorganic chemical vapor deposition and atomic layer deposition approaches for the growth of hafnium-based thin films from dialkylamide precursors for advanced CMOS gate stack applications

    NASA Astrophysics Data System (ADS)

    Consiglio, Steven P.

    To continue the rapid progress of the semiconductor industry as described by Moore's Law, the feasibility of new material systems for front end of the line (FEOL) process technologies needs to be investigated, since the currently employed polysilicon/SiO2-based transistor system is reaching its fundamental scaling limits. Revolutionary breakthroughs in complementary-metal-oxide-semiconductor (CMOS) technology were recently announced by Intel Corporation and International Business Machines Corporation (IBM), with both organizations revealing significant progress in the implementation of hafnium-based high-k dielectrics along with metal gates. This announcement was heralded by Gordon Moore as "...the biggest change in transistor technology since the introduction of polysilicon gate MOS transistors in the late 1960s." Accordingly, the study described herein focuses on the growth of Hf-based dielectrics and Hf-based metal gates using chemical vapor-based deposition methods, specifically metallorganic chemical vapor deposition (MOCVD) and atomic layer deposition (ALD). A family of Hf source complexes that has received much attention recently due to their desirable properties for implementation in wafer scale manufacturing is the Hf dialkylamide precursors. These precursors are room temperature liquids and possess sufficient volatility and desirable decomposition characteristics for both MOCVD and ALD processing. Another benefit of using these sources is the existence of chemically compatible Si dialkylamide sources as co-precursors for use in Hf silicate growth. The first part of this study investigates properties of MOCVD-deposited HfO2 and HfSixOy using dimethylamido Hf and Si precursor sources using a customized MOCVD reactor. The second part of this study involves a study of wet and dry surface pre-treatments for ALD growth of HfO2 using tetrakis(ethylmethylamido)hafnium in a wafer scale manufacturing environment. The third part of this study is an investigation of

  11. A growth factor phenotype map for ovine preimplantation development.

    PubMed

    Watson, A J; Watson, P H; Arcellana-Panlilio, M; Warnes, D; Walker, S K; Schultz, G A; Armstrong, D T; Seamark, R F

    1994-04-01

    The reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the patterns of expression for several growth factor ligand and receptor genes during ovine preimplantation development. Transcripts for insulin-like growth factor (IGF)-I, IGF-II, and the receptors for insulin and IGF-I were detected throughout ovine preimplantation development from the 1-cell to the blastocyst stage. Transforming growth factor alpha (TGF alpha) transcripts were also detected throughout ovine preimplantation development. The mRNAs encoding basic fibroblast growth factor (bFGF) were detected in all stages of the ovine preimplantation embryo, although the relative abundance of this transcript consistently decreased from the 1-cell to the blastocyst stage, suggesting that it may represent a maternal transcript in early sheep embryos. Transcripts encoding ovine trophoblast protein (oTP) were detected only within blastocyst-stage embryos. Primary ovine oviduct cell cultures express the transcripts for IGF-II, IGF-I, TGF alpha, bFGF, TGF beta 1, and the receptors for insulin and IGF-I, suggesting that paracrine growth factor circuits may exist between the oviduct epithelium and the early ovine embryo. Transcripts for insulin, epidermal growth factor (EGF), and nerve growth factor (NGF) were not detected in any stage of the ovine preimplantation embryo or within the oviduct cell preparations. The expression of growth factor transcripts very early in mammalian development would predict that these molecules fulfil a necessary role(s) in supporting the progression of early embryos through the preimplantation interval. Our future efforts will be directed to understanding the nature of these putative regulatory pathways.

  12. Lifetime growth in wild meerkats: incorporating life history and environmental factors into a standard growth model.

    PubMed

    English, Sinéad; Bateman, Andrew W; Clutton-Brock, Tim H

    2012-05-01

    Lifetime records of changes in individual size or mass in wild animals are scarce and, as such, few studies have attempted to model variation in these traits across the lifespan or to assess the factors that affect them. However, quantifying lifetime growth is essential for understanding trade-offs between growth and other life history parameters, such as reproductive performance or survival. Here, we used model selection based on information theory to measure changes in body mass over the lifespan of wild meerkats, and compared the relative fits of several standard growth models (monomolecular, von Bertalanffy, Gompertz, logistic and Richards). We found that meerkats exhibit monomolecular growth, with the best model incorporating separate growth rates before and after nutritional independence, as well as effects of season and total rainfall in the previous nine months. Our study demonstrates how simple growth curves may be improved by considering life history and environmental factors, which may be particularly relevant when quantifying growth patterns in wild populations.

  13. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth.

    PubMed

    Sferruzzi-Perri, A N; Owens, J A; Pringle, K G; Roberts, C T

    2011-01-01

    Maternal insulin-like growth factors (IGFs) play a pivotal role in modulating fetal growth via their actions on both the mother and the placenta. Circulating IGFs influence maternal tissue growth and metabolism, thereby regulating nutrient availability for the growth of the conceptus. Maternal IGFs also regulate placental morphogenesis, substrate transport and hormone secretion, all of which influence fetal growth either via indirect effects on maternal substrate availability, or through direct effects on the placenta and its capacity to supply nutrients to the fetus. The extent to which IGFs influence the mother and/or placenta are dependent on the species and maternal factors, including age and nutrition. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing degenerative diseases in adult life, understanding the role of maternal IGFs during pregnancy is essential in order to identify mechanisms underlying altered fetal growth and offspring programming.

  14. The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth

    PubMed Central

    Sferruzzi-Perri, A N; Owens, J A; Pringle, K G; Roberts, C T

    2011-01-01

    Maternal insulin-like growth factors (IGFs) play a pivotal role in modulating fetal growth via their actions on both the mother and the placenta. Circulating IGFs influence maternal tissue growth and metabolism, thereby regulating nutrient availability for the growth of the conceptus. Maternal IGFs also regulate placental morphogenesis, substrate transport and hormone secretion, all of which influence fetal growth either via indirect effects on maternal substrate availability, or through direct effects on the placenta and its capacity to supply nutrients to the fetus. The extent to which IGFs influence the mother and/or placenta are dependent on the species and maternal factors, including age and nutrition. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing degenerative diseases in adult life, understanding the role of maternal IGFs during pregnancy is essential in order to identify mechanisms underlying altered fetal growth and offspring programming. PMID:20921199

  15. Therapeutic angiogenesis using novel vascular endothelial growth factor-E/human placental growth factor chimera genes.

    PubMed

    Inoue, Natsuo; Kondo, Takahisa; Kobayashi, Koichi; Aoki, Mika; Numaguchi, Yasushi; Shibuya, Masabumi; Murohara, Toyoaki

    2007-01-01

    Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (PlGF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes with VEGF-E function but showing less antigenicity. We examined potential proangiogenic activities of these chimera genes. Four types of expression plasmids (pCDNA3.1-LacZ, phVEGF-A, pVEGF-Echimera#9, and pVEGF-Echimera#33) were administered in a rat model of hindlimb ischemia. Either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A significantly increased the ratio of ischemic/normal hindlimb blood-flow compared with the control pCDNA3.1-LacZ treated group (by 1.5-fold, 1.5-fold, and 1.4-fold, respectively, P<0.05). Histochemical staining by alkaline phosphatase also revealed that either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A increased the capillary density compared with the pCDNA3.1-LacZ treated group (1.4-fold, 1.5-fold, and 1.5-fold, respectively, P<0.05). Furthermore, immunostaining for anti-ED1 revealed that fewer macrophages had infiltrated in both pVEGF-Echimera#9 and pVEGF-Echimera#33 groups compared with the phVEGF-A group (P<0.05). Novel VEGF-E/human PlGF chimera genes, pVEGF-Echimera#9, and pVEGF-Echimera#33 significantly stimulated angiogenesis in response to tissue ischemia to an almost identical extent to that induced by phVEGF-A with fewer tissue inflammation responses.

  16. Porcine liver esterase-catalyzed enantioselective hydrolysis of a prochiral diester into its optically pure (S)-ester acid, a precursor to a growth hormone secretagogue.

    PubMed

    Chartrain, M; Maligres, P; Cohen, D; Upadhyay, V; Pecore, V; Askin, D; Greasham, R

    1999-01-01

    A limited screen of several commercially-available and internally-produced lipases and esterases identified porcine liver esterase as a suitable biocatalyst for the enantioselective hydrolysis of a diester into its (S)-ester acid with high optical purity (99%). This (S)-ester acid is a precursor to an experimental growth hormone secretagogue. After identifying xanthan gum as the best emulsifier and optimizing the reaction conditions, hydrolysis rates of 1 g/l.h and final (S)-ester acid (ee > 99%) titers of about 8.5 g/l were routinely achieved. This process supported the production of preparative amounts of optically pure (S)-ester (ee > 99%) with a high reaction yield of 82%. Upon purification, the (S)-ester was successfully used in the subsequent synthetic steps to yield the growth hormone secretagogue.

  17. Co-culture of hepatoma cells with hepatocytic precursor (stem-like) cells inhibits tumor cell growth and invasion by downregulating Akt/NF-κB expression

    PubMed Central

    Sui, Cheng-Jun; Xu, Miao; Li, Wei-Qing; Yang, Jia-Mei; Yan, Hong-Zhu; Liu, Hui-Min; Xia, Chun-Yan; Yu, Hong-Yu

    2016-01-01

    Hepatocytic stem cells (HSCs) have inhibitory effects on hepatocarcinoma cells. The present study investigated the effects of HSC activity in hepatocarcinoma cells in vitro. A Transwell co-culture system of hepatocytic precursor (stem-like) WB-F344 cells and hepatoma CBRH-7919 cells was used to assess HSC activity in metastasized hepatoma cells in vitro. Nude mouse xenografts were used to assess HSC activity in vivo. Co-culture of hepatoma CBRH-7919 cells with WB-F344 cells suppressed the growth and colony formation, tumor cell migration and invasion capacity of CBRH-7919 cells. The nude mouse xenograft assay demonstrated that the xenograft size of CBRH-7919 cells following co-culture with WB-F344 cells was significantly smaller compared with that of control cells. Furthermore, the expression levels of the epithelial markers E-cadherin and β-catenin were downregulated, while the mesenchymal markers α-SMA and vimentin were upregulated. Co-culture of CBRH-7919 cells with WB-F344 cells downregulated NF-κB and phospho-Akt expression. In conclusion, hepatocytic precursor (stem-like) WB-F344 cells inhibited the growth, colony formation and invasion capacity of metastasized hepatoma CBRH-7919 cells in vitro and in vivo by downregulating Akt/NF-κB signaling. PMID:27895771

  18. Characterization of latent transforming growth factor-beta 2 from monkey kidney cells.

    PubMed

    Lioubin, M N; Madisen, L; Roth, R A; Purchio, A F

    1991-05-01

    Serum-free medium conditioned by BSC-40 cells was analyzed for the presence of transforming growth factor-beta 2 (TGF beta 2)-related proteins. Western blot analysis was performed using site-specific antipeptide antibodies directed against the pro- and mature regions of the TGF beta 2 precursor. When conditioned medium was analyzed by polyacrylamide gel electrophoresis under reducing conditions, proteins with mol wt of 53 kDa (containing both mature and proregion sequences), 34-38 kDa (containing proregion sequences only), and 12 kDa (containing mature sequences) were detected. Under nonreducing conditions, complexes of 60- to 80-kDa, 160- to 200-kDa, as well as 24-kDa mature dimers were seen. Cleavage of mature TGF beta 2 from its precursor was inhibited by monensin and chloroquin, but not by ammonium chloride or methylamine. Two peaks of bioactivity were detected after fractionation on a TSK column corresponding to mol wt of 130 and 400 kDa. These peaks contained TGF beta 2 and pro-TGF beta 2 proteins. Partial purification of the 130-kDa complex followed by N-glyconase digestion indicated that the pro-TGF beta 2 proteins were glycosylated. These data demonstrate that BSC-40 cells secrete mature TGF beta 2 complexed with proregion-containing proteins and suggest that this association may contribute to the latency phenomena observed with respect to this growth regulator.

  19. Intrauterine growth correlation to postnatal growth--influence of risk factors and complications in pregnancy.

    PubMed

    Larsen, T; Greisen, G; Petersen, S

    1997-01-20

    In a population of 616 pregnant women with increased risk of intrauterine growth retardation, we examined the relationship of third trimester fetal growth to maternal and pregnancy risk factors, the infants condition at birth, and postnatal growth. Intrauterine growth velocity was calculated from repeated estimations of fetal weight using ultrasound. Postnatal growth up to 3 months was measured in 313 of the infants. Intrauterine growth velocity was directly correlated to birth weight deviation (R = 0.35, P < 0.0001) and inversely correlated to postnatal growth (R = 0.21, P = 0.0001). Heavy smoking throughout pregnancy was the most pronounced factor associated with loss of fetal growth percentiles (P = 0.006), and it was also associated with postnatal catchup (P = 0.01). Infants who needed neonatal care had significantly lower intrauterine growth velocities compared to the rest of the study group; no correlation was found between intrauterine growth velocity and Apgar scores or umbilical pH. It is concluded that growth retardation in the third trimester can be identified by ultrasound fetometry, and is associated with maladaptation at birth and postnatal catchup. However, the correlations were weak suggesting that deviation at birth reflects, only to a limited degree, acceleration or deceleration of growth in the third trimester.

  20. Transforming growth factor β signaling in uterine development and function.

    PubMed

    Li, Qinglei

    2014-01-01

    Transforming growth factor β (TGFβ) superfamily is evolutionarily conserved and plays fundamental roles in cell growth and differentiation. Mounting evidence supports its important role in female reproduction and development. TGFBs1-3 are founding members of this growth factor family, however, the in vivo function of TGFβ signaling in the uterus remains poorly defined. By drawing on mouse and human studies as a main source, this review focuses on the recent progress on understanding TGFβ signaling in the uterus. The review also considers the involvement of dysregulated TGFβ signaling in pathological conditions that cause pregnancy loss and fertility problems in women.

  1. [The changes of the attributable factors of child growth].

    PubMed

    Chen, Chun-ming; He, Wu; Chang, Su-ying

    2006-11-01

    To rule out the attributable factors of child growth in China and the changes of the factors in the past 15 years for the planning of future nutrition improvement of children in China. The datasets of 1990 - 2005 China Food and Nutrition Surveillance were used and the Multi-factorial Logistic Regression analysis was used. The AR% of these factors and the changes of the attributable factors during the past 15 years were presented. The main factors attributed to the growth of children under 5 in year 2005 were low education level of mothers (AR = 40.5%), floating out-for-job mothers (AR% = 35.5%), No egg introduction in the past 24 hours (AR = 24.2%), No milk introduction in the past 24 hours(18.7%) and household income below national poverty line (21.9%). Many of the attributable factors have improved significantly during the past 15 years. However, the increasing number of floating out-for-job mothers will have more impact on the quality of child feeding and child care. Social economic development is the direct factors to child growth, while other factors such as feeding and mother care are critical factors could either accelerate or counteract the positive effects of the favorable socioeconomic development. To improve height growth is essential to further enhance health and fitness of children under 5 focused nutrition and dietary intervention should be implemented.

  2. Neutrophil biology and the next generation of myeloid growth factors.

    PubMed

    Dale, David C

    2009-01-01

    Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections; bone marrow must produce approximately 10 x 10(9) neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid growth factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community, called bio-similars. Globally, new and copied versions of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.

  3. Conditional Inactivation of Upstream Binding Factor Reveals Its Epigenetic Functions and the Existence of a Somatic Nucleolar Precursor Body

    PubMed Central

    Hamdane, Nourdine; Stefanovsky, Victor Y.; Tremblay, Michel G.; Németh, Attila; Paquet, Eric; Lessard, Frédéric; Sanij, Elaine; Hannan, Ross; Moss, Tom

    2014-01-01

    Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and its ability to generate nucleosome-like nucleoprotein complexes suggest a more generalized role in chromatin structure. We previously showed that extensive depletion of UBF reduced the number of actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open the question of its requirement for RPI transcription. Using gene deletion in mouse, we now show that UBF is essential for embryo development beyond morula. Conditional deletion in cell cultures reveals that UBF is also essential for transcription of the rRNA genes and that it defines the active chromatin conformation of both gene and enhancer sequences. Loss of UBF prevents formation of the SL1/TIF1B pre-initiation complex and recruitment of the RPI-Rrn3/TIF1A complex. It is also accompanied by recruitment of H3K9me3, canonical histone H1 and HP1α, but not by de novo DNA methylation. Further, genes retain penta-acetyl H4 and H2A.Z, suggesting that even in the absence of UBF the rRNA genes can maintain a potentially active state. In contrast to canonical histone H1, binding of H1.4 is dependent on UBF, strongly suggesting that it plays a positive role in gene activity. Unexpectedly, arrest of rRNA synthesis does not suppress transcription of the 5S, tRNA or snRNA genes, nor expression of the several hundred mRNA genes implicated in ribosome biogenesis. Thus, rRNA gene activity does not coordinate global gene expression for ribosome biogenesis. Loss of UBF also unexpectedly induced the formation in cells of a large sub-nuclear structure resembling the nucleolar precursor body (NPB) of oocytes and early embryos. These somatic NPBs contain rRNA synthesis and processing factors but do not associate with the rRNA gene loci (NORs). PMID:25121932

  4. On factors controlling precursor slip fronts in the laboratory and their relation to slow slip events in nature

    NASA Astrophysics Data System (ADS)

    Selvadurai, Paul A.; Glaser, Steven D.; Parker, Jessica M.

    2017-03-01

    Spatial variations in frictional properties on natural faults are believed to be a factor influencing the presence of slow slip events (SSEs). This effect was tested on a laboratory frictional interface between two polymethyl methacrylate (PMMA) bodies. We studied the evolution of slip and slip rates that varied systematically based on the application of both high and low normal stress (σ0=0.8 or 0.4 MPa) and the far-field loading rate (VLP). A spontaneous, frictional rupture expanded from the central, weaker, and more compliant section of the fault that had fewer asperities. Slow rupture propagated at speeds Vslow˜0.8 to 26 mm s-1 with slip rates from 0.01 to 0.2 μm s-1, resulting in stress drops around 100 kPa. During certain nucleation sequences, the fault experienced a partial stress drop, referred to as precursor detachment fronts in tribology. Only at the higher level of normal stress did these fronts exist, and the slip and slip rates mimicked the moment and moment release rates during the 2013-2014 Boso SSE in Japan. The laboratory detachment fronts showed rupture propagation speeds Vslow/VR∈ (5 to 172) × 10-7 and stress drops ˜ 100 kPa, which both scaled to the aforementioned SSE. Distributions of asperities, measured using a pressure sensitive film, increased in complexity with additional normal stress—an increase in normal stress caused added complexity by increasing both the mean size and standard deviation of asperity distributions, and this appeared to control the presence of the detachment front.

  5. Phosphorylation and Dephosphorylation of the Presequence of Precursor MULTIPLE ORGANELLAR RNA EDITING FACTOR3 during Import into Mitochondria from Arabidopsis.

    PubMed

    Law, Yee-Song; Zhang, Renshan; Guan, Xiaoqian; Cheng, Shifeng; Sun, Feng; Duncan, Owen; Murcha, Monika W; Whelan, James; Lim, Boon Leong

    2015-10-01

    The nucleus-encoded mitochondria-targeted proteins, multiple organellar RNA editing factors (MORF3, MORF5, and MORF6), interact with Arabidopsis (Arabidopsis thaliana) PURPLE ACID PHOSPHATASE2 (AtPAP2) located on the chloroplast and mitochondrial outer membranes in a presequence-dependent manner. Phosphorylation of the presequence of the precursor MORF3 (pMORF3) by endogenous kinases in wheat germ translation lysate, leaf extracts, or STY kinases, but not in rabbit reticulocyte translation lysate, resulted in the inhibition of protein import into mitochondria. This inhibition of import could be overcome by altering threonine/serine residues to alanine on the presequence, thus preventing phosphorylation. Phosphorylated pMORF3, but not the phosphorylation-deficient pMORF3, can form a complex with 14-3-3 proteins and HEAT SHOCK PROTEIN70. The phosphorylation-deficient mutant of pMORF3 also displayed faster rates of import when translated in wheat germ lysates. Mitochondria isolated from plants with altered amounts of AtPAP2 displayed altered protein import kinetics. The import rate of pMORF3 synthesized in wheat germ translation lysate into pap2 mitochondria was slower than that into wild-type mitochondria, and this rate disparity was not seen for pMORF3 synthesized in rabbit reticulocyte translation lysate, the latter translation lysate largely deficient in kinase activity. Taken together, these results support a role for the phosphorylation and dephosphorylation of pMORF3 during the import into plant mitochondria. These results suggest that kinases, possibly STY kinases, and AtPAP2 are involved in the import of protein into both mitochondria and chloroplasts and provide a mechanism by which the import of proteins into both organelles may be coordinated.

  6. [Novel role of growth factors in ovary function].

    PubMed

    Amsterdam, Abraham

    2010-12-01

    The development of the DNA microarray technique facilitated systematic studies of the modulation of gene function. Considerable attention has been focused on members of the growth factor family to elucidate the main regulators of oocyte maturation and ovarian follicle rupture. Among these growth factors, it was found, both in rodents and in humans, that amphiregulin (Ar) and epiregulin (Ep) of the epidermal growth factor (EGF) family were dramatically up-regulated by gonadotrophins in the intact ovary and in primary granulosa cells, respectively. Their role in cumulus expansion and oocyte maturation was established in rodents, and their synthesis under LH stimulation in granulosa cells was demonstrated in humans. To be activated, Ar and Ep must be cleaved by a disintegrin and metalloproteinases (ADAMs) family. However, the precise processing of Ar and Ep by the cumulus cells is still obscure. Future investigations using DNA microarray technique may reveal the repertoire of genes activated in Ar- and Ep-stimulated cumulus cells and may help elucidate the molecular basis of ovulation. EFG-like factors are also involved in triggering ovarian cancer The author hypothesized that the normal ovary maintains cyclicity in the formation of these growth factors preventing the ovary from developing ovarian cancer In ovarian cancer these growth factors are continuously formed in an autocrine manner, leading to transformation and subsequently to ovarian cancer. These growth factors are essential for both normal and neoplastic transformation of the ovary. Taking into consideration these growth factors in the treatment of ovarian malfunction may be one way of curing ovarian cancer.

  7. [Enhancement of epidermal regeneration by recombinant vaccinia virus growth factor].

    PubMed

    Petrov, V S; Cheshenko, I O; Omigov, V V; Azaev, M Sh; Krendel'shchikov, A V; Ovechkina, L G; Cheshenko, N V; Malygin, E G

    1998-01-01

    Examining the specific activity has showed that recombinant vaccinia virus growth factor binds to appropriate receptors on the A-431 cell surface and prompts the healing acceleration of degree III burns in rats. This recombinant factor did not demonstrate pyrogenicity or toxicogenicity in tests on rabbits, guinea-pits, noninbred albino mice.

  8. Transforming growth factor β and platelet-derived growth factor modulation of myofibroblast development from corneal fibroblasts in vitro.

    PubMed

    Singh, Vivek; Barbosa, Flavia L; Torricelli, Andre A M; Santhiago, Marcony R; Wilson, Steven E

    2014-03-01

    The purpose of this study was to test the hypotheses that development of mature vimentin+/α-smooth muscle actin+/desmin+ (V+A+D+) myofibroblasts from corneal fibroblasts is regulated by transforming growth factor (TGF) β and platelet-derived growth factor (PDGF); and that myofibroblast development in vitro follows a similar developmental pathway as it does in vivo. Mouse corneal stromal fibroblasts (MSF) were isolated from the corneas of Swiss Webster mice and cultured in serum-free media augmented with DMEM/F12 and varying doses of TGFβ (0.1-2.0 ng/ml), with and without mouse PDGF-AA and/or PDGF-BB (2.0 ng/ml), to study the transition of the MSF to V+A+D+ myofibroblasts. The mean percentage of vimentin+, α-SMA+ and desmin+ cells was determined at each time point (2-15 days), with each growth factor concentration. MSF in vitro were noted to undergo the same developmental transition from V+A-D- to V+A+D- to V+A+D+ myofibroblasts as precursors undergo in vivo. TGFβ at a dose of 0.5 ng/ml and 1.0 ng/ml with 2.0 ng/ml PDGF-AA and 2.0 ng/ml PDGF-BB in DMEM/F12 serum-free media was optimal for the development of V+A+D+ myofibroblasts. This study defines optimal in vitro conditions to monitor the development of MSF into myofibroblasts. The combined effects of TGFβ and PDGF promote the full development of V+A+D+ myofibroblasts from MSF.

  9. Priming Dental Pulp Stem Cells With Fibroblast Growth Factor-2 Increases Angiogenesis of Implanted Tissue-Engineered Constructs Through Hepatocyte Growth Factor and Vascular Endothelial Growth Factor Secretion

    PubMed Central

    Gorin, Caroline; Rochefort, Gael Y.; Bascetin, Rumeyza; Ying, Hanru; Lesieur, Julie; Sadoine, Jérémy; Beckouche, Nathan; Berndt, Sarah; Novais, Anita; Lesage, Matthieu; Hosten, Benoit; Vercellino, Laetitia; Merlet, Pascal; Le-Denmat, Dominique; Marchiol, Carmen; Letourneur, Didier; Nicoletti, Antonino; Vital, Sibylle Opsahl; Poliard, Anne; Salmon, Benjamin; Germain, Stéphane

    2016-01-01

    Tissue engineering strategies based on implanting cellularized biomaterials are promising therapeutic approaches for the reconstruction of large tissue defects. A major hurdle for the reliable establishment of such therapeutic approaches is the lack of rapid blood perfusion of the tissue construct to provide oxygen and nutrients. Numerous sources of mesenchymal stem cells (MSCs) displaying angiogenic potential have been characterized in the past years, including the adult dental pulp. Establishment of efficient strategies for improving angiogenesis in tissue constructs is nevertheless still an important challenge. Hypoxia was proposed as a priming treatment owing to its capacity to enhance the angiogenic potential of stem cells through vascular endothelial growth factor (VEGF) release. The present study aimed to characterize additional key factors regulating the angiogenic capacity of such MSCs, namely, dental pulp stem cells derived from deciduous teeth (SHED). We identified fibroblast growth factor-2 (FGF-2) as a potent inducer of the release of VEGF and hepatocyte growth factor (HGF) by SHED. We found that FGF-2 limited hypoxia-induced downregulation of HGF release. Using three-dimensional culture models of angiogenesis, we demonstrated that VEGF and HGF were both responsible for the high angiogenic potential of SHED through direct targeting of endothelial cells. In addition, FGF-2 treatment increased the fraction of Stro-1+/CD146+ progenitor cells. We then applied in vitro FGF-2 priming to SHED before encapsulation in hydrogels and in vivo subcutaneous implantation. Our results showed that FGF-2 priming is more efficient than hypoxia at increasing SHED-induced vascularization compared with nonprimed controls. Altogether, these data demonstrate that FGF-2 priming enhances the angiogenic potential of SHED through the secretion of both HGF and VEGF. Significance The results from the present study show that fibroblast growth factor-2 (FGF-2) priming is more

  10. A Hox complex activates and potentiates the Epidermal Growth Factor signaling pathway to specify Drosophila oenocytes.

    PubMed

    Wang, Guolun; Gutzwiller, Lisa; Li-Kroeger, David; Gebelein, Brian

    2017-07-01

    Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells. Neighboring cells that receive the EGF signal initiate a largely unknown pathway to promote oenocyte fate. Here, we show that Abd-A also plays a cell autonomous role in inducing oenocyte fate by activating the expression of the Pointed-P1 (PntP1) ETS transcription factor downstream of EGF signaling. Genetic studies demonstrate that both PntP1 and PntP2 are required for oenocyte specification. Moreover, we found that PntP1 contains a conserved enhancer (PntP1OE) that is activated in oenocyte precursor cells by EGF signaling via direct regulation by the Pnt transcription factors as well as a transcription factor complex consisting of Abd-A, Extradenticle, and Homothorax. Our findings demonstrate that the same Abd-A Hox complex required for sending the EGF signal from SOP cells, enhances the competency of receiving cells to select oenocyte cell fate by up-regulating PntP1. Since PntP1 is a downstream effector of EGF signaling, these findings provide insight into how a Hox factor can both trigger and potentiate the EGF signal to promote an essential cell fate along the body plan.

  11. In situ formation of poly(vinyl alcohol)–heparin hydrogels for mild encapsulation and prolonged release of basic fibroblast growth factor and vascular endothelial growth factor

    PubMed Central

    Roberts, Justine J; Farrugia, Brooke L; Green, Rylie A; Rnjak-Kovacina, Jelena; Martens, Penny J

    2016-01-01

    Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparin-binding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol)-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications. PMID:27895888

  12. In situ formation of poly(vinyl alcohol)-heparin hydrogels for mild encapsulation and prolonged release of basic fibroblast growth factor and vascular endothelial growth factor.

    PubMed

    Roberts, Justine J; Farrugia, Brooke L; Green, Rylie A; Rnjak-Kovacina, Jelena; Martens, Penny J

    2016-01-01

    Heparin-based hydrogels are attractive for controlled growth factor delivery, due to the native ability of heparin to bind and stabilize growth factors. Basic fibroblast growth factor and vascular endothelial growth factor are heparin-binding growth factors that synergistically enhance angiogenesis. Mild, in situ encapsulation of both basic fibroblast growth factor and vascular endothelial growth factor and subsequent bioactive dual release has not been demonstrated from heparin-crosslinked hydrogels, and the combined long-term delivery of both growth factors from biomaterials is still a major challenge. Both basic fibroblast growth factor and vascular endothelial growth factor were encapsulated in poly(vinyl alcohol)-heparin hydrogels and demonstrated controlled release. A model cell line, BaF32, was used to show bioactivity of heparin and basic fibroblast growth factor released from the gels over multiple days. Released basic fibroblast growth factor promoted higher human umbilical vein endothelial cell outgrowth over 24 h and proliferation for 3 days than the poly(vinyl alcohol)-heparin hydrogels alone. The release of vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels promoted human umbilical vein endothelial cell outgrowth but not significant proliferation. Dual-growth factor release of basic fibroblast growth factor and vascular endothelial growth factor from poly(vinyl alcohol)-heparin hydrogels resulted in a synergistic effect with significantly higher human umbilical vein endothelial cell outgrowth compared to basic fibroblast growth factor or vascular endothelial growth factor alone. Poly(vinyl alcohol)-heparin hydrogels allowed bioactive growth factor encapsulation and provided controlled release of multiple growth factors which is beneficial toward tissue regeneration applications.

  13. Transcription factor complex formation and chromatin fine structure alterations at the murine c-fms (CSF-1 receptor) locus during maturation of myeloid precursor cells

    PubMed Central

    Tagoh, Hiromi; Himes, Roy; Clarke, Deborah; Leenen, Pieter J.M.; Riggs, Arthur D.; Hume, David; Bonifer, Constanze

    2002-01-01

    Expression of the gene for the macrophage colony stimulating factor receptor (CSF-1R), c-fms, has been viewed as a hallmark of the commitment of multipotent precursor cells to macrophages. Lineage-restricted expression of the gene is controlled by conserved elements in the proximal promoter and within the first intron. To investigate the developmental regulation of c-fms at the level of chromatin structure, we developed an in vitro system to examine the maturation of multipotent myeloid precursor cells into mature macrophages. The dynamics of chromatin fine structure alterations and transcription factor occupancy at the c-fms promoter and intronic enhancer was examined by in vivo DMS and UV-footprinting. We show that the c-fms gene is already transcribed at low levels in early myeloid precursors on which no CSF-1R surface expression can be detected. At this stage of myelopoiesis, the formation of transcription factor complexes on the promoter was complete. By contrast, occupancy of the enhancer was acutely regulated during macrophage differentiation. Our data show that cell-intrinsic differentiation decisions at the c-fms locus precede the appearance of c-fms on the cell surface. They also suggest that complex lineage-specific enhancers such as the c-fms intronic enhancer regulate local chromatin structure through the coordinated assembly and disassembly of distinct transcription factor complexes. PMID:12101129

  14. Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

    PubMed

    Soliman, Ashraf; De Sanctis, Vincenzo; Elalaily, Rania; Bedair, Said

    2014-11-01

    Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS.

  15. Advances in pubertal growth and factors influencing it: Can we increase pubertal growth?

    PubMed Central

    Soliman, Ashraf; De Sanctis, Vincenzo; Elalaily, Rania; Bedair, Said

    2014-01-01

    Puberty is a period of development characterized by partially concurrent changes which includes growth acceleration, alteration in body composition and appearance of secondary sex characteristics. Puberty is characterized by an acceleration and then deceleration in skeletal growth. The initiation, duration and amount of growth vary considerably during the growth spurt. Pubertal growth and biological maturation are dynamic processes regulated by a variety of genetic and environmental factors. Changes in skeletal maturation and bone mineral accretion concomitant with the stage of pubertal development constitute essential components in the evaluation of growth during this pubertal period. Genetic, endocrine and nutritional factors and ethnicity contribute variably to the amount of growth gained during this important period of rapid changes. Many studies investigated the possibility of increasing pubertal growth to gain taller final adult height in adolescents with idiopathic short stature (ISS). The pattern of pubertal growth, its relation to sex maturity rating and factors affecting them has been addressed in this review. The results of different trials to increase final adult height of adolescents using different hormones have been summarized. These data enables Endocrinologists to give in-depth explanations to patients and families about the efficacy and clinical significance as well as the safety of using these therapies in the treatment of adolescents with ISS. PMID:25538878

  16. Transforming growth factor alpha controls the transition from hypertrophic cartilage to bone during endochondral bone growth.

    PubMed

    Usmani, Shirine E; Pest, Michael A; Kim, Gunwoo; Ohora, Sara N; Qin, Ling; Beier, Frank

    2012-07-01

    We have recently identified transforming growth factor alpha (TGFα) as a novel growth factor involved in the joint disease osteoarthritis. The role of TGFα in normal cartilage and bone physiology however, has not been well defined. The objective of this study was to determine the role of TGFα in bone development through investigation of the Tgfa knockout mouse. The gross skeletons as well as the cartilage growth plates of Tgfa knockout mice and their control littermates were examined during several developmental stages ranging from newborn to ten weeks old. Knockout mice experienced skeletal growth retardation and expansion of the hypertrophic zone of the growth plate. These phenotypes were transient and spontaneously resolved by ten weeks of age. Tgfa knockout growth plates also had fewer osteoclasts along the cartilage/bone interface. Furthermore, knockout mice expressed less RUNX2, RANKL, and MMP13 mRNA in their cartilage growth plates than controls did. Tgfa knockout mice experience a delay in bone development, specifically the conversion of hypertrophic cartilage to true bone. The persistence of the hypertrophic zone of the growth plate appears to be mediated by a decrease in MMP13 and RANKL expression in hypertrophic chondrocytes and a resulting reduction in osteoclast recruitment. Overall, TGFα appears to be an important growth factor regulating the conversion of cartilage to bone during the process of endochondral ossification. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. [Role of maternal risk factors in foetal growth impairment].

    PubMed

    Cieślik, Krystyna; Waszak, Małgorzata

    2007-01-01

    Clinical goal of foetal growth evaluation is primarily to identify foetuses with an accelerated or decelerated growth rate. Chief criterion of normal intrauterine development is a timely delivery of a neonate meeting applicable health norms. Obstetrician's decisions on how a pregnancy should be handled are based on foetal development and growth forecast and take into account whether foetal growth is normal, accelerated or decelerated. Such assessment requires correct determination of foetal age, selection of the most appropriate growth rate standards and defining potential risk factors. The aim of this study was to evaluate the impact of pre-selected risk factors on foetal growth. Material was 3889 foetuses (2203 males and 1686 females) stillborn between 20th and 42nd week of pregnancy. Morphological development of the study material was characterised based upon the values of seven pre-defined somatic features and the weight of eight internal organs. Clinical classification of maternal risk factors revealed four factors of most potent impact on foetal development, ie. maternal age, number of pregnancy and artificial and natural miscarriage history. Verification of developmental status of foetuses, ie. exposed vs. non-exposed to risk factors, allowed to determine the potency of selected risk factors. The non-exposed group was characterised by normal growth rate during each of stage of development meaning that despite being stillborn these foetuses did not differ significantly in their development of the selected features from live born foetuses. In the exposed group, however, the rate of development, compared to the standard, was significantly reduced and starting from the 35th week it was below the 5th percentile. It can, therefore, be seen that the exposed group development was significantly influenced by an adverse impact of risk factors. Our results show that the risk factors for the exposed group are a group of maternal risk factors impairing foetal growth and

  18. Insulin-like growth factors act synergistically with basic fibroblast growth factor and nerve growth factor to promote chromaffin cell proliferation.

    PubMed Central

    Frödin, M; Gammeltoft, S

    1994-01-01

    We have investigated the effects of insulin-like growth factors (IGFs), basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) on DNA synthesis in cultured chromaffin cells from fetal, neonatal, and adult rats by using 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling for 24 or 48 h and immunocytochemical staining of cell nuclei. After 6 days in culture in the absence of growth factors, nuclear BrdUrd incorporation was detected in 30% of fetal chromaffin cells, 1.5% of neonatal cells, and 0.1% of adult cells. Addition of 10 nM IGF-I or IGF-II increased the fraction of BrdUrd-labeled nuclei to 50% of fetal, 20% of neonatal, and 2% of adult chromaffin cells. The ED50 value of IGF-I- and IGF-II-stimulated BrdUrd labeling in neonatal chromaffin cells was 0.3 nM and 0.8 nM, respectively. In neonatal and adult chromaffin cells, addition of 1 nM bFGF or 2 nM NGF stimulated nuclear BrdUrd incorporation to approximately the same level as 10 nM IGF-I or IGF-II. However, the response to bFGF or NGF in combination with either IGF-I or IGF-II was more than additive, indicating that the combined effect of the IGFs and bFGF or NGF is synergistic. The degree of synergism was 2- to 4-fold in neonatal chromaffin cells and 10- to 20-fold in adult chromaffin cells compared with the effect of each growth factor alone. In contrast, the action of bFGF and NGF added together in the absence of IGFs was not synergistic or additive. IGF-II acted also as a survival factor on neonatal chromaffin cells and the cell survival was further improved when bFGF or NGF was added together with IGF-II. In conclusion, we propose that IGF-I and IGF-II act in synergy with bFGF and NGF to stimulate proliferation and survival of chromaffin cells during neonatal growth and adult maintenance of the adrenal medulla. Our findings may have implications for improving the survival of chromaffin cell implants in diseased human brain. PMID:8127879

  19. Atmospheric-pressure plasma-enhanced chemical vapor deposition of a-SiCN:H films: Role of precursors on the film growth and properties

    SciTech Connect

    Guruvenket, Srinivasan; Andrie, Steven; Simon, Mark; Johnson, Kyle W.; Sailer, Robert A.

    2012-09-14

    Atmospheric pressure plasma enhanced chemical vapor deposition (AP-PECVD) using Surfx AtomflowTM 250D APPJ was utilized to synthesize amorphous silicon carbonitride coatings using tetramethyldisilizane (TMDZ) and hexamethyldisilizane (HMDZ) as the single source precursors. The effect of precursor chemistry and the substrate temperature (Ts) on the properties of a-SiCN:H films were evaluated, while nitrogen was used as the reactive gas. Surface morphology of the films was evaluated using atomic force microscopy (AFM); chemical properties were determined using Fourier transform infrared spectroscopy (FTIR); thickness and optical properties were determined using spectroscopic ellipsometry and mechanical properties were determined using nano-indentation. In general films deposited at substrate temperature (Ts) <200 °C contained organic moieties, while the films deposited at Ts >200 oC depicted strong Si-N and Si-CN absorption. Refractive indices (n) of the thin films showed values between 1.5 -2.0 depending on the deposition parameters. Mechanical properties of the films determined using nano-indentation revealed that these films have hardness between 0.5 GPa to 15 GPa depending on the Ts. AFM evaluation of the films showed high roughness (Ra) values of 2-3 nm for the films grown at low Ts (< 250 °C), while the films grown at Ts ≥ 300 °C exhibited atomically smooth surface with Ra of ~ 0.5 nm. Furthermore, based on the gas phase (plasma) chemistry, precursor chemistry and the other experimental observations, a possible growth model that prevails in the AP-PECVD of a-SiCN:H thin films is proposed.

  20. Atmospheric-pressure plasma-enhanced chemical vapor deposition of a-SiCN:H films: Role of precursors on the film growth and properties

    DOE PAGES

    Guruvenket, Srinivasan; Andrie, Steven; Simon, Mark; ...

    2012-09-14

    Atmospheric pressure plasma enhanced chemical vapor deposition (AP-PECVD) using Surfx AtomflowTM 250D APPJ was utilized to synthesize amorphous silicon carbonitride coatings using tetramethyldisilizane (TMDZ) and hexamethyldisilizane (HMDZ) as the single source precursors. The effect of precursor chemistry and the substrate temperature (Ts) on the properties of a-SiCN:H films were evaluated, while nitrogen was used as the reactive gas. Surface morphology of the films was evaluated using atomic force microscopy (AFM); chemical properties were determined using Fourier transform infrared spectroscopy (FTIR); thickness and optical properties were determined using spectroscopic ellipsometry and mechanical properties were determined using nano-indentation. In general films depositedmore » at substrate temperature (Ts) <200 °C contained organic moieties, while the films deposited at Ts >200 oC depicted strong Si-N and Si-CN absorption. Refractive indices (n) of the thin films showed values between 1.5 -2.0 depending on the deposition parameters. Mechanical properties of the films determined using nano-indentation revealed that these films have hardness between 0.5 GPa to 15 GPa depending on the Ts. AFM evaluation of the films showed high roughness (Ra) values of 2-3 nm for the films grown at low Ts (< 250 °C), while the films grown at Ts ≥ 300 °C exhibited atomically smooth surface with Ra of ~ 0.5 nm. Furthermore, based on the gas phase (plasma) chemistry, precursor chemistry and the other experimental observations, a possible growth model that prevails in the AP-PECVD of a-SiCN:H thin films is proposed.« less

  1. Discerning environmental factors affecting current tree growth in Central Europe.

    PubMed

    Cienciala, Emil; Russ, Radek; Šantrůčková, Hana; Altman, Jan; Kopáček, Jiří; Hůnová, Iva; Štěpánek, Petr; Oulehle, Filip; Tumajer, Jan; Ståhl, Göran

    2016-12-15

    We examined the effect of individual environmental factors on the current spruce tree growth assessed from a repeated country-level statistical landscape (incl. forest) survey in the Czech Republic. An extensive set of variables related to tree size, competition, site characteristics including soil texture, chemistry, N deposition and climate was tested within a random-effect model to explain growth in the conditions of dominantly managed forest ecosystems. The current spruce basal area increment was assessed from two consecutive landscape surveys conducted in 2008/2009 and six years later in 2014/2015. Tree size, age and competition within forest stands were found to be the dominant explanatory variables, whereas the expression of site characteristics, environmental and climatic drives was weaker. The significant site variables affecting growth included soil C/N ratio and soil exchangeable acidity (pH KCl; positive response) reflecting soil chemistry, long-term N-deposition (averaged since 1975) in combination with soil texture (clay content) and Standardized Precipitation Index (SPI), a drought index expressing moisture conditions. Sensitivity of growth to N-deposition was positive, although weak. SPI was positively related to and significant in explaining tree growth when expressed for the growth season. Except SPI, no significant relation of growth was determined to altitude-related variables (temperature, growth season length). We identified the current spruce growth optimum at elevations about 800ma.s.l. or higher in the conditions of the country. This suggests that at lower elevations, limitation by a more pronounced water deficit dominates, whereas direct temperature limitation may concern the less frequent higher elevations. The mixed linear model of spruce tree growth explained 55 and 65% of the variability with fixed and random effects included, respectively, and provided new insights on the current spruce tree growth and factors affecting it within the

  2. Viability and growth of feline preantral follicles in vitro cultured with insulin growth factor and epidermal growth factor supplemented medium.

    PubMed

    Alves, A E; Padilha-Nakaghi, L C; Pires-Butler, E A; Apparicio, M; Silva, Nam; Motheo, T F; Vicente, Wrr; Luvoni, G C

    2017-04-01

    In vitro culture of ovarian preantral follicles has emerged as a reproductive technology aimed at obtaining large amount of oocytes for in vitro embryo production. The addition of growth factors (GF) in the in vitro culture of preantral follicles of different species has provided superior results of follicular development, antrum formation and proliferation of granulosa cells. However, there are only few reports regarding the use of these factors on feline preantral follicle in vitro culture. Thus, the aim of this study was to investigate the effect of a combination of IGF-1 and EGF on in vitro viability and growth of preantral follicles and enclosed oocytes collected from domestic cats. A total of 64 follicles characterized by multilayer granulosa cells were isolated and individually cultured for 6 days (T6) in minimum essential medium supplemented with IGF-1+ EGF (100 ng/ml each) or without (control). A higher percentage of follicles were viable after culture with GF than without, and an increase in size when IGF-1+ EGF were added to the medium (170 ± 32.4 μm (T0) vs. 201 ± 22.3 μm (T6); p < .05) was observed. An increase in the diameter was also observed in follicles cultured without GF, but this increase was only 8.3% compared to 15.4% of those cultured with GF (p < .05). No differences were found in the diameter of oocytes contained in follicles cultured in the non-supplemented or supplemented media (107.9 ± 11.8 μm (T0) vs. 113.2 ± 15.6 μm (T6); p > .05). These data suggest that the addition of IGF-1 and EGF to the culture medium promotes the in vitro development of preantral follicles of cats. © 2016 Blackwell Verlag GmbH.

  3. Cytokine and Growth Factor Responses After Radiotherapy for Localized Ependymoma

    SciTech Connect

    Merchant, Thomas E. Li Chenghong; Xiong Xiaoping; Gaber, M. Waleed

    2009-05-01

    Purpose: To determine the time course and clinical significance of cytokines and peptide growth factors in pediatric patients with ependymoma treated with postoperative radiotherapy (RT). Methods and Materials: We measured 15 cytokines and growth factors (fibroblast growth factor, epidermal growth factor, vascular endothelial growth factor [VEGF], interleukin [IL]-1{beta}, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-{gamma}, tumor necrosis factor-{alpha}, granulocyte-macrophage colony-stimulating factor, monocyte chemoattractant protein-1, and macrophage inflammatory protein-{alpha}) from 30 patients before RT and 2 and 24 h, weekly for 6 weeks, and at 3, 6, 9, and 12 months after the initiation of RT. Two longitudinal models for the trend of log-transformed measurements were fitted, one during treatment and one through 12 months. Results: During RT, log IL-8 declined at a rate of -0.10389/wk (p = 0.0068). The rate of decline was greater (p = 0.028) for patients with an infratentorial tumor location. The decline in IL-8 after RT was significant when stratified by infratentorial tumor location (p = 0.0345) and more than one surgical procedure (p = 0.0272). During RT, the decline in log VEGF was significant when stratified by the presence of a ventriculoperitoneal shunt. After RT, the log VEGF declined significantly at a rate of -0.06207/mo. The decline was significant for males (p = 0.0222), supratentorial tumors (p = 0.0158), one surgical procedure (p = 0.0222), no ventriculoperitoneal shunt (p = 0.0005), and the absence of treatment failure (p = 0.0028). Conclusion: The pro-inflammatory cytokine IL-8 declined significantly during RT and the decline differed according to tumor location. The angiogenesis factor VEGF declined significantly during the 12 months after RT. The decline was greater in males, those without a ventriculoperitoneal shunt, and in those with favorable disease factors, including one surgical procedure, supratentorial tumor location, and

  4. Involvement of JAK1, JAK2, and JAK3 in Stimulation of Functional Activity of Mesenchymal Progenitor Cells by Fibroblast Growth Factor.

    PubMed

    Zyuz'kov, G N; Zhdanov, V V; Udut, E V; Miroshnichenko, L A; Simanina, E V; Polyakova, T Yu; Stavrova, L A; Udut, V V; Minakova, M Yu; Dygai, A M

    2016-12-01

    We studied the involvement of individual JAK kinases in the realization of the growth potential of mesenchymal precursors under the effect of fibroblast growth factor. The important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells and participation of JAK1 in this process under conditions of cytokine stimulation of progenitor cells were demonstrated. Specific inhibitors of these kinases reduced the yield of fibroblast CFU and the rate of their division. Moreover, blockade of JAK1, JAK2, and JAK3 under the effect of fibroblast growth factor was accompanied by an increase in the intensity of progenitor cell differentiation.

  5. Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina: comparative studies with basic fibroblast growth factor.

    PubMed

    Grant, M B; Mames, R N; Fitzgerald, C; Ellis, E A; Aboufriekha, M; Guy, J

    1993-04-01

    The release of growth factors from ischaemic retina has been hypothesized as the central stimulus for retinal neovascularization in proliferative diabetic retinopathy. Two of the growth factors implicated are insulin-like growth factor-I and basic fibroblast growth factor. We examined the effect of insulin-like growth factor-I on in vivo neovascularization using the established angiogenic model of the rabbit cornea (n = 30), and also compared the effects of insulin-like growth factor-I and basic fibroblast growth factor using two new in vivo systems. Either supraphysiologic concentrations of each growth factor (600 micrograms) were injected intravitreally into pigmented rabbits (n = 21) or porous polyfluorotetraethylene chambers filled with an emulsion containing collagen and growth factor (500 ng) were placed on the retina surface (n = 8). Our results demonstrate that when insulin-like growth factor-I was implanted together with a slow release carrier into the pocket of the normally avascular cornea, insulin-like growth factor-I (10 micrograms/pellet) induced angiogenesis in all rabbits. This degree of angiogenesis was comparable to that previously shown for basic fibroblast growth factor. For the intravitreal studies, the fibrotic component was greater in the basic fibroblast growth factor injected eyes, whereas the vascular component was accentuated in the eyes injected with insulin-like growth factor-I. Light and electron microscopy demonstrated areas of vascular proliferation in both groups. Porous polyfluorotetraethylene chamber studies with insulin-like growth factor-I and basic fibroblast growth factor demonstrated vascular proliferation in the vicinity of the chamber similar to the intravitreal injected eyes, but to a lesser degree than the injected eyes. Our experiments overall support the angiogenic potential of both insulin-like growth factor-I and basic fibroblast growth factor and support distinct but complimentary roles for each growth factor in the

  6. Growth factors in porcine full and partial thickness burn repair. Differing targets and effects of keratinocyte growth factor, platelet-derived growth factor-BB, epidermal growth factor, and neu differentiation factor.

    PubMed Central

    Danilenko, D. M.; Ring, B. D.; Tarpley, J. E.; Morris, B.; Van, G. Y.; Morawiecki, A.; Callahan, W.; Goldenberg, M.; Hershenson, S.; Pierce, G. F.

    1995-01-01

    The topical application of recombinant growth factors such as epidermal growth factor, platelet-derived growth factor-BB homodimer (rPDGF-BB), keratinocyte growth factor (rKGF), and neu differentiation factor has resulted in significant acceleration of healing in several animal models of wound repair. In this study, we established highly reproducible and quantifiable full and deep partial thickness porcine burn models in which burns were escharectomized 4 or 5 days postburn and covered with an occlusive dressing to replicate the standard treatment in human burn patients. We then applied these growth factors to assess their efficacy on several parameters of wound repair: extracellular matrix and granulation tissue production, percent reepithelialization, and new epithelial area. In full thickness burns, only rPDGF-BB and the combination of rPDGF-BB and rKGF induced significant changes in burn repair. rPDGF-BB induced marked extracellular matrix and granulation tissue production (P = 0.013) such that the burn defect was filled within several days of escharectomy, but had no effect on new epithelial area or reepithelialization. The combination of rPDGF-BB and rKGF in full thickness burns resulted in a highly significant increase in extracellular matrix and granulation tissue area (P = 0.0009) and a significant increase in new epithelial area (P = 0.007), but had no effect on reepithelialization. In deep partial thickness burns, rKGF induced the most consistent changes. Daily application of rKGF induced a highly significant increase in new epithelial area (P < 0.0001) but induced only a modest increase in reepithelialization (83.7% rKGF-treated versus 70.2% control; P = 0.016) 12 days postburn. rKGF also doubled the number of fully reepithelialized burns (P = 0.02) at 13 days postburn, at least partially because of marked stimulation of both epidermal and follicular proliferation as assessed by proliferating cell nuclear antigen expression. In situ hybridization for

  7. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    SciTech Connect

    Gough, Mallory Blanthorn-Hazell, Sophee Delury, Craig Parkin, Edward

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  8. An uncleavable form of pro–scatter factor suppresses tumor growth and dissemination in mice

    PubMed Central

    Mazzone, Massimiliano; Basilico, Cristina; Cavassa, Silvia; Pennacchietti, Selma; Risio, Mauro; Naldini, Luigi; Comoglio, Paolo M.; Michieli, Paolo

    2004-01-01

    Scatter factor (SF), also known as hepatocyte growth factor, is ubiquitously present in the extracellular matrix of tissues in the form of an inactive precursor (pro-SF). In order to acquire biological activity, pro-SF must be cleaved by specific proteases present on the cell surface. The mature form of SF controls invasive cues in both physiological and pathological processes through activation of its receptor, the Met tyrosine kinase. By substituting a single amino acid in the proteolytic site, we engineered an unprocessable form of pro-SF (uncleavable SF). Using lentivirus vector technology, we achieved local or systemic delivery of uncleavable SF in mice. We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF–induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions. These data show that proteolytic activation of pro-SF is a limiting step in tumor progression, thus suggesting a new strategy for the treatment or prevention of the malignant conversion of neoplastic lesions. PMID:15545993

  9. An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice.

    PubMed

    Mazzone, Massimiliano; Basilico, Cristina; Cavassa, Silvia; Pennacchietti, Selma; Risio, Mauro; Naldini, Luigi; Comoglio, Paolo M; Michieli, Paolo

    2004-11-01

    Scatter factor (SF), also known as hepatocyte growth factor, is ubiquitously present in the extracellular matrix of tissues in the form of an inactive precursor (pro-SF). In order to acquire biological activity, pro-SF must be cleaved by specific proteases present on the cell surface. The mature form of SF controls invasive cues in both physiological and pathological processes through activation of its receptor, the Met tyrosine kinase. By substituting a single amino acid in the proteolytic site, we engineered an unprocessable form of pro-SF (uncleavable SF). Using lentivirus vector technology, we achieved local or systemic delivery of uncleavable SF in mice. We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF-induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions. These data show that proteolytic activation of pro-SF is a limiting step in tumor progression, thus suggesting a new strategy for the treatment or prevention of the malignant conversion of neoplastic lesions.

  10. Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

    PubMed Central

    Robinson, Paulette M.; Blalock, Timothy D.; Yuan, Rong; Lewin, Alfred S.; Schultz, Gregory S.

    2013-01-01

    Excessive scarring (fibrosis) is a major cause of pathologies in multiple tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming growth factor- β (TGF- β) system has been shown to play a key role in regulating the formation of scar tissue throughout the body. Furthermore, connective tissue growth factor (CTGF) has been shown to mediate most of the fibrotic actions of TGF- β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. Currently, no approved drugs selectively and specifically regulate scar formation. Thus, there is a need for a drug that selectively targets the TGF- β cascade at the molecular level and has minimal off-target side effects. This chapter focuses on the design of hammerhead ribozymes, measurement of kinetic activity, and assessment of knockdown mRNAs of TGF- β and CTGF in cell cultures. PMID:22131029

  11. Advances in growth factor delivery for therapeutic angiogenesis.

    PubMed

    Said, Somiraa S; Pickering, J Geoffrey; Mequanint, Kibret

    2013-01-01

    Therapeutic angiogenesis is a new revascularization strategy involving the administration of growth factors to induce new vessel formation. The biology and delivery of angiogenic growth factors involved in vessel formation have been extensively studied but success in translating the angiogenic capacity of growth factors into benefits for vascular disease patients is still limited. This could be attributed to issues related to patient selection, growth factor delivery methods or lack of vessel maturation. Comprehensive understanding of the cellular and molecular cross-talk during the different stages of vascular development is needed for the design of efficient therapeutic strategies. The presentation of angiogenic factors either in series or in parallel using a strategy that mimics physiological events, such as concentration and spatio-temporal profiles, is an immediate requirement for functional blood vessel formation. This review provides an overview of the recent delivery strategies of angiogenic factors and discusses targeting neovascular maturation as a promising approach to induce stable and functional vessels for therapeutic angiogenesis.

  12. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    PubMed

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth.

  13. Effect of precursor concentration and bath temperature on the growth of chemical bath deposited tin sulphide thin films

    NASA Astrophysics Data System (ADS)

    Jayasree, Y.; Chalapathi, U.; Uday Bhaskar, P.; Sundara Raja, V.

    2012-01-01

    SnS is a promising candidate for a low-cost, non-toxic solar cell absorber layer. Tin sulphide thin films have been deposited by chemical bath deposition technique from a solution containing stannous chloride, thioacetamide, ammonia and triethanolamine (TEA). The effects of concentration of tin salt, triethanolamine and bath temperature on the growth of tin sulphide films have been investigated in order to optimize the growth conditions to obtain tin monosulphide (SnS) films. SnS films obtained under optimized conditions were found to be polycrystalline in nature with orthorhombic structure. The optical band gap of these films was found to be 1.5 eV.

  14. Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony- stimulating factor on the basis of Lyt-2 phenotype

    PubMed Central

    1982-01-01

    The frequencies of precursors of C57BL/6 T lymphocytes that respond to DBA/2 alloantigens by secreting the lymphokines interleukin 2 (IL-2), macrophage-activating factor (MAF), and granulocyte-macrophage colony- stimulating factor (GM-CSF) have been directly compared with cytolytic T lymphocyte precursor (CTL-P) frequencies in limiting dilution microcultures established from spleen cells positively or negatively selected on the basis of Lyt-2 phenotype. A clear dichotomy was observed between CTL-P, which were contained in the Lyt-2+ fraction, and precursors of IL-2-secreting cells, which were detected almost exclusively in the Lyt-2- population. In contrast, precursors of cells secreting MAF and GM-CSF were found in both populations: almost all responding cells from the Lyt-2- fraction produced both these factors, whereas the precursor frequency of MAF-secreting and GM-CSF-secreting cells was three- to fourfold lower in the Lyt-2+ population. These frequency data were consistent with quantitative differences observed in the average production of these lymphokines by Lyt-2+ and Lyt-2- populations. PMID:6752327

  15. Therapeutic foam scaffolds incorporating biopolymer-shelled mesoporous nanospheres with growth factors.

    PubMed

    Kim, Tae-Hyun; Eltohamy, Mohamed; Kim, Meeju; Perez, Roman A; Kim, Joong-Hyun; Yun, Ye-Rang; Jang, Jun-Hyeog; Lee, Eun-Jung; Knowles, Jonathan C; Kim, Hae-Won

    2014-06-01

    A novel therapeutic scaffolding system of engineered nanocarriers within a foam matrix for the long-term and sequential delivery of growth factors is reported. Mesoporous silica nanospheres were first functionalized to have an enlarged mesopore size (12.2nm) and aminated surface, which was then shelled by a biopolymer, poly(lactic acid) (PLA) or poly(ethylene glycol) (PEG), via electrospraying. The hybrid nanocarrier was subsequently combined with collagen to produce foam scaffolds. Bovine serum albumin (BSA), used as a model protein, was effectively loaded within the enlarged nanospheres. The biopolymer shell substantially prolonged the release period of BSA (2-3weeks from shelled nanospheres vs. within 1week from bare nanospheres), and the release rate was highly dependent on the shell composition (PEG>PLA). Collagen foam scaffolding of the shelled nanocarrier further slowed down the protein release, while enabling the incorporation of a rapidly releasing protein, which is effective for sequential protein delivery. Acidic fibroblast growth factor (aFGF), loaded onto the shelled-nanocarrier scaffolds, was released over a month at a highly sustainable rate, profiling a release pattern similar to that of BSA. The biological activity of the aFGF was evidenced by the significant proliferation of osteoblastic precursor cells in the aFGF-releasing scaffolds. Furthermore, the aFGF-delivering scaffolds implanted in rat subcutaneous tissue for 2weeks showed a substantially enhanced invasion of fibroblasts with a homogeneous population. Taken together, it is concluded that the biopolymer encapsulation of mesoporous nanospheres effectively prolongs the release of growth factors over weeks to a month, providing a nanocarrier platform for a long-term growth factor delivery. Moreover, the foam scaffolding of the nanocarrier system is a potential therapeutic three-dimensional matrix for cell culture and tissue engineering. Copyright © 2014 Acta Materialia Inc. Published by

  16. Growth factors with heparin binding affinity in human synovial fluid

    SciTech Connect

    Hamerman, D.; Taylor, S.; Kirschenbaum, I.; Klagsbrun, M.; Raines, E.W.; Ross, R.; Thomas, K.A.

    1987-12-01

    Synovial effusions were obtained from the knees of 15 subjects with joint trauma, menisceal or ligamentous injury, or osteoarthritis. Heparin-Sepharose affinity chromatography of these synovial fluids revealed, in general, three major peaks of mitogenic activity as measured by incorporation of /sup 3/H-thymidine into 3T3 cells. Gradient elution patterns showed activities at 0.5M NaCl, which is characteristic of platelet derived growth factor, and at 1.1 M NaCl and 1.6M NaCl, indicative of acidic and basic fibroblast growth factors, respectively. The identities of these mitogenic fractions were confirmed by specific immunologic and receptor-binding assays. The presence of platelet derived, acidic and basic fibroblast growth factors in the synovial fluid may contribute to wound healing in the arthritic joint.

  17. Effects of Growth Factors on Dental Stem/ProgenitorCells

    PubMed Central

    Kim, Sahng G.; Solomon, Charles; Zheng, Ying; Suzuki, Takahiro; Mo, Chen; Song, Songhee; Jiang, Nan; Cho, Shoko; Zhou, Jian; Mao, Jeremy J.

    2014-01-01

    Synopsis The primary goal of regenerative endodontics is to restore the vitality and functions of the dentin-pulp complex, as opposed to filing of the root canal with bioinert materials. Structural restoration is also important but is likely secondary to vitality and functions. Myriads growth factors regulate multiple cellular functions including migration, proliferation, differentiation and apoptosis of several cell types that are intimately involved in dentin-pulp regeneration: odontoblasts, interstitial fibroblasts, vascular-endothelial cells and sprouting nerve fibers. Recent work showing that growth factor delivery, without cell transplantation, can yield pulp-dentin like tissues in vivo provides one of the tangible pathways for regenerative endodontics. This review synthesizes our knowledge on a multitude of growth factors that are known or anticipated to be efficacious in dental pulp-dentin regeneration. PMID:22835538

  18. Heparin-conjugated gelatin as a growth factor immobilization scaffold.

    PubMed

    Nakamura, Shintaro; Kubo, Takafumi; Ijima, Hiroyuki

    2013-05-01

    Tissue engineering requires growth factors, cells and a scaffold to permit effective tissue regeneration. This study aimed to develop a scaffold with a focus on immobilizing growth factors within gelatin. We focused on the extracellular matrix and developed a heparin-conjugated gelatin (Hep-gela). Conjugation was confirmed using the alcian blue assay and X-ray diffraction patterns. The mechanical strength and stability of the Hep-gela gel in protease solution were improved compared with collagen gel. Hep-gela was able to immobilize vascular endothelial growth factor (VEGF) even in the presence of albumin, with an efficiency of 54.2%. Immobilized VEGF promoted proliferation of human umbilical vein endothelial cells. Hep-gela-immobilized VEGF maintained its native biological activity. In summary, Hep-gela has the potential to become an effective material in the field of regenerative medicine.

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

    SciTech Connect

    Story, M.T. )

    1989-05-01

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

  20. Insulin-like growth factors in the peripheral nervous system.

    PubMed

    Sakowski, Stacey A; Feldman, Eva L

    2012-06-01

    Insulin-like growth factors (IGFs) play an integral role in development, growth, and survival. This article details the current understanding of the effects of IGFs in the peripheral nervous system (PNS) during health and disease, and introduces how the IGF system regulates PNS development and impacts growth and survival of PNS cells. Also discussed are implications of IGF signaling in neurodegeneration and the status and prospects of IGF therapies for PNS conditions. There is substantial support for the application of IGF therapies in the treatment of PNS injury and disease.

  1. Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model.

    PubMed

    Santa Maria, Peter Luke; Weierich, Kendall; Kim, Sungwoo; Yang, Yunzhi Peter

    2015-08-01

    That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model. A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle. The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks. The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration. This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

  2. Resonant excitation of precursor molecules in improving the particle crystallinity, growth rate and optical limiting performance of carbon nano-onions

    NASA Astrophysics Data System (ADS)

    Gao, Y.; Zhou, Y. S.; Park, J. B.; Wang, H.; He, X. N.; Luo, H. F.; Jiang, L.; Lu, Y. F.

    2011-04-01

    A catalyst-free and highly efficient synthetic method for growing carbon nano-onions (CNOs) in open air has been developed through the laser resonant excitation of a precursor molecule, ethylene, in a combustion process. Highly concentric CNO particles with improved crystallinity were obtained at a laser wavelength of 10.532 µm through the resonant excitation of the CH2 wagging mode of the ethylene molecules. A higher growth rate up to 2.1 g h - 1 was obtained, compared with that without a laser (1.3 g h - 1). Formation of the CNOs with ordered graphitic shells is ascribed to the decomposition of polycyclic aromatic hydrocarbons (PAHs) into C2 species. The optical limiting performances of the CNOs grown by the combustion processes were investigated. CNOs grown at 10.532 µm laser excitation demonstrated improved optical limiting properties due to the improved crystallinity.

  3. Constructing a blood vessel on the porous scaffold modified with vascular endothelial growth factor and basic fibroblast growth factor

    NASA Astrophysics Data System (ADS)

    Sevostyanova, V. V.; Matveeva, V. G.; Antonova, L. V.; Velikanova, E. A.; Shabaev, A. R.; Senokosova, E. A.; Krivkina, E. O.; Vasyukov, G. Yu.; Glushkova, T. V.; Kudryavtseva, Yu. A.; Barbarash, O. L.; Barbarash, L. S.

    2016-11-01

    Incorporation of the growth factors into biodegradable polymers is a promising approach for the fabrication of tissue-engineered vascular grafts. Here we blended poly(ɛ-caprolactone) (PCL) with poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) following incorporation of either vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) and then fabricated electrospun 2 mm diameter vascular grafts. Grafts without the growth factors were used as a control group. Structure of the grafts was assessed utilizing scanning electron microscopy. We further implanted our grafts into rat abdominal aorta for 1 and 3 months with the aim to test endothelialization, cell infiltration, and patency in vivo. Histological and immunofluorescence examination demonstrated enhanced endothelialization and cell infiltration of the grafts with either VEGF or bFGF compared to those without the growth factors. Grafts with VEGF showed higher patency compared to those with bFGF; however, bFGF promoted migration of smooth muscle cells and fibroblasts into the graft. Therefore, we conclude that incorporation of VEGF and bFGF into the inner and medial/outer layer, respectively, can be a promising option for the fabrication of tissue-engineered vascular grafts.

  4. GEP, a local growth factor, is critical for odontogenesis and amelogenesis.

    PubMed

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q

    2010-11-25

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development.

  5. GEP, a Local Growth Factor, is Critical for Odontogenesis and Amelogenesis

    PubMed Central

    Cao, Zhengguo; Jiang, Baichun; Xie, Yixia; Liu, Chuan-ju; Feng, Jian Q.

    2010-01-01

    Granulin epithelin precursor (GEP) is a new growth factor that functions in brain development, chondrogenesis, tissue regeneration, tumorigenesis, and inflammation. The goal of this study was to study whether GEP was critical for odontogenesis and amelogenesis both in vivo and in vitro. The in situ hybridization and immunohistochemistry data showed that GEP was expressed in both odontoblast and ameloblast cells postnatally. Knockdown of GEP by crossing U6-ploxPneo-GEP and Sox2-Cre transgenic mice led to a reduction of dentin thickness, an increase in predentin thickness, and a reduction in mineral content in enamel. The in vitro application of recombinant GEP up-regulated molecular markers important for odontogenesis (DMP1, DSPP, and ALP) and amelogenesis (ameloblastin, amelogenin and enamelin). In conclusion, both the in vivo and the in vivo data support an important role of GEP in tooth formation during postnatal development. PMID:21152114

  6. Growth factor delivery to re-engineer periodontal tissues.

    PubMed

    Anusaksathien, Orasa; Giannobile, William V

    2002-06-01

    Repair of tooth-supporting structures destroyed by the chronic inflammatory disease periodontitis is a major goal of oral therapy. The field of tissue engineering combines materials science and biology to repair tissues and organs. Periodontal tissue engineering has been achieved with limited success by the utilization of guiding tissue (cell occlusive) membranes and bone grafting techniques. Over the past decade investigators have begun to utilize signaling molecules such as growth factors to restore lost tooth support due to periodontitis, the most common bone disease affecting humans. This review will provide information on the status of growth factor therapies being applied in periodontology to treat advanced alveolar bone loss.

  7. Growth mechanism of atomic-layer-deposited TiAlC metal gate based on TiCl4 and TMA precursors

    NASA Astrophysics Data System (ADS)

    Jinjuan, Xiang; Yuqiang, Ding; Liyong, Du; Junfeng, Li; Wenwu, Wang; Chao, Zhao

    2016-03-01

    TiAlC metal gate for the metal-oxide-semiconductor field-effect-transistor (MOSFET) is grown by the atomic layer deposition method using TiCl4 and Al(CH3)3(TMA) as precursors. It is found that the major product of the TiCl4 and TMA reaction is TiAlC, and the components of C and Al are found to increase with higher growth temperature. The reaction mechanism is investigated by using x-ray photoemission spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM). The reaction mechanism is as follows. Ti is generated through the reduction of TiCl4 by TMA. The reductive behavior of TMA involves the formation of ethane. The Ti from the reduction of TiCl4 by TMA reacts with ethane easily forming heterogenetic TiCH2, TiCH=CH2 and TiC fragments. In addition, TMA thermally decomposes, driving Al into the TiC film and leading to TiAlC formation. With the growth temperature increasing, TMA decomposes more severely, resulting in more C and Al in the TiAlC film. Thus, the film composition can be controlled by the growth temperature to a certain extent. Project supported by the Key Technology Study for 16/14 nm Program of the Ministry of Science and Technology of China (Grant No. 2013ZX02303).

  8. Placental Growth Factor Administration Abolishes Placental Ischemia-Induced Hypertension.

    PubMed

    Spradley, Frank T; Tan, Adelene Y; Joo, Woo S; Daniels, Garrett; Kussie, Paul; Karumanchi, S Ananth; Granger, Joey P

    2016-04-01

    Preeclampsia is a pregnancy-specific disorder of new-onset hypertension. Unfortunately, the most effective treatment is early delivery of the fetus and placenta. Placental ischemia appears central to the pathogenesis of preeclampsia because placental ischemia/hypoxia induced in animals by reduced uterine perfusion pressure (RUPP) or in humans stimulates release of hypertensive placental factors into the maternal circulation. The anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes and reduces bioavailable vascular endothelial growth factor and placental growth factor (PlGF), is elevated in RUPP rats and preeclampsia. Although PlGF and vascular endothelial growth factor are both natural ligands for sFlt-1, vascular endothelial growth factor also has high affinity to VEGFR2 (Flk-1) causing side effects like edema. PlGF is specific for sFlt-1. We tested the hypothesis that PlGF treatment reduces placental ischemia-induced hypertension by antagonizing sFlt-1 without adverse consequences to the mother or fetus. On gestational day 14, rats were randomized to 4 groups: normal pregnant or RUPP±infusion of recombinant human PlGF (180 μg/kg per day; AG31, a purified, recombinant human form of PlGF) for 5 days via intraperitoneal osmotic minipumps. On day 19, mean arterial blood pressure and plasma sFlt-1 were higher and glomerular filtration rate lower in RUPP than normal pregnant rats. Infusion of recombinant human PlGF abolished these changes seen with RUPP along with reducing oxidative stress. These data indicate that the increased sFlt-1 and reduced PlGF resulting from placental ischemia contribute to maternal hypertension. Our novel finding that recombinant human PlGF abolishes placental ischemia-induced hypertension, without major adverse consequences, suggests a strong therapeutic potential for this growth factor in preeclampsia. © 2016 American Heart Association, Inc.

  9. Cytokines and growth factors which regulate bone cell function

    NASA Astrophysics Data System (ADS)

    Seino, Yoshiki

    Everybody knows that growth factors are most important in making bone. Hormones enhance bone formation from a long distance. Growth factors promote bone formation as an autocrine or paracrine factor in nearby bone. BMP-2 through BMP-8 are in the TGF-β family. BMP makes bone by enchondral ossification. In bone, IGF-II is most abundant, second, TGF-β, and third IGF-I. TGF-β enhances bone formation mainly by intramembranous ossification in vivo. TGF-β affects both cell proliferation and differentiation, however, TGF-β mainly enhances bone formation by intramembranous ossification. Interestingly, TGF-β is increased by estrogen(E 2), androgen, vitamin D, TGF-β and FGF. IGF-I and IGF-II also enhance bone formation. At present it remains unclear why IGF-I is more active in bone formation than IGF-II, although IGF-II is more abundant in bone compared to IGF-I. However, if only type I receptor signal transduction promotes bone formation, the strong activity of IGF-I in bone formation is understandable. GH, PTH and E 2 promotes IGF-I production. Recent data suggest that hormones containing vitamin D or E 2 enhance bone formation through growth factors. Therefore, growth factors are the key to clarifying the mechanism of bone formation.

  10. Cystine knot growth factors and their functionally versatile proregions.

    PubMed

    Schwarz, Elisabeth

    2017-09-05

    The cystine knot disulfide pattern has been found to be widespread in nature, since it has been detected in proteins from plants, marine snails, spiders and mammals. Cystine knot proteins are secreted proteins. Their functions range from defense mechanisms as toxins, e.g. ion channel or enzyme inhibitors, to hormones, blood factors and growth factors. Cystine knot proteins can be divided into two superordinate groups. (i) The cystine knot peptides, also referred to - with other non-cystine knot proteins - as knottins, with linear and cyclic polypeptide chains. (ii) The cystine knot growth factor family, which is in the focus of this article. The disulfide ring structure of the cystine knot peptides is made up by the half-cystines 1-4 and 2-5, and the threading disulfide bond is formed by the half-cystines, 3-6. In the growth factor group, the disulfides of half-cystines 1 and 4 pass the ring structure formed by the half-cystines 2-5 and 3-6. In this review, special emphasis will be devoted to the growth factor cystine knot proteins and their proregions. The latter have shifted into the focus of scientific interest as their important biological roles are just to be unravelled.

  11. Temperature affects insulin-like growth factor I and growth of juvenile southern flounder, Paralichthys lethostigma.

    PubMed

    Luckenbach, J Adam; Murashige, Ryan; Daniels, Harry V; Godwin, John; Borski, Russell J

    2007-01-01

    Temperature profoundly influences growth of heterothermic vertebrates. However, few studies have investigated the effects of temperature on growth and insulin-like growth factor I (IGF-I) in fishes. The aim of this study was to examine effects of temperature on growth and establish whether IGF-I may mediate growth at different temperatures in southern flounder, Paralichthys lethostigma. In two experiments, juvenile flounder were reared at 23 and 28 degrees C and growth was monitored for either 117 or 197 days. Growth was similar across treatments in both experiments until fish reached approximately 100 mm total length. Body size then diverged with fish at 23 degrees C ultimately growing 65-83% larger than those at 28 degrees C. Muscle IGF-I mRNA, plasma IGF-I, and hepatosomatic index (HSI) were significantly higher in flounder at 23 degrees C, whereas hepatic IGF-I mRNA abundance did not differ with treatment. Muscle IGF-I mRNA was correlated with HSI, while plasma IGF-I was correlated with body size, hepatic IGF-I mRNA, and HSI. These results demonstrate a strong effect of temperature on flounder growth and show that temperature-induced variation in growth is associated with differences in systemic IGF-I and local (i.e., muscle) IGF-I mRNA levels. The results also support the use of plasma IGF-I and HSI as indicators of flounder growth status.

  12. Growth Factor Liberation and DPSC Response Following Dentine Conditioning.

    PubMed

    Sadaghiani, L; Gleeson, H B; Youde, S; Waddington, R J; Lynch, C D; Sloan, A J

    2016-10-01

    Liberation of the sequestrated bioactive molecules from dentine by the action of applied dental materials has been proposed as an important mechanism in inducing a dentinogenic response in teeth with viable pulps. Although adhesive restorations and dentine-bonding procedures are routinely practiced, clinical protocols to improve pulp protection and dentine regeneration are not currently driven by biological knowledge. This study investigated the effect of dentine (powder and slice) conditioning by etchants/conditioners relevant to adhesive restorative systems on growth factor solubilization and odontoblast-like cell differentiation of human dental pulp progenitor cells (DPSCs). The agents included ethylenediaminetetraacetic acid (EDTA; 10%, pH 7.2), phosphoric acid (37%, pH <1), citric acid (10%, pH 1.5), and polyacrylic acid (25%, pH 3.9). Growth factors were detected in dentine matrix extracts drawn by EDTA, phosphoric acid, and citric acid from powdered dentine. The dentine matrix extracts were shown to be bioactive, capable of stimulating odontogenic/osteogenic differentiation as observed by gene expression and phenotypic changes in DPSCs cultured in monolayer on plastic. Polyacrylic acid failed to solubilize proteins from powdered dentine and was therefore considered ineffective in triggering a growth factor-mediated response in cells. The study went on to investigate the effect of conditioning dentine slices on growth factor liberation and DPSC behavior. Conditioning by EDTA, phosphoric acid, and citric acid exposed growth factors on dentine and triggered an upregulation in genes associated with mineralized differentiation, osteopontin, and alkaline phosphatase in DPSCs cultured on dentine. The cells demonstrated odontoblast-like appearances with elongated bodies and long extracellular processes extending on dentine surface. However, phosphoric acid-treated dentine appeared strikingly less populated with cells, suggesting a detrimental impact on cell

  13. Inhibition of Epidermal Growth Factor Receptor Improves Myelination and Attenuates Tissue Damage of Spinal Cord Injury.

    PubMed

    Zhang, Si; Ju, Peijun; Tjandra, Editha; Yeap, Yeeshan; Owlanj, Hamed; Feng, Zhiwei

    2016-10-01

    Preventing demyelination and promoting remyelination of denuded axons are promising therapeutic strategies for spinal cord injury (SCI). Epidermal growth factor receptor (EGFR) inhibition was reported to benefit the neural functional recovery and the axon regeneration after SCI. However, its role in de- and remyelination of axons in injured spinal cord is unclear. In the present study, we evaluated the effects of EGFR inhibitor, PD168393 (PD), on the myelination in mouse contusive SCI model. We found that expression of myelin basic protein (MBP) in the injured spinal cords of PD treated mice was remarkably elevated. The density of glial precursor cells and oligodendrocytes (OLs) was increased and the cell apoptosis in lesions was attenuated after PD168393 treatment. Moreover, PD168393 treatment reduced both the numbers of OX42 + microglial cells and glial fibrillary acidic protein + astrocytes in damaged area of spinal cords. We thus conclude that the therapeutic effects of EGFR inhibition after SCI involves facilitating remyelination of the injured spinal cord, increasing of oligodendrocyte precursor cells and OLs, as well as suppressing the activation of astrocytes and microglia/macrophages.

  14. Nerve growth factor metabolic dysfunction in Alzheimer's disease and Down syndrome.

    PubMed

    Iulita, M Florencia; Cuello, A Claudio

    2014-07-01

    Alzheimer's disease (AD) is a devastating neurodegenerative condition and the most common type of amnestic dementia in the elderly. Individuals with Down syndrome (DS) are at increased risk of developing AD in adulthood as a result of chromosome 21 trisomy and triplication of the amyloid precursor protein (APP) gene. In both conditions, the central nervous system (CNS) basal forebrain cholinergic system progressively degenerates, and such changes contribute to the manifestation of cognitive decline and dementia. Given the strong dependency of these neurons on nerve growth factor (NGF), it was hypothesized that their atrophy was caused by NGF deficits. However, in AD, the synthesis of NGF is not affected at the transcript level and there is a marked increase in its precursor, proNGF. This apparent paradox remained elusive for many years. In this review, we discuss the recent evidence supporting a CNS deficit in the extracellular metabolism of NGF, both in AD and in DS brains. We describe the nature of this trophic disconnection and its implication for the atrophy of basal forebrain cholinergic neurons. We further discuss the potential of NGF pathway markers as diagnostic indicators of a CNS trophic disconnection.

  15. Enhanced bioavailability of nerve growth factor with phytantriol lipid-based crystalline nanoparticles in cochlea

    PubMed Central

    Bu, Meng; Tang, Jingling; Wei, Yinghui; Sun, Yanhui; Wang, Xinyu; Wu, Linhua; Liu, Hongzhuo

    2015-01-01

    Purpose Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route. Methods A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously. Results Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane. Conclusion Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants. PMID:26604754

  16. Growth and characterization of hydrogenated amorphous silicon thin films from SiH2 radical precursor: Atomic-scale analysis

    NASA Astrophysics Data System (ADS)

    Sriraman, Saravanapriyan; Aydil, Eray S.; Maroudas, Dimitrios

    2004-02-01

    Molecular-dynamics (MD) simulations of hydrogenated amorphous silicon (a-Si:H) film growth on an initially H-terminated Si(001)-(2×1) substrate at T=500 K was studied through repeated impingement of SiH2 radicals to elucidate the effects of this species on the structural quality of the deposited films. A detailed analysis of the radical-surface interaction trajectories revealed the important reactions contributing to film growth. These reactions include (i) adsorption of SiH2 onto the deposition surface, (ii) insertion of SiH2 into surface Si-Si bonds, (iii) surface dimerization of adsorbed SiH2 groups, (iv) formation of polysilane chains and islands, (SiH2)n, n⩾2, on the surface, (v) formation of higher surface hydrides through the exchange of hydrogen, and (vi) dangling-bond-mediated dissociation of surface hydrides. The MD simulations of a-Si:H film growth predict an overall surface reaction probability of 39% for the SiH2 radical. Structural and chemical characterization of the deposited films was carried out through a detailed analysis of the evolution of the structure of the film, surface morphology, and roughness, surface reactivity, and surface composition. The analysis revealed that the deposited films exhibit a high concentration of H and columnar surface morphologies. In particular, islands or polysilane chains form on the growth surface and are believed to be responsible for the columnar structural features in the deposited film. Such polysilane chain formation may have significant effects on the structural, morphological, and optical properties of the a-Si:H films.

  17. Vascular endothelial growth factors: A comparison between invertebrates and vertebrates.

    PubMed

    Kipryushina, Yulia O; Yakovlev, Konstantin V; Odintsova, Nelly A

    2015-12-01

    This review aims to summarize recent data concerning the structure and role of the members of the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) families in the context of early development, organogenesis and regeneration, with a particular emphasis on the role of these factors in the development of invertebrates. Homologs of VEGF and/or VEGFR have been found in all Eumetazoa, in both Radiata and Bilateria, where they are expressed in the descendants of different germ layers and play a pivotal role in the development of animals with and without a vascular system. VEGF is a well-known angiogenesis regulator, but this factor also control cell migration during neurogenesis and the development of branching organs (the trachea) in invertebrate and vertebrate species. A possible explanation for the origin of Vegf/Vegfr in the animal kingdom and a pathway of Vegf/Vegfr evolution are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. The Host Plant Metabolite Glucose Is the Precursor of Diffusible Signal Factor (DSF) Family Signals in Xanthomonas campestris

    PubMed Central

    Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan

    2015-01-01

    Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous addition of host plant juice or ethanol extract to the growth medium of X. campestris pv. campestris could significantly boost DSF family signal production. It was subsequently revealed that X. campestris pv. campestris produces not only DSF but also BDSF (cis-2-dodecenoic acid) and another novel DSF family signal, which was designated DSF-II. BDSF was originally identified in Burkholderia cenocepacia to be involved in regulation of motility, biofilm formation, and virulence in B. cenocepacia. Functional analysis suggested that DSF-II plays a role equal to that of DSF in regulation of biofilm dispersion and virulence factor production in X. campestris pv. campestris. Furthermore, chromatographic separation led to identification of glucose as a specific molecule stimulating DSF family signal biosynthesis in X. campestris pv. campestris. 13C-labeling experiments demonstrated that glucose acts as a substrate to provide a carbon element for DSF biosynthesis. The results of this study indicate that X. campestris pv. campestris could utilize a common metabolite of the host plant to enhance DSF family signal synthesis and therefore promote virulence. PMID:25681189

  19. The host plant metabolite glucose is the precursor of diffusible signal factor (DSF) family signals in Xanthomonas campestris.

    PubMed

    Deng, Yinyue; Liu, Xiaoling; Wu, Ji'en; Lee, Jasmine; Chen, Shaohua; Cheng, Yingying; Zhang, Chunyan; Zhang, Lian-Hui

    2015-04-01

    Plant pathogen Xanthomonas campestris pv. campestris produces cis-11-methyl-2-dodecenoic acid (diffusible signal factor [DSF]) as a cell-cell communication signal to regulate biofilm dispersal and virulence factor production. Previous studies have demonstrated that DSF biosynthesis is dependent on the presence of RpfF, an enoyl-coenzyme A (CoA) hydratase, but the DSF synthetic mechanism and the influence of the host plant on DSF biosynthesis are still not clear. We show here that exogenous addition of host plant juice or ethanol extract to the growth medium of X. campestris pv. campestris could significantly boost DSF family signal production. It was subsequently revealed that X. campestris pv. campestris produces not only DSF but also BDSF (cis-2-dodecenoic acid) and another novel DSF family signal, which was designated DSF-II. BDSF was originally identified in Burkholderia cenocepacia to be involved in regulation of motility, biofilm formation, and virulence in B. cenocepacia. Functional analysis suggested that DSF-II plays a role equal to that of DSF in regulation of biofilm dispersion and virulence factor production in X. campestris pv. campestris. Furthermore, chromatographic separation led to identification of glucose as a specific molecule stimulating DSF family signal biosynthesis in X. campestris pv. campestris. (13)C-labeling experiments demonstrated that glucose acts as a substrate to provide a carbon element for DSF biosynthesis. The results of this study indicate that X. campestris pv. campestris could utilize a common metabolite of the host plant to enhance DSF family signal synthesis and therefore promote virulence.

  20. Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor

    SciTech Connect

    Matsumoto, K.; Hashimoto, K.; Yoshikawa, K.; Nakamura, T. )

    1991-09-01

    Effect of hepatocyte growth factor (HGF) on normal human epidermal keratinocytes cultured under conditions of low Ca2+ (0.1 mM, growth-promoting condition) and physiological Ca2+ (1.8 mM, differentiation-promoting condition) was investigated. In low Ca2+, HGF markedly enhanced the migration of keratinocytes while it suppressed cell growth and DNA synthesis in a dose-dependent manner. In contrast, HGF enhanced the migration, cell growth, and DNA synthesis of keratinocytes cultured under conditions of physiological Ca2+. The maximal stimulation of DNA synthesis (2.4-fold stimulation) in physiological Ca2+ was seen at 2.5-5 ng/ml HGF and the stimulatory effect of HGF was suppressed by transforming growth factor-beta 1. Analysis of the HGF receptor using 125I-HGF as a ligand showed that human keratinocytes expressed a single class of specific, saturable receptor for HGF in both low and physiological Ca2+ conditions, exhibiting a Kd = 17.3 pM and approximately 690 binding sites/cell under physiological Ca2+. Thus, HGF is a potent factor which enhances growth and migration of normal human keratinocytes under conditions of physiological Ca2+. HGF may play an important role in epidermal tissue repair as it enhances both the migration and growth of keratinocytes.

  1. Differential in vitro phenotype pattern, transforming growth factor-beta(1) activity and mRNA expression of transforming growth factor-beta(1) in Apert osteoblasts.

    PubMed

    Locci, P; Baroni, T; Pezzetti, F; Lilli, C; Marinucci, L; Martinese, D; Becchetti, E; Calvitti, M; Carinci, F

    1999-09-01

    The phenotype of Apert osteoblasts differs from that of normal osteoblasts in the accumulation of macromolecules in the extracellular matrix. Apert osteoblasts increase type I collagen, fibronectin and glycosaminoglycans secretion compared with normal osteoblasts. Because the extracellular matrix macromolecule accumulation is greatly modulated by transforming growth factor-beta(1), we examined the ability of normal and Apert osteoblasts to secrete transforming growth factor-beta(1) by CCL-64 assay and to produce transforming growth factor-beta(1 )by analysis of the mRNA expression of transforming growth factor-beta(1). Northern blot analysis revealed an increased amount of transforming growth factor-beta(1) mRNA expression in Apert osteoblasts compared with normal ones. Moreover, the level of the active transforming growth factor-beta(1) isoform was higher in Apert than in normal media. In pathologic cells, the increase in transforming growth factor-beta(1) gene expression was associated with a parallel increase in the factor secreted into the medium. The level of transforming growth factor-beta(1) was decreased by the addition of basic fibroblast growth factor. Transforming growth factor-beta(1) is controlled temporally and spatially during skeletal tissue development and produces complex stimulatory and inhibitory changes in osteoblast functions. We hypothesise that in vitro differences between normal and Apert osteoblasts may be correlated to different transforming growth factor-beta(1) cascade patterns, probably due to an altered balance between transforming growth factor-beta(1) and basic fibroblast growth factor.

  2. Direct synthesis of thiolate-protected gold nanoparticles using Bunte salts as ligand precursors: investigations of ligand shell formation and core growth

    NASA Astrophysics Data System (ADS)

    Lohse, Samuel E.

    2011-12-01

    Applications of ligand-protected nanoparticles have increased markedly in recent years, yet their controlled synthesis remains an under-developed field. Nanoparticle syntheses are highly specialized in their execution and often possess significant limitations. For example, the synthesis of thiol-stabilized gold nanoparticles (AuNPs) with core diameters greater than 5.0 nm is difficult to achieve using existing methods. This dissertation describes the development of a synthetic strategy for thiolate-stabilized AuNPs over a wide range of core sizes using alkyl thiosulfates (Bunte salts) as ligand precursors. The use of Bunte salts permits the synthesis of larger AuNPs than can be achieved using thiols by allowing the AuNP cores to grow to larger diameters before the formation of the thiolate ligand shell. Chapter II details the development of a direct synthesis strategy using Bunte salts as ligand precursors that produces AuNPs with diameters up to 20 nm. Chapter III describes an investigation of the ligand shell formation that occurs during these syntheses. The ligand shell formation involves the adsorption of the Bunte salt to the AuNP surface, where it is converted to the thiolate. This conversion requires an excess of sodium borohydride in the synthesis of >5 nm AuNPs, but not for the synthesis of smaller AuNPs. This synthetic strategy was adapted for use in flow reactors to attain simultaneous AuNP synthesis and characterization. Chapter IV demonstrates that thiol-stabilized AuNPs can be synthesized in a microfluidic device with product monitoring provided by UV-vis absorbance spectroscopy. The development of a capillary flow reactor that permits the incorporation of new monitoring techniques is presented in Chapter V. The incorporation of Small-Angle X-ray Scattering (SAXS) analysis provides quantitative in situ determinations of AuNP diameter. The combination of synthetic control and monitoring makes capillary flow reactors powerful tools for optimization of

  3. Maternal insulin-like growth factor binding protein-1, body mass index, and fetal growth

    PubMed Central

    Holmes, R.; Holly, J; Soothill, P.

    2000-01-01

    AIM—To examine the hypothesis that the maternal insulin-like growth factor system may constrain fetal growth.
METHODS—A prospective observational study of maternal serum insulin-like growth factor binding protein-1 (IGFBP-1) and fetal growth was undertaken in neonates with birthweights below the 5th centile. They had been classified either as having fetal growth restriction (FGR) due to placental dysfunction (increased umbilical artery Doppler pulsatility index (PI); n = 25) or as being small for gestational age (SGA; normal umbilical artery PI, growth velocity and amniotic fluid; n = 27). Eighty nine controls had normal birthweights (5th-95th centile), umbilical artery PI, growth velocity, and amniotic fluid. IGFBP-1 was measured by radioimmunoassay.
RESULTS—Among the controls, there was no significant correlation between IGFBP-1 and birthweight after allowing for body mass index (BMI). Maternal BMI was high in FGR and after adjusting for this, IGFBP-1 was increased (109 ng/ml) compared with SGA babies (69ng/ml) and controls (57 ng/ml) and correlated with the umbilical artery PI.
CONCLUSIONS—Maternal IGFBP-1 is probably not part of normal placental function. Its increase in FGR could be the cause or consequence of impaired placental perfusion, but high IGFBP-1 concentrations might further reduce the availability of maternal IGF-I to the placenta. This could worsen placental function and so adversely affect fetal growth.
 PMID:10685983

  4. Selective decrease in axonal nerve growth factor and insulin-like growth factor I immunoreactivity in axonopathies of unknown etiology.

    PubMed

    Fressinaud, Catherine; Jean, Isabelle; Dubas, Frédéric

    2003-05-01

    In an attempt to approach the mechanisms underlying axonopathies of unknown etiology, we have studied by immunocytochemistry the fate of several growth factors in eight of such cases that we had previously analyzed by morphometry and which were characterized by a decrease in neurofilaments and an increase in beta tubulin immunostaining. Here we establish that, contrary to beta tubulin, growth-associated protein43 (GAP-43) immunolabeling is not up-regulated in theses cases, correlating well with the failure of regeneration. Neurotrophin-3 (NT-3) and its receptor TrkC were not modified compared to controls (five cases). On the contrary, we observed in all cases a pronounced decrease in the number of fibers labeled for nerve growth factor (NGF) and insulin-like growth factor I (IGF-I), which were both approximately half of control values. This decrease could not be ascribed to the reduction in fiber density since it was also present in cases without fiber loss (isolated large fiber atrophy). The fact that only around 50% of fibers were stained, versus all fibers in controls, probably accounted for this decrease. It contrasted also with the normality of NGF and IGF-I immunolabeling in six cases of chronic inflammatory demyelinating neuropathy that were investigated in parallel. These results differ from those reported in experimental diabetic neuropathy, during which NT-3 is also decreased. A deficient supply of specific growth factors delivered by neuronal targets may be responsible for these neuropathies and their associated axonal cytoskeleton abnormalities.

  5. Therapeutic potential of growth factors and their antagonists.

    PubMed Central

    Garner, A.

    1992-01-01

    This article describes studies with four peptides, epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), gastrin-releasing peptide/bombesin (GRP), and gastrin. The mitogenic and anti-secretory activities of EGF/TGF alpha appear to be mediated by a single class of high-affinity membrane receptors but may involve different signal transducing mechanisms. Biological activity of EGF resides in the N-terminal 42 amino acid fragment with the C-terminal undecapeptide determining binding affinity. A parenteral depot formulation of an EGF-related peptide or a small molecule agonist of the EGF receptor could have utility in treating various ulcerative disorders of the gut. Although antagonism of EGF (and thus TGF alpha) receptors and/or transducing mechanisms is frequently cited as a potential therapeutic approach to hyperproliferative diseases, blocking the action of TGF alpha, GRP, or gastrin with neutralizing antibodies or receptor antagonists did not influence the growth of a wide range of solid tumors in nude mice. These findings suggest that, unless tumor growth displays absolute dependency on one particular mitogen, antagonism of a specific growth factor is unlikely to have great effect in cancer therapy. PMID:1341074

  6. Role of various cytokines and growth factors in pubertal development.

    PubMed

    Casazza, Krista; Hanks, Lynae J; Alvarez, Jessica A

    2010-01-01

    Historical data suggest that body composition is intricately involved in pubertal development. Progression through puberty is dependent on the interaction between the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, reproductive and metabolic hormones as well as pro- and anti-inflammatory cytokines which induce alterations in feedback mechanisms and therefore mediate body composition and growth. Simultaneous increases in GH and IGF-1, and the concomitant changes in the hormonal milieu (i.e. reproductive hormones, testosterone and estrogen, and insulin)are the major contributors to anabolic effects seen throughout the pubertal transition, and are affected by various factors including (but not limited to) energy status and body composition. Orexigenic agents (i.e. ghrelin and leptin) also play a role at the level of the hypothalamus affecting not only energy intake, but also pubertal onset and progression. Effects of cytokines, many of which may be considered catabolic, extend beyond their traditionally viewed role involving the immune system, accompanying reproductive maturity further regulating aspects of energy and bone metabolism. As such, the signal(s) initiating the hypothalamic response that triggers puberty is likely reliant on a number of neural, metabolic and endocrine networks, all of which are at least partially influenced by pubertal growth factors, and act independently, antagonistically and/or synergistically to regulate anabolic pathways, therefore modifying body composition trajectory and growth during adolescence.

  7. Assessing the Factors of Regional Growth Decline of Sugar Maple

    NASA Astrophysics Data System (ADS)

    Bishop, D. A.; Beier, C. M.; Pederson, N.; Lawrence, G. B.; Stella, J. C.; Sullivan, T. J.

    2014-12-01

    Sugar maple (Acer saccharum Marsh) is among the most ecologically, economically and culturally important trees in North America, but has experienced a decline disease across much of its range. We investigated the climatic and edaphic factors associated with A. saccharum growth in the Adirondack Mountains (USA) using a well-replicated tree-ring network incorporating a range of soil fertility (base cation availability). We found that nearly 3 in 4 A. saccharum trees exhibited declining growth rates during the last several decades, regardless of tree age or size. Although diameter growth was consistently higher on base-rich soils, the negative trends in growth were largely consistent across the soil chemistry gradient. Sensitivity of sugar maple growth to climatic variability was overall weaker than expected, but were also non-stationary during the 20th century. We observed increasingly positive responses to late-winter precipitation, increasingly negative responses to growing season temperatures, and strong positive responses to moisture availability during the 1960s drought that became much weaker during the recent pluvial. Further study is needed of these factors and their interactions as potential mechanisms for sugar maple growth decline.

  8. Growth factors/cytokines/defensins and apoptosis in periodontal pathologies.

    PubMed

    Laurina, Zane; Pilmane, Mara; Care, Ruta

    2009-01-01

    In the recent past there has been an increased emphasis on morphogenetic tissue research of periodontal tissues. The aim of this study was to find qualitative and quantitative correlations in distribution and appearance of growth factors/cytokines/defensins and apoptosis in periodontal pathologies. Tissue was obtained from 5 controls and 6 chronical periodontitis patients 30-50 years of age referred to Latvian Institute of Stomatology. Histological investigations were performed at the Institute of Anatomy and Anthropology of Riga Stradins University. Epithelial cells abundantly expressed IL10 in patients. The expression of b-defensins was very variable in both sulcular and gingival epithelium. TUNEL positive cells were observed in patients and control specimens with dominance in control group. Gingival epithelium showed moderate expression of bFGF whereas few to moderate cells were positive for bFGF in sulcular epithelium. Fibroblast growth factor receptor (FGF-1R) was abundant in gingival epithelium and in connective tissue cells, but almost not detectable in sulcular epithelium. Insulin-like growth factor receptor was not expressed in gingival epithelium and was weakly seen in basal layer of sulcular epithelium. Basic nerve growth factor expresion in both types of epithelium was numerous to abundant. Staining for the NGFR in the gingival epithelium was variable, with prevalence to be moderate whereas sulcular epithelium was free from any factor immunoreactivity. 1. Finding of apoptotic cells are variable and seems to correlate with the expression of defensins in oral epithelium in patients with periodontitis. 2. FGFR was expressed more than the bFGF, but in case with NGFR and bNGF situation was opposite. Although IGFRI was found in sulcular epithelium with no expression in gingival one suggesting about stimulation in regeneration/adaptation in periodontitis affected tissue. 3. The expression of growth factors and their receptors in sulcular epithelium was lower

  9. Activation of Mechanosensitive Transcription Factors in Murine C2C12 Mesenchymal Precursors by Focused Low-Intensity Pulsed Ultrasound (FLIPUS).

    PubMed

    Puts, Regina; Rikeit, Paul; Ruschke, Karen; Kadow-Romacker, Anke; Hwang, Soyoung; Jenderka, Klaus-Vitold; Knaus, Petra; Raum, Kay

    2016-10-01

    In this paper, we investigated the mechanoresponse of C2C12 mesenchymal precursor cells to focused low-intensity pulsed ultrasound (FLIPUS). The setup has been developed for in vitro stimulation of adherent cells in the defocused far field of the ultrasound propagating through the bottom of the well plate. Twenty-four-well tissue culture plates, carrying the cell monolayers, were incubated in a temperature-controlled water tank. The ultrasound was applied at 3.6-MHz frequency, pulsed at 100-Hz repetition frequency with a 27.8% duty cycle, and calibrated at an output intensity of ISATA = 44.5 ±7.1 mW/cm(2). Numerical sound propagation simulations showed no generation of standing waves in the well plate. The response of murine C2C12 cells to FLIPUS was evaluated by measuring activation of mechanosensitive transcription factors, i.e., activator protein-1 (AP-1), specificity protein 1 (Sp1), and transcriptional enhancer factor (TEAD), and expression of mechanosensitive genes, i.e., c-fos, c-jun, heparin binding growth associated molecule (HB-GAM), and Cyr-61. FLIPUS induced 50% ( p ≤ 0.05 ) and 70% ( p ≤ 0.05 ) increases in AP-1 and TEAD promoter activities, respectively, when stimulated for 5 min. The Sp1 activity was enhanced by about 20% ( p ≤ 0.05 ) after 5-min FLIPUS exposure and the trend persisted for 30-min ( p ≤ 0.05 ) and 1-h ( p ≤ 0.05 ) stimulation times. Expressions of mechanosensitive genes c-fos ( p ≤ 0.05 ), c-jun ( p ≤ 0.05 ), HB-GAM ( p ≤ 0.05 ), and cystein-rich protein 61 ( p ≤ 0.05 ) were enhanced in response to 5-min FLIPUS stimulation. The increase in proliferation of C2C12s occurred after the FLIPUS stimulation ( p ≤ 0.05 ), with AP-1, Sp1, and TEAD possibly regulating the observed cellular activities.

  10. Heparin-Binding Epidermal Growth Factor-like Growth Factor/Diphtheria Toxin Receptor in Normal and Neoplastic Hematopoiesis

    PubMed Central

    Vinante, Fabrizio; Rigo, Antonella

    2013-01-01

    Heparin-binding EGF-like growth factor (HB-EGF) belongs to the EGF family of growth factors. It is biologically active either as a molecule anchored to the membrane or as a soluble form released by proteolytic cleavage of the extracellular domain. HB-EGF is involved in relevant physiological and pathological processes spanning from proliferation and apoptosis to morphogenesis. We outline here the main activities of HB-EGF in connection with normal or neoplastic differentiative or proliferative events taking place primitively in the hematopoietic microenvironment. PMID:23888518

  11. Growth factor delivery for oral and periodontal tissue engineering

    PubMed Central

    Kaigler, Darnell; Cirelli, Joni A; Giannobile, William V

    2008-01-01

    The treatment of oral and periodontal diseases and associated anomalies accounts for a significant proportion of the healthcare burden, with the manifestations of these conditions being functionally and psychologically debilitating. Growth factors are critical to the development, maturation, maintenance and repair of craniofacial tissues, as they establish an extracellular environment that is conducive to cell and tissue growth. Tissue-engineering principles aim to exploit these properties in the development of biomimetic materials that can provide an appropriate microenvironment for tissue development. These materials have been constructed into devices that can be used as vehicles for delivery of cells, growth factors and DNA. In this review, different mechanisms of drug delivery are addressed in the context of novel approaches to reconstruct and engineer oral- and tooth-supporting structures, namely the periodontium and alveolar bone. PMID:16948560

  12. Role of fibroblast growth factors in organ regeneration and repair.

    PubMed

    El Agha, Elie; Kosanovic, Djuro; Schermuly, Ralph T; Bellusci, Saverio

    2016-05-01

    In its broad sense, regeneration refers to the renewal of lost cells, tissues or organs as part of the normal life cycle (skin, hair, endometrium etc.) or as part of an adaptive mechanism that organisms have developed throughout evolution. For example, worms, starfish and amphibians have developed remarkable regenerative capabilities allowing them to voluntarily shed body parts, in a process called autotomy, only to replace the lost parts afterwards. The bizarre myth of the fireproof homicidal salamander that can survive fire and poison apple trees has persisted until the 20th century. Salamanders possess one of the most robust regenerative machineries in vertebrates and attempting to draw lessons from limb regeneration in these animals and extrapolate the knowledge to mammals is a never-ending endeavor. Fibroblast growth factors are potent morphogens and mitogens that are highly conserved among the animal kingdom. These growth factors play key roles in organogenesis during embryonic development as well as homeostatic balance during postnatal life. In this review, we provide a summary about the current knowledge regarding the involvement of fibroblast growth factor signaling in organ regeneration and repair. We also shed light on the use of these growth factors in previous and current clinical trials in a wide array of human diseases.

  13. Controlled growth factor release from synthetic extracellular matrices

    NASA Astrophysics Data System (ADS)

    Lee, Kuen Yong; Peters, Martin C.; Anderson, Kenneth W.; Mooney, David J.

    2000-12-01

    Polymeric matrices can be used to grow new tissues and organs, and the delivery of growth factors from these matrices is one method to regenerate tissues. A problem with engineering tissues that exist in a mechanically dynamic environment, such as bone, muscle and blood vessels, is that most drug delivery systems have been designed to operate under static conditions. We thought that polymeric matrices, which release growth factors in response to mechanical signals, might provide a new approach to guide tissue formation in mechanically stressed environments. Critical design features for this type of system include the ability to undergo repeated deformation, and a reversible binding of the protein growth factors to polymeric matrices to allow for responses to repeated stimuli. Here we report a model delivery system that can respond to mechanical signalling and upregulate the release of a growth factor to promote blood vessel formation. This approach may find a number of applications, including regeneration and engineering of new tissues and more general drug-delivery applications.

  14. The Study of the Enrollment Growth Factor. Final Report.

    ERIC Educational Resources Information Center

    Whitney, Terry N.; And Others

    This paper presents findings of a study that examined the New Mexico school-finance formula. Specifically, the study assessed the adequacy of the enrollment growth factor (EGF) and its differential impact on New Mexico school districts that grow at different rates. An EGF refers to some type of weighting in a state's basic aid formula to reflect…

  15. Sulodexide induces hepatocyte growth factor release in humans.

    PubMed

    Borawski, Jacek; Dubowski, Miroslaw; Pawlak, Krystyna; Mysliwiec, Michal

    2007-03-08

    Heparin influences numerous pleiotropic growth factors, including hepatocyte growth factor (HGF), partially by their release from endothelial and extracellular matrix stores. The effects of sulodexide, a heparin-like glycosaminoglycan medication of growing importance in medicine, on HGF liberation are not known. We performed a 2-week open-label sulodexide trial in healthy male volunteers. The drug was initially administered intravenously (i.v.) in a single dose of 1200 Lipoprotein Lipase Releasing Units (LRU), then -- orally for 12 days (500 LRU twice a day), and -- again by i.v. route (1200 LRU) on day 14. Intravenous sulodexide injections were repeatedly found to induce marked and reproducible increases in immunoreactive plasma HGF levels (more than 3500% vs baseline after 10 min, and more than 1200% after 120 min), and remained unchanged when measured 120 min following oral sulodexide administration. The percentage increments in plasma HGF evoked by i.v. sulodexide at both time points and on both days inversely correlated with baseline levels of the growth factor. On day 14, the HGF levels after 120 min and their percentage increase vs baseline were strongly and directly dependent on i.v. sulodexide dose per kg of body weight. This study shows that sulodexide has a novel, remarkable and plausibly biologically important stimulating effect on the release of pleiotropic hepatocyte growth factor in humans.

  16. Mitochondrial respiratory control is lost during growth factor deprivation

    PubMed Central

    Gottlieb, Eyal; Armour, Sean M.; Thompson, Craig B.

    2002-01-01

    The ability of cells to maintain a bioenergetically favorable ATP/ADP ratio confers a tight balance between cellular events that consume ATP and the rate of ATP production. However, after growth factor withdrawal, the cellular ATP/ADP ratio declines. To investigate these changes, mitochondria from growth factor-deprived cells isolated before the onset of apoptosis were characterized in vitro. Mitochondria from growth factor-deprived cells have lost their ability to undergo matrix condensation in response to ADP, which is accompanied by a failure to perform ADP-coupled respiration. At the time of analysis, mitochondria from growth factor-deprived cells were not depleted of cytochrome c and cytochrome c-dependent respiration was unaffected, demonstrating that the inhibition of the respiratory rate is not due to loss of cytochrome c. Agents that disrupt the mitochondrial outer membrane, such as digitonin, or maintain outer membrane exchange of adenine nucleotide, such as Bcl-xL, restored ADP-dependent control of mitochondrial respiration. Together, these data suggest that the regulation of mitochondrial outer membrane permeability contributes to respiratory control. PMID:12228733

  17. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  18. Fibroblast Growth Factor-2 Alters the Nature of Extinction

    ERIC Educational Resources Information Center

    Graham, Bronwyn M.; Richardson, Rick

    2011-01-01

    These experiments examined the effects of the NMDA-receptor (NMDAr) antagonist MK801 on reacquisition and re-extinction of a conditioned fear that had been previously extinguished before injection of fibroblast growth factor-2 (FGF2) or vehicle. Recent findings have shown that relearning and re-extinction, unlike initial learning and extinction,…

  19. Neurodevelopmental effects of insulin-like growth factor signaling

    PubMed Central

    O’Kusky, John; Ye, Ping

    2012-01-01

    Insulin-like growth factor (IGF) signaling greatly impacts the development and growth of the central nervous system (CNS). IGF-I and IGF-II, two ligands of the IGF system, exert a wide variety of actions both during development and in adulthood, promoting the survival and proliferation of neural cells. The IGFs also influence the growth and maturation of neural cells, augmenting dendritic growth and spine formation, axon outgrowth, synaptogenesis, and myelination. Specific IGF actions, however, likely depend on cell type, developmental stage, and local microenvironmental milieu within the brain. Emerging research also indicates that alterations in IGF signaling likely contribute to the pathogenesis of some neurological disorders. This review summarizes experimental studies and shed light on the critical roles of IGF signaling, as well as its mechanisms, during CNS development. PMID:22710100

  20. Brain-Derived Neurotrophic Factor Induces Cell Survival and the Migration of Murine Adult Hippocampal Precursor Cells During Differentiation In Vitro.

    PubMed

    Ortiz-López, Leonardo; Vega-Rivera, Nelly Maritza; Babu, Harish; Ramírez-Rodríguez, Gerardo Bernabé

    2017-01-01

    The generation of new neurons during adulthood involves local precursor cell migration and terminal differentiation in the dentate gyrus. These events are influenced by the hippocampal microenvironment. Brain-derived neurotrophic factor (BDNF) is relevant for hippocampal neuronal development and behavior. Interestingly, studies that have been performed in controlled in vitro systems that involve isolated precursor cells that were derived from the dentate gyrus (AHPCs) have shown that BDNF induces the activation of the TrkB receptor and, consequentially, might activate signaling pathways that favor survival and neuronal differentiation. Based on the fact that the cellular events of AHPCs that are induced by single factors can be studied in this controlled in vitro system, we investigated the ability of BDNF and the involvement of protein kinase C (PKC), as one of the TrkB-downstream activated signaling proteins, in the regulation of migration, here reflected by motility, of AHPCs. Precursor cells were cultured following a concentration-response curve (1-640 ng/ml) for 24 or 96 h. We found that BDNF favored cell survival without altering the viability under culture proliferative conditions of the AHPCs. Concomitantly, glial- and neuronal-differentiated precursor cells increased as a consequence of survival promoted by BDNF. Additionally, pharmacological approaches showed that BDNF (40 ng/ml)-induced migration of AHPCs was blocked with the compounds K252a and GF109203x, which prevent the activation of TrkB and PKC, respectively. The results indicate that in the in vitro migration of differentiated AHPCs it is involved the BDNF and TrkB cascade. Our results provide additional information about the mechanism by which BDNF impacts adult neurogenesis in the hippocampus.

  1. Stimulation of body weight increase and epiphyseal cartilage growth by insulin like growth factor

    NASA Technical Reports Server (NTRS)

    Ellis, S.

    1981-01-01

    The ability of insulin-like growth factor (IGF) to induce growth in hypophysectomized immature rats was tested by continuous infusion of the partially purified factor at daily doses of 6, 21, and 46 mU for an 8-day period. A dose-dependent growth of the proximal epiphyseal cartilage of the tibia and an associated stimulation of the primary spongiosa were produced by these amounts of IGF. The two highest doses of IGF also resulted in dose-dependent increases of body weight. Gel permeation of the sera at neutrality showed that the large-molecular-weight IGF binding protein was not induced by the infusion of IGF, whereas it ws generated in the sera of hypophysectomized rats that were infused with daily doses of 86 mU of human growth hormone.

  2. Auxins as one of the factors of plant growth improvement by plant growth promoting rhizobacteria.

    PubMed

    Ahmed, Ambreen; Hasnain, Shahida

    2014-01-01

    Plant growth promoting rhizobacteria (PGPR) promote plant growth by various mechanisms such as phytohormone production, enhanced water and nutrient uptake, improved nitrogen availability in the soil, production of ACC-deaminase for ethylene breakdown, phosphate solubilization, siderophore production etc. Microbial auxin production is the major factor not only responsible for strengthening the plant-microbe relationship but it also promotes plant growth and development in a positive manner. Thus, bacterial auxin production potential can be exploited for plant growth improvement that may be effective in reducing the hazardous effects of chemical fertilizers on the ecosystem used to obtain higher yields. The present review gives a better understanding of various factors and mechanisms involved in auxin production by PGPR that may be helpful in proper exploitation of these natural resources in a beneficial way.

  3. Steady impact factor growth for MDPI open access journals.

    PubMed

    Thiesen, Alexander

    2012-09-12

    For the past three years MDPI has announced the newly released impact factors for its Open Access journals by the means of an annual editorial [1-3]. In 2012 we are-once again-pleased to report that the growth of the impact factors of MDPI's Open Access journals continues. This year's edition of the Journal Citation Reports (JCR), which is published annually by Thomson Reuters, includes 10 journals published by MDPI, including three that have received their first official Impact Factors- International Journal of Environmental Research and Public Health (IJERPH), Materials Nutrients. Table 1 reports the latest Impact Factors for 2011. Figure 1 graphically depicts the evolution of the Impact Factors for four MDPI open access journals that have received Impact Factors in the past. Table 2 reports the ranking of the MDPI journals within the subject categories of the Science Citation Index Expanded.

  4. Acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors for atopic dermatitis in pediatric patients.

    PubMed

    Hon, Kam Lun; Pong, Nga Hin; Wang, Shuxin Susan; Lee, Vivian W; Luk, Nai Ming; Leung, Ting Fan

    2013-03-01

    Atopic eczema or dermatitis (AD) is associated with atopy and is characterized by reduced skin hydration and an impaired skin barrier in the epidermis. We investigated the patient acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors (LMF) in AD. Consecutive AD patients were recruited. Swabs and cultures were obtained from the right antecubital fossa and the worst-affected eczematous area, and disease severity [according to the SCORing Atopic Dermatitis (SCORAD) Index], skin hydration, and transepidermal water loss (TEWL) were measured prior to and after 2 weeks' use of the LMF moisturizer. The general acceptability of treatment was documented as being 'very good', 'good', 'fair', or 'poor'. Twenty-four AD patients [mean age 13.8 (standard deviation 5.7) years] were recruited. Two thirds of the patients reported very good or good acceptability of the LMF moisturizer, whereas one third reported fair or poor acceptability. There were no inter-group differences in the pre-use clinical parameters of age, objective SCORAD score, pruritus score, sleep disturbance score, skin hydration, TEWL, topical corticosteroid use, oral antihistamine use, or acceptability of previously used proprietary emollients. However, patients in the fair/poor acceptability group were more likely to have Staphylococcus aureus colonization and to be female (odds ratio 13, 95 % confidence interval 1.7-99.4; p = 0.021). Following use of the LMF moisturizer, the objective SCORAD score, pruritus score, and sleep disturbance score were lower in the very good/good acceptability group than in the fair/poor acceptability group. The mean objective SCORAD score improved (from 31.5 to 25.7; p = 0.039) and skin hydration improved [from 30.7 arbitrary units (a.u.) to 36.0 a.u.; p = 0.021] in the very good/good acceptability group. When the data were analyzed for the strength of the agreement of the rating of acceptability, the κ values were 0.338 (fair) for

  5. The effects of precursor concentration and thermal annealing on the growth of zinc oxide nanostructures grown on silicon substrate

    NASA Astrophysics Data System (ADS)

    Paculba, H. M. D.; Alguno, A. C.; Vequizo, R. M.

    2015-06-01

    This study focuses on the growth of Zinc Oxide (ZnO) nanostructures on SiO2/Si(100) substrate via chemical bath deposition (CBD) with varying NH4OH concentration and annealing temperature. The grown ZnOnanostructures were characterized via SEM-EDS for the surface morphology and elemental composition and UV-Vis spectroscopy for the reflectance measurement. Increasing the concentration of NH4OH produced denser ZnOnanostructures composed of rods having smaller diameter. It is believed that at higher concentration of NH4OH, more Zn(OH)2 seed will act as nucleation site for ZnOformation which suggests higher probability of ZnOgrowth. Thermal annealing increased the average diameter of ZnOnanorods. Annealing provided enough energy for unstable atoms to rearrange into a more suitable position. This would result to larger rods that have been formed in expense of the smaller rods. Furthermore, it is confirmed in the UV-Vis spectroscopy results that ZnOnanostructures were successfully grown on SiO2/Si(100) substrate. This successful growth of ZnOnanostructures is a promising material for solar cell technology.

  6. Effect of growth temperature on composition control for vapor deposition of YBa{sub 2}Cu{sub 3}O{sub 7−δ} precursor films

    SciTech Connect

    Liu, Chong; Wang, Lianhong; Shu, Yonghua; Fan, Jing

    2014-12-09

    This work aims at exploiting the role of growth temperature on the dynamic behavior of deposition atoms as well as its resultant impact on the composition control during the synthesis of YBa{sub 2}Cu{sub 3}O{sub 7−δ} precursor films by vapor codeposition. The codeposition of Yt, BaF{sub 2} and Cu is performed in vacuum chamber under a wide range of growth temperature from 25°C to 600°C, the mass of each element deposited on LaAlO{sub 3} substrate and thus the film composition is examined by the inductively coupled plasma atomic emission spectroscopy. It is shown that the deposition amount of Cu decreases obviously with the increase of growth temperature; however, the mass of Yt and BaF{sub 2} deposited on the substrate appears to be insensitive to growth temperature. Moreover, high temperature may also trigger the influence of adsorbates composition on Cu desorption, and therefore the deposition amount of Cu decreases almost linearly as the mol fraction of BaF{sub 2} in the adlayers increases. Nevertheless, when the deposition is conducted at room temperature, the influence of mol fraction of BaF{sub 2} on Cu desorption vanishes. The detailed mechanisms associated with above phenomena are unveiled by molecular dynamics analysis, additionally the physical picture about adsorption behaviors on the growing interface under different deposition conditions is summarized, which is valuable for handling the composition control during the vapor codeposition of different functional films.

  7. Gelatin Methacrylate Microspheres for Growth Factor Controlled Release

    PubMed Central

    Nguyen, Anh H.; McKinney, Jay; Miller, Tobias; Bongiorno, Tom; McDevitt, Todd C.

    2014-01-01

    Gelatin has been commonly used as a delivery vehicle for various biomolecules for tissue engineering and regenerative medicine applications due to its simple fabrication methods, inherent electrostatic binding properties, and proteolytic degradability. Compared to traditional chemical cross-linking methods, such as the use of glutaraldehyde (GA), methacrylate modification of gelatin offers an alternative method to better control the extent of hydrogel cross-linking. Here we examined the physical properties and growth factor delivery of gelatin methacrylate (GMA) microparticles formulated with a wide range of different cross-linking densities (15–90%). Less methacrylated MPs had decreased elastic moduli and larger mesh sizes compared to GA MPs, with increasing methacrylation correlating to greater moduli and smaller mesh sizes. As expected, an inverse correlation between microparticle cross-linking density and degradation was observed, with the lowest cross-linked GMA MPs degrading at the fastest rate, comparable to GA MPs. Interestingly, GMA MPs at lower cross-linking densities could be loaded with up to a 10-fold higher relative amount of growth factor over conventional GA cross-linked MPs, despite an order of magnitude greater gelatin content of GA MPs. Moreover, a reduced GMA cross-linking density resulted in more complete release of bone morphogenic protein 4 (BMP4) and basic fibroblast growth factor (bFGF) and accelerated release rate with collagenase treatment. These studies demonstrate that GMA MPs provide a more flexible platform for growth factor delivery by enhancing the relative binding capacity and permitting proteolytic degradation tunability, thereby offering a more potent controlled release system for growth factor delivery. PMID:25463489

  8. Expression of protooncogenes during lymphocyte activation by growth factors.

    PubMed

    Bulanova, E G; Budagyan, V M; Yarilin, A A; Mazurenko, N N

    1997-09-01

    Effects of growth factors of non-immune origin including somatotropin (ST) and platelet-derived growth factor (PDGF) on the expression of the proteins encoded by c-fos, c-myc, c-fun, and c-ets family protooncogenes were studied for the first time. The dynamics of the oncoprotein expression in activated CD(3+)-lymphocytes was investigated by immunoblotting. The accumulation of the Fos and Myc proteins was enhanced in T-lymphocytes treated with ST, PDGF, or phytohemagglutinin; the accumulation was maximum at 30-60 min and decreased in 2 h; the data indicate that the oncoproteins participate in the early lymphocyte activation by various growth factors. The Jun protein appears only in 3 h after the onset of lymphocyte activation; this suggests independent participation of Fos in the early stages of lymphocyte activation prior to the appearance of Jun, preceding the joint action of Fos and Jun within the AP-1 transcription complex. The products of the c-ets family are differentially activated by the studied growth factors. Resting lymphocytes actively accumulate the Ets-1 protein; ST and PDGF activation decreases Ets-1 expression in 2 h. The Ets-2 protein is not detected in resting cells and PDGF-activated lymphocytes, whereas lymphocyte activation by ST is associated with accumulation of Ets-2. The data suggest that the product of the c-ets-1 gene is more important in the regulation of resting cells and the product of the c-ets-2 gene is important during activation of lymphocytes by ST. The results indicate that activation of lymphocytes with growth factors of non-immune origin is mediated by several signal transduction pathways.

  9. Role of hypoxia and vascular endothelial growth factors in lymphangiogenesis

    PubMed Central

    Morfoisse, Florent; Renaud, Edith; Hantelys, Fransky; Prats, Anne-Catherine; Garmy-Susini, Barbara

    2014-01-01

    Hypoxia is known to be a major factor in the induction of angiogenesis during tumor development but its role in lymphangiogenesis remains unclear. Blood and lymphatic vasculatures are stimulated by the vascular endothelial family of growth factors – the VEGFs. In this review, we investigate the role of hypoxia in the molecular regulation of synthesis of the lymphangiogenic growth factors VEGF-A, VEGF-C, and VEGF-D. Gene expression can be regulated by hypoxia at either transcriptional or translational levels. In contrast to strong induction of DNA transcription by hypoxia-inducible factors (HIFs), the majority of cellular stresses such as hypoxia lead to inhibition of cap-dependent translation of mRNA and downregulation of protein synthesis. Here, we describe how initiation of translation of VEGF mRNA is induced by hypoxia through an internal ribosome entry site (IRES)-dependent mechanism. Considering the implications of the lymphatic vasculature for metastatic dissemination, it is crucial to understand the molecular regulation of lymphangiogenic growth factors by hypoxia to obtain new insights into cancer therapy. PMID:27308316

  10. [Nerve growth factor in neurodegeneration and neurorestorative therapy].

    PubMed

    Lorigados-Pedre, L; Bergado-Rosado, J

    The purpose of this work was to gather the information currently available about the content of nerve growth factor (NGF) in experimental models of neurodegeneration and in neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases, as well as to analyse how NGF content is affected by the application of different neurorestorative therapies (transplant and trophic therapy) in these neurological entities. Neurotrophins are proteins that promote the differentiation, growth and survival of many populations of peripheral neurons and the central nervous system during development and adulthood. NGF is the best known and most widely researched member of this family, which is also made up of the growth factor derived from the brain and neurotrophins 3, 4/5, 6 and 7. In the last few decades, significant progress has been made in the knowledge available about the biological role played by these factors, their molecular characterisation and regulation, as well as their signalling mechanisms. Yet, little is known about the role played by the neurotrophic factors in neurodegenerative diseases or whether the levels of these factors are modified following the use of neurorestorative treatment. Neurodegenerative disorders, especially Parkinson and Alzheimer, are accompanied by modifications in the levels of NGF that depend on the extent to which the disease has progressed. A model of the changes in NGF content during neurodegenerative processes is also proposed.

  11. Hepatocyte growth factor counteracts transforming growth factor-beta1, through attenuation of connective tissue growth factor induction, and prevents renal fibrogenesis in 5/6 nephrectomized mice.

    PubMed

    Inoue, Tsutomu; Okada, Hirokazu; Kobayashi, Tatsuya; Watanabe, Yusuke; Kanno, Yoshihiko; Kopp, Jeffrey B; Nishida, Takashi; Takigawa, Masaharu; Ueno, Munehisa; Nakamura, Toshikazu; Suzuki, Hiromichi

    2003-02-01

    We investigated the mechanism of the anti-fibrotic effects of hepatocyte growth factor (HGF) in the kidney, with respect to its effect on connective tissue growth factor (CTGF), a down-stream, profibrotic mediator of transforming growth factor-beta1 (TGF-beta1). In wild-type (WT) mice with 5/6 nephrectomy (Nx), HGF and TGF-beta1 mRNAs increased transiently in the remnant kidney by week 1 after the Nx, returned to baseline levels, and increased again at weeks 4 to 12. In contrast, CTGF and alpha1(I) procollagen (COLI) mRNAs increased in parallel with HGF and TGF-beta1 during the early stage, but did not re-increase during the late stage. In the case of TGF-beta1 transgenic (TG) mice with 5/6 Nx, excess TGF-beta1 derived from the transgene enhanced CTGF expression significantly in the remnant kidney, accordingly accelerating renal fibrogenesis. Administration of dHGF (5.0 mg/kg/day) to TG mice with 5/6 Nx for 4 weeks from weeks 2 to 6 suppressed CTGF expression in the remnant kidney, attenuating renal fibrosis and improving the survival rate. In an experiment in vitro, renal tubulointerstitial fibroblasts (TFB) were co-cultured with proximal tubular epithelial cells (PTEC). Pretreatment with HGF reduced significantly CTGF induction in PTEC by TGF-beta1, consequently suppressing COLI synthesis in TFB. In conclusion, HGF can block, at least partially, renal fibrogenesis promoted by TGF-beta1 in the remnant kidney, via attenuation of CTGF induction.

  12. N-Acetylcysteine, a glutathione precursor, reverts vascular dysfunction and endothelial epigenetic programming in intrauterine growth restricted guinea pigs.

    PubMed

    Herrera, Emilio A; Cifuentes-Zúñiga, Francisca; Figueroa, Esteban; Villanueva, Cristian; Hernández, Cherie; Alegría, René; Arroyo-Jousse, Viviana; Peñaloza, Estefania; Farías, Marcelo; Uauy, Ricardo; Casanello, Paola; Krause, Bernardo J

    2017-02-15

    Intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial epigenetic programming of the umbilical vessels. There is no evidence that this epigenetic programming is occurring on systemic fetal arteries. In IUGR guinea pigs we studied the functional and epigenetic programming of endothelial nitric oxide synthase (eNOS) (Nos3 gene) in umbilical and systemic fetal arteries, addressing the role of oxidative stress in this process by maternal treatment with N-acetylcysteine (NAC) during the second half of gestation. The present study suggests that IUGR endothelial cells have common molecular markers of programming in umbilical and systemic arteries. Notably, maternal treatment with NAC restores fetal growth by increasing placental efficiency and reverting the functional and epigenetic programming of eNOS in arterial endothelium in IUGR guinea pigs. In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetylcysteine (NAC) on fetal endothelial function and endothelial nitric oxide synthase (eNOS) programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, half of the sows receiving NAC in the drinking water (from day 34 until term). Fetal biometry and placental vascular resistance were followed by ultrasound throughout gestation. At term, umbilical arteries and fetal aortae were isolated to assess endothelial function by wire-myography. Primary cultures of endothelial cells (ECs) from fetal aorta, femoral and umbilical arteries were used to determine eNOS mRNA levels by quantitative PCR and analyse DNA methylation in the Nos3 promoter by pyrosequencing. Doppler ultrasound measurements showed that NAC reduced placental vascular resistance

  13. Vascular Endothelial growth factor signaling in hypoxia and Inflammation

    PubMed Central

    Ramakrishnan, S.; Anand, Vidhu; Roy, Sabita

    2014-01-01

    Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by reprogramming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions. PMID:24610033

  14. [Fibroblast growth factors and their effects in pancreas organogenesis].

    PubMed

    Gnatenko, D A; Kopantzev, E P; Sverdlov, E D

    2017-05-01

    Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells. Alterations in FGF/FGFR signaling pathway during this process lead to incorrect activation of the master genes, which leads to different pathologies during pancreas development. Understanding the full picture about role of FGF factors in pancreas development will make it possible to more accurately understand their role in other pathologies of this organ, including carcinogenesis.

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

    SciTech Connect

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

    1988-07-01

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

  16. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis.

    PubMed

    Relf, M; LeJeune, S; Scott, P A; Fox, S; Smith, K; Leek, R; Moghaddam, A; Whitehouse, R; Bicknell, R; Harris, A L

    1997-03-01

    Angiogenesis is a significant prognostic factor in breast cancer, but the factors that control angiogenesis in vivo are not well defined. Multiple angiogenic polypeptides are known, and we have determined the expression of seven of these in primary human breast cancers; the relationship of expression to estrogen receptor and vascular density was also examined. Vascular endothelial growth factor (VEGF) and its four isoforms (121, 165, 189, and 206 amino acids), transforming growth factor (TGF)-beta1, pleiotrophin, acidic and basic fibroblast growth factor (FGF), placental growth factor, and thymidine phosphorylase (platelet-derived endothelial cell growth factor) were quantitated by RNase protection analysis. beta-FGF was also measured by ELISA. The estrogen receptor (ER), epidermal growth factor receptor, and vascular density were analyzed in 64 primary breast cancers. All tumors expressed at least six different vascular growth factors. VEGF was most abundant, and the transcript for the 121-amino acid form predominated. Other angiogenic factors expressed at high levels were thymidine phosphorylase and TGF-beta1. Expression of most of the angiogenic factors did not correlate with that of ER or vascular density. However, thymidine phosphorylase did, with a correlation coefficient of 0.3 (P = 0.03). There were significant associations of pleiotrophin with acidic FGF expression (P = 0.001) and TGF-beta with platelet-derived endothelial cell growth factor expression (P = 0.001). Thus, angiogenesis may involve a coordinate regulation of some vascular growth factors. High VEGF expression correlated with poor prognosis in univariate analysis (P = 0.03), as did ER and epidermal growth factor receptor expression. Basic FGF was also assessed by ELISA and was more highly expressed in tumors than normal breast tissues (median, 346 microg/ml cytosol; range, 54-1323 versus median, 149; range, 32-509; P = 0.01). Implications for therapy are that broad spectrum agents that block

  17. [The influence of fibroblast growth factor (FGF2) on cardiomyocytes differentiation of mesenchymal stem cells of bone marrow ex vivo].

    PubMed

    Lobanok, E S; Kvacheva, Z B; Pinchuk, S V; Volk, M V; Mezhevkina, L M; Fesenko, E E; Volotovski, I D

    2014-01-01

    The influence of FGF2 on the efficiency of cardiomyocytes differentiation of mesenchymal stem cells (MSC) of bone marrow induced by 5-azacetidine (5-aza) was studied. The effect of FGF2 developing by the 14th day after the combined action of a differentiating agent and growth factor was manifested in an increase in Mef2A, Mef2D and gene transcription and a rise of ionized Ca2+ concentration in cytoplasm keeping cell viability and proliferation activity. In the presence of FGF2 this approach provided cardiomyogenesis and the increase in the formation of early precursors of cardiomyocytes.

  18. The effect of supplementation of a glutamine precursor on the growth plate, articular cartilage and cancellous bone in fundectomy-induced osteopenic bone

    PubMed Central

    TOMASZEWSKA, Ewa; DOBROWOLSKI, Piotr; PROST, Łukasz; HUŁAS-STASIAK, Monika; MUSZYŃSKI, Siemowit; BLICHARSKI, Tomasz

    2015-01-01

    The aim of the study was to investigate the effect of 2-oxoglutaric acid (2-Ox) supplementation (a precursor of glutamine and hydroxyproline, the most abundant amino acid of collagen) on cartilage and bone in pigs after fundectomy. Pigs at the age of forty days were subjected to fundectomy and divided into two groups depending on 2-Ox supplementation (at the daily dosage of 0.4 g/kg of body weight). Other pigs were sham operated. Pigs were euthanized at the age of eight months. An analysis of the morphometry of trabeculae, growth plate and articular cartilage in fundectomy-induced osteopenic bone was performed. Moreover, the levels of expression of osteocalcin, osteopontin and osteoprotegerin in trabecular bone and osteocalcin in articular cartilage were evaluated. Articular cartilage was thinnest in fundectomized pigs and thickest in 2-Ox-supplemented animals after fundectomy. Moreover, 2-Ox supplementation after fundectomy enhanced the total thickness of the growth plate and trabeculae in fundectomized pigs. The most evident signal for osteocalcin and osteoprotegerin in trabecular bone was in sham-operated and 2-Ox-supplemented pigs; a low reaction was observed in the fundectomized group. Additionally, as a long-term postoperative consequence, a change was observed in the expression of osteocalcin in articular cartilage. It seems that 2-Ox is suitable for use in preventing the negative effects of fundectomy on cancellous bone and cartilage. PMID:26725871

  19. Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates.

    PubMed

    Ozgurtas, Taner; Aydin, Ibrahim; Turan, Ozden; Koc, Esin; Hirfanoglu, Ibrahim Murat; Acikel, Cengiz Han; Akyol, Mesut; Erbil, M Kemal

    2010-05-01

    Human milk is a complex biological fluid. It contains many nutrients, anti-infectious and biologically active substance. Human milk also contains many angiogenic polypeptides. We have determined four of these: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), insulin-like growth factor- I (IGF-I) and platelet-derived growth factor (PDGF). The aim of this study was to compare the concentrations of VEGF, b-FGF, IGF-I and PDGF in human milk collected from mothers with preterm and term neonates. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (38>weeks) infants at days 3, 7 and 28 postpartum. Milk samples were analyzed for VEGF, b-FGF and PDGF by enzyme-linked immunosorbent assay and IGF-I was measured by radioimmunoassay method. Human milk levels of VEGF, IGF-I and b-FGF were significantly higher (p<0.001). Furthermore, within-preterm group concentrations of VEGF, IGF-I and PDGF significantly differed during postpartum days 3-7-28 (p<0.001, p<0.05, p<0.001, respectively), but did not do so for b-FGF concentrations. In term groups, concentrations of IGF-I and VEGF significantly differed (p<0.05, p<0.001, respectively), but did not do so for concentrations of b-FGF and PDGF. This is the first report of simultaneous measurements of four major angiogenic factors in human milk collected from mothers with preterm and term. Our results suggest that three of four angiogenic factors, VEGF, b-FGF and IGF-I, are higher concentration in human milk which collected from preterm mothers than those of terms.

  20. Osteoinductive small molecules: growth factor alternatives for bone tissue engineering.

    PubMed

    Aravamudhan, Aja; Ramos, Daisy M; Nip, Jonathan; Subramanian, Aditi; James, Roshan; Harmon, Matthew D; Yu, Xiaojun; Kumbar, Sangamesh G

    2013-01-01

    Tissue engineering aims to repair, restore, and regenerate lost or damaged tissues by using biomaterials, cells, mechanical forces and factors (chemical and biological) alone or in combination. Growth factors are routinely used in the tissue engineering approach to expedite the process of regeneration. The growth factor approach has been hampered by several complications including high dose requirements, lower half-life, protein instability, higher costs and undesired side effects. Recently a variety of alternative small molecules of both natural and synthetic origin have been explored as alternatives to growth factors for tissue regeneration applications. Small molecules are simple biochemical components that elicit certain cellular responses through signaling cascades. Small molecules present a viable alternative to biological factors. Small molecule strategies can reduce various side effects, maintain bioactivity in a biological environment and minimize cost issues associated with complex biological growth factors. This manuscript focuses on three-osteoinductive small molecules, namely melatonin, resveratrol (from natural sources) and purmorphamine (synthetically designed) as inducers of bone formation and osteogenic differentiation of stem cells. Efforts have been made to summarize possible biological pathways involved in the action of each of these drugs. Melatonin is known to affect Mitogen Activated Protein (MAP) kinase, Bone morphogenic protein (BMP) and canonical wnt signaling. Resveratrol is known to activate cascades involving Wnt and NAD-dependent deacetylase sirtuin-1 (Sirt1). Purmorphamine is a Hedgehog (Hh) pathway agonist as it acts on Smoothened (Smo) receptors. These mechanisms and the way they are affected by the respective small molecules will also be discussed in the manuscript.

  1. The importance of neuronal growth factors in the ovary.

    PubMed

    Streiter, S; Fisch, B; Sabbah, B; Ao, A; Abir, R

    2016-01-01

    The neurotrophin family consists of nerve growth factor (NGF), neurotrophin 3 (NT3) and neurotrophin 4/5 (NT4/5), in addition to brain-derived neurotrophic factor (BDNF) and the neuronal growth factors, glial cell line-derived neurotrophic factor (GDNF) and vasointestinal peptide (VIP). Although there are a few literature reviews, mainly of animal studies, on the importance of neurotrophins in the ovary, we aimed to provide a complete review of neurotrophins as well as neuronal growth factors and their important roles in normal and pathological processes in the ovary. Follicular assembly is probably stimulated by complementary effects of NGF, NT4/5 and BDNF and their receptors. The neurotrophins, GDNF and VIP and their receptors have all been identified in preantral and antral follicles of mammalian species, including humans. Transgenic mice with mutations in the genes encoding for Ngf, Nt4/5 and Bdnf and their tropomyosin-related kinase β receptor showed a reduction in preantral follicles and an abnormal ovarian morphology, whereas NGF, NT3, GDNF and VIP increased the in vitro activation of primordial follicles in rats and goats. Additionally, NGF, NT3 and GDNF promoted follicular cell proliferation; NGF, BDNF and VIP were shown to be involved in ovulation; VIP inhibited follicular apoptosis; NT4/5, BDNF and GDNF promoted oocyte maturation and NGF, NT3 and VIP stimulated steroidogenesis. NGF may also exert a stimulatory effect in ovarian cancer and polycystic ovarian syndrome (PCOS). Low levels of NGF and BDNF in follicular fluid may be associated with diminished ovarian reserve and high levels with endometriosis. More knowledge of the roles of neuronal growth factors in the ovary has important implications for the development of new therapeutic drugs (such as anti-NGF agents) for ovarian cancer and PCOS as well as various infertility problems, warranting further research.

  2. Differences in the acyl composition of the platelet-activating factor (PAF) precursor and other choline phosphoglycerides of the rabbit retinal rod outer segments and neural retina.

    PubMed

    Bazan, H E; Hurst, J S; Bazan, N G

    1994-01-01

    Choline phosphoglycerides comprise almost half of vertebrate retinal phospholipids. This lipid pool contains the precursor of the potent lipid mediator, platelet-activating factor. The acyl composition and distribution of the different subclasses of the choline phosphoglycerides (alkylacyl-[or the precursor of platelet-activating factor], alkenylacyl-[or choline plasmalogen] and diacyl-glycero-3-phosphocholine) were studied in intact rabbit retina, neural retina and rod outer segments. Choline phosphoglycerides were isolated by high performance liquid chromatography and derivatized by acetylation after phospholipase C treatment. The derivatives were purified by high performance liquid chromatography and subjected to methanolysis. Fatty acids were analyzed by capillary gas liquid chromatography. In the intact retina and in the neural retina, the alkylacyl-glycero-3-phosphocholine and alkenylacyl-glycero-3-phosphocholine comprise 1.2% and 1.5%, respectively, of the total choline phosphoglycerides, whereas the rod outer segments contain twice the proportion of the precursor of platelet-activating factor and no detectable plasmalogens. On a mole percent basis, arachidonic acid was highest in the neural retinal alkenylacyl-glycero-3-phosphocholine (27%), 18% in the alkylacyl-glycero-3-phosphocholine and only 5% in the diacyl-glycero-3-phosphocholine. However, alkylacyl-glycero-3-phosphocholine from rod outer segments was enriched in docosapentaenoic acid (18%) while arachidonic acid was in the 3-4% range. Our results suggest that, in the neural retina, alkyl-arachidonoyl-glycero-3-phosphocholine is a source of both platelet-activating factor and of arachidonic acid which may be a substrate for both prostaglandins and lipoxygenase metabolites during an inflammatory episode and may contribute to the retinal pathology.

  3. Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-beta.

    PubMed

    Kulyk, W M; Rodgers, B J; Greer, K; Kosher, R A

    1989-10-01

    This study represents a first step in investigating the possible involvement of transforming growth factor-beta (TGF-beta) in the regulation of embryonic chick limb cartilage differentiation. TGF-beta 1 and 2 (1-10 ng/ml) elicit a striking increase in the accumulation of Alcian blue, pH 1-positive cartilage matrix, and a corresponding twofold to threefold increase in the accumulation of 35S-sulfate- or 3H-glucosamine-labeled sulfated glycosaminoglycans (GAG) by high density micromass cultures prepared from the cells of whole stage 23/24 limb buds or the homogeneous population of chondrogenic precursor cells comprising the distal subridge mesenchyme of stage 25 wing buds. Moreover, TGF-beta causes a striking (threefold to sixfold) increase in the steady-state cytoplasmic levels of mRNAs for cartilage-characteristic type II collagen and the core protein of cartilage-specific proteoglycan. Only a brief (2 hr) exposure to TGF-beta at the initiation of culture is sufficient to stimulate chondrogenesis, indicating that the growth factor is acting at an early step in the process. Furthermore, TGF-beta promotes the formation of cartilage matrix and cartilage-specific gene expression in low density subconfluent spot cultures of limb mesenchymal cells, which are situations in which little, or no chondrogenic differentiation normally occurs. These results provide strong incentive for considering and further investigating the role of TGF-beta in the control of limb cartilage differentiation.

  4. Nerve Growth Factor Promoter Activity Revealed in Mice Expressing Enhanced Green Fluorescent Protein

    PubMed Central

    Kawaja, Michael D.; Smithson, Laura J.; Elliott, Janet; Trinh, Gina; Crotty, Anne-Marie; Michalski, Bernadeta; Fahnestock, Margaret

    2012-01-01

    Nerve growth factor (NGF) and its precursor proNGF are perhaps the best described growth factors of the mammalian nervous system. There remains, however, a paucity of information regarding the precise cellular sites of proNGF/NGF synthesis. Here we report the generation of transgenic mice in which the NGF promoter controls the ectopic synthesis of enhanced green fluorescent protein (EGFP). These transgenic mice provide an unprecedented resolution of both neural cells (e.g., neocortical and hippocampal neurons) and non-neural cells (e.g., renal interstitial cells and thymic reticular cells) that display NGF promoter activity from postnatal development to adulthood. Moreover, the transgene is inducible by injury. At 2 days after sciatic nerve ligation, a robust population of EGFP-positive cells is seen in the proximal nerve stump. These transgenic mice offer novel insights into the cellular sites of NGF promoter activity and can be used as models for investigating the regulation of proNGF/NGF expression after injury. PMID:21456011

  5. Identification and characterization of canine growth differentiation factor-9 and its splicing variant

    PubMed Central

    Hashimoto, Osamu; Takagi, Ryohei; Yanuma, Fuminari; Doi, Satoru; Shindo, Junji; Endo, Hideki; Hasegawa, Yoshihisa; Shimasaki, Shunichi

    2012-01-01

    Growth differentiation factor-9 (GDF-9), a member of the transforming growth factor-β (TGF-β) superfamily, is expressed exclusively in the oocyte within the ovary and plays essential roles in the ovarian function in mammals. However, a possible involvement of GDF-9 in canine ovarian physiology that has a unique ovulation process among mammals has not been studied. Interestingly, we have isolated two types of cDNA clones generated by an alternative splicing from a canine ovarian total RNA. The predominant long form cDNA shares a common precursor structure with GDF-9s in other species whereas the minor short form cDNA has a 172 amino acid truncation in the proregion. Using a transient expression system, we found that the long form cDNA has a defect in mature protein production whereas the short form cDNA readily produces mature protein. However, mutations at one or two N-glycosylation sites in the mature domain of the short form GDF-9 caused a loss in mature protein production. These results suggest that the prodomain and N-linked glycosylation of the mature domain regulate proper processing and secretion of canine GDF-9. Based on the biological functions of GDF-9, these characteristics of canine GDF-9 could be causatively linked to the unique ovulation process in the Canidae. PMID:22446043

  6. In vivo demonstration of cell types in bone that harbor epidermal growth factor receptors

    SciTech Connect

    Martineau-Doize, B.; Lai, W.H.; Warshawsky, H.; Bergeron, J.J.

    1988-08-01

    The binding and internalization of (/sup 125/I)iodoepidermal growth factor (EGF) by bone cells of the rat was demonstrated in situ by quantitative radioautography. Specific binding sites were observed on a cell profile enriched in endocytic components, including lysosome-like structures, a rough endoplasmic reticulum-rich cell profile, and a cell profile that histologically resembles an undifferentiated precursor cell. By the criteria of gel filtration and precipitability by trichloroacetic acid, most of the bound (/sup 125/I)iodo-EGF was considered intact. By morphological criteria none of the cell profiles that bound (/sup 125/I)iodo-EGF corresponded to fully formed osteoclasts or osteoblasts. The endocytic cell was found in the epiphyseal plate between the invading capillary and the transverse and longitudinal cartilage septa as well as near osteoclasts in the zone of mixed spicules. The rough endoplasmic reticulum-rich cell was present in vacated chondrocyte lacunae of the epiphyseal plate close to the metaphysis, and the poorly differentiated cell was observed between the mixed spicules of the metaphysis. Similar cell types were also found in the alveolar bone surrounding the incisors. These cells may be the origin of established bone cell lines that harbor high concentrations of EGF receptors and may also be responsible for the humoral hypercalcemia in response to the reported actions of injected EGF or transforming growth factor-alpha as well as that of malignancy.

  7. Surface proteome analysis identifies platelet derived growth factor receptor-alpha as a critical mediator of transforming growth factor-beta-induced collagen secretion.

    PubMed

    Heinzelmann, Katharina; Noskovičová, Nina; Merl-Pham, Juliane; Preissler, Gerhard; Winter, Hauke; Lindner, Michael; Hatz, Rudolf; Hauck, Stefanie M; Behr, Jürgen; Eickelberg, Oliver

    2016-05-01

    Fibroblasts are extracellular matrix-producing cells in the lung. Fibroblast activation by transforming growth factor-beta leads to myofibroblast-differentiation and increased extracellular matrix deposition, a hallmark of pulmonary fibrosis. While fibroblast function with respect to migration, invasion, and extracellular matrix deposition has been well-explored, little is known about the surface proteome of lung fibroblasts in general and its specific response to fibrogenic growth factors, in particular transforming growth factor-beta. We thus performed a cell-surface proteome analysis of primary human lung fibroblasts in presence/absence of transforming growth factor-beta, followed by characterization of our findings using FACS analysis, Western blot, and siRNA-mediated knockdown experiments. We identified 213 surface proteins significantly regulated by transforming growth factor-beta, platelet derived growth factor receptor-alpha being one of the top down-regulated proteins. Transforming growth factor beta-induced downregulation of platelet derived growth factor receptor-alpha induced upregulation of platelet derived growth factor receptor-beta expression and phosphorylation of Akt, a downstream target of platelet derived growth factor signaling. Importantly, collagen type V expression and secretion was strongly increased after forced knockdown of platelet derived growth factor receptor-alpha, an effect that was potentiated by transforming growth factor-beta. We therefore show previously underappreciated cross-talk of transforming growth factor-beta and platelet derived growth factor signaling in human lung fibroblasts, resulting in increased extracellular matrix deposition in a platelet derived growth factor receptor-alpha dependent manner. These findings are of particular importance for the treatment of lung fibrosis patients with high pulmonary transforming growth factor-beta activity.

  8. The Influence of Platelet-Derived Growth Factor and Fibroblast Growth Factor 2 on Oligodendrocyte Development and Remyelination

    DTIC Science & Technology

    2004-01-01

    AE, Bansal R (1993) The oligodendrocyte and its many cellular processes. Trends Cell Biol 3:191-197. Pluchino S, Quattrini A, Brambilla E, Gritti A...Rosenberg D, Cheung SW, Mobley WC, Fisher S, Genain CP (2000) Human nerve growth factor protects common 141 marmosets against autoimmune

  9. Therapeutic Targeting of Fibroblast Growth Factor Receptors in Gastric Cancer

    PubMed Central

    Fujimori, Yoshitaka; Otsuki, Sho; Sato, Yuya; Nakagawa, Masatoshi

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2) have become standard therapy for HER2-positive GC. An inhibitor of vascular endothelial growth factor receptor 2 or MET has also produced promising results in patients with GC. Fibroblast growth factor receptors (FGFR) play key roles in tumor growth via activated signaling pathways in GC. Genomic amplification of FGFR2 leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical relevance of FGFR in GC and examines FGFR as a potential therapeutic target in patients with GC. Preclinical studies in animal models suggest that multitargeted tyrosine kinase inhibitors (TKIs), including FGFR inhibitor, suppress tumor cell proliferation and delay tumor progression. Several TKIs are now being evaluated in clinical trials as treatment for metastatic or unresectable GC harboring FGFR2 amplification. PMID:26000013

  10. FGF19 functions as autocrine growth factor for hepatoblastoma

    PubMed Central

    Elzi, David J.; Song, Meihua; Blackman, Barron; Weintraub, Susan T.; López-Terrada, Dolores; Chen, Yidong; Tomlinson, Gail E.; Shiio, Yuzuru

    2016-01-01

    Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma. To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells. We determined that silencing FGF19 by shRNAs or neutralizing secreted FGF19 by anti-FGF19 antibody inhibits the proliferation of hepatoblastoma cells. Furthermore, blocking FGF19 signaling by an FGF receptor kinase inhibitor suppressed hepatoblastoma growth. RNA expression analysis in hepatoblastoma tumors revealed that the high expression of FGF19 signaling pathway components as well as the low expression of FGF19 signaling repression targets correlates with the aggressiveness of the tumors. These results suggest the role of FGF19 as autocrine growth factor for hepatoblastoma. PMID:27382436

  11. FGF19 functions as autocrine growth factor for hepatoblastoma.

    PubMed

    Elzi, David J; Song, Meihua; Blackman, Barron; Weintraub, Susan T; López-Terrada, Dolores; Chen, Yidong; Tomlinson, Gail E; Shiio, Yuzuru

    2016-03-01

    Hepatoblastoma is the most common liver cancer in children, accounting for over 65% of all childhood liver malignancies. Hepatoblastoma is distinct from adult liver cancer in that it is not associated with hepatitis virus infection, cirrhosis, or other underlying liver pathology. The paucity of appropriate cell and animal models has been hampering the mechanistic understanding of hepatoblastoma pathogenesis. Consequently, there is no molecularly targeted therapy for hepatoblastoma. To gain insight into cytokine signaling in hepatoblastoma, we employed mass spectrometry to analyze the proteins secreted from Hep293TT hepatoblastoma cell line we established and identified the specific secretion of fibroblast growth factor 19 (FGF19), a growth factor for liver cells. We determined that silencing FGF19 by shRNAs or neutralizing secreted FGF19 by anti-FGF19 antibody inhibits the proliferation of hepatoblastoma cells. Furthermore, blocking FGF19 signaling by an FGF receptor kinase inhibitor suppressed hepatoblastoma growth. RNA expression analysis in hepatoblastoma tumors revealed that the high expression of FGF19 signaling pathway components as well as the low expression of FGF19 signaling repression targets correlates with the aggressiveness of the tumors. These results suggest the role of FGF19 as autocrine growth factor for hepatoblastoma.

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

    SciTech Connect

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

    1991-01-01

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

  13. Thrombopoietin is a growth factor for rat hepatic progenitors.

    PubMed

    Schmelzer, Eva; Deiwick, Andrea; Bruns, Helge; Fiegel, Henning C; Bader, Augustinus

    2008-03-01

    The liver is the primary site of hematopoiesis during fetal development; it has been shown that thrombopoietin (TPO) produced by the liver during fetal development is a major regulator of megakaryocytopoiesis. As maximum liver growth and hematopoiesis occur simultaneously, we hypothesized that TPO may act as a growth factor for hepatic progenitors. Therefore, the influence of TPO on the proliferation of fetal hepatic progenitors in vitro compared with that of adult hepatocytes was analyzed. The expression of the TPO receptor, c-mpl, was investigated in fetal and adult liver. Cell proliferation was measured by bromodeoxyuridine incorporation and total cell counts. TPO and c-mpl gene expression was investigated by reverse transcription polymerase chain reaction. The cell surface expression of c-mpl was analyzed in fetal and adult human liver by immunohistochemistry. Hepatic progenitors of fetal and adult liver but not hepatocytes expressed the TPO receptor, c-mpl, on the cell surface. Fetal hepatic progenitors expressed mRNA for TPO and its receptor. TPO stimulated cell proliferation and increased cell numbers of cultured rat fetal hepatic progenitors but not adult hepatocytes. We conclude that TPO acts in addition to its known role in megakaryocytopoiesis as a growth factor for hepatic progenitors but not hepatocytes in vitro; thus, TPO represents a growth factor for hepatic progenitors during fetal liver development.

  14. Very-high-growth-factor Planar Ablative Rayleigh Taylor Experiments

    SciTech Connect

    Bradley, D K; Braun, D G; Glendinning, S G; Edwards, M J; Milovich, J L; Sorce, C M; Collins, G W; Haan, S W; Page, R H

    2006-10-30

    The Rayleigh-Taylor (RT) instability is an important factor in bounding the performance envelope of ignition targets. This paper describes an experiment for ablative RT instability that for the first time achieves growth factors close to those expected to occur in ignition targets at the National Ignition Facility (NIF). The large growth allows small seed perturbations to be detected and can be used to place an upper bound on perturbation growth at the ablation front resulting from microstructure in the preferred Be ablator. The experiments were performed on the Omega laser using a halfraum 1.2 mm long by 2 mm diameter with a 75% laser entrance hole. The halfraum was filled with {approx} 1 atm of neopentane to delay gold plasma from closing the diagnostic line of sight down the axis of the halfraum. The ablator was mounted at the base of the halfraum, and was accelerated by a two stepped X-ray pulse consisting of an early time section {approx} 100 eV to emulate the NIF foot followed by an approximately constant {approx} 150 eV drive sustained over an additional 5-7ns. It is this long pulse duration and late time observation that distinguishes the present work from previous experiments, and is responsible for the large growth that is achieved. The growth of a 2D sinusoidal perturbation machined on the drive side of the ablator was measured using face-on radiography. The diagnostic view remained open until {approx} 11 ns with maximum growth factors measured to be {approx} 200. The trajectory of the ablator was measured using streaked backlit radiography. The design and analysis of the experiments is described, and implications for experiments on ignition target ablators are discussed.

  15. [Neurotrophic action of insulin-like growth factor-I in the inner ear].

    PubMed

    Rodríguez-de la Rosa, L; Contreras-Rodríguez, J; Cediel-Algovia, R; León, Y; Sánchez-Calderón, H; Murillo-Cuesta, S; Riquelme-Galiana, R; de Diego-Sastre, J I; Prim-Espada, M P; Varela-Nieto, I

    Loss of hearing constitutes one of the most frequent disabling sensory impairments in the developed world. Different therapeutic approaches are currently being studied, including treatment with stem cells, genetic manipulation and pharmacological protection. To evaluate the role played by insulin-like growth factor-I (IGF-I) in the development, maintenance and repair of auditory functioning. Proper development of the inner ear is dependent on a suitable coordination of the cell processes of proliferation, differentiation, neurogenesis and programmed cell death, which are regulated by different factors, one of which is IGF-I. During the embryogenesis of the inner ear, this factor is expressed in abundance and is essential for cell survival and maintaining neuronal precursors. Studies conducted in Igf-1-/- null mice have highlighted its importance in the development and continued functioning of the inner ear. Mice with a deficit in this gene display morphological disorders that correspond to severe functional deficiencies, which are confirmed by analysing brainstem auditory evoked potentials. A deficit of IGF-I in humans is also accompanied by profound sensory hypoacusis. In a scenario like this, IGF-I appears as a key factor in the development of auditory functioning and a candidate for regenerative therapy of the inner ear.

  16. Placental phenotype and the insulin-like growth factors: resource allocation to fetal growth.

    PubMed

    Sferruzzi-Perri, Amanda N; Sandovici, Ionel; Constancia, Miguel; Fowden, Abigail L

    2017-03-24

    The placenta is the main determinant of fetal growth and development in utero. It supplies all the nutrients and oxygen required for fetal growth and secretes hormones that facilitate maternal allocation of nutrients to the fetus. Furthermore, the placenta responds to nutritional and metabolic signals in the mother by altering its structural and functional phenotype which can lead to changes in maternal resource allocation to the fetus. The molecular mechanisms by which the placenta senses and responds to environmental cues are poorly understood. This review discusses the role of the insulin-like growth factors (IGFs) in controlling placental resource allocation to fetal growth, particularly in response to adverse gestational environments. In particular, it assesses the impact of the IGFs and their signalling machinery on placental morphogenesis, substrate transport and hormone secretion, primarily in the laboratory species, although it draws on data from human and other species where relevant. It also considers the role of the IGFs as environmental signals in linking resource availability, to fetal growth through changes in the morphological and functional phenotype of the placenta. As altered fetal growth is associated with increased perinatal morbidity and mortality and a greater risk of developing adult-onset diseases in later life, understanding the role of IGFs during pregnancy in regulating placental resource allocation to fetal growth is important for identifying the mechanisms underlying the developmental programming of offspring phenotype by suboptimal intrauterine growth. This article is protected by copyright. All rights reserved.

  17. Intracellular processing of transforming growth factor-beta in mesangial cells.

    PubMed

    Ceol, M; Vianello, D; Baggio, B; Meani, A; Schleicher, E; Anglani, F; Gambaro, G

    1998-03-01

    Transforming growth factor beta 1 (TGF-beta 1) is a multifunctional regulator of cell-growth, differentiation and extracellular matrix formation in several physiological conditions. It plays a crucial role in the process of glomerulosclerosis. Mature TGF-beta 1 is secreted as a latent form associated with the latency associated peptide (LAP), and its activation occurs through the LAP cleavage. The intracellular localization and the mechanisms of activation of TGF-beta 1 protein have not been elucidated in the mesangial cell. In the present report we examined the intracellular processing from TGF-beta 1 precursor to the latent-TGF-beta 1 in cultured mesangial cells by immunocytochemistry, using three rabbit polyclonal antibodies directed against different epitopes of human TGF-beta 1. The anti-LAP-TGF-beta 1 precursor Ab stained mesangial cells in the perinuclear region and in the cytoplasm in the area corresponding to the rough endoplasmic reticulum; the anti-COOH-terminal fragment of TGF-beta 1 Ab reacted in the same area, in vesicular structures located in the cytoplasm and furthermore, in the mesangial cell clusters, so-called hillocks, with an extracellular pattern; the anti-NH2-terminal fragment of TGF-beta 1 Ab stained only large exocytotic vesicles at the periphery of the cytoplasma. Our investigations suggest a conformational rearrangement of pro-TGF-beta 1 molecule occurring between the rough endoplasmic reticulum and the TGF-beta 1 secretion and support the idea that in mesangial cells the activation of TGF-beta 1 occurs during the secretion process. In conclusion, the processing of TGF-beta 1 in mesangial cells seems to be similar to that one observed in other mesenchymal cells.

  18. Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis

    PubMed Central

    Larrieu-Lahargue, Frédéric; Welm, Alana L.; Bouchecareilh, Marion; Alitalo, Kari; Li, Dean Y.; Bikfalvi, Andreas; Auguste, Patrick

    2012-01-01

    Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited better overall survival. We found 66c14 cells in the lumen of tumor lymphatic vessels and in lymph nodes. FGFR-2DN-expressing tumors exhibited a decrease in VEGFR-3 (Vascular Endothelial Growth Factor Receptor-3) or podoplanin-positive lymphatic vessels, an increase in isolated intratumoral lymphatic endothelial cells and a reduction in VEGF-C (Vascular Endothelial Growth Factor-C) mRNA expression. FGFs may act in an autocrine manner as the inhibition of FGFR signaling in tumor cells suppresses VEGF-C expression in a COX-2 (cyclooxygenase-2) or HIF1-α (hypoxia-inducible factor-1 α) independent manner. FGFs may also act in a paracrine manner on tumor lymphatics by inducing expression of pro-lymphangiogenic molecules such as VEGFR-3, integrin α9, prox1 and netrin-1. Finally, in vitro lymphangiogenesis is impeded in the presence of FGFR-2DN 66c14 cells. These data confirm that both FGF and VEGF signaling are necessary for the maintenance of vascular morphogenesis and provide evidence that targeting FGFR signaling may be an interesting approach to inhibit tumor lymphangiogenesis and metastatic spread. PMID:22761819

  19. Epidermal Growth Factor-Like Growth Factors Prevent Apoptosis of Alcohol-Exposed Human Placental Cytotrophoblast Cells1

    PubMed Central

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

    2007-01-01

    Maternal alcohol abuse during pregnancy can produce an array of birth defects comprising fetal alcohol syndrome. A hallmark of fetal alcohol syndrome is intrauterine growth retardation, which is associated with elevated apoptosis of placental cytotrophoblast cells. Using a human first trimester cytotrophoblast cell line, we examined the relationship between exposure to ethanol and cytotrophoblast survival, as well as the ameliorating effects of epidermal growth factor (EGF)-like growth factors produced by human cytotrophoblast cells. After exposure to 0–100 mM ethanol, cell death was quantified by the TUNEL method, and expression of the nuclear proliferation marker, Ki67, was measured by immunohistochemistry. The mode of cell death was determined by assessing annexin V binding, caspase 3 activation, pyknotic nuclear morphology, reduction of TUNEL by caspase inhibition, and cellular release of lactate dehydrogenase. Ethanol significantly reduced proliferation and increased cell death approximately 2.5-fold through the apoptotic pathway within 1–2 h of exposure to 50 mM alcohol. Exposure to 25–50 mM ethanol significantly increased transforming growth factor alpha (TGFA) and heparin-binding EGF-like growth factor (HBEGF), but not EGF or amphiregulin (AREG). When cytotrophoblasts were exposed concurrently to 100 mM ethanol and 1 nM HBEGF or TGFA, the increase in apoptosis was prevented, while EGF ameliorated at 10 nM and AREG was weakly effective. HBEGF survival-promoting activity required ligation of either of its cognate receptors, HER1 or HER4. These findings reveal the potential for ethanol to rapidly induce cytotrophoblast apoptosis. However, survival factor induction could provide cytotrophoblasts with an endogenous cytoprotective mechanism. PMID:17392498

  20. Epidermal growth factor and hepatocyte growth factor receptors collaborate to induce multiple biological responses in bovine mammary epithelial cells.

    PubMed

    Accornero, P; Martignani, E; Miretti, S; Starvaggi Cucuzza, L; Baratta, M

    2009-08-01

    The aim of this work was to explore whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) could increase the biological responses of a mammary epithelial cell line of bovine origin when added simultaneously. We also investigated a possible molecular mechanism underlying this cooperation. The development of mammary gland requires several circulating and locally produced hormones. Hepatocyte growth factor and its tyrosine kinase receptor, mesenchymal-epithelial transition factor (MET), are expressed and temporally regulated during mammary development and differentiation. Epidermal growth factor receptor and its ligands have also been implicated in the growth and morphogenesis of the mammary epithelium. Both EGF and HGF seem to exert a morphogenic program in this tissue; therefore, we hypothesized that these cytokines could act cooperatively in bovine mammary epithelial cells. We have already shown that the bovine BME-UV cell line, a nontumorigenic mammary epithelial line, expresses both MET and EGF receptor. Simultaneous treatment with HGF and EGF elicited an increase in proliferation, dispersion, degradation of extracellular matrix, and motility. Following EGF treatment, BME-UV mammary cells exhibited an increase in MET expression at both the mRNA and protein levels. Long-term treatment of BME-UV cells with HGF and EGF together increased the level of activation of the extracellular signal-regulated kinase 1/2 and protein kinase B signaling pathways when compared with HGF or EGF alone. These data outline a possible cooperative role of the EGF and HGF pathways and indicate that cross-talk between their respective receptors may modulate mammary gland development in the cow.

  1. Growth factor choice is critical for successful functionalization of nanoparticles

    PubMed Central

    Pinkernelle, Josephine; Raffa, Vittoria; Calatayud, Maria P.; Goya, Gerado F.; Riggio, Cristina; Keilhoff, Gerburg

    2015-01-01

    Nanoparticles (NPs) show new characteristics compared to the corresponding bulk material. These nanoscale properties make them interesting for various applications in biomedicine and life sciences. One field of application is the use of magnetic NPs to support regeneration in the nervous system. Drug delivery requires a functionalization of NPs with bio-functional molecules. In our study, we functionalized self-made PEI-coated iron oxide NPs with nerve growth factor (NGF) and glial cell-line derived neurotrophic factor (GDNF). Next, we tested the bio-functionality of NGF in a rat pheochromocytoma cell line (PC12) and the bio-functionality of GDNF in an organotypic spinal cord culture. Covalent binding of NGF to PEI-NPs impaired bio-functionality of NGF, but non-covalent approach differentiated PC12 cells reliably. Non-covalent binding of GDNF showed a satisfying bio-functionality of GDNF:PEI-NPs, but turned out to be unstable in conjugation to the PEI-NPs. Taken together, our study showed the importance of assessing bio-functionality and binding stability of functionalized growth factors using proper biological models. It also shows that successful functionalization of magnetic NPs with growth factors is dependent on the used binding chemistry and that it is hardly predictable. For use as therapeutics, functionalization strategies have to be reproducible and future studies are needed. PMID:26388717

  2. Nerve Growth Factor Potentiates the Neurotoxicity of β Amyloid

    NASA Astrophysics Data System (ADS)

    Yankner, Bruce A.; Caceres, Alfredo; Duffy, Lawrence K.

    1990-11-01

    The role of growth factors in the pathogenesis of Alzheimer disease is unknown. The β-amyloid protein accumulates abnormally in the brain in Alzheimer disease and is neurotoxic to differentiated hippocampal neurons in culture. Nerve growth factor (NGF) increased the neurotoxic potency of a β-amyloid polypeptide by a factor of ≈100,000, which resulted in a reduction of the β-amyloid neurotoxic EC50 from 0.1 μM to 1 pM. This potentiating effect of NGF was reversed by a monoclonal antibody against NGF and was not observed for a variety of other neurotrophic growth factors. Exposure of hippocampal neurons to very low concentrations of β amyloid alone resulted in a marked induction of immunoreactive NGF receptors. Addition of NGF with β amyloid resulted in the appearance of neurodegenerative changes in NGF receptor-positive neurons. The early and profound degeneration of hippocampal and basal forebrain cholinergic neurons that occurs in Alzheimer disease may result from a neurotoxic interaction of β amyloid with NGF.

  3. Nutrition, insulin, insulin-like growth factors and cancer.

    PubMed

    Giovannucci, E

    2003-01-01

    The incidence of colon, pancreatic, and kidney cancers, as well as aggressive prostate cancer in men, and breast and endometrial cancer in women is invariably high in Western countries. Nutritional and related factors have been typically implicated. This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk. The model presented here summarizes the data that chronic exposure to high levels of insulin and IGF-1 may mediate many of the risk factors for some cancers that are high in Western populations. This hypothesis may help explain some of the epidemiologic patterns observed for these cancers, both from a cross-national perspective and within populations. Of particular importance is that some of relevant factors are modifiable through nutritional and lifestyle interventions. Out of a variety of perspectives presented, nutritional manipulation through the insulin pathway may be more feasible than attempting to influence total IGF-1 concentrations, which are determined largely by growth hormone. Further study is required to test these conclusions.

  4. Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor.

    PubMed

    Zhou, Hui; Vonk, Brenda; Roubos, Johannes A; Bovenberg, Roel A L; Voigt, Christopher A

    2015-12-02

    Optimizing bio-production involves strain and process improvements performed as discrete steps. However, environment impacts genotype and a strain that is optimal under one set of conditions may not be under different conditions. We present a methodology to simultaneously vary genetic and process factors, so that both can be guided by design of experiments (DOE). Advances in DNA assembly and gene insulation facilitate this approach by accelerating multi-gene pathway construction and the statistical interpretation of screening data. This is applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting of six heterologous enzymes. A 32-member fraction factorial library is designed that simultaneously perturbs expression and media composition. This is compared to a 64-member full factorial library just varying expression (0.64 Mb of DNA assembly). Statistical analysis of the screening data from these libraries leads to different predictions as to whether the expression of enzymes needs to increase or decrease. Therefore, if genotype and media were varied separately this would lead to a suboptimal combination. This is applied to the design of a strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single optimization step. This work introduces a generalizable platform to co-optimize genetic and non-genetic factors.

  5. Algorithmic co-optimization of genetic constructs and growth conditions: application to 6-ACA, a potential nylon-6 precursor

    PubMed Central

    Zhou, Hui; Vonk, Brenda; Roubos, Johannes A.; Bovenberg, Roel A.L.; Voigt, Christopher A.

    2015-01-01

    Optimizing bio-production involves strain and process improvements performed as discrete steps. However, environment impacts genotype and a strain that is optimal under one set of conditions may not be under different conditions. We present a methodology to simultaneously vary genetic and process factors, so that both can be guided by design of experiments (DOE). Advances in DNA assembly and gene insulation facilitate this approach by accelerating multi-gene pathway construction and the statistical interpretation of screening data. This is applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting of six heterologous enzymes. A 32-member fraction factorial library is designed that simultaneously perturbs expression and media composition. This is compared to a 64-member full factorial library just varying expression (0.64 Mb of DNA assembly). Statistical analysis of the screening data from these libraries leads to different predictions as to whether the expression of enzymes needs to increase or decrease. Therefore, if genotype and media were varied separately this would lead to a suboptimal combination. This is applied to the design of a strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single optimization step. This work introduces a generalizable platform to co-optimize genetic and non-genetic factors. PMID:26519464

  6. L-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway.

    PubMed

    Ma, Xi; Han, Meng; Li, Defa; Hu, Shengdi; Gilbreath, Kyler R; Bazer, Fuller W; Wu, Guoyao

    2017-05-01

    L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. L-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 μmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 μmol L-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70(S6K) and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.