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Sample records for increased crosslinker levels

  1. Experimental scleral cross-linking increases glaucoma damage in a mouse model

    PubMed Central

    Kimball, Elizabeth C.; Nguyen, Cathy; Steinhart, Matthew R.; Nguyen, Thao D.; Pease, Mary E.; Oglesby, Ericka N.; Oveson, Brian C.; Quigley, Harry A.

    2014-01-01

    The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model. CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p = 0.001), and produced a steeper pressure—strain behavior by in vitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (p = 0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice. PMID:25285424

  2. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels

    PubMed Central

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E.; Kerr, Sheena C.; Dunican, Eleanor M.; Daniel, Brian M.; Ghosh, Sudakshina; Erzurum, Serpel C.; Willard, Belinda; Hazen, Stanley L.; Huang, Xiaozhu; Carrington, Stephen D.; Oscarson, Stefan; Fahy, John V.

    2015-01-01

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  3. Oxidation increases mucin polymer cross-links to stiffen airway mucus gels.

    PubMed

    Yuan, Shaopeng; Hollinger, Martin; Lachowicz-Scroggins, Marrah E; Kerr, Sheena C; Dunican, Eleanor M; Daniel, Brian M; Ghosh, Sudakshina; Erzurum, Serpel C; Willard, Belinda; Hazen, Stanley L; Huang, Xiaozhu; Carrington, Stephen D; Oscarson, Stefan; Fahy, John V

    2015-02-25

    Airway mucus in cystic fibrosis (CF) is highly elastic, but the mechanism behind this pathology is unclear. We hypothesized that the biophysical properties of CF mucus are altered because of neutrophilic oxidative stress. Using confocal imaging, rheology, and biochemical measures of inflammation and oxidation, we found that CF airway mucus gels have a molecular architecture characterized by a core of mucin covered by a web of DNA and a rheological profile characterized by high elasticity that can be normalized by chemical reduction. We also found that high levels of reactive oxygen species in CF mucus correlated positively and significantly with high concentrations of the oxidized products of cysteine (disulfide cross-links). To directly determine whether oxidation can cross-link mucins to increase mucus elasticity, we exposed induced sputum from healthy subjects to oxidizing stimuli and found a marked and thiol-dependent increase in sputum elasticity. Targeting mucin disulfide cross-links using current thiol-amino structures such as N-acetylcysteine (NAC) requires high drug concentrations to have mucolytic effects. We therefore synthesized a thiol-carbohydrate structure (methyl 6-thio-6-deoxy-α-D-galactopyranoside) and found that it had stronger reducing activity than NAC and more potent and fast-acting mucolytic activity in CF sputum. Thus, oxidation arising from airway inflammation or environmental exposure contributes to pathologic mucus gel formation in the lung, which suggests that it can be targeted by thiol-modified carbohydrates. PMID:25717100

  4. Cross-linked Bioreducible Layer-by-layer Films for Increased Cell Adhesion and Transgene Expression

    PubMed Central

    Blacklock, Jenifer; Sievers, Torsten K.; Handa, Hitesh; You, Ye-Zi; Oupický, David; Mao, Guangzhao; Möhwald, Helmuth

    2010-01-01

    The effect of cross-linking layer-by-layer (LbL) films consisting of bioreducible poly(2-dimethylaminoethyl methacrylate) (rPDMAEMA) and DNA is examined with regards to rigidity, biodegradability, cell adhesion, and transfection activity using 1,5-diiodopentane (DIP) cross-linker. DIP chemically reacts with the tertiary amines of rPDMAEMA, altering the chemical composition of these LbL films. The result is a change in surface morphology, film swelling behavior and film rigidity, measured with AFM and ellipsometry. It is found that the apparent Young’s modulus is increased more than four times its original value upon cross-linking. Cross-linking mass is additionally confirmed with quartz crystal microbalance with dissipation (QCM-D). Comprehensive analyses of these experimental values were investigated to calculate the degree of cross-linking using the rubber elasticity theory and the Flory-Rehner theory. Additionally, the Flory-Huggins parameter, χ, was calculated. Good agreement in the two methods yields a cross-linking density of ~0.82 mmol/cm3. The Flory-Huggins parameter increased upon cross-linking from 1.07 to 1.2, indicating increased hydrophobicity of the network and formation of bulk water droplets within the films. In addition, the effects of cross-linking on film disassembly by 1,4-dithiothreitol (DTT) is found to be insignificant despite the alteration in film rigidity. Mouse fibroblast cells and smooth muscle cells are used to study the effect of cross-linking on cell adhesion and cell transfection activity. In vitro transfection activity up to seven days is quantified using secreted alkaline phosphatase (SEAP) DNA. Film cross-linking is found to enhance cell adhesion and prolong the duration of cellular transfection. These results contribute to the development of bioreducible polymer coatings for localized gene delivery. PMID:20369813

  5. Increasing Thermal Stability of Gelatin by UV-Induced Cross-Linking with Glucose

    PubMed Central

    Masutani, Evan M.; Kinoshita, Christopher K.; Tanaka, Travis T.; Ellison, Andrew K. D.; Yoza, Brandon A.

    2014-01-01

    The effects of ultraviolet (254 nm) radiation on a hydrated gelatin-glucose matrix were investigated for the development of a physiologically thermostable substrate for potential use in cell scaffold production. Experiments conducted with a differential scanning calorimeter indicate that ultraviolet irradiation of gelatin-glucose hydrogels dramatically increases thermal stability such that no melting is observed at temperatures of at least 90°C. The addition of glucose significantly increases the yield of cross-linked product, suggesting that glucose has a role in cross-link formation. Comparisons of lyophilized samples using scanning electron microscopy show that irradiated materials have visibly different densities. PMID:24963297

  6. Cross-Linking in Collagen by Nonenzymatic Glycation Increases the Matrix Stiffness in Rabbit Achilles Tendon

    PubMed Central

    2004-01-01

    Nonenzymatic glycation of connective tissue matrix proteins is a major contributor to the pathology of diabetes and aging. Previously the author and colleagues have shown that nonenzymatic glycation significantly enhances the matrix stability in the Achilles tendon (Reddy et al., 2002, Arch. Biochem. Biophys., 399, 174–180). The present study was designed to gain further insight into glycation-induced collagen cross-linking and its relationship to matrix stiffness in the rabbit Achilles tendon. The glycation process was initiated by incubating the Achilles tendons (n = 6) in phosphate-buffered saline containing ribose, whereas control tendons (n = 6) were incubated in phosphate-buffered saline without ribose. Eight weeks following glycation, the biomechanical attributes as well as the degree of collagen cross-linking were determined to examine the potential associations between matrix stiffness and molecular properties of collagen. Compared to nonglycated tendons, the glycated tendons showed increased maximum load, stress, strain, Young's modulus of elasticity, and toughness indicating that glycation increases the matrix stiffness in the tendons. Glycation of tendons resulted in a considerable decrease in soluble collagen content and a significant increase in insoluble collagen and pentosidine. Analysis of potential associations between the matrix stiffness and degree of collagen cross-linking showed that both insoluble collagen and pentosidine exhibited a significant positive correlation with the maximum load, stress, and strain, Young's modulus of elasticity, and toughness (r values ranging from .61 to .94) in the Achilles tendons. However, the soluble collagen content present in neutral salt buffer, acetate buffer, and acetate buffer containing pepsin showed an inverse relation with the various biomechanical attributes tested (r values ranging from .22 to .84) in the Achilles tendons. The results of the study demonstrate that glycation-induced collagen cross-linking

  7. Increasing FCC regenerator catalyst level

    SciTech Connect

    Wong, R.F. )

    1993-11-01

    A Peruvian FCC unit's operations were improved by increasing the regenerator's catalyst level. This increase resulted in lower stack losses, an improved temperature profile, increased catalyst activity and a lower catalyst consumption rate. A more stable operation saved this Peruvian refiner over $131,000 per year in catalyst alone. These concepts and data may be suitable for your FCC unit as well.

  8. Collagen Cross-Linking Using Rose Bengal and Green Light to Increase Corneal Stiffness

    PubMed Central

    Cherfan, Daniel; Verter, E. Eri; Melki, Samir; Gisel, Thomas E.; Doyle, Francis J.; Scarcelli, Giuliano; Yun, Seok Hyun; Redmond, Robert W.; Kochevar, Irene E.

    2013-01-01

    Purpose. Photochemical cross-linking of corneal collagen is an evolving treatment for keratoconus and other ectatic disorders. We evaluated collagen cross-linking by rose bengal plus green light (RGX) in rabbit eyes and investigated factors important for clinical application. Methods. Rose bengal (RB, 0.1%) was applied to deepithelialized corneas of enucleated rabbit eyes for 2 minutes. The diffusion distance of RB into the stroma was measured by fluorescence microscopy on frozen sections. RB-stained corneas were exposed to green (532-nm) light for 3.3 to 9.9 minutes (50–150 J/cm2). Changes in the absorption spectrum during the irradiation were recorded. Corneal stiffness was measured by uniaxial tensiometry. The spatial distribution of the stromal elastic modulus was assessed by Brillouin microscopy. Viable keratocytes were counted on H&E-stained sections 24 hours posttreatment. Results. RB penetrated approximately 100 μm into the corneal stroma and absorbed >90% of the incident green light. RGX (150 J/cm2) increased stromal stiffness by 3.8-fold. The elastic modulus increased in the anterior approximately 120 μm of stroma. RB was partially photobleached during the 2-minute irradiation, but reapplication of RB blocked light transmission by >70%. Spectral measurements suggested that RGX initiated cross-linking by an oxygen-dependent mechanism. RGX did not decrease keratocyte viability. Conclusions. RGX significantly increases cornea stiffness in a rapid treatment (≅12 minutes total time), does not cause toxicity to keratocytes and may be used to stiffen corneas thinner than 400 μm. Thus, RGX may provide an attractive approach to inhibit progression of keratoconus and other ectatic disorders. PMID:23599326

  9. Collagen Cross-linking Increases Its Biodegradation Resistance in Wet Dentin Bonding

    PubMed Central

    Xu, Changqi; Wang, Yong

    2014-01-01

    Purpose The biodegradation of exposed dentin collagen within the adhesive/dentin (a/d) interface is one of main reasons leading to composite restoration failures and seriously affects the durability of dental restorations. In the present study, the objective was to investigate whether the inclusion of the crosslinking reagent (glutaraldehyde, GA) in the adhesive would increase collagen biodegradation resistance within the a/d interface. Materials and methods The model adhesive consisted of ~60 % monomers (HEMA/BisGMA, 45/55 wt/wt) and ~ 40 % ethanol as a solvent. 5% GA was added to the above formulation. After the dentin surfaces were etched for 15 s with 35% phosphoric acid, rinsed with water and blotted dry, adhesives both with and without GA were applied and polymerized by visible light for 20 s. These a/d specimens were immersed in the biodegradation solution (prepared by adding 160 mg collagenase in 1 liter of TESCA buffer solution) for up to 30 days after proceeding with the sectioning/fracture to expose the a/d interfaces. The specimens were analyzed using SEM and micro-Raman. Results SEM results indicated that for the adhesive without GA, there were many voids and was a loss of collagen fibrils in the a/d interface after being challenged by the biodegradation solution. The Raman spectra collected from the interface showed that the amide I of collagen at 1667 cm−1 obviously decreased, indicating a removal of collagen fibrils during the degradation process. For the adhesive containing GA, the collagen fibrils within the interface did not degrade at all, which was also confirmed by the Raman results. Conclusion The results corroborate the previous findings that by using the current adhesive system and wet bonding, the collagen fibrils in the a/d interface are largely unprotected and easily undergo biodegradation. Directly including crosslinking agents in the adhesive could protect collagen fibrils from degradation in situ within the a/d interface. PMID

  10. Understanding of the Viscoelastic Response of the Human Corneal Stroma Induced by Riboflavin/UV-A Cross-Linking at the Nano Level

    PubMed Central

    Labate, Cristina; De Santo, Maria Penelope; Lombardo, Giuseppe; Lombardo, Marco

    2015-01-01

    Purpose To investigate the viscoelastic changes of the human cornea induced by riboflavin/UV-A cross-linking using Atomic Force Microscopy (AFM) at the nano level. Methods Seven eye bank donor corneas were investigated, after gently removing the epithelium, using a commercial AFM in the force spectroscopy mode. Silicon cantilevers with tip radius of 10 nm and spring elastic constants between 26- and 86-N/m were used to probe the viscoelastic properties of the anterior stroma up to 3 µm indentation depth. Five specimens were tested before and after riboflavin/UV-A cross-linking; the other two specimens were chemically cross-linked using glutaraldehyde 2.5% solution and used as controls. The Young’s modulus (E) and the hysteresis (H) of the corneal stroma were quantified as a function of the application load and scan rate. Results The Young’s modulus increased by a mean of 1.1-1.5 times after riboflavin/UV-A cross-linking (P<0.05). A higher increase of E, by a mean of 1.5-2.6 times, was found in chemically cross-linked specimens using glutaraldehyde 2.5% (P<0.05). The hysteresis decreased, by a mean of 0.9-1.5 times, in all specimens after riboflavin/UV-A cross-linking (P<0.05). A substantial decrease of H, ranging between 2.6 and 3.5 times with respect to baseline values, was observed in glutaraldehyde-treated corneas (P<0.05). Conclusions The present study provides the first evidence that riboflavin/UV-A cross-linking induces changes of the viscoelastic properties of the cornea at the scale of stromal molecular interactions. PMID:25830534

  11. Parathyroid hormone attenuates radiation-induced increases in collagen crosslink ratio at periosteal surfaces of mouse tibia.

    PubMed

    Oest, Megan E; Gong, Bo; Esmonde-White, Karen; Mann, Kenneth A; Zimmerman, Nicholas D; Damron, Timothy A; Morris, Michael D

    2016-05-01

    As part of our ongoing efforts to understand underlying mechanisms contributing to radiation-associated bone fragility and to identify possible treatments, we evaluated the longitudinal effects of parathyroid hormone (PTH) treatment on bone quality in a murine model of limited field irradiation. We hypothesized PTH would mitigate radiation-induced changes in the chemical composition and structure of bone, as measured by microscope-based Raman spectroscopy. We further hypothesized that collagen crosslinking would be especially responsive to PTH treatment. Raman spectroscopy was performed on retrieved tibiae (6-7/group/time point) to quantify metrics associated with bone quality, including: mineral-to-matrix ratio, carbonate-to-phosphate ratio, mineral crystallinity, collagen crosslink (trivalent:divalent) ratio, and the mineral and matrix depolarization ratios. Irradiation disrupted the molecular structure and orientation of bone collagen, as evidenced by a higher collagen crosslink ratio and lower matrix depolarization ratio (vs. non-irradiated control bones), persisting until 12weeks post-irradiation. Radiation transiently affected the mineral phase, as evidenced by increased mineral crystallinity and mineral-to-matrix ratio at 4weeks compared to controls. Radiation decreased bone mineral depolarization ratios through 12weeks, indicating increased mineral alignment. PTH treatment partially attenuated radiation-induced increases in collagen crosslink ratio, but did not restore collagen or mineral alignment. These post-radiation matrix changes are consistent with our previous studies of radiation damage to bone, and suggest that the initial radiation damage to bone matrix has extensive effects on the quality of tissue deposited thereafter. In addition to maintaining bone quality, preventing initial radiation damage to the bone matrix (i.e. crosslink ratio, matrix orientation) may be critical to preventing late-onset fragility fractures. PMID:26960578

  12. Molecular-level modeling of the viscoelasticity of crosslinked polymers: Effect of time and temperature

    SciTech Connect

    Simon, P.P.; Ploehn, H.J.

    1997-05-01

    We present a new molecular-level picture of chain dynamics for describing the viscoelasticity of crosslinked polymers. The associated mathematical model consists of a time-dependent momentum balance on a representative polymer segment in the crosslinked network, plus phenomenological expressions for forces acting on the segments. These include a cohesive force that accounts for intermolecular attraction, an entropic force describing the thermodynamics governing chain conformations, and a frictional force that captures the temperature dependence of relative chain motion. We treat the case of oscillatory uniaxial deformation. Solution of the model equations in the frequency domain yields the dynamic moduli as functions of temperature and frequency. The model reproduces all of the qualitative features of experimental dynamic modulus data across the complete spectrum of time and temperature, spanning the glassy zone, the {beta} transition, the dynamic glass transition, and the rubbery zone. All of the model parameters can be evaluated through the use of independent experimental data. Comparison of model predictions with experimental data yields good quantitative agreement outside of the glass transition region. {copyright} {ital 1997 Society of Rheology.}

  13. Laser welding and collagen crosslinks

    SciTech Connect

    Reiser, K.M.; Last, J.A.; Small, W. IV; Maitland, D.J.; Heredia, N.J.; Da Silva, L.B.; Matthews, D.L.

    1997-02-20

    Strength and stability of laser-welded tissue may be influenced, in part, by effects of laser exposure on collagen crosslinking. We therefore studied effects of diode laser exposure (805 nm, 1-8 watts, 30 seconds) + indocyanine green dye (ICG) on calf tail tendon collagen crosslinks. Effect of ICG dye alone on crosslink content prior to laser exposure was investigated; unexpectedly, we found that ICG-treated tissue had significantly increased DHLNL and OHP, but not HLNL. Laser exposure after ICG application reduced elevated DHLNL and OHP crosslink content down to their native levels. The monohydroxylated crosslink HLNL was inversely correlated with laser output (p<0.01 by linear regression analysis). DHLNL content was highly correlated with content of its maturational product, OHP, suggesting that precursor-product relations are maintained. We conclude that: (1)ICG alone induces DHLNL and OHP crosslink formation; (2)subsequent laser exposure reduces the ICG-induced crosslinks down to native levels; (3)excessive diode laser exposure destroys normally occurring HLNL crosslinks.

  14. Increasing the Depth of Mass-Spectrometry-Based Structural Analysis of Protein Complexes through the Use of Multiple Cross-Linkers.

    PubMed

    Ding, Yue-He; Fan, Sheng-Bo; Li, Shuang; Feng, Bo-Ya; Gao, Ning; Ye, Keqiong; He, Si-Min; Dong, Meng-Qiu

    2016-04-19

    Chemical cross-linking of proteins coupled with mass spectrometry (CXMS) is a powerful tool to study protein folding and to map the interfaces between interacting proteins. The most commonly used cross-linkers in CXMS are BS(3) and DSS, which have similar structures and generate the same linkages between pairs of lysine residues in spatial proximity. However, there are cases where no cross-linkable lysine pairs are present at certain regions of a protein or at the interface of two interacting proteins. In order to find the cross-linkers that can best complement the performance of BS(3) and DSS, we tested seven additional cross-linkers that either have different spacer arm structures or that target different amino acids (BS(2)G, EGS, AMAS, GMBS, Sulfo-GMBS, EDC, and TFCS). Using BSA, aldolase, the yeast H/ACA protein complex, and E. coli 70S ribosomes, we showed that, in terms of providing structural information not obtained through the use of BS(3) and DSS, EGS and Sulfo-GMBS worked better than the other cross-linkers that we tested. EGS generated a large number of cross-links not seen with the other amine-specific cross-linkers, possibly due to its hydrophilic spacer arm. We demonstrate that incorporating the cross-links contributed by the EGS and amine-sulfhydryl cross-linkers greatly increased the accuracy of Rosetta in docking the structure of the yeast H/ACA protein complex. Given the improved depth of useful information it can provide, we suggest that the multilinker CXMS approach should be used routinely when the amount of a sample permits. PMID:27010980

  15. Imidate-Based Cross-Linkers for Structural Proteomics: Increased Charge of Protein and Peptide Ions and CID and ECD Fragmentation Studies

    NASA Astrophysics Data System (ADS)

    Koolen, Hector H. F.; Gomes, Alexandre F.; Schwab, Nicolas V.; Eberlin, Marcos N.; Gozzo, Fabio C.

    2014-07-01

    Chemical cross-linking is an attractive low-resolution technique for structural studies of protein complexes. Distance constraints obtained from cross-linked peptides identified by mass spectrometry (MS) are used to construct and validate protein models. Amidinating cross-linkers such as diethyl suberthioimidate (DEST) have been used successfully in chemical cross-linking experiments. In this work, the application of a commercial diimidate cross-linking reagent, dimethyl suberimidate (DMS), was evaluated with model peptides and proteins. The peptides were designed with acetylated N-termini followed by random sequences containing two Lys residues separated by an Arg residue. After cross-linking reactions, intra- and intermolecular cross-linked species were submitted to CID and ECD dissociations to study their fragmentation features in the gas phase. Fragmentation of intramolecular peptides by collision induced dissociation (CID) demonstrates a unique two-step fragmentation pathway involving formation of a ketimine as intermediate. Electron capture and electron transfer dissociation (ECD and ETD) experiments demonstrated that the cyclic moiety is not dissociated. Intermolecular species demonstrated previously described fragmentation behavior in both CID and ECD experiments. The charge state distributions (CSD) obtained after reaction with DMS were compared with those obtained with disuccinimidyl suberate (DSS). CSDs for peptides and proteins were increased after their reaction with DMS, owing to the higher basicity of DMS modified species. These features were also observed in LC-MS experiments with bovine carbonic anhydrase II (BCA) after cross-linking with DMS and tryptic proteolysis. Cross-linked peptides derived from this protein were identified at high confidence and those species were in agreement with the crystal structure of BCA.

  16. The process of EDC-NHS cross-linking of reconstituted collagen fibres increases collagen fibrillar order and alignment

    SciTech Connect

    Shepherd, D. V. Shepherd, J. H.; Cameron, R. E.; Best, S. M.; Ghose, S.; Kew, S. J.

    2015-01-01

    We describe the production of collagen fibre bundles through a multi-strand, semi-continuous extrusion process. Cross-linking using an EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), NHS (N-hydroxysuccinimide) combination was considered. Atomic Force Microscopy and Raman spectroscopy focused on how cross-linking affected the collagen fibrillar structure. In the cross-linked fibres, a clear fibrillar structure comparable to native collagen was observed which was not observed in the non-cross-linked fibre. The amide III doublet in the Raman spectra provided additional evidence of alignment in the cross-linked fibres. Raman spectroscopy also indicated no residual polyethylene glycol (from the fibre forming buffer) or water in any of the fibres.

  17. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative

    PubMed Central

    Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

    2016-01-01

    Background Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Methods Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. Results All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. Conclusion PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment. PMID:26974150

  18. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up-regulation of lysyl oxidase-like 2.

    PubMed

    de Jong, Olivier G; van Balkom, Bas W M; Gremmels, Hendrik; Verhaar, Marianne C

    2016-02-01

    Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome-ECM interactions is limited. Here, we investigate whether the exosome-associated lysyl oxidase family member lysyl oxidase-like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)-derived exosomes, placing it in direct vicinity of the ECM. It is up-regulated twofold in EC-derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome-producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC-derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia-regulated focal ECM remodelling, a key process in both fibrosis and wound healing. PMID:26612622

  19. Crosslinked Polyamide

    DOEpatents

    Huang, Zhi H.; McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2002-06-04

    A crosslinked polyamide material and a process for preparing the crosslinked polyamide material are disclosed. The crosslinked polyamide material comprises a crosslinked chemical combination of (1) a polyamide of the formula: ##STR1## wherein n is between about 50 and 10,000, wherein each R is between 1 and 50 carbon atoms alone and is optionally substituted with heteroatoms, oxygen, nitrogen, sulfur, or phosphorus and combinations thereof, wherein multiple of the R are in vertically aligned spaced relationship along a backbone forming the polyamide, and wherein two or more of the R contain an amino group; and (2) a crosslinking agent containing at least two functional groups capable of reacting with the amino groups of the polyamide. In one embodiment of the invention, the crosslinking agent is an aliphatic or aromatic isocyanate compound having 2 or more --N.dbd.C.dbd.O groups. In another embodiment of the invention, the crosslinking agent is an aliphatic aldehyde or aromatic aldehyde compound having 2 or more --CHO groups. In still another embodiment of the invention, the crosslinking agent is selected from a phosphine having the general formula (A).sub.2 P(B) and mixtures thereof, wherein A is hydroxyalkyl, and B is hydroxyalkyl, alkyl, or aryl. In yet another embodiment of the invention, the crosslinking agent is selected from the group consisting of epoxy resins having more than one epoxide group per molecule.

  20. Oxidation resistant peroxide cross-linked UHMWPE produced by blending and surface diffusion

    NASA Astrophysics Data System (ADS)

    Gul, Rizwan M.; Oral, Ebru; Muratoglu, Orhun K.

    2014-06-01

    Ultra-high molecular weight polyethylene (UHMWPE) has been widely used as acetabular cup in total hip replacement (THR) and tibial component in total knee replacement (TKR). Crosslinking of UHMWPE has been successful used to improve its wear performance leading to longer life of orthopedic implants. Crosslinking can be performed by radiation or organic peroxides. Peroxide crosslinking is a convenient process as it does not require specialized equipment and the level of crosslinking can be manipulated by changing the amount of peroxide added. However, there is concern about the long-term stability of these materials due to possible presence of by-products. Vitamin E has been successfully used to promote long-term oxidative stability of UHMWPE. In this study, UHMWPE has been crosslinked using organic peroxide in the presence of Vitamin E to produce an oxidation resistant peroxide crosslinked material. Crosslinking was performed both in bulk by mixing peroxide and resin, and only on the surface using diffusion of peroxides.The results show that UHMWPE can be crosslinked using organic peroxides in the presence of vitamin E by both methods. However, the level of crosslinking decreases with the increase in vitamin E content. The wear resistance increases with the increase in crosslink density, and oxidation resistance significantly increases due to the presence of vitamin E.

  1. Physicochemical properties and bioactivity of nisin-containing cross-linked hydroxypropylmethylcellulose films.

    PubMed

    Sebti, Issam; Delves-Broughton, John; Coma, Véronique

    2003-10-22

    Cross-linked hydroxypropylmethylcellulose (HPMC) cast films with citric acid as polycarboxylic cross-linker were elaborated to study the effect of cross-linking level on various properties. Increased amounts of cross-linking agent were not connected to statistically different tensile strength and Young's modulus. Whatever the cross-linking level of the film was, the ultimate elongation parameter decreased by approximately 60% compared to the HMPC control film. Moisture sorption isotherms and water contact angle meter showed that the effect of cross-linking degree tends to reduce the hygroscopic and hydrophilic characteristics of films. In addition, to control bacteria growth on food surfaces, the antimicrobial activity of both 98% cross-linked HPMC-nisin and control HPMC-nisin films was tested on Micrococcus luteus. Despite the incorporation of a significant content of nisin, cross-linked HPMC-nisin films were completely inactive on the microbial strain compared to the HPMC-nisin control films. Cross-linking conditions likely either denatured the nisin or irreversibly bound nisin to the cross-linked HPMC. However, nisin adsorbed into films made from previously cross-linked HPMC maintained its activity. PMID:14558764

  2. Cross-linked low molecular weight glycopeptide-mediated gene delivery: relationship between DNA metabolic stability and the level of transient gene expression in vivo.

    PubMed

    Yang, Y; Park, Y; Man, S; Liu, Y; Rice, K G

    2001-12-01

    DNA co-condensates were formed by reacting [125I]DNA with an admixture of a high-mannose glycopeptide (Man9-CWK(18)) and either of two poly(ethylene glycol) peptides (PEG-VS-CWK(18) or PEG-SS-CWK(18)) followed by cross-linking with 6-50 mol equiv of glutaraldehyde. [125I]DNA co-condensates were administered intravenously in mice to determine the influence of peptide DNA formulation parameters on specific targeting to Kupffer cells. Optimal targeting to Kupffer cells required the combined use of 50 mol % Man9-CWK(18) and PEG-CWK(18) to mediate specific recognition by the mannose receptor to Kupffer cells. The cellular uptake of cross-linked Man9-CWK(18)/PEG-CWK(18) DNA co-condensates was receptor mediated since Kupffer cell targeting was inhibited by pre-administration of Man-bovine serum albumin (BSA) but not BSA. An optimized formulation targeted 60% of the dose to the liver, with 80% of the liver-targeted DNA localized to Kupffer cells. Cross-linking with either 6, 15, or 50 mol equiv of glutaraldehyde led to a corresponding decrease in the metabolism rate of DNA in liver as measured by half-live- of 4, 6, and 39 h, respectively. Tail vein dosing of 50 microg of DNA co-condensates cross-linked with 6 mol equiv of glutaraldehyde produced detectable levels of human alpha1-antitrypsin in blood after 12 h, which peaked at day six and persisted for 10 days. The level of human alpha1-antitrypsin was elevated two-fold each day when dosing with DNA co-condensates cross-linked with 15 mol equiv of glutaraldehyde, revealing a correlation between the metabolic stability of the DNA in liver and level of gene expression. In addition to possessing greater metabolic stability, DNA co-condensates cross-linked with 50 mol equiv of glutaraldehyde, but lacking a targeting ligand, avoided rapid liver uptake and possessed a prolonged pharmacokinetic half-life, providing insight into a means to target DNA condensates to peripheral tissues. PMID:11745760

  3. Building a Better Infarct: Modulation of Collagen Cross-linking to Increase Infarct Stiffness and Reduce Left Ventricular Dilation post-Myocardial Infarction

    PubMed Central

    Voorhees, Andrew P.; DeLeon-Pennell, Kristine Y.; Ma, Yonggang; Halade, Ganesh V.; Yabluchanskiy, Andriy; Iyer, Rugmani Padmanabhan; Flynn, Elizabeth; Cates, Courtney A.; Lindsey, Merry L.; Han, Hai-Chao

    2015-01-01

    Matrix metalloproteinase-9 (MMP-9) deletion attenuates collagen accumulation and dilation of the left ventricle (LV) post-myocardial infarction (MI); however the biomechanical mechanisms underlying the improved outcome are poorly understood. The aim of this study was to determine the mechanisms whereby MMP-9 deletion alters collagen network composition and assembly in the LV post-MI to modulate the mechanical properties of myocardial scar tissue. Adult C57BL/6J wild-type (WT; n=88) and MMP-9 null (MMP-9−/−; n=92) mice of both sexes underwent permanent coronary artery ligation and were compared to day 0 controls (n=42). At day 7 post-MI, WT LVs displayed a 3-fold increase in end-diastolic volume, while MMP-9−/− showed only a 2-fold increase (p<0.05). Biaxial mechanical testing revealed that MMP-9−/− infarcts were stiffer than WT infarcts, as indicated by a 1.3-fold reduction in predicted in vivo circumferential stretch (p<0.05). Paradoxically, MMP-9−/− infarcts had a 1.8-fold reduction in collagen deposition (p<0.05). This apparent contradiction was explained by a 3.1-fold increase in lysyl oxidase (p<0.05) in MMP-9−/− infarcts, indicating that MMP-9 deletion increased collagen cross-linking activity. Furthermore, MMP-9 deletion led to a 3.0-fold increase in bone morphogenetic protein-1, the metalloproteinase that cleaves pro-collagen and pro-lysyl oxidase (p<0.05) and reduced fibronectin fragmentation by 49% (p<0.05) to enhance lysyl oxidase activity. We conclude that MMP-9 deletion increases infarct stiffness and prevents LV dilation by reducing collagen degradation and facilitating collagen assembly and cross-linking through preservation of the fibronectin network and activation of lysyl oxidase. PMID:26080361

  4. Crosslinking biopolymers for biomedical applications.

    PubMed

    Reddy, Narendra; Reddy, Roopa; Jiang, Qiuran

    2015-06-01

    Biomaterials made from proteins, polysaccharides, and synthetic biopolymers are preferred but lack the mechanical properties and stability in aqueous environments necessary for medical applications. Crosslinking improves the properties of the biomaterials, but most crosslinkers either cause undesirable changes to the functionality of the biopolymers or result in cytotoxicity. Glutaraldehyde, the most widely used crosslinking agent, is difficult to handle and contradictory views have been presented on the cytotoxicity of glutaraldehyde-crosslinked materials. Recently, poly(carboxylic acids) that can crosslink in both dry and wet conditions have been shown to provide the desired improvements in tensile properties, increase in stability under aqueous conditions, and also promote cell attachment and proliferation. Green chemicals and newer crosslinking approaches are necessary to obtain biopolymeric materials with properties desired for medical applications. PMID:25887334

  5. Effect of crosslink density on some properties of electron beam-irradiated styrene-butadiene rubber

    NASA Astrophysics Data System (ADS)

    Wang, Qingguo; Wang, Fenlan; Cheng, Kuo

    2009-11-01

    Crosslink densities of electron beam (EB)-irradiated styrene-butadiene rubber (SBR) samples were measured by using a novel magnetic resonance crosslink density spectrometer (MRCDS). With 1,1,1-trimethylolpropane triacrylate (TMPTA) loading increasing, the crosslink density of EB-irradiated SBR increases up to a certain level, and then decreases in the irradiation dose range 50-200 kGy. Tensile strength, elongation at break, thermal stability and pyrolysis products of the EB-irradiated SBR samples with different crosslink densities were also studied in this paper.

  6. Crosslinking of agarose bioplastic using citric acid.

    PubMed

    Awadhiya, Ankur; Kumar, David; Verma, Vivek

    2016-10-20

    We report chemical crosslinking of agarose bioplastic using citric acid. Crosslinking was confirmed using Fourier transform infrared (FTIR) spectroscopy. The effects of crosslinking on the tensile strength, swelling, thermal stability, and degradability of the bioplastic were studied in detail. The tensile strength of the bioplastic films increased from 25.1MPa for control films up to a maximum of 52.7MPa for citric acid crosslinked films. At 37°C, the amount of water absorbed by crosslinked agarose bioplastic was only 11.5% of the amount absorbed by non-crosslinked controls. Thermogravimetric results showed that the crosslinked samples retain greater mass at high temperature (>450°C) than control samples. Moreover, while the crosslinked films were completely degradable, the rate of degradation was lower compared to non-crosslinked controls. PMID:27474543

  7. Increased cerebellar volume and BDNF level following quadrato motor training.

    PubMed

    Ben-Soussan, Tal Dotan; Piervincenzi, Claudia; Venditti, Sabrina; Verdone, Loredana; Caserta, Micaela; Carducci, Filippo

    2015-01-01

    Using whole-brain structural measures coupled to analysis of salivary brain-derived neurotrophic factor (BDNF), we demonstrate sensory motor training-induced plasticity, including cerebellar gray matter volume increment and increased BDNF level. The increase of cerebellar volume was positively correlated with the increase of BDNF level. PMID:25311848

  8. Effects of photochemical riboflavin-mediated crosslinks on the physical properties of collagen constructs and fibrils.

    PubMed

    Rich, Harvey; Odlyha, Marianne; Cheema, Umber; Mudera, Vivek; Bozec, Laurent

    2014-01-01

    The use of collagen scaffold in tissue engineering is on the rise, as modifications to mechanical properties are becoming more effective in strengthening constructs whilst preserving the natural biocompatibility. The combined technique of plastic compression and cross-linking is known to increase the mechanical strength of the collagen construct. Here, a modified protocol for engineering these collagen constructs is used to bring together a plastic compression method, combined with controlled photochemical crosslinking using riboflavin as a photoinitiator. In order to ascertain the effects of the photochemical crosslinking approach and the impact of the crosslinks created upon the properties of the engineered collagen constructs, the constructs were characterized both at the macroscale and at the fibrillar level. The resulting constructs were found to have a 2.5 fold increase in their Young's modulus, reaching a value of 650 ± 73 kPa when compared to non-crosslinked control collagen constructs. This value is not yet comparable to that of native tendon, but it proves that combining a crosslinking methodology to collagen tissue engineering may offer a new approach to create stronger, biomimetic constructs. A notable outcome of crosslinking collagen with riboflavin is the collagen's greater affinity for water; it was demonstrated that riboflavin crosslinked collagen retains water for a longer period of time compared to non-cross-linked control samples. The affinity of the cross-linked collagen to water also resulted in an increase of individual collagen fibrils' cross-sectional area as function of the crosslinking. These changes in water affinity and fibril morphology induced by the process of crosslinking could indicate that the crosslinked chains created during the photochemical crosslinking process may act as intermolecular hydrophilic nanosprings. These intermolecular nanosprings would be responsible for a change in the fibril morphology to accommodate variable

  9. Plasma FGF23 levels increase rapidly after acute kidney injury

    PubMed Central

    Christov, Marta; Waikar, Sushrut; Pereira, Renata; Havasi, Andrea; Leaf, David E.; Goltzman, David; Pajevic, Paola Divieti; Wolf, Myles; Jüppner, Harald

    2013-01-01

    Emerging evidence suggests that fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). In order to determine how early this increase occurs we used a murine folic acid nephropathy model and found that plasma FGF23 levels increased significantly from baseline already after 1 hour of AKI, with an 18-fold increase at 24 hours. Similar elevations of FGF23 levels were found when AKI was induced in mice with osteocyte-specific parathyroid hormone receptor ablation or the global deletion of parathyroid hormone or vitamin D receptor, indicating that the increase in FGF23 was independent of parathyroid hormone and vitamin D signaling. Furthermore, FGF23 levels increased to a similar extent in wild-type mice maintained on normal or phosphate-depleted diets prior to induction of AKI, indicating that the marked FGF23 elevation is at least partially independent of dietary phosphate. Bone production of FGF23 was significantly increased in AKI. The half-life of intravenously administered recombinant FGF23 was only modestly increased. Consistent with the mouse data, plasma FGF23 levels rose 15.9-fold by 24 hours following cardiac surgery in patients who developed AKI. The levels were significantly higher than in those without postoperative AKI. Thus, circulating FGF23 levels rise rapidly during AKI in rodents and humans. In mice this increase is independent of established modulators of FGF23 secretion. PMID:23657144

  10. Constitutive Modeling of Crosslinked Nanotube Materials

    NASA Technical Reports Server (NTRS)

    Odegard, G. M.; Frankland, S. J. V.; Herzog, M. N.; Gates, T. S.; Fay, C. C.

    2004-01-01

    A non-linear, continuum-based constitutive model is developed for carbon nanotube materials in which bundles of aligned carbon nanotubes have varying amounts of crosslinks between the nanotubes. The model accounts for the non-linear elastic constitutive behavior of the material in terms of strain, and is developed using a thermodynamic energy approach. The model is used to examine the effect of the crosslinking on the overall mechanical properties of variations of the crosslinked carbon nanotube material with varying degrees of crosslinking. It is shown that the presence of the crosslinks has significant effects on the mechanical properties of the carbon nanotube materials. An increase in the transverse shear properties is observed when the nanotubes are crosslinked. However, this increase is accompanied by a decrease in axial mechanical properties of the nanotube material upon crosslinking.

  11. Increased kinin levels and decreased responsiveness to kinins during aging.

    PubMed

    Pérez, Viviana; Velarde, Victoria; Acuña-Castillo, Claudio; Gómez, Christian; Nishimura, Sumiyo; Sabaj, Valeria; Walter, Robin; Sierra, Felipe

    2005-08-01

    Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals. PMID:16127100

  12. Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin

    NASA Technical Reports Server (NTRS)

    Reed, G. L.; Matsueda, G. R.; Haber, E.

    1992-01-01

    Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.

  13. Increases in Serum Estrone Sulfate Level Are Associated with Increased Mammographic Density during Menopausal Hormone Therapy

    PubMed Central

    Crandall, Carolyn J.; Guan, Min; Laughlin, Gail A.; Ursin, Giske A.; Stanczyk, Frank Z.; Ingles, Sue A.; Barrett-Connor, Elizabeth; Greendale, Gail A.

    2009-01-01

    Background Menopausal hormone therapy increases mammographic density. We determined whether increases in serum estrone sulfate (E1S) levels during menopausal hormone therapy predict increased mammographic density. Methods We measured percent mammographic density and serum E1S levels in 428 participants of the Postmenopausal Estrogen/Progestin Interventions study who were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg alone, CEE + daily medroxyprogesterone acetate (MPA) 2.5 mg, CEE + cyclical MPA (10 mg days 1-12 per 28-day cycle), or CEE + cyclical micronized progesterone (10 mg days 1-12). Serum E1S levels were determined by RIA. Information about covariates was determined by annual questionnaire. Using linear regression, we determined the association between change in E1S level from baseline to 12 months and change in percent mammographic density (by semiquantitative interactive threshold method). Results After controlling for baseline mammographic density, age, body mass index, alcohol intake, parity, smoking, ethnicity, physical activity, and age at first pregnancy, mammographic density increased by 1.3% for every 1 ng/mL increase in E1S level (P < 0.0001). The association between change in E1S level and change in mammographic density differed by treatment group (greater effect in CEE + cyclical MPA group versus CEE group; P = 0.05). After controlling for treatment group, change in the ratio of E1S to E1 was also positively associated with change in mammographic density. Conclusions Increases in serum E1S levels during menopausal hormone therapy are associated with increases in mammographic density. The relative contribution of E1S and E1 to stimulation of breast tissue awaits further elucidation. PMID:18628419

  14. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  15. Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level.

    PubMed

    Kashihara, T; Ohki, A; Kobayashi, T; Sato, T; Nishizawa, H; Ogawa, K; Tako, H; Kawakami, F; Tsuji, M; Tamaoka, K

    1998-06-01

    CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC. PMID:9658330

  16. Biologically relevant oxidants cause bound proteins to readily oxidatively cross-link at Guanine.

    PubMed

    Solivio, Morwena J; Nemera, Dessalegn B; Sallans, Larry; Merino, Edward J

    2012-02-20

    Oxidative DNA-protein cross-links have received less attention than other types of DNA damage and remain as one of the least understood types of oxidative lesion. A model system using ribonuclease A and a 27-nucleotide DNA was used to determine the propensity of oxidative cross-linking to occur in the presence of oxidants. Cross-link formation was examined using four different oxidation systems that generate singlet oxygen, superoxide, and metal-based Fenton reactions. It is shown that oxidative cross-linking occurs in yields ranging from 14% to a maximal yield of 61% in all oxidative systems when equivalent concentrations of DNA and protein are present. Because singlet oxygen is the most efficient oxidation system in generating DNA-protein cross-links, it was chosen for further analyses. Cross-linking occurred with single-stranded DNA binding protein and not with bovine serum albumin. Addition of salt lowered nonspecific binding affinity and lowered cross-link yield by up to 59%. The yield of cross-linking increased with increased ratios of protein compared with DNA. Cross-linking was highly dependent on the number of guanines in a DNA sequence. Loss of guanine content on the 27-nucleotide DNA led to nearly complete loss in cross-linking, while primer extension studies showed cross-links to predominantly occur at guanine base on a 100-nucleotide DNA. The chemical species generated were examined using two peptides derived from the ribonuclease A sequence, N-acetyl-AAAKF and N-acetyl-AYKTT, which were cross-linked to 2'-deoxyguanosine. The cross-link products were spiroiminodihydantoin, guanidinohydantoin, and tyrosyl-based adducts. Formation of tyrosine-based adducts may be competitive with the more well-studied lysine-based cross-links. We conclude that oxidative cross-links may be present at high levels in cells since the propensity to oxidatively cross-link is high and so much of the genomic DNA is coated with protein. PMID:22216745

  17. Endozepine-4 levels are increased in hepatic coma

    PubMed Central

    Malaguarnera, Giulia; Vacante, Marco; Drago, Filippo; Bertino, Gaetano; Motta, Massimo; Giordano, Maria; Malaguarnera, Michele

    2015-01-01

    AIM: To evaluate the serum levels of endozepine-4, their relation with ammonia serum levels, the grading of coma and the severity of cirrhosis, in patients with hepatic coma. METHODS: In this study we included 20 subjects with Hepatic coma, 20 subjects with minimal hepatic encephalopathy (MHE) and 20 subjects control. All subjects underwent blood analysis, Child Pugh and Model for End - stage liver disease (MELD) assessment, endozepine-4 analysis. RESULTS: Subjects with hepatic coma showed significant difference in endozepine-4 (P < 0.001) and NH3 levels (P < 0.001) compared both to MHE and controls patients. Between NH3 and endozepine-4 we observed a significant correlation (P = 0.009; Pearson correlation 0.570). There was a significant correlation between endozepine-4 and MELD (P = 0.017; Pearson correlation = 0.529). In our study blood ammonia concentration was noted to be raised in patients with hepatic coma, with the highest ammonia levels being found in those who were comatose. We also found a high correlation between endozepine-4 and ammonia (P < 0.001). In patients with grade IV hepatic coma, endozepine levels were significantly higher compared to other groups. CONCLUSION: This study suggests that an increased level of endozepine in subjects with higher levels of MELD was observed. In conclusion, data concerning involvement of the GABA-ergic system in HE coma could be explained by stage-specific alterations. PMID:26290636

  18. Nanogel-crosslinked nanoparticles increase the inhibitory effects of W9 synthetic peptide on bone loss in a murine bone resorption model.

    PubMed

    Sato, Toshimi; Alles, Neil; Khan, Masud; Nagano, Kenichi; Takahashi, Mariko; Tamura, Yukihiko; Shimoda, Asako; Ohya, Keiichi; Akiyoshi, Kazunari; Aoki, Kazuhiro

    2015-01-01

    We investigated the biological activity of W9, a bone resorption inhibitor peptide, using NanoClik nanoparticles as an injectable carrier, where acryloyl group-modified cholesterol-bearing pullulan (CHPOA) nanogels were crosslinked by pentaerythritol tetra (mercaptoethyl) polyoxyethylene. Thirty 5-week-old male C57BL/6J mice were fed a low calcium diet and received once-daily subcutaneous injections of the carrier alone, W9 24 mg/kg/day alone, W9 24 mg/kg/day incorporated in cholesterol bearing pullulan (CHP) nanogels, or W9 (8 and 24 mg/kg/day) incorporated in NanoClik nanoparticles for 4 days (n=5). Mice that received a normal calcium diet with NanoClik nanoparticle injections without W9 were used as a control group. Radiological analyses showed that administration of W9 24 mg/kg/day significantly prevented low calcium-induced reduction of bone mineral density in the long bones and lumbar vertebrae, but only when the NanoClik nanoparticles were used as a carrier. Histomorphometric analyses of the proximal tibiae revealed that W9 24 mg/kg/day incorporated in NanoClik nanoparticles prevented the increase in bone resorption indices induced by a low calcium diet, which was confirmed by measurement of serum bone resorption markers. These data suggest that NanoClik nanoparticles could be a useful carrier for peptide therapeutics, and also demonstrate that daily subcutaneous injections of the W9 peptide with the nanoparticles were able to inhibit bone loss in vivo. An osteoclastogenesis inhibition assay performed in vitro confirmed a slower release profile of W9 from NanoClik nanoparticles compared with conventional CHP nanogels. PMID:25999711

  19. Orchiectomy increases bone marrow interleukin-6 levels in mice.

    PubMed

    Zhang, J; Pugh, T D; Stebler, B; Ershler, W B; Keller, E T

    1998-03-01

    Interleukin-6 (IL-6) appears to be an important factor in disease states associated with bone resorption. There is both in vitro and in vivo evidence supporting the fact that androgens down-regulate interleukin-6 production. These observations, in combination with the fact that osteoblasts and bone marrow stromal cells produce IL-6, led us to hypothesize that orchiectomy-induced androgen loss will result in increased IL-6 expression in the bone microenvironment. To prove our hypothesis we assessed the effect of orchiectomy on IL-6 protein and mRNA expression in bone marrow and spleen. We found that orchiectomy was associated with increased serum IL-6 levels at 3 and 28 days postsurgery. Phorbol ester-stimulated IL-6 levels were also higher in supernatants from bone marrow and spleen cell cultures from orchiectomized mice compared with unoperated or sham-operated mice. Additionally, we found that steady state IL-6 mRNA levels were increased in bone marrow but not spleen cells. Finally, we found that orchiectomized mice had splenomegaly and increased bone marrow cellularity. Histopathology of the spleen revealed lymphoid hyperplasia accompanied by a marked mononuclear cell infiltration of the red pulp. We conclude that orchiectomy induces IL-6 expression in the bone marrow. These findings suggest that endocrine and cytokine interactions contribute to bone pathophysiology. PMID:9501955

  20. Increasing carbonmonoxide blood levels in Bangkok bus drivers

    SciTech Connect

    Saenghirunvattana, S.; Wananukul, W.; Mokkhavesa, C.; Opasi, N.

    1995-05-01

    In order to study the effects of air pollution in Bangkok, 31 bus drivers were examined and blood was drawn for measurement of carboxyhemoglobin (COHb) prior to and after work. The COHb level before work was 2.19{+-}2.46% (range 0.7.18). It had increased after work to 5.26{+-}2.52% (range 0-10.4) (p<0.001). Twenty-one drivers complained of chronic headaches, myalgia, and eye irritation during working hours. The COHb level was not statistically different between smokers and nonsmokers.

  1. Increased Intraocular Pressure and Hyperglycemic Level in Diabetic Patients

    PubMed Central

    Hymowitz, Maggie B.; Chang, Donny; Feinberg, Edward B.; Roy, Sayon

    2016-01-01

    Purpose To determine whether hyperglycemic levels as determined from high hemoglobin A1c (HbA1c) levels influence intraocular pressure (IOP) in patients with non-proliferative diabetic retinopathy (NPDR). Methods A retrospective chart review was performed on subjects with a diagnosis of NPDR and a corresponding HbA1c level measured within 90 days before or after an IOP measurement over a two-year period. Exclusion criteria included a diagnosis of glaucoma or treatment with IOP lowering medications or oral or topical steroids. Results Using 14.5mmHg as a baseline mean value for IOP, 42 subjects had an IOP < 14.5mmHg and mean HbA1c of 8.1±1.1, while 72 subjects had an IOP ≥ 14.5mmHg and a mean HbA1c of 9.0±2.1. Although there was an overlap in the confidence intervals, a significant difference (P = 0.01) in the mean HbA1c level was observed in regression analysis between the two groups. Importantly, diabetic subjects with elevated HbA1c levels rarely (<1%) exhibited reduced IOP levels. Conclusions Diabetic subjects with elevated HbA1c levels exhibited significantly higher IOPs compared to those with lower HbA1c levels. Findings from this study indicate an association between hyperglycemia and elevated IOP and that poor glycemic control may contribute to increased IOP levels in long-term diabetic patients. PMID:27002725

  2. The Importance of Non-accessible Crosslinks and Solvent Accessible Surface Distance in Modeling Proteins with Restraints From Crosslinking Mass Spectrometry*

    PubMed Central

    Matthew Allen Bullock, Joshua; Schwab, Jannik; Thalassinos, Konstantinos; Topf, Maya

    2016-01-01

    Crosslinking mass spectrometry (XL-MS) is becoming an increasingly popular technique for modeling protein monomers and complexes. The distance restraints garnered from these experiments can be used alone or as part of an integrative modeling approach, incorporating data from many sources. However, modeling practices are varied and the difference in their usefulness is not clear. Here, we develop a new scoring procedure for models based on crosslink data—Matched and Nonaccessible Crosslink score (MNXL). We compare its performance with that of other commonly-used scoring functions (Number of Violations and Sum of Violation Distances) on a benchmark of 14 protein domains, each with 300 corresponding models (at various levels of quality) and associated, previously published, experimental crosslinks (XLdb). The distances between crosslinked lysines are calculated either as Euclidean distances or Solvent Accessible Surface Distances (SASD) using a newly-developed method (Jwalk). MNXL takes into account whether a crosslink is nonaccessible, i.e. an experimentally observed crosslink has no corresponding SASD in a model due to buried lysines. This metric alone is shown to have a significant impact on modeling performance and is a concept that is not considered at present if only Euclidean distances are used. Additionally, a comparison between modeling with SASD or Euclidean distance shows that SASD is superior, even when factoring out the effect of the nonaccessible crosslinks. Our benchmarking also shows that MNXL outperforms the other tested scoring functions in terms of precision and correlation to Cα-RMSD from the crystal structure. We finally test the MNXL at different levels of crosslink recovery (i.e. the percentage of crosslinks experimentally observed out of all theoretical ones) and set a target recovery of ∼20% after which the performance plateaus. PMID:27150526

  3. The Importance of Non-accessible Crosslinks and Solvent Accessible Surface Distance in Modeling Proteins with Restraints From Crosslinking Mass Spectrometry.

    PubMed

    Matthew Allen Bullock, Joshua; Schwab, Jannik; Thalassinos, Konstantinos; Topf, Maya

    2016-07-01

    Crosslinking mass spectrometry (XL-MS) is becoming an increasingly popular technique for modeling protein monomers and complexes. The distance restraints garnered from these experiments can be used alone or as part of an integrative modeling approach, incorporating data from many sources. However, modeling practices are varied and the difference in their usefulness is not clear. Here, we develop a new scoring procedure for models based on crosslink data-Matched and Nonaccessible Crosslink score (MNXL). We compare its performance with that of other commonly-used scoring functions (Number of Violations and Sum of Violation Distances) on a benchmark of 14 protein domains, each with 300 corresponding models (at various levels of quality) and associated, previously published, experimental crosslinks (XLdb). The distances between crosslinked lysines are calculated either as Euclidean distances or Solvent Accessible Surface Distances (SASD) using a newly-developed method (Jwalk). MNXL takes into account whether a crosslink is nonaccessible, i.e. an experimentally observed crosslink has no corresponding SASD in a model due to buried lysines. This metric alone is shown to have a significant impact on modeling performance and is a concept that is not considered at present if only Euclidean distances are used. Additionally, a comparison between modeling with SASD or Euclidean distance shows that SASD is superior, even when factoring out the effect of the nonaccessible crosslinks. Our benchmarking also shows that MNXL outperforms the other tested scoring functions in terms of precision and correlation to Cα-RMSD from the crystal structure. We finally test the MNXL at different levels of crosslink recovery (i.e. the percentage of crosslinks experimentally observed out of all theoretical ones) and set a target recovery of ∼20% after which the performance plateaus. PMID:27150526

  4. Placental Cadmium Levels Are Associated with Increased Preeclampsia Risk

    PubMed Central

    Laine, Jessica E.; Ray, Paul; Bodnar, Wanda; Cable, Peter H.; Boggess, Kim; Offenbacher, Steven; Fry, Rebecca C.

    2015-01-01

    Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1–2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1–3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5–1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8–3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8–2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted. PMID:26422011

  5. Loss of BMP signaling through BMPR1A in osteoblasts leads to greater collagen cross-link maturation and material-level mechanical properties in mouse femoral trabecular compartments.

    PubMed

    Zhang, Yanshuai; McNerny, Erin Gatenby; Terajima, Masahiko; Raghavan, Mekhala; Romanowicz, Genevieve; Zhang, Zhanpeng; Zhang, Honghao; Kamiya, Nobuhiro; Tantillo, Margaret; Zhu, Peizhi; Scott, Gregory J; Ray, Manas K; Lynch, Michelle; Ma, Peter X; Morris, Michael D; Yamauchi, Mitsuo; Kohn, David H; Mishina, Yuji

    2016-07-01

    Bone morphogenetic protein (BMP) signaling pathways play critical roles in skeletal development and new bone formation. Our previous study, however, showed a negative impact of BMP signaling on bone mass because of the osteoblast-specific loss of a BMP receptor (i.e. BMPR1A) showing increased trabecular bone volume and mineral density in mice. Here, we investigated the bone quality and biomechanical properties of the higher bone mass associated with BMPR1A deficiency using the osteoblast-specific Bmpr1a conditional knockout (cKO) mouse model. Collagen biochemical analysis revealed greater levels of the mature cross-link pyridinoline in the cKO bones, in parallel with upregulation of collagen modifying enzymes. Raman spectroscopy distinguished increases in the mature to immature cross-link ratio and mineral to matrix ratio in the trabecular compartments of cKO femora, but not in the cortical compartments. The mineral crystallinity was unchanged in the cKO in either the trabecular or cortical compartments. Further, we tested the intrinsic material properties by nanoindentation and found significantly higher hardness and elastic modulus in the cKO trabecular compartments, but not in the cortical compartments. Four point bending tests of cortical compartments showed lower structural biomechanical properties (i.e. strength and stiffness) in the cKO bones due to the smaller cortical areas. However, there were no significant differences in biomechanical performance at the material level, which was consistent with the nanoindentation test results on the cortical compartment. These studies emphasize the pivotal role of BMPR1A in the determination of bone quality and mechanical integrity under physiological conditions, with different impact on femoral cortical and trabecular compartments. PMID:27113526

  6. Dual Ionic and Photo-Crosslinked Alginate Hydrogels for Micropatterned Spatial Control of Material Properties and Cell Behavior.

    PubMed

    Samorezov, Julia E; Morlock, Colin M; Alsberg, Eben

    2015-07-15

    Biomaterial properties such as mechanics, degradation rate, and cell adhesivity affect cell behaviors including spreading, proliferation, and differentiation. To engineer complex tissues, it is often desirable to achieve precise spatial control over these properties. Here, methacrylated alginate (MA-ALG) was used to create hydrogels comprising a single base material with regions of different types and levels of crosslinking and subsequently different material properties. Ionic and ultraviolet light crosslinking mechanisms were combined to create dual-crosslinked hydrogels with significantly increased stiffness and decreased swelling compared to calcium-crosslinked or UV-crosslinked hydrogels. MC3T3 cells showed significantly enhanced proliferation on the surface of dual-crosslinked hydrogels compared with calcium-crosslinked hydrogels. Photomasks were then used to create patterned hydrogels with precise spatial control over regions that were only calcium-crosslinked versus dual-crosslinked. This spatial variation in crosslinking mechanism permitted local regulation of the hydrogel physical properties and alignment of cells seeded on their surface. Photomasks were also used to create hydrogels with patterned presentation of cell adhesion ligands, leading to spatial control over cell attachment and proliferation. This biomaterial system can be useful for providing patterned, instructive cues to guide cell behavior for engineering complex tissues. PMID:25799217

  7. A Three Level Autonomous Software System for Increased Science Return

    NASA Astrophysics Data System (ADS)

    Robinson, P. I.; Mancinelli, R. L.; Landheim, R.

    2005-12-01

    The development of smart science instruments for autonomous operation (on Earth or in space) has the potential to increase science return and reduce the risk of experiment failure. When researchers are confronted with unexpected data/results of the experimental test system, they must determine whether the experimental setup has failed, or scientific discovery is being made. These two classes of events could have the same time series signature. To directly address this issue, we have developed a three-level software system referred to as E3, which consists of an engineering level, an experiment level, and an executive level. Each level of the software system is designed in a modular fashion using model based feedback controllers. The same feedback control mechanism is used for each level; the model itself determines the level. To determine if failure of the experimental setup can explain the data/results, researchers run calibration tests for hardware (e.g., sensors and actuators) as well as verify that the software (e.g., controls and analog to digital conversion routines) is running as planned. If anomalies are found, then modifications are made to the experimental setup, or the anomaly is accepted as the new baseline state of the instrument. The engineering level of the E3 software system is responsible for this process. To determine if scientific discovery, as opposed to failure, can explain the data/results, a researcher tries to explain the difference between the observed and expected results. These explanations are terms of the basic processes of nature to determine the rate limiting step(s) of a complex set of processes, where the flux could be due to heat transfer, mass transfer, momentum transfer, or chemical reaction processes. Once the differences are understood, modifications are made to the software control of the experiment, as well as to the model the researcher is building over the course of repeated experiments. The experiment level of the E3

  8. Genistein increases glycosaminoglycan levels in mucopolysaccharidosis type I cell models.

    PubMed

    Kingma, Sandra D K; Wagemans, Tom; IJlst, Lodewijk; Wijburg, Frits A; van Vlies, Naomi

    2014-09-01

    Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder characterized by diminished degradation of the glycosaminoglycans (GAGs) heparan sulfate and dermatan sulfate, which results in the accumulation of these GAGs and subsequent cellular dysfunction. Patients present with a variety of symptoms, including severe skeletal disease. Genistein has been shown previously to inhibit GAG synthesis in MPS fibroblasts, presumably through inhibition of tyrosine kinase activity of the epidermal growth factor receptor (EGFR). To determine the potentials of genistein for the treatment of skeletal disease, MPS I fibroblasts were induced into chondrocytes and osteoblasts and treated with genistein. Surprisingly, whereas tyrosine phosphorylation levels (as a measure for tyrosine kinase inhibition) were decreased in all treated cell lines, there was a 1.3 and 1.6 fold increase in GAG levels in MPS I chondrocytes and fibroblast, respectively (p < 0.05). Sulfate incorporation in treated MPS I fibroblasts was 2.6 fold increased (p < 0.05), indicating increased GAG synthesis despite tyrosine kinase inhibition. This suggests that GAG synthesis is not exclusively regulated through the tyrosine kinase activity of the EGFR. We hypothesize that the differences in outcomes between studies on the effect of genistein in MPS are caused by the different effects of genistein on different growth factor signaling pathways, which regulate GAG synthesis. More studies are needed to elucidate the precise signaling pathways which are affected by genistein and alter GAG metabolism in order to evaluate the therapeutic potential of genistein for MPS patients. PMID:24699889

  9. Increased levels of metallothionein in placenta of smokers.

    PubMed

    Ronco, Ana Maria; Arguello, Graciela; Suazo, Myriam; Llanos, Miguel N

    2005-03-01

    Experiments were designed to evaluate and compare metallothionein (MT), zinc and cadmium levels in human placentas of smoking and non-smoking women. Smoking was assessed by self-reported cigarette consumption and urine cotinine levels before delivery. Smoking pregnant women with urine cotinine levels higher than 130 ng/ml were included in the smoking group. Determination of placental MT was performed by western blot analysis after tissue homogenization and saturation with cadmium chloride (1000 ppm). Metallothionein was analyzed with a monoclonal antibody raised against MT-1 and MT-2 and with a second anti mouse antibody conjugated to alkaline phosphatase. Zinc and cadmium were determined by neutron activation analysis and atomic absorption spectrometry respectively. Smokers showed higher placental MT and cadmium levels, together with decreased newborn birth weights, as compared to non-smokers. The semi-quantitative analysis of western blots by band densitometry indicated that darker bands corresponded to MT present in smokers' samples. This study confirms that cigarette smoking increases cadmium accumulation in placental tissue and suggests that this element has a stimulatory effect on placental MT production. PMID:15664440

  10. Can nursing students' confidence levels increase with repeated simulation activities?

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

    In 2014, nursing faculty conducted a study with undergraduate nursing students on their satisfaction, confidence, and educational practice levels, as it related to simulation activities throughout the curriculum. The study was a voluntary survey conducted on junior and senior year nursing students. It consisted of 30 items based on the Student Satisfaction and Self-Confidence in Learning and the Educational Practices Questionnaire (Jeffries, 2012). Mean averages were obtained for each of the 30 items from both groups and were compared using T scores for unpaired means. The results showed that 8 of the items had a 95% confidence level and when combined the items were significant for p <.001. The items identified were those related to self-confidence and active learning. Based on these findings, it can be assumed that repeated simulation experiences can lead to an increase in student confidence and active learning. PMID:26599594

  11. Increased levels of copeptin before clinical diagnosis of preelcampsia.

    PubMed

    Yeung, Edwina H; Liu, Aiyi; Mills, James L; Zhang, Cuilin; Männistö, Tuija; Lu, Zhaohui; Tsai, Michael Y; Mendola, Pauline

    2014-12-01

    Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992-1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure≥90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03-2.31) when compared with controls (P=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08-3.20) than those diagnosed later (1.45; 0.91-2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone. PMID:25225209

  12. Can increased atmospheric CO2 levels trigger a runaway greenhouse?

    PubMed

    Ramirez, Ramses M; Kopparapu, Ravi Kumar; Lindner, Valerie; Kasting, James F

    2014-08-01

    Recent one-dimensional (globally averaged) climate model calculations by Goldblatt et al. (2013) suggest that increased atmospheric CO(2) could conceivably trigger a runaway greenhouse on present Earth if CO(2) concentrations were approximately 100 times higher than they are today. The new prediction runs contrary to previous calculations by Kasting and Ackerman (1986), which indicated that CO(2) increases could not trigger a runaway, even at Venus-like CO(2) concentrations. Goldblatt et al. argued that this different behavior is a consequence of updated absorption coefficients for H(2)O that make a runaway more likely. Here, we use a 1-D climate model with similar, up-to-date absorption coefficients, but employ a different methodology, to show that the older result is probably still valid, although our model nearly runs away at ∼12 preindustrial atmospheric levels of CO(2) when we use the most alarmist assumptions possible. However, we argue that Earth's real climate is probably stable given more realistic assumptions, although 3-D climate models will be required to verify this result. Potential CO(2) increases from fossil fuel burning are somewhat smaller than this, 10-fold or less, but such increases could still cause sufficient warming to make much of the planet uninhabitable by humans. PMID:25061956

  13. Viscoelastic behavior of polymers undergoing crosslinking reactions.

    NASA Technical Reports Server (NTRS)

    Moacanin, J.; Aklonis, J. J.

    1971-01-01

    Previously a method was developed for predicting the viscoelastic response of polymers undergoing scission reactions. These results are now extended to include crosslinking reactions. As for scission, at any given time the character of the network chains is determined by the instantaneous crosslink density. For scission all chains were assumed to carry the same stress; for crosslinking, however, the stress is distributed between the 'new' and 'old' chains. Equations for calculating the creep response of a system which experiences a step increase in crosslink density are derived.

  14. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks.

    PubMed

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-01-01

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment. PMID:26633522

  15. Artificially Increased Yolk Hormone Levels and Neophobia in Domestic Chicks

    PubMed Central

    Bertin, Aline; Arnould, Cécile; Moussu, Chantal; Meurisse, Maryse; Constantin, Paul; Leterrier, Christine; Calandreau, Ludovic

    2015-01-01

    In birds there is compelling evidence that the development and expression of behavior is affected by maternal factors, particularly via variation in yolk hormone concentrations of maternal origin. In the present study we tested whether variation in yolk hormone levels lead to variation in the expression of neophobia in young domestic chicks. Understanding how the prenatal environment could predispose chicks to express fear-related behaviors is essential in order to propose preventive actions and improve animal welfare. We simulated the consequences of a maternal stress by experimentally enhancing yolk progesterone, testosterone and estradiol concentrations in hen eggs prior to incubation. The chicks from these hormone-treated eggs (H) and from sham embryos (C) that received the vehicle-only were exposed to novel food, novel object and novel environment tests. H chicks approached a novel object significantly faster and were significantly more active in a novel environment than controls, suggesting less fearfulness. Conversely, no effect of the treatment was found in food neophobia tests. Our study highlights a developmental influence of yolk hormones on a specific aspect of neophobia. The results suggest that increased yolk hormone levels modulate specifically the probability of exploring novel environments or novel objects in the environment. PMID:26633522

  16. Effect of Increased Water Vapor Levels on TBC Lifetime

    SciTech Connect

    Pint, Bruce A; Garner, George Walter; Lowe, Tracie M; Haynes, James A; Zhang, Ying

    2011-01-01

    To investigate the effect of increased water vapor levels on thermal barrier coating (TBC) lifetime, furnace cycle tests were performed at 1150 C in air with 10 vol.% water vapor (similar to natural gas combustion) and 90 vol.%. Either Pt diffusion or Pt-modified aluminide bond coatings were applied to specimens from the same batch of a commercial second-generation single-crystal superalloy and commercial vapor-deposited yttria-stabilized zirconia (YSZ) top coats were applied. Three coatings of each type were furnace cycled to failure to compare the average lifetimes obtained in dry O{sub 2}, using the same superalloy batch and coating types. Average lifetimes with Pt diffusion coatings were unaffected by the addition of water vapor. In contrast, the average lifetime of Pt-modified aluminide coatings was reduced by more than 50% with 10% water vapor but only slightly reduced by 90% water vapor. Based on roughness measurements from similar specimens without a YSZ coating, the addition of 10% water vapor increased the rate of coating roughening more than 90% water vapor. Qualitatively, the amount of {beta}-phase depletion in the coatings exposed in 10% water vapor did not appear to be accelerated.

  17. Increased levels of inosine in a mouse model of inflammation

    PubMed Central

    Prestwich, Erin G; Mangerich, Aswin; Pang, Bo; McFaline, Jose L; Lonkar, Pallavi; Sullivan, Matthew R; Trudel, Laura J; Taghizedeh, Koli; Dedon, Peter C

    2013-01-01

    One possible mechanism linking inflammation with cancer involves the generation of reactive oxygen, nitrogen and halogen species by activated macrophages and neutrophils infiltrating sites of infection or tissue damage, with these chemical mediators causing damage that ultimately leads to cell death and mutation. To determine the most biologically deleterious chemistries of inflammation, we previously assessed products across the spectrum of DNA damage arising in inflamed tissues in the SJL mouse model nitric oxide over-production (Pang et al., Carcinogenesis 28: 1807–1813, 2007). Among the anticipated DNA damage chemistries, we observed significant changes only in lipid peroxidation-derived etheno adducts. We have now developed an isotope-dilution, liquid chromatography-coupled, tandem quadrupole mass spectrometric method to quantify representative species across the spectrum of RNA damage products predicted to arise at sites of inflammation, including nucleobase deamination (xanthosine, inosine), oxidation (8-oxoguanosine), and alkylation (1,N6-etheno-adenosine). Application of the method to liver, spleen, and kidney from the SJL mouse model revealed generally higher levels of oxidative background RNA damage than was observed in DNA in control mice. However, compared to control mice, RcsX treatment to induce nitric oxide overproduction resulted in significant increases only in inosine and only in the spleen. Further, the nitric oxide synthase inhibitor, N-methylarginine, did not significantly affect the levels of inosine in control and RcsX-treated mice. The differences between DNA and RNA damage in the same animal model of inflammation point to possible influences from DNA repair, RcsX-induced alterations in adenosine deaminase activity, and differential accessibility of DNA and RNA to reactive oxygen and nitrogen species as determinants of nucleic acid damage during inflammation. PMID:23506120

  18. Selective enrichment and identification of cross-linked peptides to study 3-D structures of protein complexes by mass spectrometry.

    PubMed

    Buncherd, Hansuk; Nessen, Merel A; Nouse, Niels; Stelder, Sacha K; Roseboom, Winfried; Dekker, Henk L; Arents, Jos C; Smeenk, Linde E; Wanner, Martin J; van Maarseveen, Jan H; Yang, Xiao; Lewis, Peter J; de Koning, Leo J; de Koster, Chris G; de Jong, Luitzen

    2012-04-01

    Chemical cross-linking of protein complexes combined with mass spectrometry is a powerful approach to obtain 3-D structural information by revealing amino residues that are in close spatial proximity. To increase the efficiency of mass spectrometric analysis, we have demonstrated the selective enrichment of cross-linked peptides from the 350 kDa protein complex RNA polymerase (RNAP) from Bacillus subtilis. Bis(succinimidyl)-3-azidomethyl glutarate was used as a cross-linker along with an azide-reactive cyclooctyne-conjugated resin to capture target peptides. Subsequently released peptides were fractionated by strong cation exchange chromatography and subjected to LC-MS/MS. We mapped 10 different intersubunit and 24 intrasubunit cross-links by xComb database searching supplied with stringent criteria for confirmation of the proposed structure of candidate cross-linked peptides. The cross-links fit into a homology model of RNAP. Cross-links between β lobe 1 and the β' downstream jaw, and cross-links involving the N-terminal and C-terminal parts of the α subunits suggest conformational flexibility. The analytical strategy presented here can be applied to map protein-protein interactions at the amino acid level in biological assemblies of similar complexity. Our approach enables the exploration of alternative peptide fragmentation techniques that may further facilitate cross-link analysis. PMID:22326961

  19. Increase in voice level and speaker comfort in lecture rooms.

    PubMed

    Brunskog, Jonas; Gade, Anders Christian; Bellester, Gaspar Payá; Calbo, Lilian Reig

    2009-04-01

    Teachers often suffer from health problems related to their voice. These problems are related to their working environment, including the acoustics of the lecture rooms. However, there is a lack of studies linking the room acoustic parameters to the voice produced by the speaker. In this pilot study, the main goals are to investigate whether objectively measurable parameters of the rooms can be related to an increase in the voice sound power produced by speakers and to the speakers' subjective judgments about the rooms. In six different rooms with different sizes, reverberation times, and other physical attributes, the sound power level produced by six speakers was measured. Objective room acoustic parameters were measured in the same rooms, including reverberation time and room gain, and questionnaires were handed out to people who had experience talking in the rooms. It is found that in different rooms significant changes in the sound power produced by the speaker can be found. It is also found that these changes mainly have to do with the size of the room and to the gain produced by the room. To describe this quality, a new room acoustic quantity called "room gain" is proposed. PMID:19354383

  20. Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma

    PubMed Central

    Chen, Yulong; Terajima, Masahiko; Yang, Yanan; Sun, Li; Ahn, Young-Ho; Pankova, Daniela; Puperi, Daniel S.; Watanabe, Takeshi; Kim, Min P.; Blackmon, Shanda H.; Rodriguez, Jaime; Liu, Hui; Behrens, Carmen; Wistuba, Ignacio I.; Minelli, Rosalba; Scott, Kenneth L.; Sanchez-Adams, Johannah; Guilak, Farshid; Pati, Debananda; Thilaganathan, Nishan; Burns, Alan R.; Creighton, Chad J.; Martinez, Elisabeth D.; Zal, Tomasz; Grande-Allen, K. Jane; Yamauchi, Mitsuo; Kurie, Jonathan M.

    2015-01-01

    Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde–derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde–derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma. PMID:25664850

  1. Relationship between cross-linking conditions of ethylene vinyl acetate and potential induced degradation for crystalline silicon photovoltaic modules

    NASA Astrophysics Data System (ADS)

    Jonai, Sachiko; Hara, Kohjiro; Tsutsui, Yuji; Nakahama, Hidenari; Masuda, Atsushi

    2015-08-01

    In this study, we investigated the relationship in crystalline silicon (c-Si) photovoltaic (PV) modules between the cross-linking level of copolymer of ethylene and vinyl acetate (EVA) as the encapsulant and the degree of degradation due to potential induced degradation (PID) phenomenon. We used three methods for the determination of cross-linking level of EVA: xylene method, which is one of the solvent extraction methods (SEM), curing degree by differential scanning calorimetry (DSC), and viscoelastic properties by dynamic mechanical analysis (DMA). The results indicate that degradation of PV modules by PID test depends on the cross-linking level of EVA. The PV modules encapsulated by EVA with higher cross-linking level show lower degradation degree due to PID phenomenon. Also we showed that EVA with higher cross-linking level tended to be higher volume resistivity. This tendency is similar to that for electrical resistance value during the PID test. The PID test was also done by changing thickness of EVA between front cover glass and c-Si with the same cross-linking level. The PV modules encapsulated by thicker EVA between front cover glass and c-Si cell show lower degradation by PID. From these results, the PV modules encapsulated by EVA with higher cross-linking level, higher volume resistivity and increased thickness would be tolerant of PID phenomenon.

  2. Carbodiimide cross-linking of amniotic membranes in the presence of amino acid bridges.

    PubMed

    Lai, Jui-Yang

    2015-06-01

    The purpose of this study was to investigate the carbodiimide cross-linking of amniotic membrane (AM) in the presence of amino acid bridges. The biological tissues were treated with glycine, lysine, or glutamic acid and chemically cross-linked to examine the role of amino acid types in collagenous biomaterial processing. Results of zeta potential measurements showed that the use of uncharged, positively and negatively charged amino acids dictates the charge state of membrane surface. Tensile strength and water content measurements demonstrated that the addition of lysine molecules to the cross-linking system can increase the cross-linking efficiency and dehydration degree while the introduction of glutamic acid in the AM samples decreases the number of cross-links per unit mass of chemically modified tissue collagen. The differences in the cross-linking density further determined the thermal and biological stability by differential scanning calorimetry and in vitro degradation tests. As demonstrated in matrix permeability studies, the improved formation of covalent cross-linkages imposed by lysine facilitated construction of stronger cross-linking structures. In contrast, the added glycine molecules were insufficient to enhance the resistances of the proteinaceous matrices to thermal denaturation and enzymatic degradation. The cytocompatibility of these biological tissue membranes was evaluated by using human corneal epithelial cell cultures. Results of cell viability, metabolic activity, and pro-inflammatory gene expression level showed that the AM materials cross-linked with carbodiimide in the presence of different types of amino acids are well tolerated without evidence of detrimental effect on cell growth. In addition, the amino acid treated and carbodiimide cross-linked AM implants had good biocompatibility in the anterior chamber of the rabbit eye model. Our findings suggest that amino acid type is a very important engineering parameter to mediate

  3. Computational exploration of polymer nanocomposite mechanical property modification via cross-linking topology

    SciTech Connect

    Lacevic, N; Gee, R; Saab, A; Maxwell, R

    2008-04-24

    Molecular dynamics simulations have been performed in order to study the effects of nanoscale filler cross-linking topologies and loading levels on the mechanical properties of a model elastomeric nanocomposite. The model system considered here is constructed from octa-functional polyhedral oligomeric silsesquioxane (POSS) dispersed in a poly(dimethylsiloxane) (PDMS) matrix. Shear moduli, G, have been computed for pure and for filled and unfilled PDMS as a function of cross-linking density, POSS fill loading level, and polymer network topology. The results reported here show that G increases as the cross-linking (covalent bonds formed between the POSS and the PDMS network) density increases. Further, G is found to have a strong dependence on cross-linking topology. The increase in shear modulus, G, for POSS filled PDMS is significantly higher than that for unfilled PDMS cross-linked with standard molecular species, suggesting an enhanced reinforcement mechanism for POSS. In contrast, in blended systems (POSS/PDMS mixture with no cross-linking) G was not observed to significantly increase with POSS loading. Finally, we find intriguing differences in the structural arrangement of bond strains between the cross-linked and the blended systems. In the unfilled PDMS the distribution of highly strained bonds appears to be random, while in the POSS filled system, the strained bonds form a net-like distribution that spans the network. Such a distribution may form a structural network 'holding' the composite together and resulting in increases in G compared to an unfilled, cross-linked system. These results are of importance for engineering of new POSS-based multifunctional materials with tailor-made mechanical properties.

  4. Spray assembled, cross-linked polyelectrolyte multilayer membranes for salt removal.

    PubMed

    Cho, Kwun Lun; Lomas, Hannah; Hill, Anita J; Caruso, Frank; Kentish, Sandra E

    2014-07-29

    The present study reports the synthesis of spray-coated cross-linked polyelectrolyte multilayer membranes. Membrane cross-linking was performed using alkyne-azide "click" chemistry, where alkyne and azide functional groups were used to modify the poly(acrylic acid) (PAA) and the poly(allylamine) hydrochloride (PAH) polyelectrolytes. The results demonstrate that deposition at lower ionic strength produced smoother and denser membrane structures. Pore size analysis using neutral poly(ethylene glycol) revealed a decrease in the membrane pore size as the degree of cross-linking was increased, resulting in the membrane rejecting divalent CaCl2 at levels of up to 80%, and 50% rejection of monovalent NaCl. When poly(sodium-4-styrenesulfonate) (PSS) was combined with small amounts of cross-linkable PAA, significant flux increases were observed in the multilayer membranes with no observable reduction in ion rejection. PMID:25036367

  5. Characteristics, formation, and pathophysiology of glucosepane: a major protein cross-link.

    PubMed

    Sjöberg, Johan Svantesson; Bulterijs, Sven

    2009-04-01

    Advanced glycation end products are the results of a series of chemical reactions collectively known as the Maillard reaction, or nonenzymatic glycation, and sometimes cross-link proteins, thereby impairing their normal function. Glucosepane is the most abundant protein cross-link found in vivo so far and mainly has been shown to accumulate in the extracellular matrix, where it cross-links collagen. Levels of glucosepane increase with aging. By increasing collagen stiffness, glucosepane cross-links may have significant implications in several age-related diseases, such as cardiovascular disease, diabetes, and osteoporosis. Although the formation pathways for glucosepane are relatively well researched, much is still unknown about the accumulation and pathophysiology of glucosepane. PMID:19415980

  6. Increased levels of homocysteine in patients with ulcerative colitis

    PubMed Central

    Akbulut, Sabiye; Altiparmak, Emin; Topal, Firdevs; Ozaslan, Ersan; Kucukazman, Metin; Yonem, Ozlem

    2010-01-01

    AIM: To investigate serum levels of homocysteine (Hcys) and the risk that altered levels carry for thrombosis development in ulcerative colitis (UC) patients. METHODS: 55 UC patients and 45 healthy adults were included. Hcys, vitamin B12 and folic acid levels were measured in both groups. Clinical history and thromboembolic events were investigated. RESULTS: The average Hcys level in the UC patients was 13.3 ± 1.93 μmmol/L (range 4.60-87) and was higher than the average Hcys level of the control group which was 11.2 ± 3.58 μmmol/L (range 4.00-20.8) (P < 0.001). Vitamin B12 and folic acid average values were also lower in the UC group (P < 0.001). When multivariate regression analysis was performed, it was seen that folic acid deficiency was the only risk factor for hyperhomocysteinemia. Frequencies of thromboembolic complications were not statistically significantly different in UC and control groups. When those with and without a thrombosis history in the UC group were compared according to Hcys levels, it was seen that there were no statistically significant differences. A negative linear relationship was found between folic acid levels and Hcys. CONCLUSION: We could not find any correlations between Hcys levels and history of prior thromboembolic events. PMID:20480528

  7. Estuaries May Face Increased Parasitism as Sea Levels Rise

    NASA Astrophysics Data System (ADS)

    Wendel, JoAnna

    2014-12-01

    Invertebrates in estuaries could be at a greater risk of parasitism as climate change causes sea levels to rise. A new paper published 8 December in Proceedings of the National Academy of Sciences of the United States of America (doi:10.1073/pnas.1416747111) describes how rapid sea level rise in the Holocene affected the population of parasitic flatworms called trematodes.

  8. IMPROVED PHYSICAL PROPERTIES OF ZEIN USING GLYOXAL AS A CROSSLINKER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of crosslinkers glyoxal, methylglyoxal and formaldehyde on physical properties of zein films was studied. Crosslinker concentrations varied from 0.3 to 6% by zein weight. Films crosslinked with glyoxal and formaldehyde showed a significant increase in tensile strength under certain pH c...

  9. Peptidoglycan synthesis and structure in Staphylococcus haemolyticus expressing increasing levels of resistance to glycopeptide antibiotics.

    PubMed Central

    Billot-Klein, D; Gutmann, L; Bryant, D; Bell, D; Van Heijenoort, J; Grewal, J; Shlaes, D M

    1996-01-01

    The structures of cytoplasmic peptidoglycan precursor and mature peptidoglycan of an isogenic series of Staphylococcus haemolyticus strains expressing increasing levels of resistance to the glycopeptide antibiotics teicoplanin and vancomycin (MICs, 8 to 32 and 4 to 16 microg/ml, respectively) were determined. High-performance liquid chromatography, mass spectrometry, amino acid analysis, digestion by R39 D,D-carboxypeptidase, and N-terminal amino acid sequencing were utilized. UDP-muramyl-tetrapeptide-D-lactate constituted 1.7% of total cytoplasmic peptidoglycan precursors in the most resistant strain. It is not clear if this amount of depsipeptide precursor can account for the levels of resistance achieved by this strain. Detailed structural analysis of mature peptidoglycan, examined for the first time for this species, revealed that the peptidoglycan of these strains, like that of other staphylococci, is highly cross-linked and is composed of a lysine muropeptide acceptor containing a substitution at its epsilon-amino position of a glycine-containing cross bridge to the D-Ala 4 of the donor, with disaccharide-pentapeptide frequently serving as an acceptor for transpeptidation. The predominant cross bridges were found to be COOH-Gly-Gly-Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Gly-Gly-NH2. Liquid chromatography-mass spectrometry analysis of the peptidoglycan of resistant strains revealed polymeric muropeptides bearing cross bridges containing an additional serine in place of glycine (probable structures, COOH-Gly-Ser-Ser-Gly-Gly-NH2 and COOH-Ala-Gly-Ser-Ser-Gly-NH2). Muropeptides bearing an additional serine in their cross bridges are estimated to account for 13.6% of peptidoglycan analyzed from resistant strains of S. haemolyticus. A soluble glycopeptide target (L-Ala-gamma-D-iso-glutamyl-L-Lys-D-Ala-D-Ala) was able to more effectively compete for vancomycin when assayed in the presence of resistant cells than when assayed in the presence of susceptible cells

  10. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  11. Cu(I) stabilizing crosslinked polyethyleneimine.

    PubMed

    Movahedi, Alireza; Lundin, Angelica; Kann, Nina; Nydén, Magnus; Moth-Poulsen, Kasper

    2015-07-28

    Polyethyleneimine (PEI) is known for its metal-coordinating properties and in its crosslinked form has applications in different areas ranging from drug delivery to waste water treatment and recovery of trace metals. With the aim to regulate the coordination environment of Cu(I) and Cu(II) ions in marine coatings, we have prepared a triazole cross-linking agent with 'soft' coordination that can crosslink PEI via indirect reductive amination. We have shown that this triazole crosslinker not only increases the Cu(II) absorption capacity of the crosslinked PEI in comparison to the traditionally used glutaraldehyde-crosslinked PEI (PEI-GA), but also allows the crosslinked polymer network to stabilize the Cu(I) oxidation state more effectively. The Cu(II) uptake and Cu(I) stabilization of the polymer have been determined by elemental analysis and UV-vis spectroscopy. It was found that the triazole-crosslinked polymer (PEI-TA) could coordinate up to 12 wt% of Cu(II) before and 6 wt% Cu(II) after imine reduction. PMID:26104912

  12. Pyoderma gangrenosum with increased levels of serum cytokines.

    PubMed

    Kozono, Kana; Nakahara, Takeshi; Kikuchi, Satoko; Itoh, Eriko; Kido-Nakahara, Makiko; Furue, Masutaka

    2015-12-01

    A 66-year-old woman presented after an episode of accidental trauma with a painful ulcer on her scalp which rapidly enlarged in size, accompanied by central necrosis and undermining ulceration. The patient's past history was negative for underlying systemic disease, although she had had a similar post-traumatic intractable leg ulcer 3 years prior, which was unresponsive to surgical management but successfully treated with systemic steroids. A biopsied specimen from the scalp showed marked neutrophilic infiltrates in the dermis, compatible with a diagnosis of pyoderma gangrenosum (PG). The large ulcerative lesion responded very well to oral steroid therapy, showing rapid epithelialization. Serum levels of granulocyte colony-stimulating factor and interleukin-6 were significantly elevated prior to treatment, with decrease to normal levels after treatment. Serum tumor necrosis factor (TNF)-α and granulocyte macrophage colony-stimulating factor levels were within normal limits. The significance and pathogenic role of cytokine burst in PG is reviewed and discussed. PMID:26047254

  13. THE EFFECTS OF HIGH DOSE IRRADIATION ON THE CROSS-LINKING OF VITAMIN E-BLENDED ULTRAHIGH MOLECULAR WEIGHT POLYETHYLENE

    PubMed Central

    Oral, Ebru; Beckos, Christine Godleski; Malhi, Arnaz S.; Muratoglu, Orhun K.

    2008-01-01

    Vitamin E-stabilized, highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is a promising oxidation and wear resistant UHMWPE with improved mechanical strength in comparison with the first generation, irradiated and melted UHMWPE. One approach of incorporating vitamin E in UHMWPE is through blending of vitamin E in UHMWPE powder followed by consolidation and radiation crosslinking. However radiation crosslinking efficiency of UHMWPE decreases in the presence of vitamin E. Therefore an optimum vitamin E concentration and radiation dose level needs to be determined to achieve a cross-link density comparable to 100-kGy irradiated and melted UHMWPE, which has shown excellent wear properties in vivo. We investigated the cross-link density and mechanical properties of vitamin E-blended UHMWPEs as a function of vitamin E concentration in the blend and gamma irradiation doses up to 200 kGy. We found that 0.3 wt% vitamin E-blended UHMWPE could not be cross-linked above a cross-link density achieved at a radiation dose of 65 kGy for virgin UHMWPE and 1.0 wt% vitamin E-blended UHMWPE could not be cross-linked above a cross-link density achieved at a radiation dose of 25 kGy for virgin UHMWPE even when the former were irradiated to a radiation dose of 200 kGy. In addition, higher plasticity at vitamin E concentrations at and above 0.3 wt% indicated that increased chain scissioning may be prevalent. Since the wear resistance of this irradiated UHMWPE would be expected to be low, vitamin E concentrations equal to or above 0.3 wt% are not recommended for subsequent irradiation to achieve a wear resistant cross-linked UHMWPE. The long–term oxidative stability of irradiated blends with low vitamin E concentrations has yet to be studied to determine an optimum between cross-link density and long-term oxidative stability. PMID:18514813

  14. In Vivo Oxidative Stability Changes of Highly Cross-Linked Polyethylene Bearings: An Ex Vivo Investigation.

    PubMed

    Rowell, Shannon L; Reyes, Christopher R; Malchau, Henrik; Muratoglu, Orhun K

    2015-10-01

    The development of highly cross-linked UHMWPEs focused on stabilizing radiation-induced free radicals as the sole precursor to oxidative degradation. However, secondary in vivo oxidation mechanisms have been discovered. After a preliminary post-operative analysis, we subjected highly cross-linked retrievals with 1-4 years in vivo durations and never-implanted controls to accelerated aging to predict the extent to which their oxidative stability was compromised in vivo. Lipid absorption, oxidation, and hydroperoxides were measured using infrared spectroscopy. Gravimetric swelling was used to measure cross-link density. After aging, all retrievals, except vitamin E-stabilized components, regardless of initial lipid levels or oxidation, showed significant oxidative degradation, demonstrated by subsurface oxidative peaks, increased hydroperoxides and decreased cross-link density, compared to their post-operative material properties and never-implanted counterparts, confirming oxidative stability changes. PMID:26048729

  15. Reducing nursing students' anxiety level and increasing retention of materials.

    PubMed

    Phillips, A P

    1988-01-01

    The purpose of this descriptive study is to examine the effects active learning, collaboration and modified group testing have on reducing students' anxiety and increasing learning and retention of material. Subjects consist of 34 associate degree nursing students enrolled in the Advanced Adult Health nursing class at North Georgia College. Most of the students are married, have children and work part time. A self-reporting questionnaire suggests a reduction of the students' anxiety during the quarter. The attitudinal questionnaire reveals an atmosphere of collaboration among peers. Data evaluating learning and retention of material were analyzed using the parametric (T-test) and nonparametric (Wiley Rank Sum test) methods. Examination of the Null Hypotheses I and II suggests there were increased learning and retention of material as evidenced by higher grades on the comprehensive final examination than on the quizzes given after presentation of content. Principles of andragogy as defined by Knowles (1980) and cooperation with peers as described by Johnson, Johnson, Holabec, and Roy (1984), Johnson, Johnson, and Maruyama (1983), and Johnson and Johnson (1975) form the theoretical foundation. PMID:2828575

  16. Kojak: Efficient analysis of chemically cross-linked protein complexes

    PubMed Central

    Hoopmann, Michael R.; Zelter, Alex; Johnson, Richard S.; Riffle, Michael; MacCoss, Michael J.; Davis, Trisha N.; Moritz, Robert L.

    2015-01-01

    Protein chemical cross-linking and mass spectrometry enable the analysis of protein-protein interactions and protein topologies, however complicated cross-linked peptide spectra require specialized algorithms to identify interacting sites. The Kojak cross-linking software application is a new, efficient approach to identify cross-linked peptides, enabling large-scale analysis of protein-protein interactions by chemical cross-linking techniques. The algorithm integrates spectral processing and scoring schemes adopted from traditional database search algorithms, and can identify cross-linked peptides using many different chemical cross-linkers, with or without heavy isotope labels. Kojak was used to analyze both novel and existing datasets, and was compared with existing cross-linking algorithms. The algorithm provided increased cross-link identifications over existing algorithms, and equally importantly, the results in a fraction of computational time. The Kojak algorithm is open-source, cross-platform, and freely available. This software provides both existing and new cross-linking researchers alike an effective way to derive additional cross-link identifications from new or existing datasets. For new users, it provides a simple analytical resource resulting in more cross-link identifications than other methods. PMID:25812159

  17. Increase of inherent protection level in spent nuclear fuel

    SciTech Connect

    Krasnobaev, A.; Kryuchkov, E.; Glebov, V.

    2006-07-01

    The paper is devoted to upgrading inherent proliferation protection of fissionable nuclear materials (FNM). Some possibilities were investigated to form high radiation barrier inside spent fuel assemblies (SFA) discharged from power reactors of VVER-1000 type and research reactors of IRT type. The radiation barrier is estimated in the terms of rate of equivalent dose (RED) at 30-cm distance from SFA. The values of RED were calculated with application of the computer code package SCALE 4.3. The paper considers the criteria adopted for estimation of FNM proliferation resistance. The paper presents numerical results on a component-wise analysis of the radiation barrier in SFA from reactors of VVER-1000 and IRT type and on capability of various radionuclides to prolong action of the radiation barrier. Isotopic admixtures were selected and amounts of these admixtures were evaluated for significant prolongation of the radiation barrier action at the levels of the radiation standards used for estimation of FNM proliferation resistance. The paper considers vulnerability of the radiation barriers in respect to thermal processing of spent fuel. (authors)

  18. [Diagnosis of an increased serum level of ferritin].

    PubMed

    Lorcerie, B; Audia, S; Samson, M; Millière, A; Falvo, N; Leguy-Seguin, V; Berthier, S; Bonnotte, B

    2015-08-01

    The discovery of a hyperferritinemia is most of the time fortuitous. The diagnostic approach aims at looking for the responsible etiology and at verifying if an iron hepatic overload is present or not. Three diagnostic steps are proposed. The clinical elements and a few straightforward biological tests are sufficient at first to identify one of the four main causes: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with a significant iron hepatic overload. If the transferring saturation coefficient is raised (>50%) a hereditary hemochromatosis should be discussed. Secondly, less common disorders will be discussed. Among these, only the chronic hematological disorders either acquired or congenital are at risk of iron hepatic overload. Thirdly, if a doubt persists in the etiologic research, and the serum ferritin level is very high or continues to rise, it is essential to verify that there is no iron hepatic overload. For that purpose, the MRI with study of the iron overload is the main test, which will guide the therapeutic attitude. Identification of more than a single etiology occurs in more than 40% of the cases. PMID:25640247

  19. New in situ crosslinking chemistries for hydrogelation

    NASA Astrophysics Data System (ADS)

    Roberts, Meredith Colleen

    Over the last half century, hydrogels have found immense value as biomaterials in a vast number of biomedical and pharmaceutical applications. One subset of hydrogels receiving increased attention is in situ forming gels. Gelling by either bioresponsive self-assembly or mixing of binary crosslinking systems, these technologies are useful in minimally invasive applications as well as drug delivery systems in which the sol-to-gel transition aids the formulation's performance. Thus far, the field of in situ crosslinking hydrogels has received limited attention in the development of new crosslinking chemistries. Moreover, not only does the chemical nature of the crosslinking moieties allow these systems to perform in situ, but they contribute dramatically to the mechanical properties of the hydrogel networks. For example, reversible crosslinks with finite lifetimes generate dynamic viscoelastic gels with time-dependent properties, whereas irreversible crosslinks form highly elastic networks. The aim of this dissertation is to explore two new covalent chemistries for their ability to crosslink hydrogels in situ under physiological conditions. First, reversible phenylboronate-salicylhydroxamate crosslinking was implemented in a binary, multivalent polymeric system. These gels formed rapidly and generated hydrogel networks with frequency-dependent dynamic rheological properties. Analysis of the composition-structure-property relationships of these hydrogels---specifically considering the effects of pH, degree of polymer functionality, charge of the polymer backbone and polymer concentration on dynamic theological properties---was performed. These gels demonstrate diverse mechanical properties, due to adjustments in the binding equilibrium of the pH-sensitive crosslinks, and thus have the potential to perform in a range of dynamic or bioresponsive applications. Second, irreversible catalyst-free "click" chemistry was employed in the hydrogelation of multivalent azide

  20. Corneal Collagen Cross-Linking

    PubMed Central

    Jankov II, Mirko R.; Jovanovic, Vesna; Nikolic, Ljubisa; Lake, Jonathan C.; Kymionis, Georgos; Coskunseven, Efekan

    2010-01-01

    Corneal collagen cross-linking (CXL) with riboflavin and ultraviolet-A (UVA) is a new technique of corneal tissue strengthening by using riboflavin as a photosensitizer and UVA to increase the formation of intra and interfibrillar covalent bonds by photosensitized oxidation. Keratocyte apoptosis in the anterior segment of the corneal stroma all the way down to a depth of about 300 microns has been described and a demarcation line between the treated and untreated cornea has been clearly shown. It is important to ensure that the cytotoxic threshold for the endothelium has not been exceeded by strictly respecting the minimal corneal thickness. Confocal microscopy studies show that repopulation of keratocytes is already visible 1 month after the treatment, reaching its pre-operative quantity and quality in terms of functional morphology within 6 months after the treatment. The major indication for the use of CXL is to inhibit the progression of corneal ectasias, such as keratoconus and pellucid marginal degeneration. CXL may also be effective in the treatment and prophylaxis of iatrogenic keratectasia, resulting from excessively aggressive photoablation. This treatment has also been used to treat infectious corneal ulcers with apparent favorable results. Combination with other treatments, such as intracorneal ring segment implantation, limited topography-guided photoablation and conductive keratoplasty have been used with different levels of success. PMID:20543933

  1. Extracellular glycation crosslinks: prospects for removal.

    PubMed

    Furber, John D

    2006-01-01

    Extracellular aging--accumulating molecular damage by glycation, oxidation, and crosslinking of long-lived extracellular proteins, mainly collagen and elastin--is a major cause of several important human aging pathologies. Crosslinking increases mechanical stiffness of blood vessels and urinary bladder. Crosslinking impairs the functioning of the kidney, heart, retina, and other tissues and organs. Glycation adducts trigger inflammatory signaling, provoking tissue damage and cancers. Crosslinking tightens up the extracellular matrix (ECM), hardening it against natural turnover processes. Known crosslink breakers (e.g., alagebrium, of the thiazolium halide family) are only partly effective because they break only a subset of AGE crosslink structures (sugar-derived alpha-diketone bridges). So far, no agent has been found that breaks the prevalent glucosepane and K2P crosslink structures. Enzymes that would be able to recognize and disassemble glycation products may be too big to migrate into the ECM and repair collagen or elastin in vivo. Two approaches to therapy development are presented here. ECM turnover enhancement would enhance natural processes to digest old ECM and replace it with new. It will be important to tune the collagen degradation to a rate slow enough to prevent dire side-effects, such as hemorrhage from leaky blood vessels as collagen molecules are removed and replaced. Glycation breaker discovery would use high-throughput screening and rational drug design to find molecules that are able to break glucosepane crosslinks and K2P crosslinks of extracellular proteins. Candidates would be further screened for selectivity and toxicity in order to avoid damage to other molecules. PMID:16706655

  2. Corneal cross-linking.

    PubMed

    Randleman, J Bradley; Khandelwal, Sumitra S; Hafezi, Farhad

    2015-01-01

    Since its inception in the late 1990s, corneal cross-linking has grown from an interesting concept to a primary treatment for corneal ectatic disease worldwide. Using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), the cornea can be stiffened, usually with a single application, and progressive thinning diseases such as keratoconus arrested. Despite being in clinical use for many years, some of the underlying processes, such as the role of oxygen and the optimal treatment times, are still being worked out. More than a treatment technique, corneal cross-links represent a physiological principle of connective tissue, which may explain the enormous versatility of the method. We highlight the history of corneal cross-linking, the scientific underpinnings of current techniques, evolving clinical treatment parameters, and the use of cross-linking in combination with refractive surgery and for the treatment of infectious keratitis. PMID:25980780

  3. [Crosslinking in Keratoconus].

    PubMed

    Lang, S J; Reinhard, T

    2016-06-01

    Keratoconus leads to progressive thinning and protrusion of the cornea. Young patients exhibit the highest risk for progression. Corneal crosslinking was introduced in 1998 and is intended to prevent progression of keratoconus. Only a few prospective controlled trials have been published. Six randomised controlled trials have been published. All these trials confirmed the efficacy of crosslinking through keratometric data. In two trials, progression was reported in some patients of the treatment group. This indicates that not all patients benefit from corneal crosslinking. The risks of the procedure include corneal scarring, haze, endothelial cell damage and infections of the cornea. In order to avoid these risks, patients without progression should not be treated with crosslinking. PMID:27315291

  4. Grafting functional antioxidants on highly crosslinked polyethylene

    NASA Astrophysics Data System (ADS)

    Al-Malaika, S.; Riasat, S.; Lewucha, C.

    2016-05-01

    The problem of interference of antioxidants, such as hindered phenols, with peroxide-initiated crosslinking of polyethylene was addressed through the use of functional (reactive) graftable antioxidants (g-AO). Reactive derivatives of hindered phenol and hindered amine antioxidants were synthesised, characterised and used to investigate their grafting reactions in high density polyethylene; both non-crosslinked (PE) and highly peroxide-crosslinked (PEXa). Assessment of the extent of in-situ grafting of the antioxidants, their retention after exhaustive solvent extraction in PE and PEXa, and the stabilising performance of the grafted antioxidants (g-AO) in the polymer were examined and benchmarked against conventionally stabilised crosslinked & non-crosslinked polyethylene. It was shown that the functional antioxidants graft to a high extent in PEXa, and that the level of interference of the g-AOs with the polymer crosslinking process was minimal compared to that of conventional antioxidants which bear the same antioxidant function. The much higher level of retention of the g-AOs in PEXa after exhaustive solvent extraction, compared to that of the corresponding conventional antioxidants, accounts for their superior long-term thermal stabilising performance under severe extractive conditions.

  5. CHARACTERIZATION OF CASEINS CROSSLINKED BY A NATURALLY OCCURRING CROSSLINKING AGENT-GENIPIN

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing economic and environmental pressures demand more effective utilization of natural resources. Genipin, a naturally occurring crosslinking agent obtained from the fruit of Gardenia jasminoides, has recently attracted much attention due to its low cytotoxicity compared to traditional crossli...

  6. Covalent protein crosslinks: general detection, quantitation, and characterization via modification with diphenylborinic acid.

    PubMed

    Graham, L; Gallop, P M

    1994-03-01

    Progressive crosslinking of proteins appears to be a general phenomenon in aging cells and tissues. Crosslinked proteins can form insoluble aggregates which become increasingly resistant to proteolysis as more crosslinks form. However, most evidence for progressive crosslinking with age is indirect, and little is known about the chemical mechanisms involved. We have therefore developed a method for detection and isolation of any type of stable covalent crosslink from protein hydrolysates which requires no prior knowledge of the molecular structure of whatever crosslink(s) may be present. It utilizes the specificity of the diphenylborinic acid reagent for alpha-amino acid groups and the chromatographic properties and uv absorbance of the crosslink derivatives. The method is demonstrated using eight different crosslinks from collagen and fibrin, and a general procedure is given for detection of any type of crosslink in a protein hydrolysate. PMID:8203759

  7. Cross-linked informofers.

    PubMed Central

    Prosvirnin, V V; Ruzidic, S; Samarina, O P

    1979-01-01

    The proteins of 30S RNP particles containing pre-mRNA (hnRNA) were cross-linked with bifunctional reagents (dimethyl-suberimidate and dimethyl-3,3'-dithiobispropionimidate). Further treatment with 1 or 2 M NaCl dissociates all RNA from protein. However, a significant part of protein particles--informofers being cross-linked survived high salt treatment. Their sedimentation coefficients were close to those of original particles. No RNA could be detected in the informofers even after labeling the cells with a precursor for a long period of time. Sodium dodecylsulfate or urea dissociated cross-linked informofers into oligomeric polypeptides. They could be dissociated by beta-mercaptoethanol treatment if a reversible cross-linked reagent had been used. The resulting polypeptides were represented by informatin. RNP particles (30S RNP or poly-particles) were reconstituted upon mixing of cross-linked informofers with pre-mRNA and removal of 2 M NaCl. PMID:503864

  8. Playground Designs to Increase Physical Activity Levels during School Recess: A Systematic Review

    ERIC Educational Resources Information Center

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M.

    2014-01-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A…

  9. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping Siao (Inventor); Dreyer, William J. (Inventor)

    1976-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree.C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  10. Crosslinked, porous, polyacrylate beads

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor); Yen, Shiao-Ping S. (Inventor); Dreyer, William J. (Inventor)

    1977-01-01

    Uniformly-shaped, porous, round beads are prepared by the co-polymerization of an acrylic monomer and a cross-linking agent in the presence of 0.05 to 5% by weight of an aqueous soluble polymer such as polyethylene oxide. Cross-linking proceeds at high temperature above about 50.degree. C or at a lower temperature with irradiation. Beads of even shape and even size distribution of less than 2 micron diameter are formed. The beads will find use as adsorbents in chromatography and as markers for studies of cell surface receptors.

  11. Shell-crosslinked knedel-like nanoparticles induce lower immunotoxicity than their non-crosslinked analogs

    PubMed Central

    Elsabahy, Mahmoud; Samarajeewa, Sandani; Raymond, Jeffery E.; Clark, Corrie; Wooley, Karen L.

    2013-01-01

    The development of stable nanoparticles that can withstand the changing conditions experienced in a biological setting and also be of low toxicity and immunogenicity is of particular importance to address the problems associated with currently utilized nanotechnology-based therapeutics and diagnostics. The use of crosslinked nanoparticles continues to receive special impetus, due to their robust structure and high kinetic stability, and they have recently been shown to induce lower cytotoxicity than their non-crosslinked micellar counterparts. In the current study, poly(acrylamidoethylamine)-block-poly(DL-lactide) (PAEA90-b-PDLLA40) copolymers were synthesized, self-assembled in water to yield nanoscopic polymeric micelles, and the effects of decorating the micellar surface with poly(ethylene glycol) (i.e. PEGylation) and crosslinking the PAEA layer to varying extents on the physicochemical characteristics, cytotoxicity and immunotoxicity of the nanoparticles were studied. Herein, we report for the first time that crosslinking can efficiently reduce the immunotoxicity of polymeric nanomaterials. In addition, increasing the degree of crosslinking further reduced the accessibility of biomolecules to the core of the nanoparticles and decreased their cytotoxicity and immunotoxicity. It is also highlighted that crosslinking can be more efficient than PEGylation in reducing the immunotoxicity of nanomaterials. Shell-crosslinking of block copolymer micelles, therefore, is expected to advance their clinical development beyond the earlier known effects, and to broaden the implications in the field of nanomedicine. PMID:24187610

  12. Novel naturally crosslinked electrospun nanofibrous chitosan mats for guided bone regeneration membranes: material characterization and cytocompatibility.

    PubMed

    Norowski, Peter A; Fujiwara, Tomoko; Clem, William C; Adatrow, Pradeep C; Eckstein, Eugene C; Haggard, Warren O; Bumgardner, Joel D

    2015-05-01

    Guided bone regeneration (GBR) barrier membranes are used to prevent soft tissue infiltration into the graft space during dental procedures that involve bone grafting. Chitosan materials have shown promise as GBR barrier membranes, due to their biocompatibility and predictable biodegradability, but degradation rates may still be too high for clinical applications. In this study, chitosan GBR membranes were electrospun using chitosan (70% deacetylated, 312 kDa, 5.5 w/v%), with or without the addition of 5 or 10 mm genipin, a natural crosslinking agent, in order to extend the degradation to meet the clinical target time frame of 4-6 months. Membranes were evaluated for fibre diameter, tensile strength, biodegradation rate, bond structure and cytocompatibility. Genipin addition, at 5 or 10 mm, resulted in median fibre diameters 184, 144 and 154 nm for uncrosslinked, 5 mm and 10 mm crosslinked, respectively. Crosslinking, examined by Fourier transform infrared spectroscopy, showed a decrease in N-H stretch as genipin levels were increased. Genipin-crosslinked mats exhibited only 22% degradation based on mass loss, as compared to 34% for uncrosslinked mats at 16 weeks in vitro. The ultimate tensile strength of the mats was increased by 165% to 32 MPa with 10 mm crosslinking as compared to the uncrosslinked mats. Finally, genipin-crosslinked mats supported the proliferation of SAOS-2 cells in a 5 day growth study, similar to uncrosslinked mats. These results suggest that electrospun chitosan mats may benefit from genipin crosslinking and have the potential to meet clinical degradation time frames for GBR applications. PMID:23166109

  13. Riboflavin-induced photo-crosslinking of collagen hydrogel and its application in meniscus tissue engineering.

    PubMed

    Heo, Jiseung; Koh, Rachel H; Shim, Whuisu; Kim, Hwan D; Yim, Hyun-Gu; Hwang, Nathaniel S

    2016-04-01

    A meniscus tear is a common knee injury, but its regeneration remains a clinical challenge. Recently, collagen-based scaffolds have been applied in meniscus tissue engineering. Despite its prevalence, application of natural collagen scaffold in clinical setting is limited due to its extremely low stiffness and rapid degradation. The purpose of the present study was to increase the mechanical properties and delay degradation rate of a collagen-based scaffold by photo-crosslinking using riboflavin (RF) and UV exposure. RF is a biocompatible vitamin B2 that showed minimal cytotoxicity compared to conventionally utilized photo-initiator. Furthermore, collagen photo-crosslinking with RF improved mechanical properties and delayed enzyme-triggered degradation of collagen scaffolds. RF-induced photo-crosslinked collagen scaffolds encapsulated with fibrochondrocytes resulted in reduced scaffold contraction and enhanced gene expression levels for the collagen II and aggrecan. Additionally, hyaluronic acid (HA) incorporation into photo-crosslinked collagen scaffold showed an increase in its retention. Based on these results, we demonstrate that photo-crosslinked collagen-HA hydrogels can be potentially applied in the scaffold-based meniscus tissue engineering. PMID:25809935

  14. Microbes encapsulated within crosslinkable polymers

    SciTech Connect

    Chidambaram, Devicharan; Liu, Ying; Rafailovich, Miriam H

    2013-02-05

    The invention relates to porous films comprising crosslinked electrospun hydrogel fibers. Viable microbes are encapsulated within the crosslinked electrospun hydrogel fibers. The crosslinked electrospun hydrogel fibers are water insoluble and permeable. The invention also relates to methods of making and using such porous films.

  15. Hydroxyl functionalized thermosensitive microgels with quadratic crosslinking density distribution.

    PubMed

    Elmas, Begum; Tuncel, Murvet; Senel, Serap; Patir, S; Tuncel, Ali

    2007-09-01

    N-isopropylacrylamide (NIPA) based uniform thermosensitive microgels were synthesized by dispersion polymerization by using relatively hydrophilic crosslinking agents with hydroxyl functionality. Glycerol dimethacrylate (GDMA), pentaerythritol triacrylate (PETA) and pentaerythritol propoxylate triacrylate (PEPTA) were used as crosslinking agents with different hydrophilicities. A protocol was first proposed to determine the crosslinking density distribution in the thermosensitive microgel particles by confocal laser scanning microscopy (CLSM). The microgels were fluorescently labeled by using hydroxyl group of the crosslinking agent. The CLSM observations performed with the microgels synthesized by three different crosslinking agents showed that the crosslinking density exhibited a quadratic decrease with the increasing radial distance in the spherical microgel particles. This structure led to the formation of more loose gel structure on the particle surface with respect to the center. Then the use of hydrophilic crosslinking agents in the dispersion polymerization of NIPA made possible the synthesis of thermosensitive microgels carrying long, flexible and chemically derivatizable (i.e., hydroxyl functionalized) fringes on the surface by a single-stage dispersion polymerization. The microgels with all crosslinking agents exhibited volume phase transition with the increasing temperature. The microgel obtained by the most hydrophilic crosslinking agent, GDMA exhibited higher hydrodynamic diameters in the fully swollen form at low temperatures than those obtained by PETA and PEPTA. Higher hydrodynamic size decrease from fully swollen form to the fully shrunken form was also observed with the same microgel. PMID:17532327

  16. CO2/light gas separation performance of cross-linked poly(vinylimidazolium) gel membranes as a function of ionic liquid loading and cross-linker content

    SciTech Connect

    Carlisle, TK; Nicodemus, GD; Gin, DL; Noble, RD

    2012-04-15

    A series of cross-linked poly(vinylimidazolium)-RTIL gel membranes was synthesized and evaluated for room-temperature, ideal CO2/N-2, CO2/CH4, and CO2/H-2 separation performance. The membranes were formed by photo-polymerization of oligo(ethylene glycol)-functionalized cross-linking (i.e., di-functional) and non-cross-linking (i.e., mono-functional) vinylimidazolium RTIL monomers with nonpolymerizable, "free RTIL." The effect of free RTIL ([emim][Tf2N]) loading on CO2 separation performance was evaluated by varying RTIL loading at three levels (45, 65, and 75 wt.%). The effect of cross-linker content on CO2 separation performance was also evaluated by varying the copolymer composition of cross-linked membranes from 5 to 100 mol% di-functional monomer. The substituent on the monofunctional RTIL monomer was also varied to investigate the effect of substituent structure and chemistry on CO2 separation performance. CO2 permeability was dramatically increased with higher loading of free RTIL. Increased RTIL loading had no effect on CO2/N-2 or CO2/CH4 permeability selectivity, but significantly improved CO2/H-2 permeability selectivity. Reducing the cross-linking monomer concentration generally improved CO2 permeability. However, anomalous permeability and selectivity behavior was observed below critical concentrations of cross-linker. The effect of the substituent on the monofunctional monomer on CO2 separation performance was minimal compared to the effects of RTIL loading and copolymer composition. (C) 2012 Elsevier B.V. All rights reserved.

  17. Diesterified Nitrone Rescues Nitroso-Redox Levels and Increases Myocyte Contraction Via Increased SR Ca2+ Handling

    PubMed Central

    Traynham, Christopher J.; Roof, Steve R.; Wang, Honglan; Prosak, Robert A.; Tang, Lifei; Viatchenko-Karpinski, Serge; Ho, Hsiang-Ting; Racoma, Ira O.; Catalano, Dominic J.; Huang, Xin; Han, Yongbin; Kim, Shang-U; Gyorke, Sandor; Billman, George E.

    2012-01-01

    Nitric oxide (NO) and superoxide (O2−) are important cardiac signaling molecules that regulate myocyte contraction. For appropriate regulation, NO and O2.− must exist at defined levels. Unfortunately, the NO and O2.− levels are altered in many cardiomyopathies (heart failure, ischemia, hypertrophy, etc.) leading to contractile dysfunction and adverse remodeling. Hence, rescuing the nitroso-redox levels is a potential therapeutic strategy. Nitrone spin traps have been shown to scavenge O2.− while releasing NO as a reaction byproduct; and we synthesized a novel, cell permeable nitrone, 2–2–3,4-dihydro-2H-pyrrole 1-oxide (EMEPO). We hypothesized that EMEPO would improve contractile function in myocytes with altered nitroso-redox levels. Ventricular myocytes were isolated from wildtype (C57Bl/6) and NOS1 knockout (NOS1−/−) mice, a known model of NO/O2.− imbalance, and incubated with EMEPO. EMEPO significantly reduced O2.− (lucigenin-enhanced chemiluminescence) and elevated NO (DAF-FM diacetate) levels in NOS1−/− myocytes. Furthermore, EMEPO increased NOS1−/− myocyte basal contraction (Ca2+ transients, Fluo-4AM; shortening, video-edge detection), the force-frequency response and the contractile response to β-adrenergic stimulation. EMEPO had no effect in wildtype myocytes. EMEPO also increased ryanodine receptor activity (sarcoplasmic reticulum Ca2+ leak/load relationship) and phospholamban Serine16 phosphorylation (Western blot). We also repeated our functional experiments in a canine post-myocardial infarction model and observed similar results to those seen in NOS1−/− myocytes. In conclusion, EMEPO improved contractile function in myocytes experiencing an imbalance of their nitroso-redox levels. The concurrent restoration of NO and O2.− levels may have therapeutic potential in the treatment of various cardiomyopathies. PMID:23300588

  18. Wear, debris, and biologic activity of cross-linked polyethylene in the knee: benefits and potential concerns.

    PubMed

    Fisher, John; McEwen, Hannah M J; Tipper, Joanne L; Galvin, Alison L; Ingram, Jo; Kamali, Amir; Stone, Martin H; Ingham, Eileen

    2004-11-01

    Cross-linked polyethylene currently is being introduced in knee prostheses. The wear rates, wear debris, and biologic reactivity of non cross-linked, moderately cross-linked, and highly cross-linked polyethylene have been compared in multidirectional wear tests and knee simulators. Multidirectional pin-on-plate wear studies of noncross-linked, moderately cross-linked (5 Mrad), and highly cross-linked (10 Mrad) polyethylene showed a 75% reduction in wear with the highly cross-linked material under kinematics found in the hip, but only a 33% reduction under wear in kinematics representative of the knee. In knee simulator studies, with the fixed-bearing press-fit, condylar Sigma cruciate-retaining knee under high kinematic input conditions, the wear of 5 Mrad moderately cross-linked polyethylene was 13 +/- 4 mm per 1 million cycles, which was lower (p < 0.05) than the wear of clinically used, gamma vacuum foil GUR 1020 polyethylene (23 +/- 6 mm/1 million cycles). For the low-contact stress mobile-bearing knee, the wear of moderately cross-linked polyethylene was 2 +/- 1 mm per 1 million cycles, which was lower (p < 0.05) than GVF GUR 1020 polyethylene (5 +/- 2 mm/1 million cycles). The wear debris isolated from the fixed-bearing knees showed the moderately cross-linked material had a larger percentage volume of particles smaller than 1 mum in size, compared with GVF GUR 1020 polyethylene. Direct cell culture studies of wear debris generated in sterile wear simulators using multidirectional motion showed a increase (p < 0.05) in tumor necrosis factor-alpha levels and reactivity for GUR 1050 cross-linked polyethylene debris compared with an equivalent volume of noncross-linked GUR 1050 polyethylene. The use of cross-linked polyethylene in the knee reduces the volumetric wear rate. However, the clinical significance of reduced fracture toughness, elevated wear in abrasive conditions, and the elevated tumor necrosis factor-alpha release from smaller more reactive

  19. Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA).

    PubMed

    Lecomte, François; Brander, Lukas; Jalde, Fredrick; Beck, Jennifer; Qui, Haibo; Elie, Caroline; Slutsky, Arthur S; Brunet, Fabrice; Sinderby, Christer

    2009-04-30

    This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions. PMID:19429528

  20. Chlorine resistant glutaraldehyde crosslinked polyelectrolyte multilayer membranes for desalination.

    PubMed

    Cho, Kwun Lun; Hill, Anita J; Caruso, Frank; Kentish, Sandra E

    2015-05-01

    Crosslinked polyelectrolyte multilayer membranes are synthesized with salt rejection values approaching those of commercial desalination membranes, but with increased chlorine resistance. The membranes are fabricated directly onto porous commercial substrates. Subsequent crosslinking of the polycation layers with glutaraldehyde leads to NaCl rejections of up to 97%, while the incorporation of a highly sulfonated polysulfone polyanion leads to high chlorine resistance. PMID:25776340

  1. Central injection of CDP-choline suppresses serum ghrelin levels while increasing serum leptin levels in rats.

    PubMed

    Kiyici, Sinem; Basaran, Nesrin Filiz; Cavun, Sinan; Savci, Vahide

    2015-10-01

    In this study we aimed to test central administration of CDP-choline on serum ghrelin, leptin, glucose and corticosterone levels in rats. Intracerebroventricular (i.c.v.) 0.5, 1.0 and 2.0 µmol CDP-choline and saline were administered to male Wistar-Albino rats. For the measurement of serum leptin and ghrelin levels, blood samples were obtained baseline and at 5, 15, 30, 60 and 120 min following i.c.v. CDP-choline injection. Equimolar doses of i.c.v. choline (1.0 µmol) and cytidine (1.0 µmol) were administered and measurements were repeated throughout the second round of the experiment. Atropine (10 µg) and mecamylamine (50 µg) were injected intracerebroventricularly prior to CDP-choline and measurements repeated in the third round of the experiment. After 1 µmol CDP-choline injection, serum ghrelin levels were suppressed significantly at 60 min (P=0.025), whereas serum leptin levels were increased at 60 and 120 min (P=0.012 and P=0.017 respectively). CDP-choline injections also induced a dose- and time-dependent increase in serum glucose and corticosterone levels. The effect of choline on serum leptin and ghrelin levels was similar with CDP-choline while no effect was seen with cytidine. Suppression of serum ghrelin levels was eliminated through mecamylamine pretreatment while a rise in leptin was prevented by both atropine and mecamylamine pretreatments. In conclusion; centrally injected CDP-choline suppressed serum ghrelin levels while increasing serum leptin levels. The observed effects following receptor antagonist treatment suggest that nicotinic receptors play a role in suppression of serum ghrelin levels,whereas nicotinic and muscarinic receptors both play a part in the increase of serum leptin levels. PMID:26162700

  2. Study of the effect of mixing approach on cross-linking efficiency of hyaluronic acid-based hydrogel cross-linked with 1,4-butanediol diglycidyl ether.

    PubMed

    Al-Sibani, Mohammed; Al-Harrasi, Ahmed; Neubert, Reinhard H H

    2016-08-25

    Regardless of various strategies reported for cross-linking hyaluronic acid (HA) with 1,4-butanediol diglycidyl ether (BDDE), seeking new strategies that enhance cross-linking efficiency with a low level of cross-linker is essential. In this work, we studied the influence of mixing approach on two cross-linked BDDE-HA hydrogels prepared by two different mixing approaches; the large-batch mixing approach in which the hydrogel quantities were all mixed as a single lump in one container (hydrogel 1), and the small-batches mixing approach in which the hydrogel quantities were divided into smaller batches, mixed separately at various HA/BDDE ratios then combined in one reaction mixture (hydrogel 2). The result showed that the cross-linking reaction was mixing process-dependent. Degradation tests proved that, in relation to hydrogel 1, hydrogel 2 was more stable, and exhibited a higher resistance towards hyaluronidase activity. The swelling ratio of hydrogel 1 was significantly higher than that of hydrogel 2 in distilled water; however, in phosphate buffer saline, both hydrogels showed no significant difference. SEM images demonstrated that hydrogel 2 composite showed a denser network structure and smaller pore-size than hydrogel 1. In comparison to native HA, the occurrence of chemical modification in the cross-linked hydrogels was confirmed by FTIR and NMR distinctive peaks. These peaks also provided evidence that hydrogel 2 exhibited a higher degree of modification than hydrogel 1. In conclusion, the small-batches mixing approach proved to be more effective than large-batch mixing in promoting HA-HA entanglement and increasing the probability of BDDE molecules for binding with HA chains. PMID:27312477

  3. 5 CFR 531.504 - Level of performance required for quality step increase.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... summary level used by the program; and (2) Demonstrates sustained performance of high quality... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Level of performance required for quality... SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Quality Step Increases § 531.504 Level of...

  4. 5 CFR 531.504 - Level of performance required for quality step increase.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... summary level used by the program; and (2) Demonstrates sustained performance of high quality... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Level of performance required for quality... SERVICE REGULATIONS PAY UNDER THE GENERAL SCHEDULE Quality Step Increases § 531.504 Level of...

  5. Radiation induced estane polymer crosslinking

    SciTech Connect

    Fletcher, M.; Foster, P.

    1997-12-01

    The exposure of polymeric materials to radiation has been known to induce the effects of crosslinking and degradation. The crosslinking phenomena comes about when two long chain polymers become linked together by a primary bond that extends the chain and increases the viscosity, molecular weight and the elastic modules of the polymer. This process has been observed in relatively short periods of time with fairly high doses of radiation, on the order of several megarads/hour. This paper address low dose exposure over long periods of time to determine what the radiation effects are on the polymeric binder material in PBX 9501. An experimental sample of binder material without explosives will be placed into a thermal and radiation field produced from a W-48 put mod 0. Another sample will be placed in a thermal environment without the radiation. The following is the test plan that was submitted to the Pantex process. The data presented here will be from the first few weeks of exposure and this test will be continued over the next few years. Subsequent data will hopefully be presented in the next compatibility and aging conference.

  6. Possible Increase in Serum FABP4 Level Despite Adiposity Reduction by Canagliflozin, an SGLT2 Inhibitor

    PubMed Central

    Furuhashi, Masato; Matsumoto, Megumi; Hiramitsu, Shinya; Omori, Akina; Tanaka, Marenao; Moniwa, Norihito; Yoshida, Hideaki; Ishii, Junnichi; Miura, Tetsuji

    2016-01-01

    Background Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is secreted from adipocytes in association with catecholamine-induced lipolysis, and elevated serum FABP4 level is associated with obesity, insulin resistance and atherosclerosis. Secreted FABP4 as a novel adipokine leads to insulin resistance via increased hepatic glucose production (HGP). Sodium-glucose cotransporter 2 (SGLT2) inhibitors decrease blood glucose level via increased urinary glucose excretion, though HGP is enhanced. Here we investigated whether canagliflozin, an SGLT2 inhibitor, modulates serum FABP4 level. Methods Canagliflozin (100 mg/day) was administered to type 2 diabetic patients (n = 39) for 12 weeks. Serum FABP4 level was measured before and after treatment. Results At baseline, serum FABP4 level was correlated with adiposity, renal dysfunction and noradrenaline level. Treatment with canagliflozin significantly decreased adiposity and levels of fasting glucose and HbA1c but increased average serum FABP4 level by 10.3% (18.0 ± 1.0 vs. 19.8 ± 1.2 ng/ml, P = 0.008), though elevation of FABP4 level after treatment was observed in 26 (66.7%) out of 39 patients. Change in FABP4 level was positively correlated with change in levels of fasting glucose (r = 0.329, P = 0.044), HbA1c (r = 0.329, P = 0.044) and noradrenaline (r = 0.329, P = 0.041) but was not significantly correlated with change in adiposity or other variables. Conclusions Canagliflozin paradoxically increases serum FABP4 level in some diabetic patients despite amelioration of glucose metabolism and adiposity reduction, possibly via induction of catecholamine-induced lipolysis in adipocytes. Increased FABP4 level by canagliflozin may undermine the improvement of glucose metabolism and might be a possible mechanism of increased HGP by inhibition of SGLT2. Trial Registration UMIN-CTR Clinical Trial UMIN000018151 PMID:27124282

  7. Increased UVA exposures and decreased cutaneous Vitamin D(3) levels may be responsible for the increasing incidence of melanoma.

    PubMed

    Godar, Dianne E; Landry, Robert J; Lucas, Anne D

    2009-04-01

    Cutaneous malignant melanoma (CMM) has been increasing at a steady exponential rate in fair-skinned, indoor workers since before 1940. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) exposure than outdoor workers get, yet only indoor workers have an increasing incidence of CMM. Thus, another "factor(s)" is/are involved that increases the CMM risk for indoor workers. We hypothesize that one factor involves indoor exposures to UVA (321-400 nm) passing through windows, which can cause mutations and can break down vitamin D(3) formed after outdoor UVB (290-320 nm) exposure, and the other factor involves low levels of cutaneous vitamin D(3). After vitamin D(3) forms, melanoma cells can convert it to the hormone, 1,25-dihydroxyvitamin D(3), or calcitriol, which causes growth inhibition and apoptotic cell death in vitro and in vivo. We measured the outdoor and indoor solar irradiances and found indoor solar UVA irradiances represent about 25% (or 5-10 W/m(2)) of the outdoor irradiances and are about 60 times greater than fluorescent light irradiances. We calculated the outdoor and indoor UV contributions toward different biological endpoints by weighting the emission spectra by the action spectra: erythema, squamous cell carcinoma, melanoma (fish), and previtamin D(3). Furthermore, we found production of previtamin D(3) only occurs outside where there is enough UVB. We agree that intense, intermittent outdoor UV overexposures and sunburns initiate CMM; we now propose that increased UVA exposures and inadequately maintained cutaneous levels of vitamin D(3) promotes CMM. PMID:19155143

  8. Gelatin microspheres crosslinked with genipin for local delivery of growth factors

    PubMed Central

    Solorio, Luis; Zwolinski, Christopher; Lund, Amanda W.; Farrell, Megan J.; Stegemann, Jan P.

    2010-01-01

    A main challenge in tissue engineering and regenerative medicine is achieving local and efficient growth factor release to guide cell function. Gelatin is a denatured form of collagen that cells can bind to and degrade through enzymatic action. In this study, gelatin microspheres were used to release bone morphogenetic protein 2 (BMP2). Spherical microparticles with diameters in the range of 2–6 µm were created by an emulsification process and were stabilized by crosslinking with the small molecule genipin. The degree of crosslinking was varied by controlling the incubation time in genipin solution. Loading rate studies, using soy bean trypsin inhibitor as a model protein, showed rapid protein uptake over the first 24 h, followed by a levelling off and then a further increase after approximately 3 days, as the microspheres swelled. Growth factor release studies using microspheres crosslinked to 20%, 50% and 80% of saturation and then loaded with BMP2 showed that higher degrees of crosslinking resulted in higher loading efficiency and slower protein release. After 24 h, the concentration profiles produced by all microsphere formulations were steady and approximately equal. Microspheres incubated with adult human mesenchymal stem cells accumulated preferentially on the cell surface, and degraded over time in culture. BMP2-loaded microspheres caused a three- to eight-fold increase in expression of the bone sialoprotein gene after 14 days in culture, with more crosslinked beads producing a greater effect. These results demonstrate that genipin-crosslinked gelatin microspheres can be used to deliver growth factors locally to cells in order to direct their function. PMID:20872738

  9. Effect of dual modification with hydroxypropylation and cross-linking on physicochemical properties of taro starch.

    PubMed

    Hazarika, Bidyut Jyoti; Sit, Nandan

    2016-04-20

    Dual modification of taro starch by hydroxypropylation and cross-linking was carried out and the properties of the modified starches were investigated. Two different levels of hydroxypropylation (5 and 10%) and cross-linking (0.05 and 0.10%) were used in different sequences. The amylose contents of the starch decreased due to single and dual modification. For the dual-modified starches, the swelling, solubility and clarity was found to increase with level of hydroxypropylation and decrease with level of cross-linking. The freeze-thaw stability of the dual-modified starches was also affected by the sequence of modification. The viscosities of the cross-linked and dual-modified starches were more than native and hydroxypropylated starches. The firmness of the dual-modified starches was also higher than native and single modified starches. The dual-modified starches have benefits of both type of modifications and could be used for specific purposes e.g. food products requiring high viscosity as well as freeze-thaw stability. PMID:26876854

  10. Acute UV irradiation increases heparan sulfate proteoglycan levels in human skin.

    PubMed

    Jung, Ji-Yong; Oh, Jang-Hee; Kim, Yeon Kyung; Shin, Mi Hee; Lee, Dayae; Chung, Jin Ho

    2012-03-01

    Glycosaminoglycans are important structural components in the skin and exist as various proteoglycan forms, except hyaluronic acid. Heparan sulfate (HS), one of the glycosaminoglycans, is composed of repeated disaccharide units, which are glucuronic acids linked to an N-acetyl-glucosamine or its sulfated forms. To investigate acute ultraviolet (UV)-induced changes of HS and HS proteoglycans (HSPGs), changes in levels of HS and several HSPGs in male human buttock skin were examined by immunohistochemistry and real-time quantitative polymerase chain reaction (qPCR) after 2 minimal erythema doses (MED) of UV irradiation (each n = 4-7). HS staining revealed that 2 MED of UV irradiation increased its expression, and staining for perlecan, syndecan-1, syndecan-4, CD44v3, and CD44 showed that UV irradiation increased their protein levels. However, analysis by real-time qPCR showed that UV irradiation did not change mRNA levels of CD44 and agrin, and decreased perlecan and syndecan-4 mRNA levels, while increased syndecan-1 mRNA level. As HS-synthesizing or -degrading enzymes, exostosin-1 and heparanase mRNA levels were increased, but exostosin-2 was decreased by UV irradiation. UV-induced matrix metalloproteinase-1 expression was confirmed for proper experimental conditions. Acute UV irradiation increases HS and HSPG levels in human skin, but their increase may not be mediated through their transcriptional regulation. PMID:22379342

  11. Effects of Collagen Crosslinking on Bone Material Properties in Health and Disease.

    PubMed

    Saito, Mitsuru; Marumo, Keishi

    2015-09-01

    Data have accumulated to show that various types of collagen crosslinking are implicated in the health of individuals, as well as in a number of disease states, such as osteoporosis, diabetes mellitus, chronic kidney disease, inflammatory bowel disease, or in conditions of mild hyperhomocysteinemia, or when glucocorticoid use is indicated. Collagen crosslinking is a posttranslational modification of collagen molecules and plays important roles in tissue differentiation and in the mechanical properties of collagenous tissue. The crosslinking of collagen in the body can form via two mechanisms: one is enzymatic crosslinking and the other is nonenzymatic crosslinking. Lysyl hydroxylases and lysyl oxidases regulate tissue-specific crosslinking patterns and quantities. Enzymatic crosslinks initially form via immature divalent crosslinking, and a portion of them convert into mature trivalent forms such as pyridinoline and pyrrole crosslinks. Nonenzymatic crosslinks form as a result of reactions which create advanced glycation end products (AGEs), such as pentosidine and glucosepane. These types of crosslinks differ in terms of their mechanisms of formation and function. Impaired enzymatic crosslinking and/or an increase of AGEs have been proposed as a major cause of bone fragility associated with aging and numerous disease states. This review focuses on the effects of collagen crosslinking on bone material properties in health and disease. PMID:25791570

  12. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host-parasitoid food chain.

    PubMed

    Sanders, Dirk; Moser, Andrea; Newton, Jason; van Veen, F J Frank

    2016-03-16

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host-parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary-secondary-tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ(15)N increased with trophic level, with trophic discrimination factors (Δ(15)N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host-parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. PMID:26962141

  13. Trophic assimilation efficiency markedly increases at higher trophic levels in four-level host–parasitoid food chain

    PubMed Central

    Moser, Andrea; van Veen, F. J. Frank

    2016-01-01

    Trophic assimilation efficiency (conversion of resource biomass into consumer biomass) is thought to be a limiting factor for food chain length in natural communities. In host–parasitoid systems, which account for the majority of terrestrial consumer interactions, a high trophic assimilation efficiency may be expected at higher trophic levels because of the close match of resource composition of host tissue and the consumer's resource requirements, which would allow for longer food chains. We measured efficiency of biomass transfer along an aphid-primary–secondary–tertiary parasitoid food chain and used stable isotope analysis to confirm trophic levels. We show high efficiency in biomass transfer along the food chain. From the third to the fourth trophic level, the proportion of host biomass transferred was 45%, 65% and 73%, respectively, for three secondary parasitoid species. For two parasitoid species that can act at the fourth and fifth trophic levels, we show markedly increased trophic assimilation efficiencies at the higher trophic level, which increased from 45 to 63% and 73 to 93%, respectively. In common with other food chains, δ15N increased with trophic level, with trophic discrimination factors (Δ15N) 1.34 and 1.49‰ from primary parasitoids to endoparasitic and ectoparasitic secondary parasitoids, respectively, and 0.78‰ from secondary to tertiary parasitoids. Owing to the extraordinarily high efficiency of hyperparasitoids, cryptic higher trophic levels may exist in host–parasitoid communities, which could alter our understanding of the dynamics and drivers of community structure of these important systems. PMID:26962141

  14. Strategies for Mitigating the Reduction in Economic Value of Variable Generation with Increasing Penetration Levels

    SciTech Connect

    Mills, Andrew; Wiser, Ryan

    2014-03-03

    In this report, we evaluate individual options that have the potential to stem the decline in the marginal value of variable generation (VG) with increasing penetration levels. We focus only on the effectiveness of mitigation measures for wind and PV.

  15. Increasing levels of assistance in refinement of knowledge-based retrieval systems

    NASA Technical Reports Server (NTRS)

    Baudin, Catherine; Kedar, Smadar; Pell, Barney

    1994-01-01

    The task of incrementally acquiring and refining the knowledge and algorithms of a knowledge-based system in order to improve its performance over time is discussed. In particular, the design of DE-KART, a tool whose goal is to provide increasing levels of assistance in acquiring and refining indexing and retrieval knowledge for a knowledge-based retrieval system, is presented. DE-KART starts with knowledge that was entered manually, and increases its level of assistance in acquiring and refining that knowledge, both in terms of the increased level of automation in interacting with users, and in terms of the increased generality of the knowledge. DE-KART is at the intersection of machine learning and knowledge acquisition: it is a first step towards a system which moves along a continuum from interactive knowledge acquisition to increasingly automated machine learning as it acquires more knowledge and experience.

  16. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity. PMID:24164734

  17. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    PubMed

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels. PMID:26342297

  18. Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms

    PubMed Central

    Pettorruso, Mauro; De Berardis, Domenico; Varasano, Paola Annunziata; Lucidi Pressanti, Gabriella; De Remigis, Valeria; Valchera, Alessandro; Ricci, Valerio; Di Nicola, Marco; Janiri, Luigi; Biggio, Giovanni; Di Giannantonio, Massimo

    2016-01-01

    Background: Agomelatine modulates brain-derived neurotrophic factor expression via its interaction with melatonergic and serotonergic receptors and has shown promising results in terms of brain-derived neurotrophic factor increase in animal models. Methods: Twenty-seven patients were started on agomelatine (25mg/d). Venous blood was collected and brain-derived neurotrophic factor serum levels were measured at baseline and after 2 and 8 weeks along with a clinical assessment, including Hamilton Depression Rating Scale and Snaith-Hamilton Pleasure Scale. Results: Brain-derived neurotrophic factor serum concentration increased after agomelatine treatment. Responders showed a significant increase in brain-derived neurotrophic factor levels after 2 weeks of agomelatine treatment; no difference was observed in nonresponders. Linear regression analysis showed that more prominent brain-derived neurotrophic factor level variation was associated with lower baseline BDNF levels and greater anhedonic features at baseline. Conclusions: Patients affected by depressive disorders showed an increase of brain-derived neurotrophic factor serum concentration after a 2-week treatment with agomelatine. The increase of brain-derived neurotrophic factor levels was found to be greater in patients with lower brain-derived neurotrophic factor levels and marked anhedonia at baseline. PMID:26775293

  19. Cytokines and migraine: increase of IL-5 and IL-4 plasma levels.

    PubMed

    Munno, I; Centonze, V; Marinaro, M; Bassi, A; Lacedra, G; Causarano, V; Nardelli, P; Cassiano, M A; Albano, O

    1998-06-01

    Thirty-two patients suffering from migraine without aura were assessed during in interictal period to evaluate the contribution of cytokines to the pathophysiology of migraine. To this end, plasma levels of IFN-gamma, IL-4, IL-5, and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) techniques. Plasma levels of both IFN-gamma and IL-10 were not increased in the patients and did not differ significantly from healthy controls. Of interest, we observed a strong increase of IL-5 levels in 84.3% as well as increased IL-4 levels in 37.5% of patients with migraine without aura. These results suggests a preferential enhancement of some Th2-type cytokines, and may support the growing arguments of an immunoallergic mechanism in the pathophysiology of migraine. PMID:9664752

  20. DNA Photolithography with Cinnamate Crosslinkers

    NASA Technical Reports Server (NTRS)

    Feng, Lang (Inventor); Chaikin, Paul Michael (Inventor)

    2016-01-01

    The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

  1. Increased DHT levels in androgenic alopecia have been selected for to protect men from prostate cancer.

    PubMed

    Bhargava, Shiva

    2014-04-01

    Androgenic alopecia, a condition characterized by increased levels of DHT could have been selected for due to the benefits that prostaglandin D2 (PGD(2)) has on the prostate. A DHT metabolite can increase the transcription of prostaglandin D2 synthase through estrogen receptor beta. The increase of PGD(2) can decrease the risk of prostate cancer and proliferation of prostate cancer cells. Therefore, the mechanisms behind male pattern baldness may also curtail the advancement of prostate cancer. PMID:24548754

  2. Preparation of DNA-crosslinked polyacrylamide hydrogels.

    PubMed

    Previtera, Michelle L; Langrana, Noshir A

    2014-01-01

    Mechanobiology is an emerging scientific area that addresses the critical role of physical cues in directing cell morphology and function. For example, the effect of tissue elasticity on cell function is a major area of mechanobiology research because tissue stiffness modulates with disease, development, and injury. Static tissue-mimicking materials, or materials that cannot alter stiffness once cells are plated, are predominately used to investigate the effects of tissue stiffness on cell functions. While information gathered from static studies is valuable, these studies are not indicative of the dynamic nature of the cellular microenvironment in vivo. To better address the effects of dynamic stiffness on cell function, we developed a DNA-crosslinked polyacrylamide hydrogel system (DNA gels). Unlike other dynamic substrates, DNA gels have the ability to decrease or increase in stiffness after fabrication without stimuli. DNA gels consist of DNA crosslinks that are polymerized into a polyacrylamide backbone. Adding and removing crosslinks via delivery of single-stranded DNA allows temporal, spatial, and reversible control of gel elasticity. We have shown in previous reports that dynamic modulation of DNA gel elasticity influences fibroblast and neuron behavior. In this report and video, we provide a schematic that describes the DNA gel crosslinking mechanisms and step-by-step instructions on the preparation DNA gels. PMID:25226067

  3. Age-related crosslink in skin collagen

    SciTech Connect

    Yamauchi, M.; Mechanic, G.

    1986-05-01

    A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.

  4. Image guided thermal ablation of tumors increases the plasma level of IL-6 and IL-10

    PubMed Central

    Erinjeri, Joseph P; Thomas, Contessa T; Samoila, Alaiksandra; Fleisher, Martin; Gonen, Mithat; Sofocleous, Constantinos T.; Thornton, Raymond H; Siegelbaum, Robert H.; Covey, Anne M.; Brody, Lynn A.; Alago, William; Maybody, Majid; Brown, Karen T.; Getrajdman, George; Solomon, Stephen B.

    2014-01-01

    PURPOSE To identify changes in plasma cytokine levels following image-guided thermal ablation of human tumors and to identify the factors that independently predict changes in plasma cytokine levels. MATERIALS AND METHODS Whole blood samples were collected from 36 patients at 3 time points: pre-ablation, post-ablation (within 48 hours), and in follow-up (1–5 weeks after ablation). Plasma levels of IL-1a, IL-2, IL-6, IL-10 and TNFa were measured using a multiplex immunoassay. Univariate and multivariate analyses were performed using cytokine level as the dependent variable and sample collection, time, age, sex, primary diagnosis, metastatic status, ablation site, and ablation type as the independent variables. RESULTS There was a significant increase in the plasma level of IL-6 post-ablation when compared to pre-ablation (9.6+/−31 fold, p<0.002). IL-10 also showed a significant increase postablation (1.9 +/−2.8 fold, p<0.02). Plasma levels of IL-1a, IL-2, and TNFa were not significantly changed after ablation. Cryoablation resulted in the largest change in IL-6 level (>54 fold), while radiofrequency and microwave ablation showed 3.6 and 3.4-fold changes, respectively. Ablation of melanomas showed the largest change in IL-6 48 hours after ablation (92×), followed by ablation of kidney (26×), liver (8×), and lung (6×) cancers. Multivariate analysis revealed that ablation type (p<0.0003), and primary diagnosis (p<0.03) were independent predictors of changes to IL-6 following ablation. Age was the only independent predictor of IL-10 levels following ablation (p<0.019). CONCLUSION Image guided thermal ablation of tumors increases the plasma level of IL-6 and IL-10, without increasing the plasma level of IL-1a, IL-2, or TNFa. PMID:23582441

  5. Structural response of human corneal and scleral tissues to collagen cross-linking treatment with riboflavin and ultraviolet A light.

    PubMed

    Choi, Samjin; Lee, Seung-Chan; Lee, Hui-Jae; Cheong, Youjin; Jung, Gyeong-Bok; Jin, Kyung-Hyun; Park, Hun-Kuk

    2013-09-01

    High success rates in clinical trials on keratoconic corneas suggest the possibility of efficient treatment against myopic progression. This study quantitatively investigated the in vitro ultrastructural effects of a photooxidative collagen cross-linking treatment with photosensitizer riboflavin and UVA light in human corneo-scleral collagen fibrils. A total of 30.8 × 2 mm corneo-scleral strips from donor tissue were sagittally dissected using a scalpel. The five analytic parameters namely fibril density, fibril area, corneo-scleral thickness, fibril diameter, and fibril arrangement were investigated before and after riboflavin-UVA-catalyzed collagen cross-linking treatment. Collagen cross-linking effects were measured at the corneo-scleral stroma and were based on clinical corneal cross-linking procedures. The structural response levels were assessed by histology, digital mechanical caliper measurement, scanning electron microscopy, and atomic force microscopy. Riboflavin-UVA-catalyzed collagen cross-linking treatment led to an increase in the area, density, and diameters of both corneal (110, 112, and 103 %) and scleral (133, 133, and 127 %) stromal collagens. It also led to increases in corneal (107 %) and scleral (105 %) thickness. Collagen cross-linking treatment through riboflavin-sensitized photoreaction may cause structural property changes in the collagen fibril network of the cornea and sclera due to stromal edema and interfibrillar spacing narrowing. These changes were particularly prominent in the sclera. This technique can be used to treat progressive keratoconus in the cornea as well as progressive myopia in the sclera. Long-term collagen cross-linking treatment of keratoconic and myopic progression dramatically improves weakened corneo-scleral tissues. PMID:23179311

  6. Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

    PubMed Central

    Nocturne, Gaetane; Pavy, Stephan; Boudaoud, Saida; Seror, Raphaèle; Goupille, Philippe; Chanson, Philippe; van der Heijde, Désirée; van Gaalen, Floris; Berenbaum, Francis; Mariette, Xavier; Briot, Karine; Feydy, Antoine; Claudepierre, Pascal; Dieudé, Philippe; Nithitham, Joanne; Taylor, Kimberly E.; Criswell, Lindsey A.; Dougados, Maxime; Roux, Christian; Miceli-Richard, Corinne

    2015-01-01

    Objectives To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors. Methods The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls. Results Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10−9), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels. Conclusions DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels. PMID:26313358

  7. Preparation and characterization of IPN hydrogels composed of chitosan and gelatin cross-linked by genipin.

    PubMed

    Cui, Li; Jia, Junfang; Guo, Yi; Liu, Yun; Zhu, Ping

    2014-01-01

    The interpenetrating polymer networks (IPN) hydrogels based on chitosan and gelatin using genipin as the cross-linker were prepared and characterized. The IPN formation of the genipin-cross-linked chitosan/gelatin hydrogel was confirmed by means of the instrinsic viscosity measurement, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and the ninhydrin assays. The instrinsic viscosity measurement, FT-IR and SEM suggested that chitosan and gelatin were miscible in the molecular level. The miscibility leads to the formation of IPN after cross-linking. FT-IR also examined the cross-linking mechanism of genipin with primary amino groups. The degree of cross-linking increased with increase genipin concentration. Swelling results revealed that the IPN hydrogels are pH-sensitive, exhibiting reversibility and rather rapidly response in swelling to pH changes. It is expected this IPN hydrogel has potential as controlled drug delivery system or as alternative sorbents for biomedical and environmental use as pH altered. PMID:24274476

  8. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  9. Modeling Caspian Sea water level oscillations under different scenarios of increasing atmospheric carbon dioxide concentrations

    PubMed Central

    2012-01-01

    The rapid rise of Caspian Sea water level (about 2.25 meters since 1978) has caused much concern to all five surrounding countries, primarily because flooding has destroyed or damaged buildings and other engineering structures, roads, beaches and farm lands in the coastal zone. Given that climate, and more specifically climate change, is a primary factor influencing oscillations in Caspian Sea water levels, the effect of different climate change scenarios on future Caspian Sea levels was simulated. Variations in environmental parameters such as temperature, precipitation, evaporation, atmospheric carbon dioxide and water level oscillations of the Caspian sea and surrounding regions, are considered for both past (1951-2006) and future (2025-2100) time frames. The output of the UKHADGEM general circulation model and five alternative scenarios including A1CAI, BIASF, BIMES WRE450 and WRE750 were extracted using the MAGICC SCENGEN Model software (version 5.3). The results suggest that the mean temperature of the Caspian Sea region (Bandar-E-Anzali monitoring site) has increased by ca. 0.17°C per decade under the impacts of atmospheric carbon dioxide changes (r=0.21). The Caspian Sea water level has increased by ca. +36cm per decade (r=0.82) between the years 1951-2006. Mean results from all modeled scenarios indicate that the temperature will increase by ca. 3.64°C and precipitation will decrease by ca. 10% (182 mm) over the Caspian Sea, whilst in the Volga river basin, temperatures are projected to increase by ca. 4.78°C and precipitation increase by ca. 12% (58 mm) by the year 2100. Finally, statistical modeling of the Caspian Sea water levels project future water level increases of between 86 cm and 163 cm by the years 2075 and 2100, respectively. PMID:23369617

  10. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    PubMed

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P < 0.05 vs. vehicle). A significant 20% reduction in hepatic LDL receptor protein expression was also observed with empagliflozin. Importantly, none of these parameters were changed by empagliflozin in fed conditions. Empagliflozin significantly reduced the catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion. PMID:27207551

  11. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  12. Playground designs to increase physical activity levels during school recess: a systematic review.

    PubMed

    Escalante, Yolanda; García-Hermoso, Antonio; Backx, Karianne; Saavedra, Jose M

    2014-04-01

    School recess provides a major opportunity to increase children's physical activity levels. Various studies have described strategies to increase levels of physical activity. The purpose of this systematic review is therefore to examine the interventions proposed as forms of increasing children's physical activity levels during recess. A systematic search of seven databases was made from the July 1 to July 5, 2012, leading to a final set of eight studies (a total of 2,383 subjects-599 "preschoolers" and 1,784 "schoolchildren") meeting the inclusion criteria. These studies were classified according to the intervention used: playground markings, game equipment, playground markings plus physical structures, and playground markings plus game equipment. The results of these studies indicate that the strategies analyzed do have the potential to increase physical activity levels during recess. The cumulative evidence was (a) that interventions based on playground markings, game equipment, or a combination of the two, do not seem to increase the physical activity of preschoolers and schoolchildren during recess and (ii) that interventions based on playground markings plus physical structures do increase the physical activity of schoolchildren during recess in the short to medium term. PMID:23836828

  13. Increased steroid hormone dehydroepiandrosterone and pregnenolone levels in post-mortem brain samples of alcoholics.

    PubMed

    Kärkkäinen, Olli; Häkkinen, Merja R; Auriola, Seppo; Kautiainen, Hannu; Tiihonen, Jari; Storvik, Markus

    2016-05-01

    Intra-tissue levels of steroid hormones (e.g., dehydroepiandrosterone [DHEA], pregnenolone [PREGN], and testosterone [T]) may influence the pathological changes seen in neurotransmitter systems of alcoholic brains. Our aim was to compare levels of these steroid hormones between the post-mortem brain samples of alcoholics and non-alcoholic controls. We studied steroid levels with quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) in post-mortem brain samples of alcoholics (N = 14) and non-alcoholic controls (N = 10). Significant differences were observed between study groups in DHEA and PREGN levels (p values 0.0056 and 0.019, respectively), but not in T levels. Differences between the study groups were most prominent in the nucleus accumbens (NAC), anterior cingulate cortex (ACC), and anterior insula (AINS). DHEA levels were increased in most alcoholic subjects compared to controls. However, only a subgroup of alcoholics showed increased PREGN levels. Negative Spearman correlations between tissue levels of PREGN and previous reports of [(3)H]naloxone binding to μ-opioid receptors were observed in the AINS, ACC, NAC, and frontal cortex (R values between -0.6 and -0.8; p values ≤ 0.002), suggesting an association between the opioid system and brain PREGN levels. Although preliminary, and from relatively small diagnostic groups, these results show significantly increased levels of DHEA and PREGN in the brains of alcoholics, and could be associated with the pathology of alcoholism. PMID:27139239

  14. Increased Heme Levels in the Heart Lead to Exacerbated Ischemic Injury

    PubMed Central

    Sawicki, Konrad Teodor; Shang, Meng; Wu, Rongxue; Chang, Hsiang-Chun; Khechaduri, Arineh; Sato, Tatsuya; Kamide, Christine; Liu, Ting; Naga Prasad, Sathyamangla V; Ardehali, Hossein

    2015-01-01

    Background Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. Methods and Results We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to nontransgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death observed with ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to nonischemic cardiomyopathy. Conclusions Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a

  15. High D-dimer levels increase the likelihood of pulmonary embolism.

    PubMed

    Tick, L W; Nijkeuter, M; Kramer, M H H; Hovens, M M C; Büller, H R; Leebeek, F W G; Huisman, M V

    2008-08-01

    Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied. PMID:18452520

  16. Climbing the goal ladder: how upcoming actions increase level of aspiration.

    PubMed

    Koo, Minjung; Fishbach, Ayelet

    2010-07-01

    Pursuing a series of progressive (e.g., professional) goals that form a goal ladder often leads to a trade-off between moving up to a more advanced level and repeating the same goal level. This article investigates how monitoring one's current goal in terms of remaining actions versus completed actions influences the desire to move up the goal ladder. The authors propose that a focus on remaining (vs. completed) actions increases the motivation to move up to a more advanced level, whereas the focus on completed (vs. remaining) actions increases the satisfaction derived from the present level. They find support for these predictions across several goal ladders, ranging from academic and professional ladders to simple, experimental tasks. They further find that individuals strategically attend to information about remaining (vs. completed) actions to prepare to move up the goal ladder. PMID:20565182

  17. Increased levels of a particular phosphatidylcholine species in senescent human dermal fibroblasts in vitro.

    PubMed

    Naru, Eiji; Takanezawa, Yasukazu; Kobayashi, Misako; Misaki, Yuko; Kaji, Kazuhiko; Arakane, Kumi

    2008-08-01

    Plasma membranes are essential components of living cells, and phospholipids are major components of cellular membranes. Here, we used liquid chromatography/mass spectrometry to investigate changes in the membrane phospholipid content that occur in association with aging. Our results indicate that the levels of a particular species of phosphatidylcholine comprised of stearic acid and arachidonic acid increased with age. To determine the reason for the increased levels of this particular phosphatidylcholine, we examined the effect of highly unsaturated fatty acids, such as arachidonic acid and eicosapentaenoic acid, on cellular aging. Applied arachidonic acid was incorporated into phosphatidylcholine molecules, but neither arachidonic acid nor other related unsaturated fatty acids had any effect. We conclude that increased levels of this distinctive phosphatidylcholine are a result of in vitro senescence. PMID:18667023

  18. CSF levels of prostaglandins, especially the level of prostaglandin D2, are correlated with increasing propensity towards sleep in rats.

    PubMed

    Ram, A; Pandey, H P; Matsumura, H; Kasahara-Orita, K; Nakajima, T; Takahata, R; Satoh, S; Terao, A; Hayaishi, O

    1997-03-14

    The concentration of PGD2, PGE2, and of PGF2 alpha was measured in the cerebrospinal fluid (CSF) collected from the cisterna magna of conscious rats (n = 29), which, chronically implanted with a catheter for the CSF sampling, underwent deprivation of daytime sleep. Significant elevation of the CSF level of PGD2 was observed following 2.5-h sleep deprivation (SD), and the elevation became more marked following 5- and 10-h SD, apparently reaching the maximum at 5-h SD (703 +/- 140 pg/ml (mean +/- S.E.M.) for baseline vs. 1734 +/- 363 pg/ml for SD, n = 10). The levels of PGE2, and PGF2 alpha also significantly increased following 5- and 10-h SD, but not following 2.5-h SD. It is unlikely that these changes were simply caused by some responses of the animals to stress stimuli, because stress stimuli derived from restraint of the animal at the supine position to a board for 1 h did not produce any acute responses in the CSF levels of prostaglandins (n = 13). In a different group of animals (n = 11) implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) in addition to the catheter, the levels of the prostaglandins in CSF were determined for slow-wave sleep (SWS) and wakefulness in the day and for SWS and wakefulness in the night. The highest PGD2 value was obtained at daytime SWS, whereas the lowest was at night wakefulness; furthermore, a significant difference was observed between SWS and wakefulness rather than between day and night. The CSF level of PGE2 also showed a similar tendency. In an additional group of animals (n = 6), not only PGD2 but also PGE2 and PGF2 alpha significantly increased the sleeping time of the animal when applied into the subarachnoid space underlying the ventral surface area of the rostral basal forebrain, the previously defined site of action for the sleep-promoting effect of PGD2. The promotion of sleep by PGE2 applied to the subarachnoid space was an effect completely opposite to the well

  19. Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis

    PubMed Central

    Bhatt, Dhaval P.; Houdek, Heidi M.; Watt, John A.; Rosenberger, Thad A.

    2013-01-01

    Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/Kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4 hr following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP + ½ ADP) / (ATP + ADP + AMP)] when compared to controls. However, after 4 hr of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

  20. Calpain expression in lymphoid cells. Increased mRNA and protein levels after cell activation.

    PubMed

    Deshpande, R V; Goust, J M; Chakrabarti, A K; Barbosa, E; Hogan, E L; Banik, N L

    1995-02-10

    Although calpain is ubiquitously present in human tissues and is thought to play a role in demyelination, its activity is very low in resting normal lymphocytes. To determine the nature of calpain expression at the mRNA and protein levels in human lymphoid cells, we studied human T lymphocytic, B lymphocytic, and monocytic lines as well as peripheral blood mononuclear cells. Stimulation of cells with the phorbol ester phorbol myristate acetate and the calcium ionophore A23187 resulted in increased calpain mRNA and protein expression. Calpain mRNA expression is also increased in human T cells stimulated with anti-CD3. A dissociation between the increases of RNA and protein suggested that calpain could be released from the cells; the subsequent experiments showed its presence in the extracellular environment. 5,6-Dichloro-1b-D-ribofuranosylbenzimidazole, a reversible inhibitor of mRNA synthesis, reduced calpain mRNA levels by 50-67% and protein levels by 72-91%. Its removal resulted in resumption of both calpain mRNA and protein synthesis. Cycloheximide, a translational inhibitor, reduced calpain protein levels by 77-81% and calpain mRNA levels by 96% in activated THP-1 cells. Interferon-gamma induced calpain mRNA and protein in U-937 and THP-1 cells. Dexamethasone increased mRNA expression in THP-1 cells. Our results indicate that activation of lymphoid cells results in de novo synthesis and secretion of calpain. PMID:7852311

  1. Single Aggressive Interactions Increase Urinary Glucocorticoid Levels in Wild Male Chimpanzees

    PubMed Central

    Weltring, Anja; Deschner, Tobias; Zuberbühler, Klaus

    2015-01-01

    A basic premise in behavioural ecology is the cost-benefit arithmetic, which determines both behavioural decisions and evolutionary processes. Aggressive interactions can be costly on an energetic level, demanding increased energy or causing injuries, and on a psychological level, in the form of increased anxiety and damaged relationships between opponents. Here we used urinary glucocorticoid (uGC) levels to assess the costs of aggression in wild chimpanzees of Budongo Forest, Uganda. We collected 169 urine samples from nine adult male chimpanzees following 14 aggressive interactions (test condition) and 10 resting events (control condition). Subjects showed significantly higher uGC levels after single aggressive interactions compared to control conditions, likely for aggressors as well as victims. Higher ranking males had greater increases of uGC levels after aggression than lower ranking males. In contrast, uGC levels showed no significant change in relation to aggression length or intensity, indicating that psychological factors might have played a larger role than mere energetic expenditure. We concluded that aggressive behaviour is costly for both aggressors and victims and that costs seem poorly explained by energetic demands of the interaction. Our findings are relevant for studies of post-conflict interactions, since we provide evidence that both aggressors and victims experience a stress response to conflict. PMID:25714095

  2. Cannabis use is associated with increased CCL11 plasma levels in young healthy volunteers.

    PubMed

    Fernandez-Egea, Emilio; Scoriels, Linda; Theegala, Swathi; Giro, Maria; Ozanne, Susan E; Burling, Keith; Jones, Peter B

    2013-10-01

    Cannabis is a widely used recreational drug. Its effect on human health and psychosis remains controversial. In this study, we aimed to explore the possibility that cannabis use influenced CCL11 plasma levels. Increased CCL11 chemokine has been reported in schizophrenia and cannabis is a known trigger of schizophrenia. Additionally, plasma levels of the chemokine CCL11 have recently been shown to increase with age and with cognitive deficits and hippocampal neurogenesis. For this study, a total of 87 healthy volunteers (68% men, age range 18-35 years) completed the Cannabis Experience Questionnaire that included information on sociodemographic and morphometric data and provided a blood sample for CCL11 measurement. 'Current users' of cannabis (n=18) had significantly higher CCL11 plasma levels compared to 'past users' (n=33) and 'never users' (n=36) [F(3,84)=3.649; p=0.030]. The latter two groups had similar CCL11 levels. Higher CCL11 plasma levels could not be attributed to gender, age, body mass index, physical activity or use of other legal/illegal drugs. These results suggest that cannabis use increases CCL11 plasma levels and the effects are reversible when cannabis use ceases. PMID:23820464

  3. Does instruction in the use of personal digital assistants increase medical students' comfort and skill level?

    PubMed

    Guerrieri, Rose; Kokinova, Margarita

    2009-01-01

    Reference librarians developed an assessment tool to determine if formal classroom instruction on the use of PDAs benefits medical students. The questionnaire on PDA concepts and skills, designed to assess both comfort level and self-described skill level, was administered to students before and after a mandatory hands-on PDA class. Of 105 students surveyed, 90 (85.7%) felt the class was immediately beneficial. Mean scores on all questions increased from pre-session to post-session. Score increases were statistically significant (p < .05) for almost all questions, demonstrating to faculty, students, and instructors that the PDA class is beneficial, necessary, and should remain mandatory. PMID:19197742

  4. Stress-relaxation behavior in gels with ionic and covalent crosslinks

    NASA Astrophysics Data System (ADS)

    Zhao, Xuanhe; Huebsch, Nathaniel; Mooney, David J.; Suo, Zhigang

    2010-03-01

    Long-chained polymers in alginate hydrogels can form networks by either ionic or covalent crosslinks. This paper shows that the type of crosslinks can markedly affect the stress-relaxation behavior of the gels. In gels with only ionic crosslinks, stress relaxes mainly through breaking and subsequent reforming of the ionic crosslinks, and the time scale of the relaxation is independent of the size of the sample. By contrast, in gels with only covalent crosslinks, stress relaxes mainly through migration of water, and the relaxation slows down as the size of the sample increases. Implications of these observations are discussed.

  5. Ultraviolet B radiation was increased at ground level in scotland during a period of ozone depletion.

    PubMed

    Moseley, H; Mackie, R M

    1997-07-01

    The potentially harmful effects associated with stratospheric ozone depletion are widely acknowledged. As the ozone layer principally absorbs ultraviolet (UV) radiation of wavelengths below 290 nm, reductions in stratospheric ozone levels are likely to result in increased UVB at the earth's surface, with the risk of increased incidence of skin cancer. Measuring the sun's spectrum at ground level requires sophisticated and reliable spectral instruments. Results are reported for this for the first time in the U.K. using spectral instruments, showing a significant increase in short wavelength UV radiation at a time of depleted stratospheric ozone. If this trend increases, future ozone depletion could contribute to known risks for cutaneous malignancies of all types. PMID:9274633

  6. A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men

    SciTech Connect

    Kervinen, K.; Savolainen, J.J.; Kesaeniemi, Y.A. )

    1991-01-01

    Plasma concentrations of lipoprotein (a) (Lp(a)) were studied in 11 male alcoholics at the end of a drinking period and monitored during subsequent abstinence. Lp(a) levels showed a daily increase for four consecutive days after the beginning of abstinence, the values for the third and the fourth day being significantly higher than those of the first day. The changes in Lp(a) showed no association with the changes in low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels. In one alcoholic subject with a heterozygous form of familial hypercholesterolemia who was monitored for 11 days, the Lp(a) levels rose up to the fourth day and remained at a high level thereafter. These results suggest that ethanol ingestion may be associated with a lower of Lp(a) levels, which may contribute to the delayed progression of atherosclerosis observed in alcohol drinkers.

  7. Immunological aspects in migraine: increase of IL-10 plasma levels during attack.

    PubMed

    Munno, I; Marinaro, M; Bassi, A; Cassiano, M A; Causarano, V; Centonze, V

    2001-09-01

    In the present study, 23 patients with migraine without aura were monitored during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and interferon-gamma were measured by enzyme-linked immunosorbent assay techniques. Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels were undetectable in all patients. After treatment with sumatriptan, 10 patients showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5 plasma levels. Although these findings are derived from a limited number of patients, the apparent return to the IL-4 and IL-5 cytokine profile observed during the interictal period leads us to speculate that a preferential enhancement of TH2-type cytokine production may contribute to the pathogenesis of migraine. PMID:11576199

  8. Increased serum inhibin B levels in postmenopausal women with altered thyroid function.

    PubMed

    Viceconti, N; Luisi, S; Nardo, S; Gargano, L; Franchi, A; Sibilla, R; Canettieri, G; Petraglia, F; Centanni, M

    2003-08-01

    Hyper- and hypothyroidism have significant effects on the female reproductive system. However, little in the way of data is available on the relationship between ovarian paracrine control and thyroid function. This study was aimed at characterising the serum levels of inhibin B in relation to altered thyroid function. Serum inhibin B and FSH levels were measured in 91 women (51 regularly cycling and 40 postmenopausal). The mean serum concentration of inhibin B in euthyroid cycling women (0.025 +/- 0.018 microg/l) was similar to that observed in hyper- and hypothyroid patients (0.022 +/- 0.015 and 0.018 +/- 0.014 microg/l, respectively, p=ns). Inhibin B levels were obviously reduced (-72%) in euthyroid postmenopausal women. In contrast, in hyper- and hypothyroid postmenopausal women, inhibin B levels remained substantially at the premenopausal level. So far, serum inhibin B appeared to be significantly increased in both hyperthyroid patients (0.025 +/- 0.014 microg/l; p<0.0001) and in hypothyroid patients (0.016 +/- 0.006 microg/l; p=0.0006). Altered thyroid function did not affect FSH levels at fertile age. However, a significant decrease of FSH levels was observed in hyper- and hypothyroid (-52% and -43%, respectively) postmenopausal women. Nevertheless, these FSH levels remained in the postmenopausal range. These results indicate that an altered thyroid function affects serum inhibin B levels in postmenopausal women. PMID:12953168

  9. Coated-Platelet Levels Increase with Number of Injuries in Patients with Mild Traumatic Brain Injury.

    PubMed

    Prodan, Calin I; Vincent, Andrea S; Dale, George L

    2016-05-01

    Coated-platelets are procoagulant platelets that are elevated in stroke and are associated with stroke recurrence. In a previous study, prompted by data showing an increased risk for stroke following traumatic brain injury (TBI), we found that coated-platelet levels are elevated in patients with combat-related mild TBI (mTBI) several years after the injury, compared with controls. We now investigate in an expanded patient population whether parameters commonly recorded in mTBI are related to increased coated-platelet potential. Coated-platelet levels were assayed in 120 mTBI patients at intervals ranging from 6 months to 10 years from the last injury. Correlations were calculated between coated-platelet levels and age, gender, race/ethnicity, loss of consciousness, alteration in consciousness, post-traumatic amnesia, number of injuries, mechanism of injury, time since first and last injury, smoking, medications that may influence coated-platelet levels, and pertinent comorbid conditions. Significant correlations were detected between coated-platelet levels and number of injuries (p = 0.026), gender (p = 0.01), and time since last injury (p = 0.04). A multi-variable linear model analysis, including these three parameters and an additional three parameters (race/ethnicity, smoking, and mechanism of injury) that reached a p value of <0.2, showed that the number of injuries were predictive of coated-platelet levels (p = 0.004). These results support a mechanistic link between increased coated-platelet levels and repeated injuries in mTBI. Long-term studies will be required to determine the impact of increased prothrombotic potential in mTBI patients. PMID:26414016

  10. Licochalcone A induces T24 bladder cancer cell apoptosis by increasing intracellular calcium levels.

    PubMed

    Yang, Xinhui; Jiang, Jiangtao; Yang, Xinyan; Han, Jichun; Zheng, Qiusheng

    2016-07-01

    Licochalcone A (LCA) has been reported to significantly inhibit cell proliferation, increase reactive oxygen species (ROS) levels, and induce apoptosis of T24 human bladder cancer cells via mitochondria and endoplasmic reticulum (ER) stress-triggered signaling pathways. Based on these findings, the present study aimed to investigate the mechanisms by which LCA induces apoptosis of T24 cells. Cultured T24 cells were treated with LCA, and cell viability was measured using the sulforhodamine B assay. Apoptosis was detected by flow cytometry with Annexin V/propidium iodide staining, and by fluorescent microscopy with Hoechst 33258 staining. The levels of intracellular free calcium ions were determined using Fluo-3 AM dye marker. Intracellular ROS levels were assessed using the 2',7'-dichlorodihydrofluorescein diacetate probe assay. The mitochondrial membrane potential was measured using 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazole carbocyanine iodide. Furthermore, the mRNA expression levels of B‑cell lymphoma (Bcl)‑extra large, Bcl‑2‑associated X protein, Bcl‑2‑interacting mediator of cell death, apoptotic protease activating factor‑1 (Apaf‑1), calpain 2, cysteinyl aspartate specific proteinase (caspase)‑3, caspase‑4 and caspase‑9 were determined using reverse transcription semiquantitative and quantitative polymerase chain reaction analyses. Treatment with LCA inhibited proliferation and induced apoptosis of T24 cells, and increased intracellular Ca2+ levels and ROS production. Furthermore, LCA induced mitochondrial dysfunction, decreased mitochondrial membrane potential, and increased the mRNA expression levels of Apaf‑1, caspase‑9 and caspase‑3. Exposure of T24 cells to LCA also triggered calpain 2 and caspase‑4 activation, resulting in apoptosis. These findings indicated that LCA increased intracellular Ca2+ levels, which may be associated with mitochondrial dysfunction. In addition, the ER stress pathway may be

  11. Projected Carbon Dioxide to Increase Grass Pollen and Allergen Exposure Despite Higher Ozone Levels

    PubMed Central

    Albertine, Jennifer M.; Manning, William J.; DaCosta, Michelle; Stinson, Kristina A.; Muilenberg, Michael L.; Rogers, Christine A.

    2014-01-01

    One expected effect of climate change on human health is increasing allergic and asthmatic symptoms through changes in pollen biology. Allergic diseases have a large impact on human health globally, with 10–30% of the population affected by allergic rhinitis and more than 300 million affected by asthma. Pollen from grass species, which are highly allergenic and occur worldwide, elicits allergic responses in 20% of the general population and 40% of atopic individuals. Here we examine the effects of elevated levels of two greenhouse gases, carbon dioxide (CO2), a growth and reproductive stimulator of plants, and ozone (O3), a repressor, on pollen and allergen production in Timothy grass (Phleum pratense L.). We conducted a fully factorial experiment in which plants were grown at ambient and/or elevated levels of O3 and CO2, to simulate present and projected levels of both gases and their potential interactive effects. We captured and counted pollen from flowers in each treatment and assayed for concentrations of the allergen protein, Phl p 5. We found that elevated levels of CO2 increased the amount of grass pollen produced by ∼50% per flower, regardless of O3 levels. Elevated O3 significantly reduced the Phl p 5 content of the pollen but the net effect of rising pollen numbers with elevated CO2 indicate increased allergen exposure under elevated levels of both greenhouse gases. Using quantitative estimates of increased pollen production and number of flowering plants per treatment, we estimated that airborne grass pollen concentrations will increase in the future up to ∼200%. Due to the widespread existence of grasses and the particular importance of P. pratense in eliciting allergic responses, our findings provide evidence for significant impacts on human health worldwide as a result of future climate change. PMID:25372614

  12. Increased platelet oxidative metabolism, blood oxidative stress and neopterin levels after ultra-endurance exercise.

    PubMed

    de Lucas, Ricardo Dantas; Caputo, Fabrizio; Mendes de Souza, Kristopher; Sigwalt, André Roberto; Ghisoni, Karina; Lock Silveira, Paulo Cesar; Remor, Aline Pertile; da Luz Scheffer, Débora; Guglielmo, Luiz Guilherme Antonacci; Latini, Alexandra

    2014-01-01

    The purpose of the present investigation was to identify muscle damage, inflammatory response and oxidative stress blood markers in athletes undertaking the ultra-endurance MultiSport Brazil race. Eleven well-trained male athletes (34.3 ± 3.1 years, 74.0 ± 7.6 kg; 172.2 ± 5.1 cm) participated in the study and performed the race, which consisted of about 90 km of alternating off-road running, mountain biking and kayaking. Twelve hours before and up to 15 minutes after the race a 10 mL blood sample was drawn in order to measure the following parameters: lactate dehydrogenase and creatine kinase activities, lipid peroxidation, catalase activity, protein carbonylation, respiratory chain complexes I, II and IV activities, oxygen consumption and neopterin concentrations. After the race, plasma lactate dehydrogenase and creatine kinase activities were significantly increased. Erythrocyte TBA-RS levels and plasma protein carbonylation were markedly augmented in post-race samples. Additionally, mitochondrial complex II activity and oxygen consumption in post-race platelet-rich plasma were also increased. These altered biochemical parameters were accompanied by increased plasma neopterin levels. The ultra-endurance event provoked systemic inflammation (increased neopterin) accompanied by marked oxidative stress, likely by increasing oxidative metabolism (increased oxidative mitochondrial function). This might be advantageous during prolonged exercise, mainly for efficient substrate oxidation at the mitochondrial level, even when tissue damage is induced. PMID:24117160

  13. Epoxy Crosslinked Silica Aerogels (X-Aerogels)

    NASA Technical Reports Server (NTRS)

    fabrizio, Eve; Ilhan, Faysal; Meador, Mary Ann; Johnston, Chris; Leventis, Nicholas

    2004-01-01

    NASA is interested in the development of strong lightweight materials for the dual role of thermal insulator and structural component for space vehicles; freeing more weight for useful payloads. Aerogels are very-low density materials (0.010 to 0.5 g/cc) that, due to high porosity (meso- and microporosity), can be, depending on the chemical nature of the network, ideal thermal insulators (thermal conductivity approx. 15 mW/mK). However, aerogels are extremely fragile. For practical application of aerogels, one must increase strength without compromising the physical properties attributed to low density. This has been achieved by templated growth of an epoxy polymer layer that crosslinks the "pearl necklace" network of nanoparticles: the framework of a typical silica aerogel. The requirement for conformal accumulation of the epoxy crosslinker is reaction both with the surface of silica and with itself. After cross-linking, the strength of a typical aerogel monolith increases by a factor of 200, in the expense of only a 2-fold increase in density. Strength is increased further by coupling residual unreacted epoxides with diamine.

  14. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels.

    PubMed

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  15. Increased serum levels of soluble vascular endothelial-cadherin in patients with systemic vasculitis.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Cao, Na; Qin, Sha; Li, Meng-Meng; Jia, Rui-Zhen

    2014-08-01

    Henoch-Schönlein purpura (HSP) is a commonest systemic vasculitis (SV) in childhood characterized by an inflammatory reaction directed at vessels. Endothelial damage and perivascular leukocyte infiltrates are vital in the development of HSP. Vascular endothelial (VE)-cadherin is an endothelial cell-specific adhesion molecule, which plays critical roles in angiogenesis and endothelial integrity. Herein, we investigated the serum levels of soluble VE-cadherin (sVE-cadherin) in patients with HSP and other forms of SV. The serum levels of sVE-cadherin in 30 patients with HSP, together with patients with urticarial vasculitis, allergic vasculitis, Behcet disease, psoriasis vulgaris (PV) and atopic dermatitis (AD) and 26 health controls were measured by enzyme-linked immunosorbent assay. Serum levels of sVE-cadherin were significantly increased in patients with HSP in acute stage and patients with other forms of SV but not in patients with PV or AD. Moreover, Serum sVE-cadherin levels in HSP patients were correlated with the severity of this disease and serum concentrations of IgA anticardiolipin antibodies and vascular endothelial growth factor. Taken together, we show firstly that serum sVE-cadherin is abnormally increased in HSP patients. Increased serum levels of sVE-cadherin might be a novel biomarker for evaluating the severity of HSP and useful for identifying the presence of SV in inflammatory skin conditions. PMID:24469639

  16. N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids

    PubMed Central

    Grillo, Stephanie L; Keereetaweep, Jantana; Grillo, Michael A; Chapman, Kent D; Koulen, Peter

    2013-01-01

    N-Palmitoylethanolamine (NAE 16:0) is an endogenous lipid signaling molecule that has limited water solubility, and its action is short-lived due to its rapid metabolism. This poses a problem for use in vivo as oral administration requires a high concentration for significant levels to reach target tissues, and injection of the compound in a dimethyl sulfoxide- or ethanol-based vehicle is usually not desirable during long-term treatment. A depot injection of NAE 16:0 was successfully emulsified in sterile corn oil (10 mg/kg) and administered in young DBA/2 mice in order to elevate baseline levels of NAE 16:0 in target tissues. NAE 16:0 levels were increased in various tissues, particularly in the retina, 24 and 48 hours following injections. Increases ranged between 22% and 215% (above basal levels) in blood serum, heart, brain, and retina and induced an entourage effect by increasing levels of other 18 carbon N-Acylethanolamines (NAEs), which ranged between 31% and 117% above baseline. These results indicate that NAE 16:0 can be used as a depot preparation, avoiding the use of inadequate vehicles, and can provide the basis for designing tissue-specific dosing regimens for therapies involving NAEs and related compounds. PMID:23976843

  17. Short communication: artificial ultraviolet B light exposure increases vitamin D levels in cow plasma and milk.

    PubMed

    Jakobsen, Jette; Jensen, Søren Krogh; Hymøller, Lone; Andersen, Elisabeth Wreford; Kaas, Poul; Burild, Anders; Jäpelt, Rie Bak

    2015-09-01

    The number of dairy cows without access to pasture or sunlight is increasing; therefore, the content of vitamin D in dairy products is decreasing. Ultimately, declining vitamin D levels in dairy products will mean that dairy products are a negligible source of natural vitamin D for humans. We tested the ability of a specially designed UVB lamp to enhance the vitamin D3 content in milk from dairy cows housed indoors. This study included 16 cows divided into 4 groups. Each group was exposed daily to artificial UVB light simulating 1, 2, 3, or 4 h of summer sun at 56°N for 24 d, and the group with simulated exposure to 2 h of summer sun daily continued to be monitored for 73 d. We found a significant increase in 25-hydroxyvitamin D3 (25OHD3) levels in plasma as well as vitamin D3 and 25OHD3 levels in milk after daily exposure for 24 d in all treatment groups. Extending daily exposure to artificial UVB light to 73 d did not lead to an increase of vitamin D3 or 25OHD3 level in the milk. In conclusion, the change in production facilities for dairy cows providing cows with no access to pasture and sunlight causes a decrease of vitamin D levels in dairy products. This decrease may be prevented by exposing cows to artificial UVB light in the stable. PMID:26117346

  18. Increased serum brain-derived neurotrophic factor (BDNF) levels in patients with narcolepsy.

    PubMed

    Klein, Anders B; Jennum, Poul; Knudsen, Stine; Gammeltoft, Steen; Mikkelsen, Jens D

    2013-06-01

    Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, sudden loss of muscle tone (cataplexy), fragmentation of nocturnal sleep and sleep paralysis. The symptoms of the disease strongly correlate with a reduction in hypocretin levels in CSF and a reduction in hypocretin neurons in hypothalamus in post-mortem tissue. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are important for activity-dependent neuronal function and synaptic modulation and it is considered that these mechanisms are important in sleep regulation. We hypothesized that serum levels of these factors are altered in patients with narcolepsy compared to healthy controls without sleep disturbances. Polysomnography data was obtained and serum BDNF and NGF levels measured using ELISA, while hypocretin was measured using RIA. Serum BDNF levels were significantly higher in narcolepsy patients than in healthy controls (64.2±3.9 ng/ml vs. 47.3±2.6 ng/ml, P<0.01), while there were no significant differences in NGF levels. As expected, narcolepsy patients had higher BMI compared to controls, but BMI did not correlate with the serum BDNF levels. The change in BDNF levels was not related to disease duration and sleep parameters did not correlate with BDNF in narcolepsy patients. The mechanisms behind the marked increase in BDNF levels in narcolepsy patients remain unknown. PMID:23570723

  19. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  20. The Relationship Between Listening and Reading Comprehension of Different Types of Text at Increasing Grade Levels

    ERIC Educational Resources Information Center

    Diakidoy, Irene-Anna; Stylianou, Polyxeni; Karefillidou, Christina; Papageorgiou, Panayiota

    2004-01-01

    This study examined the hypotheses that (a) the relationship between listening and reading comprehension becomes stronger after decoding mastery; (b) the difference between listening and reading decreases with increasing grade level; and (c) similar patterns of relationship and difference are obtained with narrative and expository texts. The…

  1. ASSESSING THE IMPACTS OF AN INCREASE IN WATER LEVEL ON WETLAND VEGETATION

    EPA Science Inventory

    Three different approaches for assessing the impact of a permanent increase in water level on wetland vegetation were studied using a long-term, controlled, and replicated experiment. hese approaches were (1) digitized vegetation maps derived from aerial photographs; (2) vegetati...

  2. Increased circulating urocortin-3 levels is associated with polycystic ovary syndrome.

    PubMed

    Temur, Muzaffer; Yilmaz, Özgür; Aksun, Saliha; Özün Özbay, Pelin; Calan, Mehmet; Küme, Tuncay; Karakulak, Murat; Korkmaz, Hüseyin Anıl

    2016-01-01

    This study was aimed to compare serum urocortin-3 (UCN3) levels in women with polycystic ovary syndrome (PCOS) and healthy women, and establish what role UCN3 levels play in PCOS. Fifty-two patients with PCOS and 55 healthy women were included in the study, matched for age and body mass index. Fasting blood glucose (FBG), insulin, hs-CRP, UCN3 and free-testosterone levels of the all participants were measured. HOMA-IR was used to calculate the insulin resistance. Circulating UCN3 levels were significantly increased in women with PCOS than in control subjects (54.49 ± 5.77 versus 51.28 ± 5.86 pmol/l, p = 0.005). Serum insulin, hs-CRP and HOMA-IR levels were higher in women with PCOS than in control group. UCN3 levels positively correlated with hs-CRP in PCOS group (r = 0.391, p = 0.004). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curves were 0.732 (95% CI 0.634-0.830, p < 0.001) for UCN3 levels. The optimal cut-off value of UCN3 for detecting PCOS was ≥51.46 pmol/l, at which the sensitivity was 75% and specificity was 68%. Our results suggest that there is a potential link between PCOS and UCN3 levels. The results of this study support the presence of increased UCN3 levels for the association of inflammation with PCOS. PMID:26488073

  3. Metabolic Implications of Surgical Fat Removal: Increase of Adiponectin Plasma Levels After Reduction Mammaplasty and Abdominoplasty.

    PubMed

    Vinci, Valeriano; Valaperta, Serenella; Klinger, Marco; Montanelli, Alessandro; Specchia, Claudia; Forcellini, Davide; Maione, Luca; Klinger, Francesco Maria; Caviggioli, Fabio

    2016-06-01

    Recent studies tried to identify new indicators of risk in the development of insulin resistance, cardiovascular disease, and metabolic syndrome; recently, breast size has been proposed as a new measure of risk for type 2 diabetes mellitus in women. To understand the role of breast adipose tissue and subcutaneous adipose tissue in lipidic and glucose metabolism, we decided to evaluate the variation on levels of adiponectin in plasma and other well-known metabolic markers before and after surgical fat reduction.We formed 2 groups: breast reduction group (M-) and abdominoplasty group (ADD). For all patients enrolled in the study, we recorded anthropometric measurements 1 hour before surgery (that we considered as time zero). At time zero, we always performed a blood sample to observe the assay of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, CRP, TNF-α, IL-1, IL-6, and adiponectin. The dosage of the above parameters was repeated 40 days after the surgical intervention with the aim of assessing whether they showed a statistically significant change after surgery.Adiponectin levels increased significantly in both groups of patients after surgery: in patients undergoing reduction mammaplasty and abdominoplasty, the mean increase was equal to 1.68 (P = 0.007) and 4.28 (P = 0.019), respectively. The variation in increase was not statistically different between the 2 groups (P = 0.254).Moreover, in the M- group, we observed that HDL levels increased and glycemia decreased significantly.Our study shows that reduction mammaplasty is a surgical procedure associated with a significant improvement in adiponectin level, HDL cholesterol level, and a significant decrease in glycemia level.The effective correlation between the role of breast adipose tissue and appearance of disease is still to be determined. PMID:25003417

  4. Increased levels of ambient fungal spores in Taiwan are associated with dust events from China

    NASA Astrophysics Data System (ADS)

    Wu, Pei-Chih; Tsai, Jui-Chen; Li, Fang-Chun; Lung, Shih-Chun; Su, Huey-Jen

    2004-09-01

    Fungi are ubiquitous in nature and their spores are often dispersed into the atmosphere through turbulent airstreams. As yellow sandstorm blown from deserts in China had affected the ambient air quality with increasing levels of ambient particulates, often including significant amounts of biologically active particles has therefore become imperative for concerns of their health implications. Our study was aimed to examine the effects of yellow sandstorm events on the fungal composition and concentrations in ambient air. Atmospheric fungal spores were continuously collected using Burkard Volumetric Spore Trap. Samples collected between December 2000 and April 2001 were selected for priority analysis from days when the yellow sandstorms were reported to affect Taiwan according to the Central Weather Bureau in Taiwan. The composition of dominant spores such as Basidiospore, Penicillium/Aspergillus, Nigrospora, Arthrinium, Curvularia, Rusts, Stemphylium, Cercospora, Pithomyces, and unidentified fungi were significantly higher than those of background days. The increase of Basidiospore, Penicillium/Aspergillus, Nigrospora, and those unidentified fungi seems to be significantly associated with the increase of ambient particulate levels with regression coefficients ranging from 0.887 to 31.98. Our study has identified increasing ambient concentrations during sandstorm episodes are observed for some major fungi, Basidiospore, Penicillium, Aspergillus, and those unidentified fungi and the trends of the increase seems to associate with ambient particulate levels. Further efforts to clarify the relationship between those high fungal spore exposures and clinical adverse health effects are suggested in the future. In addition, effects of climatic factors and other particulate levels on the variation of ambient fungal spore levels are also desired in further study. Additional monitoring of ambient fungal spores in the first line of west coastline is hoped to assist in

  5. Exercise increases serum endostatin levels in female and male patients with diabetes and controls

    PubMed Central

    2014-01-01

    Background Type 2 diabetes mellitus (T2DM) is often associated with atherosclerotic changes in coronary vessels, most notably plaques. The angiostatic parameter endostatin is able to inhibit angiogenesis in tissue as well as in plaques and therefore plays an important role in physiological and pathological neovascularisation. The aim of the present study was to investigate sex-specific differences and the influence of exercise on circulating endostatin levels in patients suffering from diabetes, and control subjects. Methods In total, 42 T2DM-patients and 45 control subjects were investigated. They underwent a graded physical stress test (ergometry). Serum endostatin levels were measured in venous blood at rest and directly after reaching maximum workload. Results Females showed significantly higher endostatin levels at baseline measurements compared to men, independently of their underlying disease. In both female and male T2DM-patients endostatin levels were significantly lower compared to controls. Both groups and sexes showed a significant increase of endostatin after physical stress, whereas the extent of endostatin-increase was between 10.59-15.05%. Conclusion Middle-aged healthy female individuals as well as female T2DM-patients showed higher circulating serum endostatin levels compared to males, suggesting a hormonal influence on baseline circulating endostatin amounts. Exercise-induced increase in endostatin is also observable in patients suffering from T2DM. Concerning vascularisation, lower endostatin levels in T2DM might be advantageous. Concerning plaque stability, lower levels might be prejudicial. Trial registration Clinical Trial Registration-URL: http://clinicaltrials.gov/ct2/results?term=NCT01165515 PMID:24393402

  6. [Effect of the increasing levels of soil radioactive pollution on the biochemical composition of plants].

    PubMed

    Gromova, V S; Pchelenok, O A; Kozlova, N M

    2012-01-01

    The study was undertaken to study a relationship between the changes of some parameters of the biochemical and mineral composition of different plants, such as rape, pods, and lentil, and the levels of soil radiation pollution, by using the conventional methods. Radioactive pollution of dark-grey forest soils was found to cause a change in the biochemical composition of plant seeds even at the level of cesium 137 (137Cs) within the present temporary permissible levels (TPL) (600 Bq/kg): there were elevated concentrations of salts of potassium, phosphorus, ammonia nitrogen, catechols, sucrose, and some amino acids. With the radioactive cesium level exceeding the TPL, biochemical changes in the seeds depended on the species of the plants: in the rape seeds, the additional formation of sucrose and amino acids continued, but less intensively than with its lower radiation; the pod beans were significantly positively correlated with the increasing amounts of catechols. PMID:22834257

  7. Methodology for Prototyping Increased Levels of Automation for Spacecraft Rendezvous Functions

    NASA Technical Reports Server (NTRS)

    Hart, Jeremy J.; Valasek, John

    2007-01-01

    The Crew Exploration Vehicle necessitates higher levels of automation than previous NASA vehicles, due to program requirements for automation, including Automated Rendezvous and Docking. Studies of spacecraft development often point to the locus of decision-making authority between humans and computers (i.e. automation) as a prime driver for cost, safety, and mission success. Therefore, a critical component in the Crew Exploration Vehicle development is the determination of the correct level of automation. To identify the appropriate levels of automation and autonomy to design into a human space flight vehicle, NASA has created the Function-specific Level of Autonomy and Automation Tool. This paper develops a methodology for prototyping increased levels of automation for spacecraft rendezvous functions. This methodology is used to evaluate the accuracy of the Function-specific Level of Autonomy and Automation Tool specified levels of automation, via prototyping. Spacecraft rendezvous planning tasks are selected and then prototyped in Matlab using Fuzzy Logic techniques and existing Space Shuttle rendezvous trajectory algorithms.

  8. Increased initial levels of chromosome damage and heterogeneous chromosome repair in ataxia telangiectasia heterozygote cells.

    PubMed

    Pandita, T K; Hittelman, W N

    1994-10-01

    Individuals heterozygous for ataxia telangiectasia (AT) appear clinically normal but have a 2-3-fold overall excess risk of cancer. Various approaches have been used to identify AT heterozygotes, however, the results are ambiguous. We recently reported that AT homozygotes exhibit more initial chromosome damage after irradiation than normal cells despite identical levels of DNA double strand breaks (DSBs) as well as a reduced fast repair component at both the DNA and chromosome levels. To determine whether AT heterozygotes exhibit the AT or normal cellular phenotype, we compared four AT heterozygote lymphoblastoid cell lines with normal control and AT homozygote lymphoblastoid cells with regard to cell survival, initial levels of damage, and repair at the DNA and chromosome levels after gamma-irradiation in G1, S, and G2 phase (estimated by neutral DNA filter elution and premature chromosome condensation). There was no significant difference in survival, induction and repair of DNA DSBs, or chromosome repair between AT heterozygote and normal cells. In contrast, all four AT heterozygote cell lines showed increased levels of chromosome damage; G1 phase cells showed intermediate levels and G2 phase cells showed levels equivalent to the AT homozygote phenotype. These results suggest that premature chromosome condensation may be useful for detecting AT heterozygotes. PMID:7523872

  9. Elevated plasma levels of Th17-related cytokines are associated with increased risk of atrial fibrillation

    PubMed Central

    Wu, Na; Xu, Bin; Liu, Yuan; Chen, Xinghua; Tang, He; Wu, Long; Xiang, Ying; Zhang, Mengxuan; Shu, Maoqing; Song, Zhiyuan; Li, Yafei; Zhong, Li

    2016-01-01

    We performed a matched case-control study using a propensity score matching, to assess the association of Th17-related cytokines, including interleukin (IL) 17A (IL-17A), IL-17F, IL-21, IL-22 and IL-6, along with interferon-γ (IFN-γ), IL-10, IL-9, and IL-4, with the risk of AF. A total of 336 patients with AF were matched 1:1 with patients without AF. Plasma levels of cytokines were measured using Luminex xMAP assays. The plasma levels of all examined cytokines were significantly higher in AF patients than controls (P < 0.05), and these cytokines were highly correlated with each other (P < 0.01). A multivariate conditional logistic regression analysis showed that elevated plasma levels of IL-17A, IL-17F, IL-21, IL-22, IFN-γ, IL-10, IL-9 and IL-6 were significantly associated with AF risk independently of potential confounders. There were no significant differences in plasma levels of examined cytokines between paroxysmal and chronic AF patients. IL-17A, IL-21, IL-10 and IL-6 levels were positively correlated with left atrial diameter; IL-17F level was negatively correlated with left ventricle ejection fraction among AF patients (P < 0.05). Elevated plasma levels of Th17-related cytokines were independently associated with increased an risk of AF; hence, Th17-related cytokines may be involved in the pathogenesis of AF. PMID:27198976

  10. Increased serum levels of apoptosis in deficit syndrome schizophrenia patients: a preliminary study

    PubMed Central

    Beyazyüz, Murat; Küfeciler, Tarkan; Bulut, Leyla; Ünsal, Cüneyt; Albayrak, Yakup; Akyol, Esra Soydaş; Baykal, Saliha; Kuloglu, Murat; Hashimoto, Kenji

    2016-01-01

    Background Schizophrenia is a chronic and debilitating disorder, the etiology of which remains unclear. Apoptosis is a programmed cell death mechanism that might be implicated in neuropsychiatric disorders, including schizophrenia. In this study, we aimed to compare the serum levels of apoptosis among deficit schizophrenia (DS) syndrome patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). Patients and methods After the inclusion and exclusion criteria were applied, 23 DS patients, 46 NDS patients, and 33 HCs were included in the study. The serum apoptosis levels were measured using a quantitative sandwich enzyme immunoassay with human monoclonal antibodies directed against DNA and histones. Results There was a significant difference among the three groups in terms of the levels of apoptosis (F2,96=16.58; P<0.001). The serum apoptosis levels in the DS and NDS groups were significantly higher than those in the HC group. Furthermore, the serum apoptosis levels in the DS group were significantly higher than the levels in the NDS group. Conclusion This study suggests that increased levels of apoptosis may be implicated in the pathophysiology of DS syndrome. However, further studies are needed to support the role of apoptosis in DS. PMID:27307738

  11. Chronic ethanol treatment potientials ethanol-induced increases in interstitial nucleus accumbens endocannabinoid levels in rats

    PubMed Central

    Alvarez-Jaimes, Lily; Stouffer, David G.; Parsons, Loren H.

    2013-01-01

    We employed in vivo microdialysis to characterize the effect of an ethanol challenge injection on endocannabinoid levels in the nucleus accumbens of ethanol-naïve and chronic ethanol-treated rats. Ethanol (0.75 and 2 g/kg, i.p.) dose-dependently increased dialysate 2-arachidonoylglycerol (to a maximum 157 ± 20% of baseline) and decreased anandamide (to a minimum 52 ± 9% of baseline) in ethanol-naïve rats. The endocannabinoid clearance inhibitor N-(4-hydrophenyl) arachidonoylamide (AM404; 3 mg/kg) potentiated ethanol effects on 2-arachidonoylglycerol levels but did not alter ethanol-induced decreases in anandamide. AM404 alone did not alter dialysate levels of either endocannabinoid. Then, we characterized the effect of ethanol challenge on nucleus accumbens endocannabinoid levels in rats previously maintained on an ethanol-containing liquid diet. Ethanol challenge produced a greater and more prolonged increase in 2-arach-idonoylglycerol (to a maximum 394 ± 135% of baseline) in ethanol-experienced than in ethanol-naïve rats. The profile in ethanol-experienced rats was similar to that produced by AM404 pre-treatment in ethanol-naïve rats. AM404 in ethanol-experienced rats led to a further enhancement in the 2-arachidonoylglycerol response to ethanol challenge (to a maximum 704 ± 174% of baseline). Our findings demonstrate that ethanol-induced increases in nucleus accumbens 2-arachidonoylglycerol are potentiated in animals with a history of ethanol consumption. PMID:19650871

  12. Increased Cord Blood Betatrophin Levels in the Offspring of Mothers with Gestational Diabetes

    PubMed Central

    Wu, Shimin; Zhao, Yue; Du, Caiqi; Yuan, Guandou; Ning, Qin; McCormick, Kenneth; Luo, Xiaoping

    2016-01-01

    Aim Exposing a fetus to hyperglycemia can increase the risk for later-life metabolic disorders. Betatrophin has been proposed as a key regulator of pancreatic beta cell proliferation and lipid regulation. Highly responsive to nutritional signals, serum betatrophin concentrations have been found to be altered by various physiological and pathological conditions. We hypothesized that betatrophin levels are increased in the cord blood in offspring exposed to intrauterine hyperglycemia. Methods This was a cross-sectional study including 54 mothers who underwent uncomplicated Cesarean delivery in a university hospital. Maternal gestational glucose concentration was determined at 24–48 weeks gestation after a 75-g OGTT. Cord blood and placental tissue was collected immediately post delivery. Metabolic parameters were determined in the Clinical Laboratory. Cord blood betatrophin levels were assayed using a commercially available ELISA kit. Placental mitochondrial content was determined by real-time PCR. Results Cord blood betatrophin levels were increased in the gestational diabetes mellitus (GDM) group compared with the normoglycemic group. Furthermore, betatrophin levels were positively correlated with maternal gestational 2h post-OGTT glucose, cord blood insulin, HOMA-IR, and inversely correlated with placental mitochondrial content. Conclusions Cord blood betatrophin may function as a potential biomarker of maternal intrauterine hyperglycemia and fetal insulin resistance, which may presage for long-term metabolic impact of GDM on offspring. PMID:27196053

  13. A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation.

    PubMed

    delBarco-Trillo, Javier; García-Álvarez, Olga; Soler, Ana Josefa; Tourmente, Maximiliano; Garde, José Julián; Roldan, Eduardo R S

    2016-03-16

    Sperm competition, a prevalent evolutionary process in which the spermatozoa of two or more males compete for the fertilization of the same ovum, leads to morphological and physiological adaptations, including increases in energetic metabolism that may serve to propel sperm faster but that may have negative effects on DNA integrity. Sperm DNA damage is associated with reduced rates of fertilization, embryo and fetal loss, offspring mortality, and mutations leading to genetic disease. We tested whether high levels of sperm competition affect sperm DNA integrity. We evaluated sperm DNA integrity in 18 species of rodents that differ in their levels of sperm competition using the sperm chromatin structure assay. DNA integrity was assessed upon sperm collection, in response to incubation under capacitating or non-capacitating conditions, and after exposure to physical and chemical stressors. Sperm DNA was very resistant to physical and chemical stressors, whereas incubation in non-capacitating and capacitating conditions resulted in only a small increase in sperm DNA damage. Importantly, levels of sperm competition were positively associated with sperm DNA fragmentation across rodent species. This is the first evidence showing that high levels of sperm competition lead to an important cost in the form of increased sperm DNA damage. PMID:26936246

  14. Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis

    PubMed Central

    Yang, Deng-Ho; Chiang, Tsay-I; Chang, I-Chang; Lin, Fu-Huang; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-01-01

    Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis. PMID:24688308

  15. Dietary alpha-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Collison, Lauren W; Jolly, Christopher A; Murphy, Eric J

    2005-08-01

    Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation. PMID:16296397

  16. Stomatal numbers are sensitive to increases in CO2 from pre-industrial levels

    NASA Astrophysics Data System (ADS)

    Woodward, F. I.

    1987-06-01

    Recent measurements of atmospheric CO2 levels in ice cores1 have shown that global CO2 has increased by about 60 µmol mol-1 over the past 200 years. Evidence for the response of plants in the field to this change in CO2 levels is here presented in the form of a significant change in stomatal density-an anatomical response of considerable ecophysiological importance. A 40% decrease in density of stomata was observed in herbarium specimens of leaves of eight temperate arboreal species collected over the last 200 years. This decline was confirmed for some of the species observed as herbarium specimens by experiments under controlled environmental conditions. In these an increase in the mole fraction of CO2 from 280 μmol mol-1 to the current ambient level of 340 µmol mol-1 was found to cause a decrease in stomatal density of 67%. Experiments have shown that the combination of this previously unreported response of stomatal density to the level of CO2, with the known responses of stomatal aperture2, cause water use efficiency to be much lower than expected at low levels of CO2 and over a wide range of humidities.

  17. Increasing Level of Leisure Physical Activity Could Reduce the Risk of Hip Fracture in Older Women

    PubMed Central

    Rong, Ke; Liu, Xiao-yu; Wu, Xu-hua; Li, Xiao-liu; Xia, Qing-quan; Chen, Jiong; Yin, Xiao-fan

    2016-01-01

    Abstract We carried out the study to investigate and quantitatively assess the potential association between current level of physical activity and the risk of osteoporosis hip fracture in older women. Relevant publications before October 2015 were identified using the PubMed and Ovid searching tools. A dose–response meta-analysis was carried out to combine and analysis results. Fourteen prospective studies were included in the meta-analysis. A general analysis of 9 studies showed a significant inverse relationship between increasing level of physical activity and risk of hip fracture in older women [relative risk (RR) = 0.93, 95% confidence interval (95% CI): 0.91–0.96]. The result of a sensitivity analysis was consistent with the general analysis (RR = 0.94, 95% CI: 0.93–0.96). The association between increasing level of physical activity and risk of wrist fracture was not statistically significant in a general analysis of three studies (RR = 1.004, 95% CI: 0.98–1.03). A potential direct association between increasing level of physical activity and risk of wrist fracture was observed after removing 1 study with the greatest weight (RR = 1.01, 95% CI: 1.00–1.03). No significant publication bias was observed in our analysis. Our results show that increasing level of physical activity within an appropriate range may reduce the risk of hip fracture but not the risk of wrist fracture in older women. PMID:26986111

  18. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress

    SciTech Connect

    Mazière, Cécile; Salle, Valéry; Gomila, Cathy; Mazière, Jean-Claude

    2013-10-18

    Highlights: •Oxidized LDL enhances RANKL level in human smooth muscle cells. •The effect of OxLDL is mediated by the transcription factor NFAT. •UVA, H{sub 2}O{sub 2} and buthionine sulfoximine also increase RANKL level. •All these effects are observed in human fibroblasts and endothelial cells. -- Abstract: Receptor Activator of NFκB Ligand (RANKL) and its decoy receptor osteoprotegerin (OPG) have been shown to play a role not only in bone remodeling but also in inflammation, arterial calcification and atherosclerotic plaque rupture. In human smooth muscle cells, Cu{sup 2+}-oxidized LDL (CuLDL) 10–50 μg/ml increased reactive oxygen species (ROS) and RANKL level in a dose-dependent manner, whereas OPG level was not affected. The lipid extract of CuLDL reproduced the effects of the whole particle. Vivit, an inhibitor of the transcription factor NFAT, reduced the CuLDL-induced increase in RANKL, whereas PKA and NFκB inhibitors were ineffective. LDL oxidized by myeloperoxidase (MPO-LDL), or other pro-oxidant conditions such as ultraviolet A (UVA) irradiation, incubation with H{sub 2}O{sub 2} or with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis{sub ,} also induced an oxidative stress and enhanced RANKL level. The increase in RANKL in pro-oxidant conditions was also observed in fibroblasts and endothelial cells. Since RANKL is involved in myocardial inflammation, vascular calcification and plaque rupture, this study highlights a new mechanism whereby OxLDL might, by generation of an oxidative stress, exert a deleterious effect on different cell types of the arterial wall.

  19. Diffuse radiation increases global ecosystem-level water-use efficiency

    NASA Astrophysics Data System (ADS)

    Moffat, A. M.; Reichstein, M.; Cescatti, A.; Knohl, A.; Zaehle, S.

    2012-12-01

    Current environmental changes lead not only to rising atmospheric CO2 levels and air temperature but also to changes in air pollution and thus the light quality of the solar radiation reaching the land-surface. While rising CO2 levels are thought to enhance photosynthesis and closure of stomata, thus leading to relative water savings, the effect of diffuse radiation on transpiration by plants is less clear. It has been speculated that the stimulation of photosynthesis by increased levels of diffuse light may be counteracted by higher transpiration and consequently water depletion and drought stress. Ultimately, in water co-limited systems, the overall effect of diffuse radiation will depend on the sensitivity of canopy transpiration versus photosynthesis to diffuse light, i.e. whether water-use efficiency changes with relative levels of diffuse light. Our study shows that water-use efficiency increases significantly with higher fractions of diffuse light. It uses the ecosystem-atmosphere gas-exchange observations obtained with the eddy covariance method at 29 flux tower sites. In contrast to previous global studies, the analysis is based directly on measurements of diffuse radiation. Its effect on water-use efficiency was derived by analyzing the multivariate response of carbon and water fluxes to radiation and air humidity using a purely empirical approach based on artificial neural networks. We infer that per unit change of diffuse fraction the water-use efficiency increases up to 40% depending on diffuse fraction levels and ecosystem type. Hence, in regions with increasing diffuse radiation positive effects on primary production are expected even under conditions where water is co-limiting productivity.

  20. Increased Sclerostin Levels after Further Ablation of Remnant Estrogen by Aromatase Inhibitors

    PubMed Central

    Kim, Wonjin; Chung, Yoonjung; Kim, Se Hwa; Park, Sehee; Bae, Jae Hyun; Kim, Gyuri; Lee, Su Jin; Kim, Jo Eun; Park, Byeong-Woo; Lim, Sung-Kil

    2015-01-01

    Background Sclerostin is a secreted Wnt inhibitor produced almost exclusively by osteocytes, which inhibits bone formation. Aromatase inhibitors (AIs), which reduce the conversion of steroids to estrogen, are used to treat endocrine-responsive breast cancer. As AIs lower estrogen levels, they increase bone turnover and lower bone mass. We analyzed changes in serum sclerostin levels in Korean women with breast cancer who were treated with an AI. Methods We included postmenopausal women with endocrine-responsive breast cancer (n=90; mean age, 57.7 years) treated with an AI, and compared them to healthy premenopausal women (n=36; mean age, 28.0 years). The subjects were randomly assigned to take either 5 mg alendronate with 0.5 µg calcitriol (n=46), or placebo (n=44) for 6 months. Results Postmenopausal women with breast cancer had significantly higher sclerostin levels compared to those in premenopausal women (27.8±13.6 pmol/L vs. 23.1±4.8 pmol/L, P<0.05). Baseline sclerostin levels positively correlated with either lumbar spine or total hip bone mineral density only in postmenopausal women (r=0.218 and r=0.233; P<0.05, respectively). Serum sclerostin levels increased by 39.9%±10.2% 6 months after AI use in postmenopausal women; however, no difference was observed between the alendronate and placebo groups (39.9%±10.2% vs. 55.9%±9.13%, P>0.05). Conclusion Serum sclerostin levels increased with absolute deficiency of residual estrogens in postmenopausal women with endocrine-responsive breast cancer who underwent AI therapy with concurrent bone loss. PMID:25827459

  1. Evaluating Dimethyldiethoxysilane for use in Polyurethane Crosslinked Silica Aerogels

    NASA Technical Reports Server (NTRS)

    Randall, Jason P.; Meador, Mary Ann B.; Jana, Sadhan C.

    2008-01-01

    Silica aerogels are highly porous materials which exhibit exceptionally low density and thermal conductivity. Their "pearl necklace" nanostructure, however, is inherently weak; most silica aerogels are brittle and fragile. The strength of aerogels can be improved by employing an additional crosslinking step using isocyanates. In this work, dimethyldiethoxysilane (DMDES) is evaluated for use in the silane backbone of polyurethane crosslinked aerogels. Approximately half of the resulting aerogels exhibited a core/shell morphology of hard crosslinked aerogel surrounding a softer, uncrosslinked center. Solid state NMR and scanning electron microscopy results indicate the DMDES incorporated itself as a conformal coating around the outside of the secondary silica particles, in much the same manner as isocyanate crosslinking. Response surface curves were generated from compression data, indicating levels of reinforcement comparable to that in previous literature, despite the core/shell morphology.

  2. Increasing hippocampal acetylcholine levels enhance behavioral performance in an animal model of diencephalic amnesia.

    PubMed

    Roland, Jessica J; Mark, Katherine; Vetreno, Ryan P; Savage, Lisa M

    2008-10-01

    Pyrithiamine-induced thiamine deficiency (PTD) was used to produce a rodent model of Wernicke-Korsakoff syndrome that results in acute neurological disturbances, thalamic lesions, and learning and memory impairments. There is also cholinergic septohippocampal dysfunction in the PTD model. Systemic (Experiment 1) and intrahippocampal (Experiment 2) injections of the acetylcholinesterase inhibitor physostigmine were administered to determine if increasing acetylcholine levels would eliminate the behavioral impairment produced by PTD. Prior to spontaneous alternation testing, rats received injections of either physostigmine (systemic=0.075 mg/kg; intrahippocampal=20, 40 ng/muL) or saline. In Experiment 2, intrahippocampal injections of physostigmine significantly enhanced alternation rates in the PTD-treated rats. In addition, although intrahippocampal infusions of 40 ng of physostigmine increased the available amount of ACh in both pair-fed (PF) and PTD rats, it did so to a greater extent in PF rats. The increase in ACh levels induced by the direct hippocampal application of physostigmine in the PTD model likely increased activation of the extended limbic system, which was dysfunctional, and therefore led to recovery of function on the spontaneous alternation task. In contrast, the lack of behavioral improvement by intrahippocampal physostigmine infusion in the PF rats, despite a greater rise in hippocampal ACh levels, supports the theory that there is an optimal range of cholinergic tone for optimal behavioral and hippocampal function. PMID:18706897

  3. Oxidized LDL levels are increased in HIV infection and may drive monocyte activation

    PubMed Central

    Zidar, David A.; Juchnowski, Steven; Ferrari, Brian; Clagett, Brian; Pilch-Cooper, Heather A.; Rose, Shawn; Rodriguez, Benigno; McComsey, Grace A.; Sieg, Scott F.; Mehta, Nehal N.; Lederman, Michael M.; Funderburg, Nicholas T.

    2015-01-01

    Background Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk, and this risk correlates with markers of monocyte activation. We have shown that HIV is associated with a prothrombotic monocyte phenotype, which can be partially mitigated by statin therapy. We therefore explored the relationship between oxidized LDL particles and monocyte activation. Methods We performed phenotypic analysis of monocytes using flow cytometry on fresh whole blood in 54 patients with HIV and 24 controls without HIV. Plasma levels of oxLDL, soluble CD14, IL-6, soluble CD163 were measured by ELISA. In vitro experiments were performed using flow cytometry. Results Plasma levels of oxLDL were significantly increased in HIV-infection compared to controls (60.1 units vs 32.1 units, p<0.001). Monocyte expression of the oxLDL receptors, CD36 and Toll-like receptor 4, were also increased in HIV. OxLDL levels correlated with markers of monocyte activation, including soluble CD14, TF expression on inflammatory monocytes, and CD36. In vitro, stimulation with oxLDL, but not to LDL, resulted in expansion of inflammatory monocytes and increased monocyte expression of TF, recapitulating the monocyte profile we find in HIV disease. Conclusions OxLDL may contribute to monocyte activation and further study in the context of HIV disease is warranted. PMID:25647528

  4. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it. PMID:26634573

  5. Increased extracellular levels of glutamate in the hippocampus of chronically epileptic rats.

    PubMed

    Soukupova, M; Binaschi, A; Falcicchia, C; Palma, E; Roncon, P; Zucchini, S; Simonato, M

    2015-08-20

    An increase in the release of excitatory amino acids has consistently been observed in the hippocampus during seizures, both in humans and animals. However, very little or nothing is known about the extracellular levels of glutamate and aspartate during epileptogenesis and in the interictal chronic period of established epilepsy. The aim of this study was to systematically evaluate the relationship between seizure activity and changes in hippocampal glutamate and aspartate extracellular levels under basal and high K(+)-evoked conditions, at various time-points in the natural history of experimental temporal lobe epilepsy, using in vivo microdialysis. Hippocampal extracellular glutamate and aspartate levels were evaluated: 24h after pilocarpine-induced status epilepticus (SE); during the latency period preceding spontaneous seizures; immediately after the first spontaneous seizure; in the chronic (epileptic) period. We found that (i) basal (spontaneous) glutamate outflow is increased in the interictal phases of the chronic period, whereas basal aspartate outflow remains stable for the entire course of the disease; (ii) high K(+) perfusion increased glutamate and aspartate outflow in both control and pilocarpine-treated animals, and the overflow of glutamate was clearly increased in the chronic group. Our data suggest that the glutamatergic signaling is preserved and even potentiated in the hippocampus of epileptic rats, and thus may favor the occurrence of spontaneous recurrent seizures. Together with an impairment of GABA signaling (Soukupova et al., 2014), these data suggest that a shift toward excitation occurs in the excitation/inhibition balance in the chronic epileptic state. PMID:26073699

  6. Global increasing of mean sea level and erroneous treatment of a role of thermal factors

    NASA Astrophysics Data System (ADS)

    Barkin, Yu. V.

    2009-04-01

    Satellite methods of studies of the ocean surface - methods of altimetry - have been obtained intensive development in the last decades (since 1993). However, altimetry studies with the help of special satellites such as TOPEX-Poseidon not only have not cleared up understanding of the phenomenon of increase of sea level (SLR), but have even more confused and without that a complex question on the reasons of increase of sea level. Appeared, that classical determinations of average velocity of increase of sea level on coastal observations (1.4-1.7 mm / yr) approximately for 0.8-1.0 mm / yr it is less, rather than by modern satellite determinations of satellites TOPEX - Poseidon etc. (2.5 - 2.8 mm / yr). On the basis of the data of altimetry observations of TOPEX-Poseidon and Jason for the period 1993-2003 for geocentric velocity of increase of sea level (of global ocean) the value 2.8+/-0.4 mm / yr [1] has been obtained. In the given report the full answer is actually is given to a question put by leading experts on research of the sea level: "The TOPEX/Poseidon and Jason satellite altimeter missions provided a 12 year record of sea level change, which show increase of global mean sea level of 2.8+/-0.4 mm/yr, with considerable geographic variation. An important question for climate studies is to determine the cause of this change - specifically how much of the change is due to steric (heating) versus eustatic (runoff, melting ice, etc.) contribution?" [1]. There is, a big value of average velocity of increase of the sea level on the satellite data, it is possible to explain only by kinematical effect in data of observations. The motion of the satellite "is concerned" to the centre of mass of our planet, and its position is determined by a geocentric radius - vector. Therefore northern drift of the centre of mass in the Earth body [2] as though results in reduction of distances from the satellite up to the sea surface in the southern hemisphere and to their reduction

  7. GABAA Receptor Blockade Enhances Memory Consolidation by Increasing Hippocampal BDNF Levels

    PubMed Central

    Kim, Dong Hyun; Kim, Jong Min; Park, Se Jin; Cai, Mudan; Liu, Xiaotong; Lee, Seungheon; Shin, Chan Young; Ryu, Jong Hoon

    2012-01-01

    Memory consolidation is the process by which acquired information is converted to something concrete to be retrieved later. Here we examined a potential role for brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory consolidation induced by the GABAA receptor antagonist, bicuculline methiodide. With the administration of an acquisition trial in naïve mice using a passive avoidance task, mature BDNF (mBDNF) levels were temporally changed in the hippocampal CA1 region, and the lowest levels were observed 9 h after the acquisition trial. In the passive avoidance task, bicuculline methiodide administration within 1 h of training but not after 3 h significantly increased latency time in the retention trial 24 h after the acquisition trial. Concomitantly, 1 h post-training administration of bicuculline methiodide, which enhanced memory consolidation, significantly increased mBDNF levels 9 h after training compared to those of the vehicle-treated control group. In addition, exogenous human recombinant BDNF (hrBDNF) administration 9 h after training into the hippocampal CA1 region facilitated memory consolidation confirming that the increase in mBDNF at around 9 h after training plays a key role in the enhancement of memory consolidation. Moreover, the increases in latency time and immediate early gene expressions by bicuculline methiodide or hrBDNF were significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings suggest that the increase in the level of mBDNF and its function during a restricted time window after training are required for the enhancement of memory consolidation by GABAA receptor blockade. PMID:21900885

  8. Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

    PubMed Central

    Gómez-Sánchez, Rubén; Gegg, Matthew E.; Bravo-San Pedro, José M.; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M.; González-Polo, Rosa Ana; Schapira, Anthony H.V.

    2014-01-01

    Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. PMID:24184327

  9. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity

    NASA Technical Reports Server (NTRS)

    Smart, D. R.; Ritchie, K.; Stark, J. M.; Bugbee, B.

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity.

  10. Histone deacetylases 6 increases the cyclic adenosine monophosphate level and promotes renal cyst growth.

    PubMed

    Wu, Ming; Mei, Changlin

    2016-07-01

    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal enhanced cell proliferation and fluid secretion, which are triggered by increased levels of cyclic adenosine monophosphate (cAMP). Cebotaru et al. showed that a HDAC6 inhibitor reduced the cAMP level and inhibited cyst formation in Pkd1 knockout mice, which may become a new potential therapeutic agent for ADPKD. This study also raised several intriguing questions that might advance our understanding of the molecular pathogenesis of ADPKD. PMID:27312442

  11. Intrahypothalamic injection of cannabidiol increases the extracellular levels of adenosine in nucleus accumbens in rats.

    PubMed

    Mijangos-Moreno, Stephanie; Poot-Aké, Alwin; Arankowsky-Sandoval, Gloria; Murillo-Rodríguez, Eric

    2014-07-01

    Cannabidiol (CBD) is a constituent of Cannabis sativa that promotes wakefulness as well as enhances endogenous levels of wake-related neurotransmitters, including dopamine. However, at this date, the effects of CBD on the sleep-inducing molecules, such as adenosine (AD), are unknown. Here, we report that intrahypothalamic injection of CBD (10μg/1μL) increases the extracellular levels of AD collected from nucleus accumbens. Furthermore, the pharmacodynamic of this drug shows that effects on the contents of AD last 2h post-injection. These preliminary findings suggest that CBD promotes the endogenous accumulation of AD. PMID:24800644

  12. Evidence that elevated CO2 levels can indirectly increase rhizosphere denitrifier activity.

    PubMed Central

    Smart, D R; Ritchie, K; Stark, J M; Bugbee, B

    1997-01-01

    We examined the influence of elevated CO2 concentration on denitrifier enzyme activity in wheat rhizoplanes by using controlled environments and solution culture techniques. Potential denitrification activity was from 3 to 24 times higher on roots that were grown under an elevated CO2 concentration of 1,000 micromoles of CO2 mol-1 than on roots grown under ambient levels of CO2. Nitrogen loss, as determined by a nitrogen mass balance, increased with elevated CO2 levels in the shoot environment and with a high NO3- concentration in the rooting zone. These results indicated that aerial CO2 concentration can play a role in rhizosphere denitrifier activity. PMID:11536820

  13. Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.

    PubMed Central

    Bonini, S; Lambiase, A; Bonini, S; Angelucci, F; Magrini, L; Manni, L; Aloe, L

    1996-01-01

    Nerve growth factor (NGF) serum levels were measured in 49 patients with asthma and/or rhinoconjunctivitis and/or urticaria-angioedema. Clinical and biochemical parameters, such as bronchial reactivity, total and specific serum IgE levels, and circulating eosinophil cationic protein levels, were evaluated in relation to NGF values in asthma patients. NGF was significantly increased in the 42 allergic (skin-test- or radioallergosorbent-test-positive) subjects (49.7 +/- 28.8 pg/ml) versus the 18 matched controls (3.8 +/- 1.7 pg/ml; P < 0.001). NGF levels in allergic patients with asthma, rhinoconjunctivitis, and urticaria-angioedema were 132.1 +/- 90.8, 17.6 +/- 6.1, and 7.6 +/- 1.8 pg/ml (P < 0.001, P < 0.002, and P < 0.05 versus controls), respectively. Patients with more than one allergic disease had higher NGF serum values than those with a single disease. When asthma patients were considered as a group, NGF serum values (87.6 +/- 59.8 pg/ml) were still significantly higher than those of control groups (P < 0.001), but allergic asthma patients had elevated NGF serum levels compared with nonallergic asthma patients (132.1 +/- 90.8 versus 4.9 +/- 2.9 pg/ml; P < 0.001). NGF serum levels correlate to total IgE serum values (rho = 0.43; P < 0.02). The highest NGF values were found in patients with severe allergic asthma, a high degree of bronchial hyperreactivity, and high total IgE and eosinophil cationic protein serum levels. This study represents the first observation (that we know of) that NGF is increased in human allergic inflammatory diseases and asthma. Images Fig. 2 PMID:8855290

  14. Increased serum osteopontin levels in autistic children: relation to the disease severity.

    PubMed

    Al-ayadhi, Laila Y; Mostafa, Gehan A

    2011-10-01

    Autoimmunity to brain may play an etiopathogenic role in autism. Osteopontin is a pro-inflammatory cytokine that has been shown to play an important role in various autoimmune neuroinflammatory diseases. Osteopontin induces IL-17 production by T-helper 17 lymphocytes, the key players in the pathogenesis of autoimmune disorders. Anti-osteopontin treatment reduces the clinical severity of some autoimmune neuroinflammatory diseases by reducing IL-17 production. We are the first to measure serum osteopontin levels, by ELISA, in 42 autistic children in comparison to 42 healthy-matched children. The relationship between serum osteopontin levels and the severity of autism, which was assessed by using the Childhood Autism Rating Scale (CARS), was also studied. Autistic children had significantly higher serum osteopontin levels than healthy controls (P<0.001). Increased serum osteopontin levels were found in 80.95% (34/42) of autistic children. Children with severe autism had significantly higher serum osteopontin levels than patients with mild to moderate autism (P=0.02). Moreover, serum osteopontin levels of autistic patients had significant positive correlations with CARS (P=0.007). In conclusions, serum osteopontin levels were increased in many autistic children and they were significantly correlated to the severity of autism. Further wide-scale studies are warranted to shed light on the etiopathogenic role of osteopontin in autism and to investigate its relation to IL-17 and brain-specific auto-antibodies, which are indicators of autoimmunity, in these patients. The therapeutic role of anti-osteopontin antibodies in amelioration of autistic manifestations should also be studied. PMID:21521652

  15. Increased levels of messenger RNAs for neurotrophic factors in the brain during kindling epileptogenesis.

    PubMed

    Ernfors, P; Bengzon, J; Kokaia, Z; Persson, H; Lindvall, O

    1991-07-01

    Kindling, induced by repeated subconvulsive electrical or chemical stimulations leads to progressive and permanent amplification of seizure activity, culminating in generalized seizures. We report that kindling induced by electrical stimulation in the ventral hippocampus leads to a marked and transient increase in mRNA for NGF and BDNF in the dentate gyrus, the parietal cortex, and the piriform cortex. BDNF mRNA increased also in the pyramidal layer of hippocampus and in the amygdaloid complex. No change was seen in the level of HDNF/NT-3 mRNA. The increased expression of NGF and BDNF mRNAs was not influenced by pretreatment with the NMDA receptor antagonist MK801, but was partially blocked by the quisqualate, AMPA receptor antagonist NBQX. The presumed subsequent increase of the trophic factors themselves may be important for kindling-associated plasticity in specific neuronal systems in the hippocampus, which could promote hyperexcitability and contribute to the development of epileptic syndromes. PMID:1829904

  16. Benefits and costs of increased levels of corticosterone in seabird chicks.

    PubMed

    Kitaysky, A S; Kitaiskaia, E V; Piatt, J F; Wingfield, J C

    2003-01-01

    Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. PMID:12614644

  17. Benefits and costs of increased levels of corticosterone in seabird chicks

    USGS Publications Warehouse

    Kitaysky, A.S.; Kitaiskaia, E.V.; Piatt, J.F.; Wingfield, J.C.

    2003-01-01

    Seabird chicks respond to food shortages by increasing corticosterone (cort) secretion, which is probably associated with fitness benefits and costs. To examine this, we experimentally increased levels of circulating cort in captive black-legged kittiwake chicks fed ad libitum. We found that cort-implanted chicks begged more frequently and were more aggressive compared to controls. These behavioral modifications must be beneficial to chicks as they facilitate acquisition of food from the parents and might trigger brood reduction and reduced competition for food. Cort-implanted chicks also increased food intake; however, their growth rates were similar to controls. To examine the costs of chronically increased circulating levels of cort, we removed cort implants and, after a 10-day recovery period, tested cognitive abilities of young kittiwakes. We found that the ability of kittiwakes to associate a visual cue with the presence of food in a choice situation was compromised by the experimental elevation of cort during development. To examine the long-term costs of increased levels of cort, 8 months later we tested the performance of the same individuals in a spatial task requiring them to make a detour around a barrier in order to escape from an enclosure. Individuals treated with cort during development took significantly more time to solve this task compared to controls. The results of this study suggest that the adrenocortical response of a developing bird to environmental stressors is associated with both benefits (increased food intake, foraging behavior, and aggression) and costs (low growth efficiency and compromised cognitive abilities later in life). This provides an evolutionary framework for relating juvenile physiological traits to fitness of birds in subsequent life-history stages. ?? 2003 Elsevier Science (USA). All rights reserved.

  18. Serum Amyloid-Beta Levels are Increased in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Bu, Xian-Le; Cao, Guo-Qiang; Shen, Lin-Lin; Xiang, Yang; Jiao, Shu-Sheng; Liu, Yu-Hui; Zhu, Chi; Zeng, Fan; Wang, Qing-Hua; Wang, Ye-Ran; He, Yong; Zhou, Hua-Dong; Wang, Yan-Jiang

    2015-11-01

    Chronic obstructive pulmonary disease (COPD) is associated with cognitive decline, but the molecular link between COPD and dementia or Alzheimer's disease (AD) remains unclear. This study was aimed to investigate whether serum Aβ levels are correlated with COPD. 77 cognitively normal COPD patients and 45 age- and gender-matched normal controls were admitted to the study. Serum Aβ40 and Aβ42 levels were measured using ELISA kits. Serum C-reactive protein (CRP), interleukin 6 (IL-6), and procalcitonin (PCT) measurements were done using standard laboratory methods. Pulmonary function tests were performed to assess the pulmonary function and determine the degree of lung damage. Significantly increased levels of serum Aβ40, Aβ42, and total Aβ levels were found in patients with COPD in comparison with normal controls. In COPD patients, serum Aβ levels were higher in subjects with serum CRP, IL-6, and PCT upper the limit of normal. Moreover, serum Aβ levels were dramatically higher in COPD patients with worse pulmonary function. Our study suggests that cognitively normal COPD patients may undergo AD-related pathological changes, and COPD might facilitate AD-type pathogenesis. PMID:26243505

  19. Increased circulating macrophage migration inhibitory factor levels are associated with coronary artery disease

    PubMed Central

    Yüksel, Arif; Bilgir, Ferda; Bilgir, Oktay; Calan, Mehmet; Bozkaya, Giray

    2015-01-01

    BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. PMID:26017646

  20. A gene stacking approach leads to engineered plants with highly increased galactan levels in Arabidopsis

    SciTech Connect

    Gondolf, Vibe M.; Stoppel, Rhea; Ebert, Berit; Rautengarten, Carsten; Liwanag, April J.M.; Loqué, Dominique; Scheller, Henrik V.

    2014-12-10

    Background: Engineering of plants with a composition of lignocellulosic biomass that is more suitable for downstream processing is of high interest for next-generation biofuel production. Lignocellulosic biomass contains a high proportion of pentose residues, which are more difficult to convert into fuels than hexoses. Therefore, increasing the hexose/pentose ratio in biomass is one approach for biomass improvement. A genetic engineering approach was used to investigate whether the amount of pectic galactan can be specifically increased in cell walls of Arabidopsis fiber cells, which in turn could provide a potential source of readily fermentable galactose. Results: First it was tested if overexpression of various plant UDP-glucose 4-epimerases (UGEs) could increase the availability of UDP-galactose and thereby increase the biosynthesis of galactan. Constitutive and tissue-specific expression of a poplar UGE and three Arabidopsis UGEs in Arabidopsis plants could not significantly increase the amount of cell wall bound galactose. We then investigated co-overexpression of AtUGE2 together with the β-1,4-galactan synthase GalS1. Co-overexpression of AtUGE2 and GalS1 led to over 80% increase in cell wall galactose levels in Arabidopsis stems, providing evidence that these proteins work synergistically. Furthermore, AtUGE2 and GalS1 overexpression in combination with overexpression of the NST1 master regulator for secondary cell wall biosynthesis resulted in increased thickness of fiber cell walls in addition to the high cell wall galactose levels. Immunofluorescence microscopy confirmed that the increased galactose was present as β-1,4-galactan in secondary cell walls. Conclusions: This approach clearly indicates that simultaneous overexpression of AtUGE2 and GalS1 increases the cell wall galactose to much higher levels than can be achieved by overexpressing either one of these proteins alone. Moreover, the increased galactan content in

  1. A gene stacking approach leads to engineered plants with highly increased galactan levels in Arabidopsis

    DOE PAGESBeta

    Gondolf, Vibe M.; Stoppel, Rhea; Ebert, Berit; Rautengarten, Carsten; Liwanag, April J.M.; Loqué, Dominique; Scheller, Henrik V.

    2014-12-10

    Background: Engineering of plants with a composition of lignocellulosic biomass that is more suitable for downstream processing is of high interest for next-generation biofuel production. Lignocellulosic biomass contains a high proportion of pentose residues, which are more difficult to convert into fuels than hexoses. Therefore, increasing the hexose/pentose ratio in biomass is one approach for biomass improvement. A genetic engineering approach was used to investigate whether the amount of pectic galactan can be specifically increased in cell walls of Arabidopsis fiber cells, which in turn could provide a potential source of readily fermentable galactose. Results: First it was tested ifmore » overexpression of various plant UDP-glucose 4-epimerases (UGEs) could increase the availability of UDP-galactose and thereby increase the biosynthesis of galactan. Constitutive and tissue-specific expression of a poplar UGE and three Arabidopsis UGEs in Arabidopsis plants could not significantly increase the amount of cell wall bound galactose. We then investigated co-overexpression of AtUGE2 together with the β-1,4-galactan synthase GalS1. Co-overexpression of AtUGE2 and GalS1 led to over 80% increase in cell wall galactose levels in Arabidopsis stems, providing evidence that these proteins work synergistically. Furthermore, AtUGE2 and GalS1 overexpression in combination with overexpression of the NST1 master regulator for secondary cell wall biosynthesis resulted in increased thickness of fiber cell walls in addition to the high cell wall galactose levels. Immunofluorescence microscopy confirmed that the increased galactose was present as β-1,4-galactan in secondary cell walls. Conclusions: This approach clearly indicates that simultaneous overexpression of AtUGE2 and GalS1 increases the cell wall galactose to much higher levels than can be achieved by overexpressing either one of these proteins alone. Moreover, the increased galactan content in fiber cells while

  2. Increased plasma levels and blunted effects of brain natriuretic peptide in rats with congestive heart failure.

    PubMed

    Hoffman, A; Grossman, E; Keiser, H R

    1991-07-01

    The hemodynamic and renal effects of brain natriuretic peptide (BNP) were studied in conscious rats with experimental congestive heart failure (CHF) produced by an aortocaval fistula. The peptide had potent hypotensive, diuretic, and natriuretic effects in control rats, all of which were abolished in CHF. Plasma levels of BNP increased time-dependently during the development of CHF, and were more than four-fold higher in sodium retaining rats than in control rats. The data suggest that BNP secretion from the atria is increased in CHF, and that resistance to BNP, in addition to the relative resistance to atrial natriuretic factor, may contribute to sodium retention in CHF. PMID:1831369

  3. Cytotoxic evaluation of biomechanically improved crosslinked ovine collagen on human dermal fibroblasts.

    PubMed

    Awang, M A; Firdaus, M A B; Busra, M B; Chowdhury, S R; Fadilah, N R; Wan Hamirul, W K; Reusmaazran, M Y; Aminuddin, M Y; Ruszymah, B H I

    2014-01-01

    Earlier studies in our laboratory demonstrated that collagen extracted from ovine tendon is biocompatible towards human dermal fibroblast. To be able to use this collagen as a scaffold in skin tissue engineering, a mechanically stronger scaffold is required that can withstand manipulation before transplantation. This study was conducted to improve the mechanical strength of this collagen sponge using chemical crosslinkers, and evaluate their effect on physical, chemical and biocompatible properties. Collagen sponge was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). Tensile test, FTIR study and mercury porosimetry were used to evaluate mechanical properties, chemical property and porosity, respectively. MTT assay was performed to evaluate the cytotoxic effect of crosslinked collagen sponge on human dermal fibroblasts. The FTIR study confirmed the successful crosslinking of collagen sponge. Crosslinking with EDC and GA significantly increased the mechanical strength of collagen sponge, with GA being more superior. Crosslinking of collagen sponge significantly reduced the porosity and the effect was predominant in GA-crosslinked collagen sponge. The GA-crosslinked collagen showed significantly lower, 60% cell viability towards human dermal fibroblasts compared to that of EDC-crosslinked collagen, 80% and non-crosslinked collagen, 100%. Although the mechanical strength was better when using GA but the more toxic effect on dermal fibroblast makes EDC a more suitable crosslinker for future skin tissue engineering. PMID:24948455

  4. Can Population Levels of Physical Activity be Increased? Global Evidence and Experience

    PubMed Central

    Pratt, Michael; Perez, Lilian G.; Goenka, Shifalika; Brownson, Ross C.; Bauman, Adrian; Sarmiento, Olga Lucia; Hallal, Pedro C.

    2016-01-01

    Physical inactivity is one of the most important contributors to the global burden of disease and has become a global public health priority. We review the evidence on physical activity (PA) interventions, actions, and strategies that have the greatest potential to increase PA at the population level. Using the socio-ecological framework to conceptualize PA interventions, we show that PA can be targeted at multiple levels of influence and by multiple sectors outside the health system. Examples of promoting PA on a national scale are presented from Finland, Canada, Brazil, and Colombia. A strong policy framework, consistent investment in public health programs, multi-sectoral support and actions, and good surveillance characterize each of these success stories. Increasing PA globally will depend on successfully applying and adapting these lessons around the world taking into account country, culture, and context. PMID:25304047

  5. Mannosylerythritol lipid increases levels of galactoceramide in and neurite outgrowth from PC12 pheochromocytoma cells.

    PubMed

    Shibahara, M; Zhao, X; Wakamatsu, Y; Nomura, N; Nakahara, T; Jin, C; Nagaso, H; Murata, T; Yokoyama, K K

    2000-07-01

    We report here that a microbial extracellular glycolipid,mannosylerythritol lipid (MEL), induces the outgrowth ofneurites from and enhances the activity of acetylcholinesterase(AChE) in PC12 pheochromocytoma cells. Furthermore, treatment ofPC12 cells with MEL increased levels of galactosylceramide(Galbeta1-1'Cer; GalCer). Exposure of PC12 cells to exogenous GalCer caused the dose-dependent outgrowth ofneurites. By contrast, treatment of PC12 cells with nerve growthfactor (NGF) did not increase the level of GalCer in the cells. The neurite-related morphological changes induced by GalCerdifferend from those induced by NGF, indicating differencesbetween the signal transduction pathways triggered by NGF and by GalCer. PMID:19002832

  6. Increased erythropoietin levels as a biomarker of pancreatic adenocarcinoma: A case report

    PubMed Central

    KHAN, RAFAY; NAI, QIANG; ZHANG, PING; LUO, HONGXIU; SEN, SHRAMAN; SIDHOM, IBRAHIM; MATHEW, TEENA; ISLAM, MOHAMMAD; SEN, SHUVENDU; YOUSIF, ABDALLA

    2016-01-01

    Pancreatic cancer is one of the deadliest cancers commonly diagnosed at an advanced stage. Early diagnosis is crucial for the timely and potentially curative treatment of this highly fatal disease. Although screening tests have improved the survival rate in malignancies such as colon, breast, cervical and prostate cancer, there is currently no effective screening method available for the early detection of pancreatic cancer. As the sensitivity and specificity of existing biomarkers, such as carbohydrate antigen 19-9, for the early detection of pancreatic cancer is low, there is a pressing need for the identification of novel cancer markers. An increase in erythropoietin (EPO) levels has been observed in several cases of pancreatic neoplasms. However, the potential role of EPO as a biomarker of pancreatic cancer or malignant transformation requires further investigation. We herein present a case of increased EPO levels in an adult male patient with stage IV pancreatic cancer. PMID:26870372

  7. Increased Plasma Levels of Pentraxin 3 Are Associated with Poor Prognosis of Colorectal Carcinoma Patients.

    PubMed

    Zhang, Jie; Wang, Tai-Yong; Niu, Xue-Cai

    2016-01-01

    Colorectal carcinoma (CRC) is one of the most common cancers globally. It is essential to identify a prognostic predictor for CRC. Pentraxin 3 (PTX3) is a glycoprotein that is secreted by a variety of human cells. It plays an important role in inflammation and immune regulation. Increasing evidence reveals that elevated PTX3 expression is related to poor prognosis in various cancers. The aim of the study was to determine the usefulness of plasma PTX3 level as a prognostic predictor in CRC. Total 184 CRC patients and 216 controls were included. Plasma levels of PTX3 were determined using Enzyme-linked immunosorbent assays. On admission, plasma PTX3 levels in CRC patients were higher than those in controls (11.8 ± 2.5 ng/ml vs. 3.1 ± 0.9 ng/ml, P < 0.001). After resection, plasma PTX3 levels in patients were decreased (6.0 ± 1.4 ng/ml, P = 0.007), and were elevated at the time of relapse (10.8 ± 2.8 ng/ml, P < 0.001). During the 60-month follow-up period, 108 patients suffered from relapse. Plasma PTX3 levels of ≥ 12 ng/ml on admission were associated with relapse (OR: 3.11, 95% CI: 1.74 ~ 6.29), and tumor-free survival rate in those patients with plasma PTX3 levels of ≥ 12 ng/ml was lower than that in other patients (P = 0.001). Furthermore, plasma PTX3 levels on admission showed positive linear correlations with plasma complement 3, 4 and 5b9 levels (P < 0.001, P < 0.001, P < 0.001). Therefore, we propose that PTX3 is an independent prognostic indicator in CRC. PMID:27568661

  8. Tenascin-C Deficiency in Apo E−/− Mouse Increases Eotaxin Levels: Implications for Atherosclerosis

    PubMed Central

    Wang, Lai; Shah, Prediman K.; Wang, Wei; Song, Lei; Yang, Mingjie; Sharifi, Behrooz G.

    2013-01-01

    Aim To investigate the potential role of inflammatory cytokines in apo E−/− mouse in response to deletion of Tenascin-C (TNC) gene. Methods and results We used antibody array and ELISA to compare the profile of circulating inflammatory cytokines in apo E−/− mice and apo E−/− TNC−/− double knockout mice. In addition, tissue culture studies were performed to investigate the activity of cells from each mouse genotype in vitro. Cytokine array analysis and subsequent ELISA showed that circulating eotaxin levels were selectively and markedly increased in response to TNC gene deletion in apo E−/− mice. In addition, considerable variation was noted in the circulating level of eotaxin among the control apo E−/− mouse group. Inbreeding of apo E−/− mice with high or low levels of plasma eotaxin showed that the level of eotaxin per se determines the extent of atherosclerosis in this mouse genotype. While endothelial cells from apo E−/− mice had low level of eotaxin expression, cells derived from apo E−/−TNC−/− mice expressed a high level of eotaxin. Transient transfection of eotaxin promoter-reporter constructs revealed that eotaxin expression is regulated at the transcriptional level by TNC. Histochemical analysis of aortic sections revealed the massive accumulation of mast cells in the adventitia of double KO mice lesions whereas no such accumulation was detected in the control group. Plasma from the apo E−/−TNC−/− mice markedly stimulated mast cell migration whereas plasma from the apo E−/− mice had no such effect. Conclusion These observations support the emerging hypothesis that TNC expression controls eotaxin level in apo E−/− mice and that this chemokine plays a key role in the development of atherosclerosis. PMID:23433402

  9. Bis-(2-ethylhexyl) Phthalate Increases Insulin Expression and Lipid Levels in Drosophila melanogaster.

    PubMed

    Cao, Hao; Wiemerslage, Lyle; Marttila, Petra S K; Williams, Michael J; Schiöth, Helgi B

    2016-09-01

    Bis-(2-ethylhexyl) phthalate (DEHP) is one of the most widely used plasticizers, and human beings are exposed to DEHP via polyvinyl chloride (PVC) materials, medical equipment and even drinking water. While DEHP has been implicated to influence metabolism and endocrine functions, important questions remain about the molecular mechanisms of these effects. We employed the model organism Drosophila melanogaster and examined physiological, molecular and behavioural effects from DEHP-contaminated food. We found that DEHP, at levels comparable to human exposure, made male flies more resistant to starvation and increased lipid levels, while decreasing circulating carbohydrates. Moreover, DEHP-fed male flies had higher expression levels of an insulin-like peptide known to regulate metabolism, as well as the insulin receptor. Our results suggest that long-term DEHP feeding may induce diabetes-like dysfunctions. These findings provide a molecular background of how DEHP may have detrimental effects on metabolic functions. PMID:27009472

  10. Does rosuvastatin increase serum levels of 25-hydroxy-vitamin D?

    PubMed Central

    Glossmann, Hartmut H.; Blumthaler, Mario

    2012-01-01

    An observational study and a “clinical trial” seem to prove that rosuvastatin (but not fluvastatin) dramatically increases serum levels of 25-(OH)-D3 (three-fold above starting values). A critical analysis of the two publications, presented below, raises serious concerns. Conclusions from these two studies have already been drawn in the scientific literature.It is argued that claiming or believing in a “novel pleiotropic effect of rosuvastatin” may be misleading and premature. PMID:22870344

  11. Role of Increased Guanosine Triphosphate Cyclohydrolase-1 Expression and Tetrahydrobiopterin Levels upon T Cell Activation

    PubMed Central

    Chen, Wei; Li, Li; Brod, Torben; Saeed, Omar; Thabet, Salim; Jansen, Thomas; Dikalov, Sergey; Weyand, Cornelia; Goronzy, Jorg; Harrison, David G.

    2011-01-01

    Tetrahydrobiopterin (BH4) is an essential co-factor for the nitric-oxide (NO) synthases, and in its absence these enzymes produce superoxide (O2˙̄) rather than NO. The rate-limiting enzyme for BH4 production is guanosine triphosphate cyclohydrolase-1 (GTPCH-1). Because endogenously produced NO affects T cell function, we sought to determine whether antigen stimulation affected T cell GTPCH-1 expression and ultimately BH4 levels. Resting T cells had minimal expression of inducible NOS (NOS2), endothelial NOS (NOS3), and GTPCH-1 protein and nearly undetectable levels of BH4. Anti-CD3 stimulation of T cells robustly stimulated the coordinated expression of NOS2, NOS3, and GTPCH-1 and markedly increased both GTPCH-1 activity and T cell BH4 levels. The newly expressed GTPCH-1 was phosphorylated on serine 72 and pharmacological inhibition of casein kinase II reduced GTPCH-1 phosphorylation and blunted the increase in T cell BH4. Inhibition of GTPCH-1 with diaminohydroxypyrimidine (1 mmol/liter) prevented T cell BH4 accumulation, reduced NO production, and increased T cell O2˙̄ production, due to both NOS2 and NOS3 uncoupling. GTPCH-1 inhibition also promoted TH2 polarization in memory CD4 cells. Ovalbumin immunization of mice transgenic for an ovalbumin receptor (OT-II mice) confirmed a marked increase in T cell BH4 in vivo. These studies identify a previously unidentified consequence of T cell activation, promoting BH4 levels, NO production, and modulating T cell cytokine production. PMID:21343293

  12. Temporal aspects of increases in eye-neck activation levels during visually deficient near work.

    PubMed

    Richter, Hans O; Camilla, Lodin; Forsman, Mikael

    2012-01-01

    In an experimental study two levels of oculomotor load were induced via optical trial lenses. Trapezius muscle activity was measured with bipolar surface electromyography and normalized to a submaximal contraction. Sixty-six subjects with a median age of 36 (range 19-47, std 8) viewed a black and white Gabor grating (5 c/deg) for two 7-min periods monocularly through a 0 D lens or binocularly through -3.5 D lenses. The effect of time was separately regressed to EMG in two different subgroups of responders: a High-Oculomotor-Load (HOL) and a Low-Oculomotor-Load (LOL) group. A linear regression model was fitted on group level with exposure time on the x-axis and normalized trapezius muscle EMG (%RVE) on the y-axis. The slope coefficient was significantly positive in the -D blur condition for only the HOL subgroup of responders: 0.926 + Time(min 1-7) × 0.088 (p = 0.002, r(2)=0.865). There was no obvious sign of this activity to level off or to stabilize. These results suggest that professional information technology users that are exposed to a high level of oculomotor load, during extended times, are at an increased risk of exhibiting an increased trap.m. activity. PMID:22317234

  13. Neurons detect increases and decreases in oxygen levels using distinct guanylate cyclases.

    PubMed

    Zimmer, Manuel; Gray, Jesse M; Pokala, Navin; Chang, Andy J; Karow, David S; Marletta, Michael A; Hudson, Martin L; Morton, David B; Chronis, Nikos; Bargmann, Cornelia I

    2009-03-26

    Homeostatic sensory systems detect small deviations in temperature, water balance, pH, and energy needs to regulate adaptive behavior and physiology. In C. elegans, a homeostatic preference for intermediate oxygen (O2) levels requires cGMP signaling through soluble guanylate cyclases (sGCs), proteins that bind gases through an associated heme group. Here we use behavioral analysis, functional imaging, and genetics to show that reciprocal changes in O2 levels are encoded by sensory neurons that express alternative sets of sGCs. URX sensory neurons are activated by increases in O2 levels, and require the sGCs gcy-35 and gcy-36. BAG sensory neurons are activated by decreases in O2 levels, and require the sGCs gcy-31 and gcy-33. The sGCs are instructive O2 sensors, as forced expression of URX sGC genes causes BAG neurons to detect O2 increases. Both sGC expression and cell-intrinsic dynamics contribute to the differential roles of URX and BAG in O2-dependent behaviors. PMID:19323996

  14. Comparing Canadian and American cybersecurity awareness levels: Educational strategies to increase public awareness

    NASA Astrophysics Data System (ADS)

    Hoggard, Amy

    Cybersecurity awareness is an important issue that affects everyone who uses a computer or a mobile device. Canada and the United States both recognize the value of mitigating cybersecurity risks in terms of national safety, economic stability and protection of their citizens. The research performed compared the levels of cybersecurity awareness in Canadian and American Internet users. Canadian and American users were equally aware of cybersecurity measures, but were not implementing best practices to keep themselves safe. The research suggested users needed to understand why a cybersecurity measure was important before being motivated to implement it. Educational strategies were reviewed in both Canada and the United States and it was determined that although there were significant resources available, they were not being utilized by both the educators and the public. In order to increase cybersecurity awareness levels, nations should focus on increasing the public's awareness by using various types of messaging, such as cartoons, in media. One possible consideration is a compulsory awareness model before accessing the Internet. Cybersecurity topics should be included in the curriculum for students at all levels of education and a focus on providing training and resources to teachers will help increase the cybersecurity knowledge of children and youth.

  15. Pesticide exposure in honey bees results in increased levels of the gut pathogen Nosema

    NASA Astrophysics Data System (ADS)

    Pettis, Jeffery S.; Vanengelsdorp, Dennis; Johnson, Josephine; Dively, Galen

    2012-02-01

    Global pollinator declines have been attributed to habitat destruction, pesticide use, and climate change or some combination of these factors, and managed honey bees, Apis mellifera, are part of worldwide pollinator declines. Here we exposed honey bee colonies during three brood generations to sub-lethal doses of a widely used pesticide, imidacloprid, and then subsequently challenged newly emerged bees with the gut parasite, Nosema spp. The pesticide dosages used were below levels demonstrated to cause effects on longevity or foraging in adult honey bees. Nosema infections increased significantly in the bees from pesticide-treated hives when compared to bees from control hives demonstrating an indirect effect of pesticides on pathogen growth in honey bees. We clearly demonstrate an increase in pathogen growth within individual bees reared in colonies exposed to one of the most widely used pesticides worldwide, imidacloprid, at below levels considered harmful to bees. The finding that individual bees with undetectable levels of the target pesticide, after being reared in a sub-lethal pesticide environment within the colony, had higher Nosema is significant. Interactions between pesticides and pathogens could be a major contributor to increased mortality of honey bee colonies, including colony collapse disorder, and other pollinator declines worldwide.

  16. Social challenge increases cortisol and hypothalamic monoamine levels in matrinxã (Brycon amazonicus).

    PubMed

    Wolkers, Carla Patrícia Bejo; Serra, Mônica; Urbinati, Elisabeth Criscuolo

    2015-12-01

    The neural circuitry for social behavior and aggression appears to be evolutionarily conserved across the vertebrate subphylum and involves a complex neural network that includes the hypothalamus as a key structure. In the present study, we evaluated the changes in monoamine levels in the hypothalamus and on serum cortisol and plasma glucose of resident matrinxã (Brycon amazonicus) submitted to a social challenge (introduction of an intruder in their territory). The fight promoted a significant increase in hypothalamic 5-HT, NA and DA levels and on the metabolites 5-HIAA and DOPAC, and decreased 5-HIAA/5-HT and DOPAC/DA ratios in resident fish. Furthermore, an increase in serum cortisol and plasma glucose was also observed after the fight. Resident fish presented a high aggressiveness even with increased 5-HT levels in the hypothalamus. The alteration in hypothalamic monoaminergic activity of matrinxã suggests that this diencephalic region is involved in aggression and stress modulation in fish; however, it does not exclude the participation of other brain areas not tested here. PMID:26205527

  17. Pollination Increases Gibberellin Levels in Developing Ovaries of Seeded Varieties of Citrus.

    PubMed Central

    Ben-Cheikh, W.; Perez-Botella, J.; Tadeo, F. R.; Talon, M.; Primo-Millo, E.

    1997-01-01

    Reproductive and vegetative tissues of the seeded Pineapple cultivars of sweet orange (Citrus sinensis L.) contained the following C-13 hydroxylated gibberellins (GAs): GA53, GA17, GA19, GA20, GA1, GA29, and GA8, as well as GA97, 3-epi-GA1, and several uncharacterized GAs. The inclusion of 3-epi-GA1 as an endogenous substance was based on measurements of the isomerization rates of previously added [2H2]GA1. Pollination enhanced amounts of GA19, GA20, GA29, and GA8 in developing ovaries. Levels of GA1 increased from 5.0 to 9.5 ng/g dry weight during anthesis and were reduced thereafter. The amount of GA in mature pollen was very low. Emasculation reduced GA levels and caused a rapid 100% ovary abscission. This effect was partially counteracted by either pollination or application of GA3. In pollinated ovaries, repeated paclobutrazol applications decreased the amount of GA and increased ovary abscission, although the pattern of continuous decline was different from the sudden abscission induced by emasculation. The above results indicate that, in citrus, pollination increases GA levels and reduces ovary abscission and that the presence of exogenous GA3 in unpollinated ovaries also suppresses abscission. Evidence is also presented that pollination and GAs do not, as is generally assumed, suppress ovary abscission through the reactivation of cell division. PMID:12223728

  18. Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma

    PubMed Central

    Hurabielle, Charlotte; Pillebout, Evangéline; Stehlé, Thomas; Pagès, Cécile; Roux, Jennifer; Schneider, Pierre; Chevret, Sylvie; Chaffaut, Cendrine; Boutten, Anne; Mourah, Samia; Basset-Seguin, Nicole; Vidal-Petiot, Emmanuelle; Lebbé, Céleste; Flamant, Martin

    2016-01-01

    Context Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. Objective We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. Methods We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. Results 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Conclusion Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective. PMID:26930506

  19. Increased acetyl and total histone levels in post-mortem Alzheimer's disease brain.

    PubMed

    Narayan, Pritika J; Lill, Claire; Faull, Richard; Curtis, Maurice A; Dragunow, Mike

    2015-02-01

    Histone acetylation is an epigenetic modification that plays a critical role in chromatin remodelling and transcriptional regulation. There is increasing evidence that epigenetic modifications may become compromised in aging and increase susceptibility to the development of neurodegenerative disorders such as Alzheimer's disease. Immunohistochemical labelling of free-floating sections from the inferior temporal gyrus (Alzheimer's disease, n=14; control, n=17) and paraffin-embedded tissue microarrays containing tissue from the middle temporal gyrus (Alzheimer's disease, n=29; control, n=28) demonstrated that acetyl histone H3 and acetyl histone H4 levels, as well as total histone H3 and total histone H4 protein levels, were significantly increased in post-mortem Alzheimer's disease brain tissue compared to age- and sex-matched neurologically normal control brain tissue. Changes in acetyl histone levels were proportional to changes in total histone levels. The increase in acetyl histone H3 and H4 was observed in Neuronal N immunopositive pyramidal neurons in Alzheimer's disease brain. Using immunolabelling, histone markers correlated significantly with the level of glial fibrillary acidic protein and HLA-DP, -DQ and -DR immunopositive cells and with the pathological hallmarks of Alzheimer's disease (hyperphosphorylated tau load and β-amyloid plaques). Given that histone acetylation changes were correlated with changes in total histone protein, it was important to evaluate if protein degradation pathways may be compromised in Alzheimer's disease. Consequently, significant positive correlations were also found between ubiquitin load and histone modifications. The relationship between histone acetylation and ubiquitin levels was further investigated in an in vitro model of SK-N-SH cells treated with the proteasome inhibitor Mg132 and the histone deacetylase inhibitor valproic acid. In this model, compromised protein degradation caused by Mg132 lead to elevated histone

  20. Potential population-level effects of increased haulout-related mortality of Pacific walrus calves

    USGS Publications Warehouse

    Udevitz, Mark S.; Taylor, Rebecca L.; Garlich-Miller, Joel L.; Quakenbush, Lori T.; Snyder, Jonathan A.

    2013-01-01

    Availability of summer sea ice has been decreasing in the Chukchi Sea during recent decades, and increasing numbers of Pacific walruses have begun using coastal haulouts in late summer during years when sea ice retreats beyond the continental shelf. Calves and yearlings are particularly susceptible to being crushed during disturbance events that cause the herd to panic and stampede at these large haulouts, but the potential population-level effects of this mortality are unknown. We used recent harvest data, along with previous assumptions about demographic parameters for this population, to estimate female population size and structure in 2009 and project these numbers forward using a range of assumptions about future harvests and haulout-related mortality that might result from increased use of coastal haulouts during late summer. We found that if demographic parameters were held constant, the levels of harvest that occurred during 1990–2008 would have allowed the population to grow during that period. Our projections indicate, however, that an increase in haulout-related mortality affecting only calves has a greater effect on the population than an equivalent increase in harvest-related mortality distributed among all age classes. Therefore, disturbance-related mortality of calves at coastal haulouts may have relatively important population consequences.

  1. Increase of hypophyseal hormone levels in male head and neck cancer patients.

    PubMed

    Remenár, Eva; Számel, Irén; Budai, Barna; Vincze, Borbála; Gaudi, István; Gundy, Sarolta; Kásler, Miklós

    2007-01-01

    Head and neck squamous cell carcinoma (HNSCC) develops in at least 80% of cases in men with a history of smoking and heavy alcohol consumption, still it is only diagnosed in a small proportion of alcoholics. Endocrine milieu is an important factor in carcinogenesis and prognosis of several cancer types. The aim of our study was to investigate sex steroid and hypophyseal hormone status of male HNSCC patients in comparison to healthy volunteers and to patients with alcoholic liver disease, to determine possible hormonal alterations characteristic of cancer. Liver function (GGT level), and serum levels of gonadotropic hormones (FSH, LH, prolactin), sex steroids (estradiol, progesterone, testosterone) and sex hormone-binding globulin (SHBG) were compared in 130 male HNSCC patients, 54 patients with alcoholic liver disease but no known cancer, and 56 healthy controls. We found abnormal values of liver function in both HNSCC patients and alcoholics compared to healthy controls, suggesting the presence of alcoholic liver disease in the former group as well. On the other hand, a significant elevation in the level of DHEA, FSH and LH was observed in cancer patients exclusively. As a conclusion, abnormal alterations in sex steroid hormone levels can frequently be found in HNSCC patients, which may be caused in part by the alcoholic liver damage accompanying the disease. The significant increase in FSH and LH serum levels, observed only in the cancer patients, indicates that these hormones may play a role in the development and/or progression of HNSCC. PMID:18158570

  2. Reversible increase of serum activin A levels in women with Graves' disease.

    PubMed

    Centanni, M; Viceconti, N; Luisi, S; Reis, F M; Gargano, L; Maiani, F; Franchi, A; Canettieri, G; Petraglia, F

    2002-12-01

    The aim of this study was to analyze the serum levels of activin A in hyperthyroid patients with Graves' disease. Serum activin A and FSH levels were measured in a total of 93 females (64 regularly cycling and 29 post-menopausal). Of these, 20 were hyperthyroid patients with Graves disease, 33 were euthyroid goitrous patients (20 had autoimmune thyroiditis AT and 13 only had goiter) representing the internal control group and 40 were healthy subjects representing the external control group. Serum levels of activin A were higher in goitrous patients with AT than in control subjects (p=0.0388). Activin A levels were almost doubled in the cycling and in post-menopausal hyperthyroid women (0.91+/-0.21 vs 0.43+/-0.07 microg/l; p<0.0001 and 0.92+/-0.22 vs 0.48+/-0.24 microg/l; p=0.0001, respectively). In 10 cycling hyperthyroid patients, studied even after methimazole treatment, that increase was substantially reversed, once euthyroidism was attained (p=0.002). These findings indicate that thyroid function and autoimmune processes significantly affect serum levels of activin A in patients with Graves' disease. PMID:12553556

  3. Increased Mercury Levels in Patients with Celiac Disease following a Gluten-Free Regimen

    PubMed Central

    Elli, Luca; Rossi, Valentina; Conte, Dario; Ronchi, Anna; Tomba, Carolina; Passoni, Manuela; Bardella, Maria Teresa; Roncoroni, Leda; Guzzi, Gianpaolo

    2015-01-01

    Background and Aim. Although mercury is involved in several immunological diseases, nothing is known about its implication in celiac disease. Our aim was to evaluate blood and urinary levels of mercury in celiac patients. Methods. We prospectively enrolled 30 celiac patients (20 treated with normal duodenal mucosa and 10 untreated with duodenal atrophy) and 20 healthy controls from the same geographic area. Blood and urinary mercury concentrations were measured by means of flow injection inductively coupled plasma mass spectrometry. Enrolled patients underwent dental chart for amalgam fillings and completed a food-frequency questionnaire to evaluate diet and fish intake. Results. Mercury blood/urinary levels were 2.4 ± 2.3/1.0 ± 1.4, 10.2 ± 6.7/2.2 ± 3.0 and 3.7 ± 2.7/1.3 ± 1.2 in untreated CD, treated CD, and healthy controls, respectively. Resulting mercury levels were significantly higher in celiac patients following a gluten-free diet. No differences were found regarding fish intake and number of amalgam fillings. No demographic or clinical data were significantly associated with mercury levels in biologic samples. Conclusion. Data demonstrate a fourfold increase of mercury blood levels in celiac patients following a gluten-free diet. Further studies are needed to clarify its role in celiac mechanism. PMID:25802516

  4. Intra-spike crosslinking overcomes antibody evasion by HIV-1.

    PubMed

    Galimidi, Rachel P; Klein, Joshua S; Politzer, Maria S; Bai, Shiyu; Seaman, Michael S; Nussenzweig, Michel C; West, Anthony P; Bjorkman, Pamela J

    2015-01-29

    Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV's low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a "molecular ruler" to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders of magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection. PMID:25635457

  5. The colibactin warhead crosslinks DNA

    NASA Astrophysics Data System (ADS)

    Vizcaino, Maria I.; Crawford, Jason M.

    2015-05-01

    Members of the human microbiota are increasingly being correlated to human health and disease states, but the majority of the underlying microbial metabolites that regulate host-microbe interactions remain largely unexplored. Select strains of Escherichia coli present in the human colon have been linked to the initiation of inflammation-induced colorectal cancer through an unknown small-molecule-mediated process. The responsible non-ribosomal peptide-polyketide hybrid pathway encodes ‘colibactin’, which belongs to a largely uncharacterized family of small molecules. Genotoxic small molecules from this pathway that are capable of initiating cancer formation have remained elusive due to their high instability. Guided by metabolomic analyses, here we employ a combination of NMR spectroscopy and bioinformatics-guided isotopic labelling studies to characterize the colibactin warhead, an unprecedented substituted spirobicyclic structure. The warhead crosslinks duplex DNA in vitro, providing direct experimental evidence for colibactin's DNA-damaging activity. The data support unexpected models for both colibactin biosynthesis and its mode of action.

  6. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels.

    PubMed

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes. PMID:26503801

  7. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    PubMed Central

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-01-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46–212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130–160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28–48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes. PMID:26503801

  8. Ocean acidification increases the accumulation of toxic phenolic compounds across trophic levels

    NASA Astrophysics Data System (ADS)

    Jin, Peng; Wang, Tifeng; Liu, Nana; Dupont, Sam; Beardall, John; Boyd, Philip W.; Riebesell, Ulf; Gao, Kunshan

    2015-10-01

    Increasing atmospheric CO2 concentrations are causing ocean acidification (OA), altering carbonate chemistry with consequences for marine organisms. Here we show that OA increases by 46-212% the production of phenolic compounds in phytoplankton grown under the elevated CO2 concentrations projected for the end of this century, compared with the ambient CO2 level. At the same time, mitochondrial respiration rate is enhanced under elevated CO2 concentrations by 130-160% in a single species or mixed phytoplankton assemblage. When fed with phytoplankton cells grown under OA, zooplankton assemblages have significantly higher phenolic compound content, by about 28-48%. The functional consequences of the increased accumulation of toxic phenolic compounds in primary and secondary producers have the potential to have profound consequences for marine ecosystem and seafood quality, with the possibility that fishery industries could be influenced as a result of progressive ocean changes.

  9. Sea-level Rise Increases the Frequency of Nuisance Flooding in Coastal Regions

    NASA Astrophysics Data System (ADS)

    Moftakhari Rostamkhani, H.; Aghakouchak, A.; Sanders, B. F.; Feldman, D.; Sweet, W.; Matthew, R.; Luke, A.

    2015-12-01

    The global warming-drivensea-level rise (SLR) posesa serious threat for population and assets in flood-prone coastal zones over the next century. The rate of SLR is accelerated in recent decades and is expected to increase based on current trajectories of anthropogenic activities and greenhouse gas emissions. Over the 20th century, an increase in the frequency of nuisance (minor) flooding has been reported due to the reduced gap between tidal datum and flood stage. Nuisance flooding (NF), however non-destructive, causes public inconvenience, business interruption, and substantial economic losses due to impacts such as road closures and degradation of infrastructure. It also portends an increased risk in severe floods. Here we report substantial increases in NF along the coasts of United States due to SLR over the past decades. We then take the projected SLR under the least and the most extreme representative concentration pathways (e.gRCP2.6 and RCP 8.5) to estimate the increase in NF in the near- (2030) and mid-term (2050) future. The results suggest that projected SLR will cause up to two-fold more frequent NF by 2050, compared with the 20th century. The projected increase in NF will have significant socio-economic impacts and pose public health risks especially in rapidly urbanized coastal regions.

  10. TBT-induced imposex in marine neogastropods is mediated by an increasing androgen level

    NASA Astrophysics Data System (ADS)

    Bettin, C.; Oehlmann, J.; Stroben, E.

    1996-09-01

    Tributyltin (TBT) exposure at different concentrations (5, 60, and 100 ng TBT as Sn/l) induces a concentration- and time-dependent imposex (=pseudohermaphroditism) development in female Nucella lapillus and Hinia reticulata. In both species the average imposex stage, termed as vas deferens sequence (VDS) index, and the average female penis length increases with increasing TBT concentration and duration of TBT exposure. Testosterone added at a concentration of 500 ng/l induces a faster and more intensive imposex development compared to that induced by the TBT concentrations used in the present experiments. Radioimmunological determination of endogenous steroid content reveals increasing testosterone titres in female gastropods exposed to TBT which correlate with the TBT concentration used and the duration of the experiment. The most marked and highest increase of the endogenous testosterone level is exhibited by females, of both species exposed to testosterone. Simulataneous exposure to TBT and to the antiandrogen cyproterone acetate which suppresses imposex development completely in N. lapillus and reduces imposex development strongly in H. reticulata proves that the imposex-inducing effects of TBT are mediated by an increasing androgen level and are not caused directly by the organotin compound itself. Further-more, TBT-induced imposex development can be suppressed in both snails by adding estrogens to the aqueous medium. These observations suggest that TBT causes an inhibition of the cytochrome P-450 dependent aromatase system which catalyses the aromatization of androgens to estrogens. The increase of the androgen content or the shift of the androgen-estrogen balance in favour of androgens induces the development of pseudohermaphroditism in marine prosobranchs. Artificial inhibition of the cytochrome P-450 dependent aromatase system using SH 489 (1-methyl-1,4-androstadiene-3,17-dione) as a steroidal aromatase inhibitor and flavone as a nonsteroidal aromatase

  11. Sympathetic arousal increases a negative memory bias in young women with low sex hormone levels.

    PubMed

    Nielsen, Shawn E; Barber, Sarah J; Chai, Audrey; Clewett, David V; Mather, Mara

    2015-12-01

    Emotionally arousing events are typically better attended to and remembered than neutral ones. Current theories propose that arousal-induced increases in norepinephrine during encoding bias attention and memory in favor of affectively salient stimuli. Here, we tested this hypothesis by manipulating levels of physiological arousal prior to encoding and examining how it influenced memory for emotionally salient images, particularly those that are negative rather than positive in valence. We also tested whether sex steroid hormones interact with noradrenergic activity to influence these emotional memory biases in women. Healthy naturally cycling women and women on hormonal contraception completed one of the following physiological arousal manipulations prior to viewing a series of negative, positive and neutral images: (1) immediate handgrip arousal-isometric handgrip immediately prior to encoding, (2) residual handgrip arousal-isometric handgrip 15min prior to encoding, or (3) no handgrip. Sympathetic arousal was measured throughout the session via pupil diameter changes. Levels of 17β-estradiol and progesterone were measured via salivary samples. Memory performance was assessed approximately 10min after encoding using a surprise free recall test. The results indicated that handgrip successfully increased sympathetic arousal compared to the control task. Under immediate handgrip arousal, women showed enhanced memory for negative images over positive images; this pattern was not observed in women assigned to the residual and no-handgrip arousal conditions. Additionally, under immediate handgrip arousal, both high estradiol and progesterone levels attenuated the memory bias for negative over positive images. Follow-up hierarchical linear models revealed consistent effects when accounting for trial-by-trial variability in normative International Affective Picture System valence and arousal ratings. These findings suggest that heightened sympathetic arousal interacts

  12. Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers.

    PubMed

    Politis, Marios; Lahiri, Nayana; Niccolini, Flavia; Su, Paul; Wu, Kit; Giannetti, Paolo; Scahill, Rachael I; Turkheimer, Federico E; Tabrizi, Sarah J; Piccini, Paola

    2015-11-01

    Previous studies have shown activation of the immune system and altered immune response in Huntington's disease (HD) gene carriers. Here, we hypothesized that peripheral and central immune responses could be concurrent pathophysiological events and represent a global innate immune response to the toxic effects of mutant huntingtin in HD gene carriers. We sought to investigate our hypothesis using [(11)C]PK11195 PET as a translocator protein (TSPO) marker of central microglial activation, together with assessment of peripheral plasma cytokine levels in a cohort of premanifest HD gene carriers who were more than a decade from predicted symptomatic conversion. Data were also compared to those from a group of healthy controls matched for age and gender. We found significantly increased peripheral plasma IL-1β levels in premanifest HD gene carriers compared to the group of normal controls (P=0.018). Premanifest HD gene carriers had increased TSPO levels in cortical, basal ganglia and thalamic brain regions (P<0.001). Increased microglial activation in somatosensory cortex correlated with higher plasma levels of IL-1β (rs=0.87, P=0.013), IL-6 (rs=0.85, P=0.013), IL-8 (rs=0.68, P=0.045) and TNF-α (rs=0.79; P=0.013). Our findings provide first in vivo evidence for an association between peripheral and central immune responses in premanifest HD gene carriers, and provide further supporting evidence for the role of immune dysfunction in the pathogenesis of HD. PMID:26297319

  13. Role of Transglutaminase 2 in Liver Injury via Cross-linking and Silencing of Transcription Factor Sp1

    PubMed Central

    TATSUKAWA, HIDEKI; FUKAYA, YAYOI; FRAMPTON, GORDON; MARTINEZ–FUENTES, ANTONIO; SUZUKI, KENJI; KUO, TING–FANG; NAGATSUMA, KEISUKE; SHIMOKADO, KENTARO; OKUNO, MASATAKA; WU, JIAN; IISMAA, SIIRI; MATSUURA, TOMOKAZU; TSUKAMOTO, HIDEKAZU; ZERN, MARK A.; GRAHAM, ROBERT M.; KOJIMA, SOICHI

    2016-01-01

    Background & Aims Despite high morbidity and mortality of alcoholic liver disease worldwide, the molecular mechanisms underlying alcohol-induced liver cell death are not fully understood. Transglutaminase 2 (TG2) is a cross-linking enzyme implicated in apoptosis. TG2 levels and activity are increased in association with various types of liver injury. However, how TG2 induces hepatic apoptosis is not known. Methods Human hepatic cells or primary hepatocytes from rats or TG2+/+ and TG2−/− mice were treated with ethanol. Mice were administered anti-Fas antibody or alcohol. Liver sections were prepared from patients with alcoholic steatohepatitis. Changes in TG2 levels, Sp1 cross-linking and its activities, expression of hepatocyte growth factor receptor, c-Met, and hepatic apoptosis were measured. Results Ethanol induced apoptosis in hepatic cells, enhanced activity and nuclear accumulation of TG2 as well as accumulation of cross-linked and inactivated Sp1, and reduced expression of the Sp1-responsive gene, c-Met. These effects were rescued by TG2 knockdown, restoration of functional Sp1, or addition of hepatocyte growth factor, whereas apoptosis was reproduced by Sp1 knockdown or TG2 overexpression. Compared with TG2+/+ mice, TG2−/− mice showed markedly reduced hepatocyte apoptosis and Sp1 cross-linking following ethanol or anti-Fas treatment. Treatment of TG2+/+ mice with the TG2 inhibitors putrescine or cystamine blocked anti-Fas–induced hepatic apoptosis and Sp1 silencing. Moreover, enhanced expression of cross-linked Sp1 and TG2 was evident in hepatocyte nuclei of patients with alcoholic steatohepatitis. Conclusions TG2 induces hepatocyte apoptosis via Sp1 cross-linking and inactivation, with resultant inhibition of the expression of c-Met required for hepatic cell viability. PMID:19208340

  14. Novel psychoactive benzofurans strongly increase extracellular serotonin level in mouse corpus striatum.

    PubMed

    Fuwa, Tatsu; Suzuki, Jin; Tanaka, Toyohito; Inomata, Akiko; Honda, Yoshiko; Kodama, Tohru

    2016-01-01

    We examined the effects of three benzofurans [1-(Benzofuran-5-yl)-N-methylpropan-2-amine (5-MAPB), 1-(Benzofuran-2-yl)-N-methylpropan-2-amine (2-MAPB), and 1-(Benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB)] on the extracellular monoamine level in mouse corpus striatum by the microdialysis method and compared them with the effects of psychoactive 3,4-Methylenedioxymethamphetamine (MDMA). The effects of benzofurans on the extracellular monoamine level were qualitatively analogous to that of MDMA, with an increase in serotonin (5-HT) level exceeding dopamine (DA) level. The effects of 2-MAPB and 5-EAPB were almost the same as the effect of MDMA. However, 5-MAPB strongly increased extracellular monoamine level than MDMA. These differences in the potency appear to have a structure-activity relationship. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) resulted in the death of two-thirds of the mice. The same dose of MDMA did not cause any deaths. The administration of 5-MAPB (1.6 × 10(-4) mol/kg B.W.) produced a 3.41°C ± 0.28°C rise in rectal temperature after 1 hr, whereas the administration of MDMA (1.6 × 10(-4) mol/kg B.W.) produced an approximate 1.85°C ± 0.26°C rise. These results suggest that benzofurans have 5-HT toxicity similar to MDMA, and 5-MAPB has a higher risk of lethal intoxication than MDMA. Furthermore, 5-APB, the metabolic product of 5-MAPB demethylation, may be involved in the acute 5-HT toxicity and may cause lethal intoxication in mice. PMID:27193726

  15. Increased serum gamma-glutamyltransferase levels are associated with ventricular instability in type 2 diabetes.

    PubMed

    Wang, Kun; Li, Ling; Wu, Yang; Yang, Yu; Chen, Jie; Zhang, Danyu; Liu, Zhoujun; Xu, Juan; Cao, Meng; Mao, Xiaodong; Liu, Chao

    2016-04-01

    The purpose of our study is to examine the association between serum GGT levels and ventricular instability in Chinese patients with T2DM. We conducted a cross-sectional, community-based study in Nanjing, China from June to November 2011. Among 10,050 patients aged 40-79 years, we enrolled 2444 with pre-diabetes, 2496 with T2DM, and 4521 without diabetes (non-diabetes). Electrocardiograms were performed to measure the QT interval corrected for heart rate (QTc) and QT interval dispersion (QTd). Serum GGT levels, metabolic parameters, body mass index, and blood pressure were also measured. We found that there were no significant associations of increased QTc/QTd with serum GGT levels in participants with pre-existing T2DM and non-diabetes, after adjusting for age, duration of diabetes, and metabolic parameters. Even after adjustment, higher risks of QTc ≥ 440 ms/√s and QTd ≥ 58 ms were found in participants with serum GGT levels ≥49 U/L compared with those with <15 U/L in the pre-diabetes (QTc: OR 1.96, 95 % CI 1.23-2.47; QTd: OR 1.34, 95 % CI 1.07-1.94) and newly diagnosed T2DM (QTc: OR 2.01, 95 % CI 1.39-2.51; QTd: OR 1.53, 95 % CI 1.03-1.99) groups. We conclude that Increased serum GGT levels are associated with some markers of ventricular repolarization abnormalities in the early stage of T2DM. PMID:26433737

  16. Increased levels of phosphoinositides cause neurodegeneration in a Drosophila model of amyotrophic lateral sclerosis

    PubMed Central

    Forrest, Stuart; Chai, Andrea; Sanhueza, Mario; Marescotti, Manuela; Parry, Katherine; Georgiev, Atanas; Sahota, Virender; Mendez-Castro, Raquel; Pennetta, Giuseppa

    2013-01-01

    The Vesicle-associated membrane protein (VAMP)-Associated Protein B (VAPB) is the causative gene of amyotrophic lateral sclerosis 8 (ALS8) in humans. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective death of motor neurons leading to spasticity, muscle atrophy and paralysis. VAP proteins have been implicated in various cellular processes, including intercellular signalling, synaptic remodelling, lipid transport and membrane trafficking and yet, the molecular mechanisms underlying ALS8 pathogenesis remain poorly understood. We identified the conserved phosphoinositide phosphatase Sac1 as a Drosophila VAP (DVAP)-binding partner and showed that DVAP is required to maintain normal levels of phosphoinositides. Downregulating either Sac1 or DVAP disrupts axonal transport, synaptic growth, synaptic microtubule integrity and the localization of several postsynaptic components. Expression of the disease-causing allele (DVAP-P58S) in a fly model for ALS8 induces neurodegeneration, elicits synaptic defects similar to those of DVAP or Sac1 downregulation and increases phosphoinositide levels. Consistent with a role for Sac1-mediated increase of phosphoinositide levels in ALS8 pathogenesis, we found that Sac1 downregulation induces neurodegeneration in a dosage-dependent manner. In addition, we report that Sac1 is sequestered into the DVAP-P58S-induced aggregates and that reducing phosphoinositide levels rescues the neurodegeneration and suppresses the synaptic phenotypes associated with DVAP-P58S transgenic expression. These data underscore the importance of DVAP–Sac1 interaction in controlling phosphoinositide metabolism and provide mechanistic evidence for a crucial role of phosphoinositide levels in VAP-induced ALS. PMID:23492670

  17. Effect of modified starch and nanoclay particles on biodegradability and mechanical properties of cross-linked poly lactic acid.

    PubMed

    Shayan, M; Azizi, H; Ghasemi, I; Karrabi, M

    2015-06-25

    Mechanical properties and biodegradation of cross-linked poly(lactic acid) (PLA)/maleated thermoplastic starch (MTPS)/montmorillonite (MMT) nanocomposite were studied. Crosslinking was carried out by adding di-cumyl peroxide (DCP) in the presence of triallyl isocyanurate (TAIC) as coagent. At first, MTPS was prepared by grafting maleic anhydride (MA) to thermoplastic starch in internal mixer. Experimental design was performed by using Box-Behnken method at three variables: MTPS, nanoclay and TAIC at three levels. Results showed that increasing TAIC amount substantially increased the gel fraction, enhanced tensile strength, and caused a decrease in elongation at break. Biodegradation was prevented by increasing TAIC amount in nanocomposite. Increasing MTPS amount caused a slight increase in gel fraction and decreased the tensile strength of nanocomposite. Also, MTPS could increase the elongation at break of nanocomposite and improve the biodegradation. Nanoclay had no effect on the gel fraction, but it improved tensile strength. PMID:25839817

  18. Dynamics of Actively Driven Crosslinked Microtubule Networks

    NASA Astrophysics Data System (ADS)

    Yadav, Vikrant; Stanhope, Kasimira; Evans, Arthur A.; Ross, Jennifer L.

    We have designed a model experiment to explore dynamics of crosslinked active microtubule clusters crosslinked with MAP65. Microtubule clusters are allowed to settle on a slide coated with kinesin-1 molecular motors, which move microtubules. We systematically tune either concentration of cross linkers bound to microtubule (ρc) or the global concentration of microtubules (ρMT) . We quantified the shape of the cluster by measuring the standard deviation (σ) of the cluster outline. At low ρMTor ρc the network is in an expanding state. At higher ρMTor ρc expansion slows down, reaches zero at a critical density, and become negative indicating contraction. Further increase of ρMTor ρc halts any kind of dynamics. The ρMT-ρc phase space shows distinct regions of extensile, contractile and static regimes. We model these results using active hydrodynamic theory. Microtubules are modeled as active rods whereas effect of crosslinkers is modeled using a collision term that prefers anti-parallel alignment of microtubules. A linearized analysis of hydrodynamic equation predicts existence of density driven expanding, contracting, and static phases for microtubule clusters.

  19. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux

    PubMed Central

    Patterson, Robert N; Johnston, Brian T; Ardill, Joy E S; Heaney, Liam G; McGarvey, Lorcan P A

    2007-01-01

    Background Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally‐mediated oesophageal‐tracheobronchial reflex with airway sensory nerve activation and tachykinin release. Aim To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux. Methods Thirty‐two patients with airways disease (16 with mild asthma and 16 non‐asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH <4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and α2‐macroglobulin were determined. Results SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p = 0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p = 0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p = 0.035; NKA: median (interquartile range 108 (85–120) pg/ml vs 75 (2–98) pg/ml, p = 0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r = 0.59, p = 0.01) and NKA levels (r = 0.56, p = 0.02). Non‐significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p = 0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p = 0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. Conclusion This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with

  20. Longer-term increased cortisol levels in young people with mental health problems

    PubMed Central

    Heinze, Kareen; Lin, Ashleigh; Reniers, Renate L.E.P.; Wood, Stephen J.

    2016-01-01

    Disturbance of hypothalamus–pituitary–adrenal axis activity is commonly reported in a range of mental disorders in blood, saliva and urine samples. This study aimed to look at longer-term cortisol levels and their association with clinical symptoms. Hair strands of 30 young people (16–25 years) presenting with mental health problems (Mage±SD=21±2.4, 26 females) and 28 healthy controls (HC, Mage±SD=20±2.9, 26 females) were analyzed for cortisol concentrations, representing the past 6 months prior to hair sampling. Clinical participants completed an assessment on psychiatric symptoms, functioning and lifestyle factors. All participants completed the Perceived Stress Scale. Hair cortisol concentrations representing the past 3 (but not 3–6) months were significantly increased in clinical participants compared to HC. Perceived stress in the past month was significantly higher in clinical participants compared to HC, but not significantly correlated with hair cortisol. Hair cortisol levels were not significantly associated with any other measures. Hair segment analyses revealed longer-term increased levels of cortisol in the past 3 months in early mental health problems. Further insight into the role of cortisol on the pathogenesis of mental illnesses requires longitudinal studies relating cortisol to psychopathology and progression of illness. PMID:26749569

  1. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  2. Cysteamine-related agents could be potential antidepressants through increasing central BDNF levels.

    PubMed

    Tsai, Shih-Jen

    2006-01-01

    Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application. PMID:16797865

  3. Naloxone-precipitated morphine withdrawal increases pontine glutamate levels in the rat.

    PubMed

    Zhang, T; Feng, Y; Rockhold, R W; Ho, I K

    1994-01-01

    Extracellular fluid (ECF) levels of glutamate (Glu) and aspartate (Asp) were measured in the locus coeruleus (LC) during morphine withdrawal by using microdialysis in conscious morphine-dependent Sprague-Dawley rats. Guide cannulae were implanted chronically and rats were given intracerebroventricular (i.c.v.) infusions of morphine (26 nmol/1 microliters/hr) or saline (1 microliters/hr) for 3 days. Microdialysis probes (2 mm tip) were inserted into the LC 24 hr before precipitation of withdrawal by i.c.v. injection of naloxone (12 or 48 nmol/5 microliters). Behavioral evidence of withdrawal (teeth-chattering, wet-dog shakes, etc.) was detected following naloxone challenge in morphine, but not in saline-infused rats. Increases (P < 0.01) in ECF levels of Glu (and Asp, to a lesser degree) were noted after naloxone-precipitated withdrawal only in the morphine group. The ECF Glu levels in the LC increased from 9.6 +/- 2.7 to 15.5 +/- 5.0 microM following 12 nmol/5 microliters naloxone, and from 9.5 +/- 1.9 to 20.5 +/- 3.3 microM following 48 nmol/5 microliters naloxone, before and in the first 15 min sample after the precipitation of withdrawal in the morphine-dependent rats, respectively. These results provide direct evidence to support the role of excitatory amino acids within the LC in morphine withdrawal. PMID:7912397

  4. Cadmium-induced cell killing in Sacharomyces cerevisiae involves increases in intracellular NO levels.

    PubMed

    Wu, Lihua; Chen, Yanfei; Gao, Huixian; Yin, Jingjing; Huang, Liqun

    2016-03-01

    Cadmium is a widespread environmental pollutant and poses some potential risks to human health. However, the signaling events controlling cadmium toxicity are not fully understood. In this study, we examined the effect of cadmium chloride on cell viability and the intracellular nitric oxide (NO) level in yeast cells. The results showed that exposure of yeast cells to cadmium (0-100 μM) could induce cell killing with significantly increased intracellular NO levels. Morphological analysis of the nuclei with 4('),6-diamidino-2-phenylindole staining and DNA strand breaks analysis showed that cadmium at 50 μM can induce cell apoptosis in yeast cells. Treatment of yeast cells with cadmium (50 μM) and the nitric oxide scavenger c-PTIO [2-(4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-1-oxyl-3-oxide; 0.2 mM] showed that c-PTIO attenuated the cadmium-induced cell killing. Our findings indicated that cadmium-induced yeast cell killing is mediated by a directly increased intracellular NO level. PMID:26872495

  5. Dietary whey protein hydrolysates increase skeletal muscle glycogen levels via activation of glycogen synthase in mice.

    PubMed

    Kanda, Atsushi; Morifuji, Masashi; Fukasawa, Tomoyuki; Koga, Jinichiro; Kanegae, Minoru; Kawanaka, Kentaro; Higuchi, Mitsuru

    2012-11-14

    Previously, we have shown that consuming carbohydrate plus whey protein hydrolysates (WPHs) replenished muscle glycogen after exercise more effectively than consuming intact whey protein or branched-chain amino acids (BCAAs). The mechanism leading to superior glycogen replenishment after consuming WPH is unclear. In this 5 week intervention, ddY mice were fed experimental diets containing WPH, a mixture of whey amino acids (WAAs), or casein (control). After the intervention, gastrocnemius muscle glycogen levels were significantly higher in the WPH group (4.35 mg/g) than in the WAA (3.15 mg/g) or control (2.51 mg/g) groups. In addition, total glycogen synthase (GS) protein levels were significantly higher in the WPH group (153%) than in the WAA (89.2%) or control groups, and phosphorylated GS levels were significantly decreased in the WPH group (51.4%). These results indicate that dietary WPH may increase the muscle glycogen content through increased GS activity. PMID:23113736

  6. Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia.

    PubMed

    Strømmen, Kenneth; Lyche, Jan Ludvig; Blakstad, Elin Wahl; Moltu, Sissel Jennifer; Veierød, Marit Bragelien; Almaas, Astrid Nylander; Sakhi, Amrit Kaur; Thomsen, Cathrine; Nakstad, Britt; Brække, Kristin; Rønnestad, Arild Erlend; Drevon, Christian André; Iversen, Per Ole

    2016-01-01

    Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219. PMID:26922148

  7. Cross-linking and the molecular packing of corneal collagen

    NASA Technical Reports Server (NTRS)

    Yamauchi, M.; Chandler, G. S.; Tanzawa, H.; Katz, E. P.

    1996-01-01

    We have quantitatively characterized, for the first time, the cross-linking in bovine cornea collagen as a function of age. The major iminium reducible cross-links were dehydro-hydroxylysinonorleucine (deH-HLNL) and dehydro-histidinohydroxymerodesmosine (deH-HHMD). The former rapidly diminished after birth; however, the latter persisted in mature animals at a level of 0.3 - 0.4 moles/mole of collagen. A nonreducible cross-link, histidinohydroxylysinonorleucine (HHL), previously found only in skin, was also found to be a major mature cross-link in cornea. The presence of HHL indicates that cornea fibrils have a molecular packing similar to skin collagen. However, like deH-HHMD, the HHL content in corneal fibrils only reaches a maximum value with time about half that of skin. These data suggest that the corneal fibrils are comprised of discrete filaments that are internally stabilized by HHL and deH-HHMD cross-links. This pattern of intermolecular cross-linking would facilitate the special collagen swelling property required for corneal transparency.

  8. Increased Blood Lactate Level Deteriorates Running Economy in World Class Endurance Athletes.

    PubMed

    Hoff, Jan; Støren, Øyvind; Finstad, Arnstein; Wang, Eivind; Helgerud, Jan

    2016-05-01

    Hoff, J, Støren, Ø, Finstad, A, Wang, E, and Helgerud, J. Increased blood lactate level deteriorates running economy in world class endurance athletes. J Strength Cond Res 30(5): 1373-1378, 2016-Blood lactate accumulation is associated with development of muscle fatigue and negatively correlated to endurance performance. No research has quantified the effects of lactate presence at moderate levels of lactate accumulation. The purpose of this study was to test whether 2 moderate blood lactate concentration levels affect running economy (RE) when running at the individual lactate threshold (LT). Seven male world class endurance athletes with an average V[Combining Dot Above]O2max of 80.7 ± 2.7 ml·kg·min or 5.8 ± 0.5 L·min participated in this study. After the V[Combining Dot Above]O2max test, the subjects were resting or walking and in a random order tested for RE at their LT velocity when the blood lactate level reached either 3 mmol·L or 5 mmol·L. After a new 5-minute exercising period at maximal aerobic velocity, the crossover lactate value RE testing was performed. Running economy was significantly (p ≤ 0.05) deteriorated from 0.668 ± 0.044 to 0.705 ± 0.056 ml·kg·m or 5.5% (p ≤ 0.05) for blood lactate level of 3 mmol·L compared with 5 mmol·L, respectively. Increased lactate level from 3 to 5 mmol·L is thus accompanied by deteriorated RE at LT running velocity. The deteriorated RE at moderate levels of lactate concentration emphasizes the importance of avoiding intensities above LT in the early parts of a dominantly aerobic endurance competition. It also emphasizes the importance of a high V[Combining Dot Above]O2max for aerobic endurance athletes and may partly explain the V[Combining Dot Above]O2 slow component as impaired RE. PMID:26817745

  9. Increase California-Oregon Coastal Summer Sea Level Fog from 1950 to 2007

    NASA Astrophysics Data System (ADS)

    Dorman, C. E.

    2015-12-01

    An analysis is presented of the marine fog distribution based upon the International Comprehensive Ocean-Atmosphere Data Set (ICOADS) ship observations taken during 1950-2007. Deep fog occurrence is reported in routine weather reports that are encoded in an ICOADS ship observation. Occurrence is estimated by the number of deep fog observations divided by the total present weather observations in a one-degree area centered on latitude and longitude grid point intersections. The mean fog occurrence for the summer (June-July-August) 1950-2007 was computed for each one degree point. There is a long term, deep fog occurrence maximum on the California-Oregon coast with its highest value of 16.6 % at 38° N 123° W. This fog maximum is coincident with coldest June-July-August sea surface temperatures (SST) along the coast. To compute annual averages of the maximum, a block average was based on the 19 over water grid points with the deep fog occurrences generally greater than 0.6 times the highest long term maximum value that extended along the California-Oregon coast from 37° N to 44° N. The June-July-August block averaged, annual value computed for each of the 58 summers for the period 1950-2007 has a distinct positive trend. A line fitted to the data has a deep fog percent occurrence increase of +7.4 % from 1950 through 2007 or a trend of +0.13 % per year. The Mann-Kendall test was applied and the trend is significant at the 0.05 level. The increase in long term coastal fog is coincident with a decrease in the California-Oregon coastal SST. The SST decrease is consistent with interior California land temperatures increasing, increasing the cross shore sea level pressure gradient, and increasing the along coast winds creating a positive feedback that causes more upwelling and lower SST.

  10. Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

    PubMed Central

    Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

    2012-01-01

    It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

  11. Injected tryptophan increases brain but not plasma tryptophan levels more in ethanol treated rats

    SciTech Connect

    Haleem, D.J. )

    1990-01-01

    In the present study ethanol treatment given for two weeks decreased hepatic apo-tryptophan pyrrolase but not total tryptophan pyrrolase activity in rats. Tryptophan levels in plasma and brain did not increase significantly. But there was a marked increase of 5-HT but not 5-hydroxyindoleacetic acid (5-HIAA) concentration in brain, suggesting a possible increase in the activity of tryptophan hydroxylase. The effect of a tryptophan load on brain 5-HT metabolism was therefore compared in controls and ethanol treated rats. One hour after tryptophan injection plasma concentrations of total and free tryptophan were identical in controls and ethanol treated rats, but the increases of brain tryptophan 5-HT and 5-HIAA were considerably greater in the latter group. The results are consistent with long term ethanol treatment enhancing brain serotonin metabolism and show that brain uptake/utilization of exogenous tryptophan is increased in ethanol treated rats and may be useful to understand the role and possible mechanism of tryptophan/serotonin involvement in mood regulation.

  12. Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome.

    PubMed

    Jenkins, E C; Schupf, N; Genovese, M; Ye, L L; Kapell, D; Canto, B; Harris, M; Devenny, D; Lee, J H; Brown, W T

    1997-01-20

    During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21. PMID:9028448

  13. Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome

    SciTech Connect

    Jenkins, E.C.; Genovese, M.; Ye, Ling Ling

    1997-01-20

    During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes {open_quotes}low-level{close_quotes} mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21. 30 refs., 5 tabs.

  14. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    DOE PAGESBeta

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized.more » Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.« less

  15. Local increase level of chondroitin sulfate induces changes in the rhombencephalic neural crest migration.

    PubMed

    Moro Balbás, J A; Gato, A; Alonso, M; Barbosa, E

    1998-03-01

    Numerous studies suggest that chondroitin sulfate proteoglycan (CSPG) inhibits neural crest cells (NCC) migration at the trunk level. However, its action on the cephalic neural crest is not clear. To determine this action, we have microinjected 0.5 nl of different concentrations of chondroitin sulfate (CS) at the anterior rhombencephalon level in 9 stage chick embryos, as well as subgerminally administering beta-D-xyloside to 8 stage chick embryos. Beta-D-xyloside disrupts CSPG synthesis, producing an increase in CS free chains in several embryonal anlages. Chondroitin sulfate microinjected embryos and beta-D xyloside treated embryos were reincubated until attaining 12 stage. Results obtained for both experimental groups were similar. Immunoreactivity with HNK-1 antibody revealed that NCC did not migrate, remaining near the rhombencephalon dorsal wall; in addition, several NCC did not separate from the neural fold, becoming invaginated towards the rhombencephalon cavity. Our findings indicate that an increase in CS free chains in cephalic neural crest migratory routes not only disrupts their migration, but also impedes delamination and detachment of the rhombencephalic neuroepithelium NCC. These data suggest that the inhibitory action upon the neural crest migration attributed to CSPG may rest on its glycosaminoglycan (GAG). We cannot, however, rule out the possibility that increases in other GAGs apart from CS, may produce similar effects on neural crest migration. PMID:9551866

  16. Towards increased waste loading in high level waste glasses: Developing a better understanding of crystallization behavior

    SciTech Connect

    Marra, James C.; Kim, Dong -Sang

    2014-12-18

    A number of waste components in US defense high level radioactive wastes (HLW) have proven challenging for current Joule heated ceramic melter (JCHM) operations and have limited the ability to increase waste loadings beyond already realized levels. Many of these ''troublesome'' waste species cause crystallization in the glass melt that can negatively impact product quality or have a deleterious effect on melter processing. Thus, recent efforts at US Department of Energy laboratories have focused on understanding crystallization behavior within HLW glass melts and investigating approaches to mitigate the impacts of crystallization so that increases in waste loading can be realized. Advanced glass formulations have been developed to highlight the unique benefits of next-generation melter technologies such as the Cold Crucible Induction Melter (CCIM). Crystal-tolerant HLW glasses have been investigated to allow sparingly soluble components such as chromium to crystallize in the melter but pass out of the melter before accumulating. The Hanford site AZ-101 tank waste composition represents a waste group that is waste loading limited primarily due to high concentrations of Fe2O3 (with higher Al2O3). Systematic glass formulation development utilizing slightly higher process temperatures and higher tolerance to spinel crystals demonstrated that an increase in waste loading of more than 20% could be achieved for this waste composition, and by extension higher loadings for wastes in the same group.

  17. IL-33 circulating serum levels are increased in patients with non-segmental generalized vitiligo.

    PubMed

    Vaccaro, Mario; Cicero, Francesca; Mannucci, Carmen; Calapai, Gioacchino; Spatari, Giovanna; Barbuzza, Olga; Cannavò, Serafinella P; Gangemi, Sebastiano

    2016-09-01

    IL-33 is a recently identified cytokine, encoded by the IL-33 gene, which is a member of the IL-1 family that drives the production of T-helper-2 (Th-2)-associated cytokines. Serum levels of IL-33 have been reported to be up-regulated in various T-helper (Th)-1/Th-17-mediated diseases, such as psoriasis, rheumatoid arthritis, and inflammatory bowel. To investigate whether cytokine imbalance plays a role in the pathogenesis of vitiligo, we performed a case-control association study by enzyme-linked immunosorbent assay of IL-33 in our patients. IL-33 serum levels were measured by a quantitative enzyme immunoassay technique in patients with non-segmental generalized vitiligo and compared with those of healthy controls. IL-33 serum levels in patients with vitiligo were significantly increased than those in healthy controls. There was a positive correlation of IL-33 serum levels with extension of vitiligo and disease activity. This study suggests a possible systemic role of IL-33 in the pathogenesis of vitiligo. Inhibiting IL-33 activity might be a novel therapeutic strategy in the treatment of autoimmune inflammatory disease, like vitiligo. PMID:27388717

  18. Increased Gustatory Response Score in Obesity and Association Levels with IL-6 and Leptin

    PubMed Central

    Remla, Nesrine; Hadjidj, Zeyneb; Ghezzaz, Kamel; Moulessehoul, Soraya; Aribi, Mourad

    2016-01-01

    Background. The aim of this study was to investigate the relationship between the circulating IL-6 and leptin levels with taste alteration in young obese patients. Methods. A retrospective case-control study was conducted in thirty obese patients and thirty age- and sex-matched healthy controls. Results. Circulating levels of IL-6 and leptin were significantly increased in obese patients than in controls. However, catalase and ORAC levels were significantly decreased in obese patients compared to controls. Additionally, obese participants had high scores for the detection of fats (gustatory response scores [GRS]; p < 0.001). Moreover, IL-6 and leptin were strongly associated with GRS alteration among patients with GRS 4 (resp., OR =17.5 [95% CI, 1.56–193.32; p = 0.007]; OR = 16 [95% CI, 1.69–151.11; p = 0.006]). For the Mantel-Haenszel common odds ratio estimate (MH OR), IL-6 and leptin were strongly associated with obesity, in patients with either GRS 4 or GRS > 4 (resp., MH OR = 8.77 [95% CI, 2.06–37.44; p = 0.003]; MH OR = 5.76 [95% CI, 1.64–20.24; p = 0.006]). Conclusions. In a low grade inflammation linked to obesity, taste alteration is associated with high levels of IL-6 and leptin. PMID:27413547

  19. Steroid injection for shoulder pain causes prolonged increased glucose level in type 1 diabetics

    PubMed Central

    Povlsen, Bo; Povlsen, Sebastian D

    2014-01-01

    Shoulder pain is very common in diabetic patients and often treated with steroid injections, with subsequent increases in blood glucose levels or the need for additional insulin being questioned. We report a case of significant and prolonged elevation of blood glucose levels and resultant insulin requirement in a type 1 diabetic man after a single 40 mg injection of triamcinolone for shoulder pain. Within 48 h, the shoulder pain as assessed by a visual analogue scale (0–10) was reduced to zero, but the elevated insulin requirements continued for 4 weeks after the injection. This finding suggests that steroid injections for shoulder pain in diabetics may not always be as safe as previously thought. We propose that medical practitioners advise their patients to monitor their glucose levels more carefully after such injections and that caution is exercised when considering administrating these injections to those who have poorly controlled blood glucose levels preinjection to avoid ketoacidosis. PMID:25199186

  20. Bothrops jararaca Venom Metalloproteinases Are Essential for Coagulopathy and Increase Plasma Tissue Factor Levels during Envenomation

    PubMed Central

    Yamashita, Karine M.; Alves, André F.; Barbaro, Katia C.; Santoro, Marcelo L.

    2014-01-01

    Background/Aims Bleeding tendency, coagulopathy and platelet disorders are recurrent manifestations in snakebites occurring worldwide. We reasoned that by damaging tissues and/or activating cells at the site of the bite and systemically, snake venom toxins might release or decrypt tissue factor (TF), resulting in activation of blood coagulation and aggravation of the bleeding tendency. Thus, we addressed (a) whether TF and protein disulfide isomerase (PDI), an oxireductase involved in TF encryption/decryption, were altered in experimental snake envenomation; (b) the involvement and significance of snake venom metalloproteinases (SVMP) and serine proteinases (SVSP) to hemostatic disturbances. Methods/Principal Findings Crude Bothrops jararaca venom (BjV) was preincubated with Na2-EDTA or AEBSF, which are inhibitors of SVMP and SVSP, respectively, and injected subcutaneously or intravenously into rats to analyze the contribution of local lesion to the development of hemostatic disturbances. Samples of blood, lung and skin were collected and analyzed at 3 and 6 h. Platelet counts were markedly diminished in rats, and neither Na2-EDTA nor AEBSF could effectively abrogate this fall. However, Na2-EDTA markedly reduced plasma fibrinogen consumption and hemorrhage at the site of BjV inoculation. Na2-EDTA also abolished the marked elevation in TF levels in plasma at 3 and 6 h, by both administration routes. Moreover, increased TF activity was also noticed in lung and skin tissue samples at 6 h. However, factor VII levels did not decrease over time. PDI expression in skin was normal at 3 h, and downregulated at 6 h in all groups treated with BjV. Conclusions SVMP induce coagulopathy, hemorrhage and increased TF levels in plasma, but neither SVMP nor SVSP are directly involved in thrombocytopenia. High levels of TF in plasma and TF decryption occur during snake envenomation, like true disseminated intravascular coagulation syndrome, and might be implicated in engendering

  1. Increased Complement C1q Level Marks Active Disease in Human Tuberculosis

    PubMed Central

    Zhang, Mingxia; Liu, Haiying; Zhang, Guoliang; Deng, Qunyi; Huang, Jian; Gao, Zhiliang; Zhou, Boping; Feng, Carl G.; Chen, Xinchun

    2014-01-01

    Background Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis. Methods Complement gene expression in peripheral blood mononuclear cells of tuberculosis patients and controls were determined using whole genome transcriptional microarray assays. The mRNA and protein levels of three C1q components, C1qA, C1qB, and C1qC, were further validated by qRT-PCR and enzyme-linked immunosorbent assay, respectively. The percentages of C1q expression in CD14 positive cells were determined by flow cytometry. Finally, C1qC protein level was quantified in the pleural fluid of tuberculosis and non-tuberculosis pleurisy. Results C1q expression increases significantly in the peripheral blood of patients with active tuberculosis compared to healthy controls and individuals with latent TB infection. The percentage of C1q-expressing CD14 positive cells is significantly increased in active TB patients. C1q expression in the peripheral blood correlates with sputum smear positivity in tuberculosis patients and is reduced after anti-tuberculosis chemotherapy. Notably, receiver operating characteristic analysis showed that C1qC mRNA levels in peripheral blood efficiently discriminate active from latent tuberculosis infection and healthy controls. Additionally, C1qC protein level in pleural effusion shows improved power in discriminating tuberculosis from non-tuberculosis pleurisy when compared to other inflammatory markers, such as IL-6 and TNF-α. Conclusions C1q expression correlates with active disease in human tuberculosis. C1q could be a potential diagnostic marker to discriminate active tuberculosis from latent tuberculosis infection as well as tuberculosis pleurisy from non-tuberculosis pleurisy. PMID:24647646

  2. Increasing TNF levels solely in the rat hippocampus produces persistent pain-like symptoms.

    PubMed

    Martuscello, Regina T; Spengler, Robert N; Bonoiu, Adela C; Davidson, Bruce A; Helinski, Jadwiga; Ding, Hong; Mahajan, Supriya; Kumar, Rajiv; Bergey, Earl J; Knight, Paul R; Prasad, Paras N; Ignatowski, Tracey A

    2012-09-01

    The manifestation of chronic, neuropathic pain includes elevated levels of the cytokine tumor necrosis factor-alpha (TNF). Previously, we have shown that the hippocampus, an area of the brain most notable for its role in learning and memory formation, plays a fundamental role in pain sensation. Using an animal model of peripheral neuropathic pain, we have demonstrated that intracerebroventricular infusion of a TNF antibody adjacent to the hippocampus completely alleviated pain. Furthermore, intracerebroventricular infusion of rTNF adjacent to the hippocampus induced pain behavior in naïve animals similar to that expressed during a model of neuropathic pain. These data support our premise that enhanced production of hippocampal-TNF is integral in pain sensation. In the present study, TNF gene expression was induced exclusively in the hippocampus, eliciting increased local bioactive TNF levels, and animals were assessed for pain behaviors. Male Sprague-Dawley rats received stereotaxic injection of gold nanorod (GNR)-complexed cDNA (control or TNF) plasmids (nanoplasmidexes), and pain responses (i.e., thermal hyperalgesia and mechanical allodynia) were measured. Animals receiving hippocampal microinjection of TNF nanoplasmidexes developed thermal hyperalgesia bilaterally. Sensitivity to mechanical stimulation also developed bilaterally in the rat hind paws. In support of these behavioral findings, immunoreactive staining for TNF, bioactive levels of TNF, and levels of TNF mRNA per polymerase chain reaction analysis were assessed in several brain regions and found to be increased only in the hippocampus. These findings indicate that the specific elevation of TNF in the hippocampus is not a consequence of pain, but in fact induces these behaviors/symptoms. PMID:22770843

  3. Tomato juice decreases LDL cholesterol levels and increases LDL resistance to oxidation.

    PubMed

    Silaste, Marja-Leena; Alfthan, Georg; Aro, Antti; Kesäniemi, Y Antero; Hörkkö, Sohvi

    2007-12-01

    High dietary intakes of tomato products are often associated with a reduced risk of CVD, but the atheroprotective mechanisms have not been established. This study was conducted to investigate the effects of increased dietary intake of tomato products on plasma lipids and LDL oxidation. The diet intervention included a baseline period, a 3-week low tomato diet (no tomato products allowed) and a 3-week high tomato diet (400 ml tomato juice and 30 mg tomato ketchup daily). Twenty-one healthy study subjects participated in the study. Total cholesterol concentration was reduced by 5.9 (sd 10) % (P = 0.002) and LDL cholesterol concentration by 12.9 (sd 17.0) % (P = 0.0002) with the high tomato diet compared to the low tomato diet. The changes in total and LDL cholesterol concentrations correlated significantly with the changes in serum lycopene (r 0.56, P = 0.009; r 0.60, P = 0.004, total and LDL, respectively), beta-carotene (r 0.58, P = 0.005; r 0.70, P < 0.001) and gamma-carotene concentrations (r 0.64, P = 0.002; r 0.64, P = 0.002). The level of circulating LDL to resist formation of oxidized phospholipids increased 13 % (P = 0.02) in response to the high tomato diet. In conclusion, a high dietary intake of tomato products had atheroprotective effects, it significantly reduced LDL cholesterol levels, and increased LDL resistance to oxidation in healthy normocholesterolaemic adults. These atheroprotective features associated with changes in serum lycopene, beta-carotene and gamma-carotene levels. PMID:17617941

  4. High Levels of Heavy Metals Increase the Prevalence of Sarcopenia in the Elderly Population

    PubMed Central

    Yoo, Jun-Il; Lee, Young-Kyun; Koo, Kyung-Hoi

    2016-01-01

    Background Despite increasing concern regarding health problems as a result of environmental pollutants, no association of toxic heavy metals with sarcopenia has been demonstrated in the general population. We investigated the association of heavy metals, including lead, mercury and cadmium, with sarcopenia in the Korean population. Methods Participants included 344 males and 360 females older than 65 years based on data from the fourth and fifth Korea National Health and Nutritional Examination Surveys. Measurements of blood lead, mercury and cadmium levels were performed. To evaluate the cumulative effect of the three heavy metals, subjects were categorized into quartiles. Sarcopenia was defined according to the criteria for the Asia Working Group for Sarcopenia (AWGS) (SMI<5.4 kg/m2 in females and <7.0 kg/m2 in males). Results Of 704 elderly persons (344 in males and 360 in females), prevalences of sarcopenia were 26.7% (92/344) in male and 7.5% (27/360) in female. Mean serum levels of lead in sarcopenia group were significantly higher than non-sarcopenia males (P=0.03). After adjustment for confounding factors, odds ratio for sarcopenia were increased with concentration category of lead (P=0.005 and P<0.001), mercury (P=0.001 and P<0.001) and cadmium (P=0.010 and P<0.001) in males and females, respectively. Conclusions This study demonstrates that high levels of blood lead, mercury and cadmium increase the prevalence of sarcopenia in both genders of elderly populations. PMID:27294082

  5. Collagen cross-link excretion during space flight and bed rest

    NASA Technical Reports Server (NTRS)

    Smith, S. M.; Nillen, J. L.; Leblanc, A.; Lipton, A.; Demers, L. M.; Lane, H. W.; Leach, C. S.; LeBlanc, A. (Principal Investigator)

    1998-01-01

    Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

  6. Increased CSF Levels of Phosphorylated Neurofilament Heavy Protein following Bout in Amateur Boxers

    PubMed Central

    Neselius, Sanna; Zetterberg, Henrik; Blennow, Kaj; Marcusson, Jan; Brisby, Helena

    2013-01-01

    Introduction Diagnosis of mild TBI is hampered by the lack of imaging or biochemical measurements for identifying or quantifying mild TBI in a clinical setting. We have previously shown increased biomarker levels of protein reflecting axonal (neurofilament light protein and tau) and glial (GFAP and S-100B) damage in cerebrospinal fluid (CSF) after a boxing bout. The aims of this study were to find other biomarkers of mild TBI, which may help clinicians diagnose and monitor mild TBI, and to calculate the role of APOE ε4 allele genotype which has been associated with poor outcome after TBI. Materials and Methods Thirty amateur boxers with a minimum of 45 bouts and 25 non-boxing matched controls were included in a prospective cohort study. CSF and blood were collected at one occasion between 1 and 6 days after a bout, and after a rest period for at least 14 days (follow up). The controls were tested once. CSF levels of neurofilament heavy (pNFH), amyloid precursor proteins (sAPPα and sAPPβ), ApoE and ApoA1 were analyzed. In blood, plasma levels of Aβ42 and ApoE genotype were analyzed. Results CSF levels of pNFH were significantly increased between 1 and 6 days after boxing as compared with controls (p<0.001). The concentrations decreased at follow up but were still significantly increased compared to controls (p = 0.018). CSF pNFH concentrations correlated with NFL (r =  0.57 after bout and 0.64 at follow up, p<0.001). No significant change was found in the other biomarkers, as compared to controls. Boxers carrying the APOE ε4 allele had similar biomarker concentrations as non-carriers. Conclusions Subconcussive repetitive trauma in amateur boxing causes a mild TBI that may be diagnosed by CSF analysis of pNFH, even without unconsciousness or concussion symptoms. Possession of the APOE ε4 allele was not found to influence biomarker levels after acute TBI. PMID:24260563

  7. A seven day running training period increases basal urinary hepcidin levels as compared to cycling

    PubMed Central

    2014-01-01

    Background This investigation compared the effects of an extended period of weight-bearing (running) vs. non-weight-bearing (cycling) exercise on hepcidin production and its implications for iron status. Methods Ten active males performed two separate exercise training blocks with either running (RTB) or cycling (CTB) as the exercise mode. Each block consisted of five training sessions (Day 1, 2, 4, 5, 6) performed over a seven day period that were matched for exercise intensity. Basal venous blood samples were obtained on Day 1 (D1), and on Recovery Days 3 (R3) and 7 (R7) to assess iron status, while basal and 3 h post-exercise urinary hepcidin levels were measured on D1, D2, D6, as well as R3 and R7 (basal levels only) for each condition. Results Basal urinary hepcidin levels were significantly elevated (p ≤ 0.05) at D2, R3 and R7 as compared to D1 in RTB. Furthermore, 3 h post-exercise urinary hepcidin levels on D1 were also significantly higher in RTB compared to CTB (p ≤ 0.05). In CTB, urinary hepcidin levels were not statistically different on D1 as compared to R7. Iron parameters were not significantly different at D1 compared to R3 and R7 during both conditions. Conclusions These results suggest that basal hepcidin levels may increase over the course of an extended training program, especially if a weight-bearing exercise modality is undertaken. However, despite any variations in hepcidin production, serum iron parameters in both RTB and CTB were unaffected, possibly due to the short duration of each training block. In comparing running to cycling, non-weight-bearing activity may require more training sessions, or sessions of extended duration, before any significant changes in basal hepcidin levels appear. Chronic elevations in hepcidin levels may help to explain the high incidence of iron deficiency in athletes. PMID:24716892

  8. Impact of the Increased Recommended Dosage of Isoniazid on Pyridoxine Levels in Children and Adolescents.

    PubMed

    Rodà, Diana; Rozas, Librada; Fortuny, Clàudia; Sierra, Cristina; Noguera-Julian, Antoni

    2016-05-01

    Isoniazid exposure causes dose-dependent pyridoxine deficiency. Recently, the recommended dosage of isoniazid in children was increased from 5 (4-6) to 10 (10-15) mg/kg/day. We aimed to analyze longitudinally pyridoxine levels in a cohort of previously healthy children and adolescents treated with isoniazid. Mild symptom-free pyridoxine deficiency was observed in 4/75 (5.6%) and 3/40 (7.5%) at baseline and at 3-month follow-up, respectively. Classical age-related risk factors identified patients at risk of pyridoxine deficiency. Our preliminary results support current recommendations regarding pyridoxine supplementation in healthy children. PMID:26862674

  9. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    PubMed

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID

  10. Photocontrolled Cargo Release from Dual Cross-Linked Polymer Particles.

    PubMed

    Tan, Shereen; Cui, Jiwei; Fu, Qiang; Nam, Eunhyung; Ladewig, Katharina; Ren, Jing M; Wong, Edgar H H; Caruso, Frank; Blencowe, Anton; Qiao, Greg G

    2016-03-01

    Burst release of a payload from polymeric particles upon photoirradiation was engineered by altering the cross-linking density. This was achieved via a dual cross-linking concept whereby noncovalent cross-linking was provided by cyclodextrin host-guest interactions, and irreversible covalent cross-linking was mediated by continuous assembly of polymers (CAP). The dual cross-linked particles (DCPs) were efficiently infiltrated (∼80-93%) by the biomacromolecule dextran (molecular weight up to 500 kDa) to provide high loadings (70-75%). Upon short exposure (5 s) to UV light, the noncovalent cross-links were disrupted resulting in increased permeability and burst release of the cargo (50 mol % within 1 s) as visualized by time-lapse fluorescence microscopy. As sunlight contains UV light at low intensities, the particles can potentially be incorporated into systems used in agriculture, environmental control, and food packaging, whereby sunlight could control the release of nutrients and antimicrobial agents. PMID:26862769

  11. Organohalogen levels in harbor seal (Phoca vitulina) pups increase with duration of nursing.

    PubMed

    Neale, Jennifer C C; Schmelzer, Kara R; Gulland, Frances M D; Berg, Elizabeth A; Tjeerdema, Ronald S

    2005-05-14

    Maternal transfer of persistent marine contaminants to offspring via milk has been documented in marine mammals, but temporal dynamics of this phenomenon throughout the lactation period are poorly understood. Exposures to organohalogens were investigated in harbor seal pups admitted to a rehabilitation center in north central California during the lactation periods of 2001 and 2002. Ten congeners of PCBs, three congeners of PBDEs, and p,p'-DDE were quantified in whole blood samples. Levels of contaminants increased with admit date, assumed to correlate positively with pup age. This trend was significant when latitude of stranding site, body condition, and body length were included as variables in the model. Contaminant-admit date relationships appeared nonlinear (i.e., threshold or exponential), with greatest increases in contaminant concentrations during late lactation. PMID:16020196

  12. Energized by love: thinking about romantic relationships increases positive affect and blood glucose levels.

    PubMed

    Stanton, Sarah C E; Campbell, Lorne; Loving, Timothy J

    2014-10-01

    We assessed the impact of thinking of a current romantic partner on acute blood glucose responses and positive affect over a short period of time. Participants in romantic relationships were randomly assigned to reflect on their partner, an opposite-sex friend, or their morning routine. Blood glucose levels were assessed prior to reflection, as well as at 10 and 25 min postreflection. Results revealed that individuals in the routine and friend conditions exhibited a decline in glucose over time, whereas individuals in the partner condition did not exhibit this decline (rather, a slight increase) in glucose over time. Reported positive affect following reflection was positively associated with increases in glucose, but only for individuals who reflected on their partner, suggesting this physiological response reflects eustress. These findings add to the literature on eustress in relationships and have implications for relationship processes. PMID:24924647

  13. Serum Prosaposin Levels Are Increased in Patients with Advanced Prostate Cancer

    PubMed Central

    Koochekpour, Shahriar; Hu, Siyi; Vellasco-Gonzalez, Cruz; Bernardo, Ruiz; Azabdaftari, Gissue; Dalin, Guo-xiang; Zhau, Haiyen E.; Chung, Leland W.; Vessella, Robert L.

    2012-01-01

    BACKGROUND We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum-PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stage II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum-PSAP level was detected before puberty, peaked at the most reproductive age group (20–39 years old), and then, decreased to a range between the two groups for men above 40 years old. Regardless of age and when compared with normal individuals, serum-PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum-PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa. PMID:21630292

  14. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T S; Janssens, Ivan A; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including "all" papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  15. Future Climate CO2 Levels Mitigate Stress Impact on Plants: Increased Defense or Decreased Challenge?

    PubMed Central

    AbdElgawad, Hamada; Zinta, Gaurav; Beemster, Gerrit T. S.; Janssens, Ivan A.; Asard, Han

    2016-01-01

    Elevated atmospheric CO2 can stimulate plant growth by providing additional C (fertilization effect), and is observed to mitigate abiotic stress impact. Although, the mechanisms underlying the stress mitigating effect are not yet clear, increased antioxidant defenses, have been held primarily responsible (antioxidant hypothesis). A systematic literature analysis, including “all” papers [Web of Science (WoS)-cited], addressing elevated CO2 effects on abiotic stress responses and antioxidants (105 papers), confirms the frequent occurrence of the stress mitigation effect. However, it also demonstrates that, in stress conditions, elevated CO2 is reported to increase antioxidants, only in about 22% of the observations (e.g., for polyphenols, peroxidases, superoxide dismutase, monodehydroascorbate reductase). In most observations, under stress and elevated CO2 the levels of key antioxidants and antioxidant enzymes are reported to remain unchanged (50%, e.g., ascorbate peroxidase, catalase, ascorbate), or even decreased (28%, e.g., glutathione peroxidase). Moreover, increases in antioxidants are not specific for a species group, growth facility, or stress type. It seems therefore unlikely that increased antioxidant defense is the major mechanism underlying CO2-mediated stress impact mitigation. Alternative processes, probably decreasing the oxidative challenge by reducing ROS production (e.g., photorespiration), are therefore likely to play important roles in elevated CO2 (relaxation hypothesis). Such parameters are however rarely investigated in connection with abiotic stress relief. Understanding the effect of elevated CO2 on plant growth and stress responses is imperative to understand the impact of climate changes on plant productivity. PMID:27200030

  16. Effect of glucose content on thermally cross-linked fibrous gelatin scaffolds for tissue engineering.

    PubMed

    Siimon, Kaido; Reemann, Paula; Põder, Annika; Pook, Martin; Kangur, Triin; Kingo, Külli; Jaks, Viljar; Mäeorg, Uno; Järvekülg, Martin

    2014-09-01

    Thermally cross-linked glucose-containing electrospun gelatin meshes were studied as possible cell substrate materials. FTIR analysis was used to study the effect of glucose on cross-linking reactions. It was found that the presence of glucose increases the extent of cross-linking of fibrous gelatin scaffolds, which in return determines scaffold properties and their usability in tissue engineering applications. Easy to handle fabric-like scaffolds were obtained from blends containing up to 15% glucose. Maximum extent of cross-linking was reached at nearly 20% glucose content. Cross-linking effectively resulted in decreased solubility and increased resistance to enzymatic degradation. Preliminary short-term cell culture experiments indicate that such thermally cross-linked gelatin-glucose scaffolds are suitable for tissue engineering applications. PMID:25063151

  17. Increased Circulating miR-21 Levels Are Associated with Kidney Fibrosis

    PubMed Central

    Gnemmi, Viviane; Buob, David; Van der Hauwaert, Cynthia; Lo-Guidice, Jean-Marc; Bouyé, Sébastien; Hazzan, Marc; Pottier, Nicolas; Perrais, Michaël

    2013-01-01

    MicroRNAs (miRNAs) are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA). Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001). By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03), and between miR-21 levels and aMDRD (ß = −0.398, p = 0.006). Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis. PMID:23469132

  18. Peripherally cross-linking the shell of core-shell polymer micelles decreases premature release of physically loaded combretastatin A4 in whole blood and increases its mean residence time and subsequent potency against primary murine breast tumors after IV administration

    PubMed Central

    Wakaskar, Rajesh R.; Bathena, Sai Praneeth R.; Tallapaka, Shailendra; Ambardekar, Vishakha V.; Gautum, Nagsen; Thakare, Rhishikesh N.; Simet, Samantha M.; Curran, Stephen M.; Singh, Rakesh K.; Dong, Yuxiang

    2014-01-01

    Purpose Determine the feasibility and potential benefit of peripherally cross-linking the shell of core-shell polymer micelles on the premature release of physically loaded hydrophobic drug in whole blood and subsequent potency against solid tumors. Methods Individual Pluronic F127 polymer micelles (F127 PM) peripherally cross-linked with ethylenediamine at 76% of total PEO blocks (X-F127 PM) were physically loaded with combretastatin A4 (CA4) by the solid dispersion method and compared to CA4 physically loaded in uncross-linked F127 PM, CA4 in DMSO in vitro, or water-soluble CA4 phosphate (CA4P) in vivo. Results X-F127 PM had similar CA4 loading and aqueous solubility as F127 PM up to 10 mg CA4 / mL at 22.9 wt% and did not aggregate in PBS or 90% (v/v) human serum at 37°C for at least 24 h. In contrast, X-F127 PM decreased the unbound fraction of CA4 in whole blood (fu) and increased the mean plasma residence time and subsequent potency of CA4 against the vascular function and growth of primary murine 4T1 breast tumors over CA4 in F127 PM and water-soluble CA4P after IV administration. Conclusions Given that decreasing the fu is an indication of decreased drug release, peripherally cross-linking the shell of core-shell polymer micelles may be a simple approach to decrease premature release of physically loaded hydrophobic drug in the blood and increase subsequent potency in solid tumors. PMID:25223962

  19. Increased level of Eimeria sensitivity to diclazuril after using a live coccidial vaccine.

    PubMed

    Mathis, G F; Broussard, C

    2006-09-01

    Anticoccidial vaccine and an anticoccidial drug rotation program were compared to determine which program was more effective in producing coccidia populations sensitive of 1 ppm diclazuril. The study used an anticoccidial drug-sensitivity battery test (AST) to determine the baseline level of diclazuril sensitivity to field isolates of Eimeria spp. from seven broiler complexes that had used diclazuril. Based on percentage reduction in weight gain and lesion scores, 25% or fewer of the isolates were effectively controlled by diclazuril. Following the baseline sampling, four of the complexes switched to a nondiclazuril in-feed anticoccidial drug program and three of the complexes switched to a vaccination program for two broiler grow-out cycles as the sole coccidiosis-control program. This study demonstrated that the vaccine used (Coccivac-B) contained anticoccidial drug-sensitive strains. Eimeria isolates were subsequently collected from the identical houses and diclazuril AST results were compared with the baseline AST results. Following the two grow-out cycles, sensitivity of the isolates to diclazuril from the four complexes that continued to use in-feed anticoccidial drugs remained essentially unchanged. The isolates from the three complexes that switched to the vaccination program demonstrated a marked increase in diclazuril sensitivity, with 60%-100% of the isolates from each complex effectively controlled by diclazuril. Vaccination with the anticoccidial drug-sensitive strains produced a measurable increase in the level of sensitivity to diclazuril. PMID:17039828

  20. Increases in 1,5-anhydroglucitol levels in germinating amaranth seeds and in ripening banana.

    PubMed

    Konishi, Y; Hashima, K; Kishida, K

    2000-11-01

    To examine whether 1,5-anhydroglucitol (AG) is derived from starch degradation in plant tissues, we colorimetrically measured AG contents of germinating amaranth seeds and ripening banana pulp. In both cases, as starch degradation proceeded, AG levels were significantly increased, but were 1,700-5,000 times lower than those of total soluble carbohydrates. alpha-1,4-Glucan lyase activity, which is measured by the 1,5-anhydrofructose (AF) liberated from non-reducing glucose residues of starch or glycogen, was too low to be detected in amaranth or banana by the 3,5-dinitrosalicylic acid method. On the other hand, AF reductase, which reduces AF to AG, was detected in germinating amaranth seeds and banana pulp. Thus, the increases in AG levels are conceived to be derived from starch breakdown, although further investigation is needed to answer whether the starch degradation pathway via alpha-1,4-glucan lyase/AF reductase exists in plant tissues. PMID:11193417

  1. S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

    PubMed Central

    2010-01-01

    Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT) inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF) levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model. PMID:20932295

  2. In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone

    SciTech Connect

    Morrissey, P.J.; Charrier, K.; Alpert, A.; Bressler, L.

    1988-09-01

    Administration of IL-1 alpha or IL-1 beta to normal mice induces a decrease in thymic cellularity, the magnitude of which depends on the number of injections and dose of IL-1. Twice daily injections of 200 ng of IL-1 alpha or -beta for 4 days results in a 90% decrease in thymic cellularity, which regenerated after cessation of treatment. Study of thymocyte subpopulations revealed that the number of CD4+/CD8+ thymocytes was dramatically decreased in IL-1-treated mice. Functional assessment of the CD4-/CD8- population from treated animals showed that these cells had adequate mitogenic responses in vitro and that the proportion of these cells in cycle was not different from control CD4-/CD8- cells. IL-1 treatment also prevented the regeneration of thymic cellularity after irradiation. The use of strains of mice differing genetically at the Ly 1 locus to construct radiation bone marrow chimeras demonstrated that bone marrow-derived thymocyte precursors were able to seed the thymus in the IL-1-treated animals. Again, however, the CD4+/CD8+ thymocyte population was significantly decreased. Thymic repopulation occurred upon cessation of IL-1 therapy. Finally, we determined that a single i.p. injection of IL-1 caused a three-fold increase in serum corticosterone levels, which peaked approximately 3 h after IL-1 administration. Thus, an IL-1-dependent increase in serum corticosterone levels may be responsible for the observed thymic hypoplasia.

  3. Syringe Exchange in the United States: A National Level Economic Evaluation of Hypothetical Increases in Investment

    PubMed Central

    Weir, Brian W.; Des Jarlais, Don C.; Pinkerton, Steven D.; Holtgrave, David R.

    2014-01-01

    To examine whether increasing investment in needle/syringe exchange programs (NSPs) in the US would be cost-effective for HIV prevention, we modeled HIV incidence in hypothetical cases with higher NSP syringe supply than current levels, and estimated number of infections averted, cost per infection averted, treatment costs saved, and financial return on investment. We modified Pinkerton’s model, which was an adaptation of Kaplan’s simplified needle circulation theory model, to compare different syringe supply levels, account for syringes from non-NSP sources, and reflect reduction in syringe sharing and contamination. With an annual $10 to $50 million funding increase, 194–816 HIV infections would be averted (cost per infection averted $51,601– $61,302). Contrasted with HIV treatment cost savings alone, the rate of financial return on investment would be 7.58–6.38. Main and sensitivity analyses strongly suggest that it would be cost-saving for the US to invest in syringe exchange expansion. PMID:24824043

  4. Excitotoxic and Radiation Stress Increase TERT Levels in the Mitochondria and Cytosol of Cerebellar Purkinje Neurons.

    PubMed

    Eitan, Erez; Braverman, Carmel; Tichon, Ailone; Gitler, Daniel; Hutchison, Emmette R; Mattson, Mark P; Priel, Esther

    2016-08-01

    Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors: a sub-lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress. PMID:26374457

  5. Modeling effectiveness of gradual increases in source level to mitigate effects of sonar on marine mammals.

    PubMed

    Von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

    2014-02-01

    Ramp-up or soft-start procedures (i.e., gradual increase in the source level) are used to mitigate the effect of sonar sound on marine mammals, although no one to date has tested whether ramp-up procedures are effective at reducing the effect of sound on marine mammals. We investigated the effectiveness of ramp-up procedures in reducing the area within which changes in hearing thresholds can occur. We modeled the level of sound killer whales (Orcinus orca) were exposed to from a generic sonar operation preceded by different ramp-up schemes. In our model, ramp-up procedures reduced the risk of killer whales receiving sounds of sufficient intensity to affect their hearing. The effectiveness of the ramp-up procedure depended strongly on the assumed response threshold and differed with ramp-up duration, although extending the duration of the ramp up beyond 5 min did not add much to its predicted mitigating effect. The main factors that limited effectiveness of ramp up in a typical antisubmarine warfare scenario were high source level, rapid moving sonar source, and long silences between consecutive sonar transmissions. Our exposure modeling approach can be used to evaluate and optimize mitigation procedures. PMID:24471782

  6. Increasing the maximally random jammed density with electric field to reduce the fat level in chocolate

    NASA Astrophysics Data System (ADS)

    Tao, R.; Tang, H.

    Chocolate is one of the most popular food types and flavors in the world. Unfortunately, at present, chocolate products contain too much fat, leading to obesity. For example, a typical molding chocolate has various fat up to 40% in total and chocolate for covering ice cream has fat 50 -60%. Especially, as children are the leading chocolate consumers, reducing the fat level in chocolate products to make them healthier is important and urgent. While this issue was called into attention and elaborated in articles and books decades ago and led to some patent applications, no actual solution was found unfortunately. Why is reducing fat in chocolate so difficult? What is the underlying physical mechanism? We have found that this issue is deeply related to the basic science of soft matters, especially to their viscosity and maximally random jammed (MRJ) density φx. All chocolate productions are handling liquid chocolate, a suspension with cocoa solid particles in melted fat, mainly cocoa butter. The fat level cannot be lower than 1-φxin order to have liquid chocolate to flow. Here we show that that with application of an electric field to liquid chocolate, we can aggregate the suspended particles into prolate spheroids. This microstructure change reduces liquid chocolate's viscosity along the flow direction and increases its MRJ density significantly. Hence the fat level in chocolate can be effectively reduced. We are looking forward to a new class of healthier and tasteful chocolate coming to the market soon. Dept. of Physics, Temple Univ, Philadelphia, PA 19122.

  7. Increased cortisol levels in hair of recent Ecstasy/MDMA users.

    PubMed

    Parrott, A C; Sands, H R; Jones, L; Clow, A; Evans, P; Downey, L A; Stalder, T

    2014-03-01

    Previous research has revealed an acute 8-fold increase in salivary cortisol following self-administrated Ecstasy/MDMA in dance clubbers. It is currently not known to what extent repeated usage impacts upon activity of the hypothalamic-pituitary-adrenal axis over a more prolonged period of time. This study investigated the integrated cortisol levels in 3-month hair samples from recent Ecstasy/MDMA users and non-user controls. One hundred and one unpaid participants (53 males, 48 females; mean age 21.75 years) completed the University of East London recreational drug use questionnaire, modified to cover the past 3-months of usage. They comprised 32 light recent Ecstasy/MDMA users (1-4 times in last 3 months), 23 recent heavy MDMA users (+5 times in last 3 months), and 54 non-user controls. Volunteers provided 3 cm hair samples for cortisol analysis. Hair cortisol levels were observed to be significantly higher in recent heavy MDMA users (mean = 55.0 ± 80.1 pg/mg), compared to recent light MDMA users (19.4 ± 16.0 pg/mg; p=0.015), and to non-users (13.8 ± 6.1 pg/mg; p<0.001). Hence the regular use of Ecstasy/MDMA was associated with almost 4-fold raised hair cortisol levels, in comparison with non-user controls. The present results are consistent with the bio-energetic stress model for Ecstasy/MDMA, which predicts that repeated stimulant drug use may increase cortisol production acutely, and result in greater deposits of the hormone in hair. These data may also help explain the neurocognitive, psychiatric, and other psychobiological problems of some abstinent users. Future study design and directions for research concerning the psychoneuroendocrinological impact of MDMA are also discussed. PMID:24333019

  8. Increase of exhaled nitric oxide in children exposed to low levels of ambient ozone.

    PubMed

    Nickmilder, Marc; de Burbure, Claire; Carbonnelle, Sylviane; Sylviane, Carbonnelle; Dumont, Xavier; Xavier, Dumont; Bernard, Alfred; Alfred, Bernard; Derouane, Alain; Alain, Derouane

    2007-02-01

    Ozone (O3) is known to induce lung function impairment and airways inflammation during episodes of photochemical smog. The aim of the present study was to assess the inflammatory effect of ambient O3 in healthy children using nitric oxide in exhaled air (eNO) as a noninvasive test. The study was performed on 6 groups of children (n = 11-15), aged 6.5 to 15 yr, who attended summer camps in rural areas of the south of Belgium in 2002. Ambient O3 concentrations continuously monitored in the camps ranged from 48 to 221 microg/m3 (1-h maximal concentration). Children remained outdoors during the experimental days, doing various recreational activities but no sports. Lung function tests (forced expiratory volume in 1 s [FEV1] and forced vital capacity [FVC]) and eNO were measured twice in each child in the morning and in the evening. While lung function tests did not show any consistent pattern of decrease at these O3 levels, a highly significant increase in eNO was found in all subjects from an ambient 1-h O3 level of 167 microg/m3. A multivariate analysis did not reveal any influence of age, gender, height, weight, and body mass index (BMI) of the children. The threshold for this O3-induced increase in eNO estimated benchmark dose analysis was 135 microg/m3 for 1-h exposure and 110 microg/m3 for 8-h exposure. These observations suggest that ambient ozone produces early inflammatory changes in the airways of children at levels slightly below current air quality standards. PMID:17365589

  9. Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

    PubMed Central

    Korver, K; Radl, J; Schellekens, P T; Vossen, J M

    1988-01-01

    Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation. PMID:3044651

  10. Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level

    PubMed Central

    Choi, Min-Koo; Song, Im-Sook

    2016-01-01

    This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2–75 μM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 μL/min while passive diffusion clearance was 0.31 μL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level. PMID:26797108

  11. Blockade of P-Glycoprotein Decreased the Disposition of Phenformin and Increased Plasma Lactate Level.

    PubMed

    Choi, Min-Koo; Song, Im-Sook

    2016-03-01

    This study aimed to investigate the in vivo relevance of P-glycoprotein (P-gp) in the pharmacokinetics and adverse effect of phenformin. To investigate the involvement of P-gp in the transport of phenformin, a bi-directional transport of phenformin was carried out in LLC-PK1 cells overexpressing P-gp, LLC-PK1-Pgp. Basal to apical transport of phenformin was 3.9-fold greater than apical to basal transport and became saturated with increasing phenformin concentration (2-75 μM) in LLC-PK1-Pgp, suggesting the involvement of P-gp in phenformin transport. Intrinsic clearance mediated by P-gp was 1.9 μL/min while passive diffusion clearance was 0.31 μL/min. Thus, P-gp contributed more to phenformin transport than passive diffusion. To investigate the contribution of P-gp on the pharmacokinetics and adverse effect of phenformin, the effects of verapamil, a P-gp inhibitor, on the pharmacokinetics of phenformin were also examined in rats. The plasma concentrations of phenformin were increased following oral administration of phenformin and intravenous verapamil infusion compared with those administerd phenformin alone. Pharmacokinetic parameters such as Cmax and AUC of phenformin increased and CL/F and Vss/F decreased as a consequence of verapamil treatment. These results suggested that P-gp blockade by verapamil may decrease the phenformin disposition and increase plasma phenformin concentrations. P-gp inhibition by verapamil treatment also increased plasma lactate concentration, which is a crucial adverse event of phenformin. In conclusion, P-gp may play an important role in phenformin transport process and, therefore, contribute to the modulation of pharmacokinetics of phenformin and onset of plasma lactate level. PMID:26797108

  12. Tuning nanoscale viscoelasticity of polyelectrolyte complexes with multiple types of cross-links

    NASA Astrophysics Data System (ADS)

    Ma, Tianzhu; Han, Biao; Lee, Daeyeon; Han, Lin

    Mechanical properties of hydrogels are manifestation of cross-link type and density, fixed charges and water-polymer interactions. In this study, we revealed how different types of cross-links regulate the nanoscale viscoelasticity of polyelectrolyte networks. Ionically cross-linked PAH/PAA layer-by-layer complexes were modified to include covalent cross-links using EDC. AFM-nanoindentation and force relaxation were performed at various ionic strength (0.01-1M) and pH (1.5-5.5). As-assembled networks, held only by ionic cross-links, underwent >95% relaxation, dominated by cross-link breaking and re-formation. Addition of covalent cross-links increased the instantaneous modulus by 1.6-fold and attenuated relaxation to ~80% of net neutral states (pH >=3.5), as covalent cross-links provide additional elastic components. The network remained stabilized when all ionic cross-links were dissociated at pH <=1.5, whereby further attenuation to 31% in relaxation could be due to viscoelastic polymer conformational changes and fluid flow-induced poroelasticity. Taken together, this study demonstrates the potential of using multiple cross-linking types to tune the viscoelastic mechanisms in polyelectrolyte complexes.

  13. Retrieved Highly Crosslinked UHMWPE Acetabular Liners Have Similar Wear Damage as Conventional UHMWPE

    PubMed Central

    Schroder, David T.; Kelly, Natalie H.; Parks, Michael L.

    2010-01-01

    Background Highly crosslinked UHMWPE is associated with increased wear resistance in hip simulator and clinical studies. Laboratory and case studies, however, have described rim fracture in crosslinked acetabular liners. Controversy exists, therefore, on the relative merits of crosslinked liners over conventional liners in terms of wear performance versus resistance to fatigue cracking. Questions/purposes We asked whether crosslinked liners would show less surface damage than conventional liners but would be more susceptible to fatigue damage. Methods We examined 36 conventional UHMWPE and 39 crosslinked UHMWPE retrieved implants with similar patient demographics and identical design for evidence of wear damage, including articular surface damage, impingement, screw-hole creep, and rim cracks. Results We observed no difference in wear damage scores for the two liners. Conventional liners more frequently impinged but were more often elevated with smaller head sizes. We observed creep in approximately 70% of both types of liners. Incipient rim cracks were found in five crosslinked liners, and one liner had a rim fracture. Only one conventional liner had an incipient rim crack. Conclusions Contrary to our expectation, damage was similar between crosslinked and conventional UHMWPE liners. Moreover, the 15% occurrence (six of 39) of incipient or complete fractures in crosslinked liners as compared with a 3% occurrence (one of 36) in conventional liners may have implications for the long-term performance of crosslinked liners. Longer-term studies will be necessary to establish the fate of rim cracks and thus the overall clinical fatigue performance of crosslinked liners. PMID:20844998

  14. UV Crosslinking of Donor Corneas Confers Resistance to Keratolysis

    PubMed Central

    Arafat, Samer N.; Robert, Marie-Claude; Shukla, Anita N.; Dohlman, Claes H.; Chodosh, James; Ciolino, Joseph B.

    2014-01-01

    Purpose To develop a modified ex vivo corneal crosslinking method that increases stromal resistance to enzymatic degradation for use as a carrier for the Boston keratoprosthesis. Methods Ex vivo crosslinking of human corneas was performed using Barron® artificial anterior chambers. The corneas were de-epithelialized, pre-treated with riboflavin solution (0.1% riboflavin/20% dextran) and irradiated with ultraviolet A (UVA) light (λ=370nm, irradiance=3mW/cm2) for various durations. The combined effect of UVA and gamma (γ) irradiation was also assessed using the commercially available γ-irradiated corneal donors. The corneas were then trephined and incubated at 37 degrees Celsius with 0.3% collagenase A solution. The time to dissolution of each cornea was compared across treatments. Results De-epithelialized corneas (no UV light, no riboflavin) dissolved in 5.8 ± 0.6 hours. Crosslinked corneas demonstrated increased resistance to dissolution, with a time to dissolution of 17.8 +/− 2.6 hours (p < 0.0001). The corneal tissues’ resistance to collagenase increased with longer UVA exposure, reaching a plateau at 30 minutes. Crosslinking both the anterior and posterior corneas did not provide added resistance when compared to crosslinking the anterior corneas only (p>0.05). γ-irradiated corneas dissolved as readily as de-epithelialized controls regardless of whether they were further crosslinked (5.6 ± 1.2 hours) or not (6.1 ± 0.6 hours) (p=0.43) Conclusions Collagen crosslinking of the de-epithelialized anterior cornea surface for 30 minutes conferred optimal resistance to in vitro keratolysis by collagenase A. PMID:25014151

  15. Can Increased CO2 Levels Trigger a Runaway Greenhouse on the Earth?

    NASA Astrophysics Data System (ADS)

    Ramirez, R.

    2014-04-01

    Recent one-dimensional (globally averaged) climate model calculations suggest that increased atmospheric CO2 could conceivably trigger a runaway greenhouse if CO2 concentrations were approximately 100 times higher than today. The new prediction runs contrary to previous calculations, which indicated that CO2 increases could not trigger a runaway, even at Venus-like CO2 concentrations. Goldblatt et al. argue that this different behavior is a consequence of updated absorption coefficients for H2O that make a runaway more likely. Here, we use a 1-D cloud-free climate model with similar, up-to-date absorption coefficients, but with a self-consistent methodology, to demonstrate that CO2 increases cannot induce a runaway greenhouse on the modern Earth. However, these initial calculations do not include cloud feedback, which may be positive at higher temperatures, destabilizing Earth's climate. We then show new calculations demonstrating that cirrus clouds cannot trigger a runaway, even in the complete absence of low clouds. Thus, the habitability of an Earth-like planet at Earth's distance appears to be ensured, irrespective of the sign of cloud feedback. Our results are of importance to Earth-like planets that receive similar insolation levels as does the Earth and to the ongoing question about cloud response at higher temperatures.

  16. Methylene blue reduces Aβ levels and rescues early cognitive deficit by increasing proteasome activity

    PubMed Central

    Medina, David X.; Caccamo, Antonella; Oddo, Salvatore

    2010-01-01

    Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduces Aβ levels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action. PMID:20731659

  17. Risk of cancer in an occupationally exposed cohort with increased level of chromosomal aberrations.

    PubMed Central

    Smerhovsky, Z; Landa, K; Rössner, P; Brabec, M; Zudova, Z; Hola, N; Pokorna, Z; Mareckova, J; Hurychova, D

    2001-01-01

    We used cytogenetic analysis to carry out a cohort study in which the major objective was to test the association between frequency of chromosomal aberrations and subsequent risk of cancer. In spite of the extensive use of the cytogenetic analysis of human peripheral blood lymphocytes in biomonitoring of exposure to various mutagens and carcinogens on an ecologic level, the long-term effects of an increased frequency of chromosomal aberrations in individuals are still uncertain. Few epidemiologic studies have addressed this issue, and a moderate risk of cancer in individuals with an elevated frequency of chromosomal aberrations has been observed. In the present study, we analyzed data on 8,962 cytogenetic tests and 3,973 subjects. We found a significant and strong association between the frequency of chromosomal aberrations and cancer incidence in a group of miners exposed to radon, where a 1% increase in frequency of chromosomal aberrations was followed by a 64% increase in risk of cancer (p < 0.000). In contrast, the collected data are inadequate for a critical evaluation of the association with exposure to other chemicals. PMID:11171523

  18. mTORC1 signaling activates NRF1 to increase cellular proteasome levels

    PubMed Central

    Zhang, Yinan; Manning, Brendan D

    2015-01-01

    Defects in the maintenance of protein homeostasis, or proteostasis, has emerged as an underlying feature of a variety of human pathologies, including aging-related diseases. Proteostasis is achieved through the coordinated action of cellular systems overseeing amino acid availability, mRNA translation, protein folding, secretion, and degradation. The regulation of these distinct systems must be integrated at various points to attain a proper balance. In a recent study, we found that the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) pathway, well known to enhance the protein synthesis capacity of cells while concordantly inhibiting autophagy, promotes the production of more proteasomes. Activation of mTORC1 genetically, through loss of the tuberous sclerosis complex (TSC) tumor suppressors, or physiologically, through growth factors or feeding, stimulates a transcriptional program involving the sterol-regulatory element binding protein 1 (SREBP1) and nuclear factor erythroid-derived 2-related factor 1 (NRF1; also known as NFE2L1) transcription factors leading to an increase in cellular proteasome content. As discussed here, our findings suggest that this increase in proteasome levels facilitates both the maintenance of proteostasis and the recovery of amino acids in the face of an increased protein load consequent to mTORC1 activation. We also consider the physiological and pathological implications of this unexpected new downstream branch of mTORC1 signaling. PMID:26017155

  19. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients

    PubMed Central

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation. PMID:26466367

  20. Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients.

    PubMed

    El-Najjar, Nahed; Orsó, Evelyn; Wallner, Stefan; Liebisch, Gerhard; Schmitz, Gerd

    2015-01-01

    Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation. PMID:26466367

  1. Textural performance of crosslinked or reduced-calcium milk protein ingredients in model high-protein nutrition bars.

    PubMed

    Banach, J C; Clark, S; Metzger, L E; Lamsal, B P

    2016-08-01

    Transglutaminase (Tgase) crosslinking and calcium reduction were investigated as ways to improve the texture and storage stability of high-protein nutrition (HPN) bars formulated with milk protein concentrate (MPC) and micellar casein concentrate (MCC). The MPC and MCC crosslinked at none, low, and high levels, and a reduced-calcium MPC (RCMPC) were each formulated into model HPN bars. Hardness, crumbliness, moisture content, pH, color, and water activity of the HPN bars were measured during accelerated storage. The HPN bars prepared with MPC were harder and more cohesive than those prepared with MCC. Higher levels of Tgase crosslinking improved HPN bar cohesiveness and decreased hardening during storage. The RCMPC produced softer, yet crumblier HPN bars. Small textural differences were observed for the HPN bars formulated with the transglutaminase crosslinked proteins or RCMPC when compared with their respective controls. However, modification only slightly improved protein ingredient ability to slow hardening while balancing cohesion and likely requires further improvement for increased applicability in soft-texture HPN bars. PMID:27236767

  2. Ketoconazole increases fingolimod blood levels in a drug interaction via CYP4F2 inhibition.

    PubMed

    Kovarik, John M; Dole, Kiran; Riviere, Gilles-Jacques; Pommier, Francoise; Maton, Steve; Jin, Yi; Lasseter, Kenneth C; Schmouder, Robert L

    2009-02-01

    The sphingosine-1-phosphate receptor modulator fingolimod is predominantly hydroxylated by cytochrome CYP4F2. In vitro experiments showed that ketoconazole significantly inhibited the oxidative metabolism of fingolimod by human liver microsomes and by recombinant CYP4F2. The authors used ketoconazole as a putative CYP4F2 inhibitor to quantify its influence on fingolimod pharmacokinetics in healthy subjects. In a 2-period, single-sequence, crossover study, 22 healthy subjects received a single 5-mg dose of fingolimod in period 1. In period 2, subjects received ketoconazole 200 mg twice daily for 9 days and a single 5-mg dose of fingolimod coadministered on the 4th day of ketoconazole treatment. Ketoconazole did not affect fingolimod t(max) or half-life, but there was a weak average increase in C(max) of 1.22-fold (90% confidence interval, 1.15-1.30). The AUC over the 5 days of ketoconazole coadministration increased 1.40-fold (1.31-1.50), and the full AUC to infinity increased 1.71-fold (1.53-1.91). The AUC of the active metabolite fingolimod-phosphate was increased to a similar extent by 1.67-fold (1.50-1.85). Ketoconazole predose plasma levels were not altered by fingolimod. The magnitude of this interaction suggests that a proactive dose reduction of fingolimod is not necessary when adding ketoconazole to a fingolimod regimen. The clinician, however, should be aware of this interaction and bear in mind the possibility of a fingolimod dose reduction based on clinical monitoring. PMID:19118083

  3. Stabilization of collagen nanofibers with l-lysine improves the ability of carbodiimide cross-linked amniotic membranes to preserve limbal epithelial progenitor cells

    PubMed Central

    Lai, Jui-Yang; Wang, Pei-Ran; Luo, Li-Jyuan; Chen, Si-Tan

    2014-01-01

    To overcome the drawbacks associated with limited cross-linking efficiency of carbodiimide modified amniotic membrane, this study investigated the use of l-lysine as an additional amino acid bridge to enhance the stability of a nanofibrous tissue matrix for a limbal epithelial cell culture platform. Results of ninhydrin assays and zeta potential measurements showed that the amount of positively charged amino acid residues incorporated into the tissue collagen chains is highly correlated with the l-lysine-pretreated concentration. The cross-linked structure and hydrophilicity of amniotic membrane scaffolding materials affected by the lysine molecular bridging effects were determined. With an increase in the l-lysine-pretreated concentration from 1 to 30 mM, the cross-linking density was significantly increased and water content was markedly decreased. The variations in resistance to thermal denaturation and enzymatic degradation were in accordance with the number of cross-links per unit mass of amniotic membrane, indicating l-lysine-modulated stabilization of collagen molecules. It was also noteworthy that the carbodiimide cross-linked tissue samples prepared using a relatively high l-lysine-pretreated concentration (ie, 30 mM) appeared to have decreased light transmittance and biocompatibility, probably due to the influence of a large nanofiber size and a high charge density. The rise in stemness gene and protein expression levels was dependent on improved cross-link formation, suggesting the crucial role of amino acid bridges in constructing suitable scaffolds to preserve limbal progenitor cells. It is concluded that mild to moderate pretreatment conditions (ie, 3–10 mM l-lysine) can provide a useful strategy to assist in the development of carbodiimide cross-linked amniotic membrane as a stable stem cell niche for corneal epithelial tissue engineering. PMID:25395849

  4. Increased levels of circulating adrenomedullin following treatment with TU‑100 in patients with Crohn's disease.

    PubMed

    Kominato, Ken; Yamasaki, Hiroshi; Mitsuyama, Keiichi; Takedatsu, Hidetoshi; Yoshioka, Shinichiro; Kuwaki, Kotaro; Kobayashi, Teppei; Yamauchi, Ryosuke; Fukunaga, Shuhei; Tsuruta, Osamu; Torimura, Takuji

    2016-09-01

    Daikenchuto (TU‑100) is a traditional Japanese medicine that is widely used to treat intestinal symptoms. The mechanisms underlying it effects on the circulating levels of adrenomedullin (ADM) are of interest. In addition, the effect of TU‑100 in the treatment of Crohn's disease (CD) in humans remains to be elucidated. The primary objective of the present study was to evaluate the effect of TU‑100 on the circulating ADM levels in patients with active CD. An additional objective was to assess the effect of the drug on the disease activity and its potential side effects. In an open‑label study, 10 patients with active CD received 15 g TU‑100 per day for 8 consecutive weeks, and baseline anti‑inflammatory therapy was continued. The pre‑ and post‑treatment blood plasma levels of total ADM (t‑ADM) and mature‑ADM (m‑ADM) were determined using enzyme‑linked immunosorbent assays. The response of patients to the treatment was evaluated clinically using the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) score. The plasma levels of t‑ADM (16.4±1.1 vs. 20.2±1.7 fmol/ml, P=0.0218) and m‑ADM (1.7±0.1 vs. 2.2±0.1 fmol/ml, P=0.0284) increased following 8 weeks of TU‑100 treatment, compared with control. The IOIBD score of patients also improved, with a significant decrease in the score from 3.9±0.5 at 0 weeks to 2.4±0.4 at 8 weeks (P=0.0284). Out of the 10 components of the IOIBD scoring system, the scores for abdominal pain and tenderness, decreased significantly (P=0.014 and P=0.046). Therefore, TU‑100 was safe and well‑tolerated by the patients that participated in the current study. The present study determined that the pharmacologic action of TU‑100 is associated with changes in the circulating ADM levels and that treatment with TU‑100 may aid in the management of CD. These promising findings warrant further investigation in larger, multicenter studies. PMID:27432470

  5. Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms.

    PubMed

    Georgin-Lavialle, S; Launay, J-M; Côté, F; Soucié, E; Soria, A; Damaj, G; Moura, D S; Canioni, D; Hanssens, K; Chandesris, M-O; Barète, S; Dubreuil, P; Lortholary, O; Hermine, O; Sokol, H

    2016-03-01

    The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases. PMID:26841279

  6. Sea-Level Anomalies Facilitate Beach Erosion and Increase Barrier Island Vulnerability to Storms and Sea-Level Rise

    NASA Astrophysics Data System (ADS)

    Theuerkauf, E. J.; Rodriguez, A. B.; Fegley, S. R.; Luettich, R. A., Jr.

    2014-12-01

    Sea-level anomalies are intra-seasonal (weeks to months) periods of high water level induced by oceanographic and meteorological processes, such as reduced Gulf Stream transport strength or persistent northeasterly winds. Although flooding associated with sea-level anomalies has been documented along continental coastlines (e.g. U.S. East Coast), these phenomena are not presently included in coastal models and management plans. We present the first measurements of beach erosion after a year with frequent sea-level anomalies. Erosion during this year, which was not impacted by large storms, was similar to a year with a hurricane, indicating that sea-level anomalies are important facilitators of coastal erosion. Beach erosion was measured at Onslow Beach, NC (OB) in a year with frequent sea-level anomalies (2009-2010) and compared to erosion during a year with no major events (2010-2011) and the year with Hurricane Irene (2011-2012). Sea-level anomalies were identified in water level data from a NOAA tide gauge in Wrightsville Beach, NC. From 2009-2010 anomalously high sea level occurred ~40% of the time, compared to ~8% from 2010-2011 and ~10% from 2011-2012. Significant wave heights, measured from an acoustic wave and current profiler and NOAA buoys offshore of OB, were not statistically different among these 3 years. The average backshore, high intertidal, and mid intertidal maximum depth of erosion for all sites along OB in the year with frequent sea-level anomalies were ~25, 50, and 55 cm, respectively. These values are greater than those measured after the year with no major events (~13, 29, and 32 cm) and similar to those measured after the year with Hurricane Irene (~27, 49, and 40 cm). OB has high along-strike variability in barrier island morphology, thus results apply to many beaches and barrier islands. Our results suggest that anomalies are important mechanisms of coastal change and likely amplify erosion in response to accelerated sea-level rise and

  7. Simulations of Polymer Crazing: Effect of Crosslinks and Dilution

    NASA Astrophysics Data System (ADS)

    Robbins, Mark O.; Barsky, Sandra

    2000-03-01

    Molecular dynamics simulations were used to study the growth and structure of crazes in adhesive films of entangled linear polymers that have been either (a) crosslinked or (b) diluted by smaller molecules. The films were ruptured by separating the two bounding walls (adherends) at a small constant velocity. In all systems the force on the walls rose to the same value before the first yield event caused cavities to form in the film. These cavities grew as the walls were displaced further. In systems that formed a stable craze, cavity growth was eventually stopped by entanglements or crosslinks. Stress concentrations then caused new cavities to form in neighboring regions. This process continued at a constant plateau stress until the entire film had been stretched by an extension ratio λ. The plateau stress increased slightly with increasing crosslink density, and decreased with decreasing fraction of long chains in diluted systems. As in experiments, when the fraction decreased below about 30plateau stress vanished and there was no longer a stable craze. The extension ratio fell with increasing crosslink density and rose as the fraction of long chains dropped. These changes can be fit with a simple geometric model based on the ability to stretch a random coil whose length is the mean spacing between crosslinks or entanglements. No chain scission was found for reasonable bond strengths. Void formation and elastic constants were also studied.

  8. Protein folding: Turbo-charged crosslinking

    NASA Astrophysics Data System (ADS)

    Craik, David J.

    2012-08-01

    The efficient production of stable bioactive proteins often requires the selective formation of several disulfide crosslinks. Two recent studies have now shown that replacing cysteine with selenocysteine in the unfolded protein can autocatalyse the formation of the desired crosslinks.

  9. Enterostatin decreases postprandial pancreatic UCP2 mRNA levels and increases plasma insulin and amylin.

    PubMed

    Arsenijevic, Denis; Gallmann, Eva; Moses, William; Lutz, Thomas; Erlanson-Albertsson, Charlotte; Langhans, Wolfgang

    2005-07-01

    This study investigated the chronic effect of enterostatin on body weight and some of the associated changes in postprandial metabolism. Rats were adapted to 6 h of food access/day and a choice of low-fat and high-fat (HF) food and then given enterostatin or vehicle by an intraperitoneally implanted minipump delivering 160 nmol enterostatin/h continuously over a 5-day infusion period. Enterostatin resulted in a slight but significant reduction of HF intake and body weight. After the last 6-h food access period, enterostatin-treated animals had lower plasma triglyceride and free fatty acid but higher plasma glucose and lactate levels than control animals. Enterostatin infusion resulted in increased uncoupling protein-2 (UCP2) expression in various tissues, including epididymal fat and liver. UCP2 was reduced in the pancreas of enterostatin-treated animals, and this was associated with increased plasma levels of insulin and amylin. Whether these two hormones are involved in the observed decreased food intake due to enterostatin remains to be determined. As lipid metabolism appeared to be altered by enterostatin, we measured peroxisome proliferator-activated receptor (PPAR) expression in tissues and observed that PPARalpha, -beta, -gamma1, and -gamma2 expression were modified by enterostatin in epididymal fat, pancreas, and liver. This further links altered lipid metabolism with body weight loss. Our data suggest that alterations in UCP2 and PPARgamma2 play a role in the control of insulin and amylin release from the pancreas. This implies that enterostatin changes lipid and carbohydrate metabolic pathways in addition to its effects on food intake and energy expenditure. PMID:15713687

  10. Increase of adenosine plasma levels after oral trimetazidine: a pharmacological preconditioning?

    PubMed

    Blardi, Patrizia; de Lalla, Arianna; Volpi, Luciana; Auteri, Alberto; Di Perri, Tullio

    2002-01-01

    Trimetazidine (1-[2,3,4-trimethoxybenzyl] piperazine) (TMZ) is a cellular anti-ischemic agent able to prevent intracellular ATP decrease, limit intracellular acidosis, protect against oxygen-free radical-induced toxicity and inhibit neutrophil infiltration. However, its definitive mechanism of action had not been identified. Recent studies showed the existence of an endogenous mechanism of cellular protection against ischemia, defined as 'ischemic preconditioning'. This mechanism was related mainly to cellular liberation of adenosine, a nucleoside with protective effects in myocardial ischemia. Since TMZ acts by increasing cell tolerance to ischemia and adenosine is the mediator of ischemic preconditioning, in this study we investigated a possible interaction between TMZ and adenosine. Two groups of patients affected by angina pectoris, were admitted to the study. They received a single oral dose of TMZ. One group was treated, during different sessions, with TMZ 10 and 20 mg, the other group with TMZ 40 and 80 mg. After a 3 day wash-out from drug administration, each group received a placebo. Blood samples were collected at baseline (time 0) and 1, 2, 3, 4, 6, 8 h after drug administration, in order to detect plasma levels of adenosine by a high-performance liquid chromatography method. We observed that the administration of TMZ at doses of 10, 20, 40 and 80 mg induced an increase of adenosine plasma levels of 19, 50, 62 and 62%, respectively. We hypothesized that the activity of TMZ could depend, at least in part, on adenosine mediation and this interaction opens a new interpretation of the drug antischemic effect. PMID:11820865

  11. Microzooplankton grazing and phytoplankton growth in marine mesocosms with increased CO2 levels

    NASA Astrophysics Data System (ADS)

    Suffrian, K.; Simonelli, P.; Nejstgaard, J. C.; Putzeys, S.; Carotenuto, Y.; Antia, A. N.

    2008-01-01

    Microzooplankton grazing and algae growth responses to increasing pCO2 levels (350, 700 and 1050 μatm) were investigated in nitrate and phosphate fertilized mesocosms during the PeECE III experiment 2005. Grazing and growth rates were estimated by the dilution technique combined with taxon specific HPLC pigment analysis. Phytoplankton and microzooplankton composition were determined by light microscopy. Despite a range up to 3 times the present CO2 levels, there were no clear differences in any measured parameter between the different CO2 treatments. Thus, during the first 9 days of the experiment the algae community standing stock (SS), measured as chlorophyll a (Chl a), showed the highest instantaneous grow rates (0.02-0.99 d-1) and increased from ca 2-3 to 6-12 μg l-1, in all mesocosms. Afterwards the phytoplankton SS decreased in all mesocosms until the end of the experiment. The microzooplankton SS, that was mainly dinoflagellates and ciliates varied between 23 and 130 μg C l-1, peaking on day 13-15, apparently responding to the phytoplankton development. Instantaneous Chl a growth rates were generally higher than the grazing rates, indicating only a limited overall effect of microzooplankton grazing on the most dominant phytoplankton. Diatoms and prymnesiophytes were significantly grazed (14-43% of the SS d-1) only in the pre-bloom phase when they were in low numbers and in the post-bloom phase when they were already limited by low nutrients and/or virus lysis. The cyanobacteria populations appeared more effected by microzooplankton grazing, generally removing 20-65% of the SS d-1.

  12. Microzooplankton grazing and phytoplankton growth in marine mesocosms with increased CO2 levels

    NASA Astrophysics Data System (ADS)

    Suffrian, K.; Simonelli, P.; Nejstgaard, J. C.; Putzeys, S.; Carotenuto, Y.; Antia, A. N.

    2008-08-01

    Microzooplankton grazing and algae growth responses to increasing pCO2 levels (350, 700 and 1050 μatm) were investigated in nitrate and phosphate fertilized mesocosms during the PeECE III experiment 2005. Grazing and growth rates were estimated by the dilution technique combined with taxon specific HPLC pigment analysis. Microzooplankton composition was determined by light microscopy. Despite a range of up to 3 times the present CO2 levels, there were no clear differences in any measured parameter between the different CO2 treatments. During days 3 9 of the experiment the algae community standing stock, measured as chlorophyll a (Chl-a), showed the highest instantaneous grow rates (k=0.37 0.99 d-1) and increased from ca. 2 3 to 6 12 μg l-1, in all mesocosms. Afterwards the phytoplankton standing stock decreased in all mesocosms until the end of the experiment. The microzooplankton standing stock, that was mainly constituted by dinoflagellates and ciliates, varied between 23 and 130 μg C l-1 (corresponding to 1.9 and 10.8 μmol C l-1), peaking on day 13 15, apparently responding to the phytoplankton development. Instantaneous Chl-a growth rates were generally higher than the grazing rates, indicating only a limited overall effect of microzooplankton grazing on the most dominant phytoplankton. Diatoms and prymnesiophytes were significantly grazed (12 43% of the standing stock d-1) only in the pre-bloom phase when they were in low numbers, and in the post-bloom phase when they were already affected by low nutrients and/or viral lysis. The cyanobacteria populations appeared more affected by microzooplankton grazing which generally removed 20 65% of the standing stock per day.

  13. Increase in upper tropospheric and lower stratospheric aerosol levels and its potential connection with Asian pollution

    PubMed Central

    Vernier, J-P; Fairlie, T D; Natarajan, M; Wienhold, F G; Bian, J; Martinsson, B G; Crumeyrolle, S; Thomason, L W; Bedka, K M

    2015-01-01

    Satellite observations have shown that the Asian Summer Monsoon strongly influences the upper troposphere and lower stratosphere (UTLS) aerosol morphology through its role in the formation of the Asian Tropopause Aerosol Layer (ATAL). Stratospheric Aerosol and Gas Experiment II solar occultation and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) lidar observations show that summertime UTLS Aerosol Optical Depth (AOD) between 13 and 18 km over Asia has increased by three times since the late 1990s. Here we present the first in situ balloon measurements of aerosol backscatter in the UTLS from Western China, which confirm high aerosol levels observed by CALIPSO since 2006. Aircraft in situ measurements suggest that aerosols at lower altitudes of the ATAL are largely composed of carbonaceous and sulfate materials (carbon/sulfur elemental ratio ranging from 2 to 10). Back trajectory analysis from Cloud-Aerosol Lidar with Orthogonal Polarization observations indicates that deep convection over the Indian subcontinent supplies the ATAL through the transport of pollution into the UTLS. Time series of deep convection occurrence, carbon monoxide, aerosol, temperature, and relative humidity suggest that secondary aerosol formation and growth in a cold, moist convective environment could play an important role in the formation of ATAL. Finally, radiative calculations show that the ATAL layer has exerted a short-term regional forcing at the top of the atmosphere of −0.1 W/m2 in the past 18 years. Key Points Increase of summertime upper tropospheric aerosol levels over Asia since the 1990s Upper tropospheric enhancement also observed by in situ backscatter measurements Significant regional radiative forcing of −0.1 W/m2 PMID:26691186

  14. Thyroid sialyltransferase mRNA level and activity are increased in Graves' disease.

    PubMed

    Kiljański, Jacek; Ambroziak, Michał; Pachucki, Janusz; Jazdzewski, Krystian; Wiechno, Wieslaw; Stachlewska, Elzbieta; Górnicka, Barbara; Bogdańska, Magdalena; Nauman, Janusz; Bartoszewicz, Zbigniew

    2005-07-01

    Sialylation of cell components is an important immunomodulating mechanism affecting cell response to hormones and adhesion molecules. To study alterations in sialic acid metabolism in Graves' disease (GD) we measured the following parameters in various human thyroid tissues: lipid-bound sialic acid (LBSA) content, ganglioside profile, total sialyltransferase activity, and the two major sialyltransferase mRNAs for sialyltransferase-1 (ST6Gal I) and for sialyltransferase-4A (ST3Gal I). Fragments of toxic thyroid nodules (TN), nontoxic thyroid nodules (NN) and nontumorous tissue from patients with nodular goiter or thyroid cancer were used as a control (C). The LBSA content and sialyltransferase activity were the highest in the GD group (164 +/- 4.44 versus 120 +/- 2.00 nmoL/g, p = 0.005 and 1625 +/- 283.5 versus 324 +/- 54.2 cpm/mg of protein, p < 0.005 compared to control group C). Ganglioside profile in the GD group was similar to that in control tissues. Sialyltransferase- 1 mRNA and sialyltransferase-4A mRNA levels were significantly higher in the GD group than in the control group (12.52 +/- 6.90 versus 2.54 +/- 1.24 arbitrary units, p < 0.005 and 2,49 +/- 1.16 versus 1.23 +/- 0.46 arbitrary units, p < 0.05, respectively). There was a positive correlation between the increased sialyltransferase-1 mRNA level and the TSH-receptor antibody titer determined by the TRAK test. These results indicate that sialyltransferases expression and activity are increased in GD. Exact mechanism of this upregulation remains unknown, though one of possible explanations is the activation of the thyrotropin (TSH) receptor. PMID:16053379

  15. Cross-linked network development in compatibilized alkyd/acrylic hybrid latex films for the creation of hard coatings.

    PubMed

    Wang, Tao; de las Heras Alarcón, Carolina; Goikoetxea, Monika; Beristain, Itxaso; Paulis, Maria; Barandiaran, Maria J; Asua, José M; Keddie, Joseph L

    2010-09-01

    Hybrids made from an alkyd resin and an acrylic copolymer can potentially combine the desired properties of each component. Alkyd/acrylic hybrid latex particles were synthesized via miniemulsion polymerization and used to create films at room temperature. Comparisons of the alkyd auto-oxidative cross-linking rates and the associated network development are made between two alkyd resins (with differing levels of hydrophilicity as measured by their acid numbers). The effects of increasing the compatibilization between the alkyd and the acrylic phase via functionalization with glycidyl methacrylate (GMA) are investigated. Magnetic resonance profiling and microindentation measurements reveal that film hardening occurs much faster in a GMA-functionalized alkyd hybrid than in the standard hybrid. The film's hardness increases by a factor of 4 over a 5-day period. The rate of cross-linking is significantly slower in nonfunctionalized alkyd hybrid films and when the more hydrophilic alkyd resin is used. Tensile deformation of the hybrid latex films reveals the effects of GMA functionalization and drier concentration in creating a denser cross-linked network. Modeling of the tensile deformation behavior of the hybrid films used a combination of the upper convected Maxwell model (to describe the viscoelastic component) and the Gent model (to describe the elastic component). The modeling provides a correlation between the cross-linked network formation and the resulting mechanical properties. PMID:20704338

  16. Modification of chitosan by swelling and crosslinking using epichlorohydrin as heavy metal Cr (VI) adsorbent in batik industry wastes

    NASA Astrophysics Data System (ADS)

    Hastuti, B.; Masykur, A.; Hadi, S.

    2016-02-01

    Study on chitosan modification by swelling and crosslinking and its application as a selective adsorbent for heavy metals Cr (VI) in batik industry wastes was done. Swelling is intended to improve chitosan porosity, whereas crosslinking is to increase the resistance of chitosan against acid. Natural samples are generally acidic, thus limiting chitosan application as an adsorbent. Modification of chitosan by combining swelling and crosslinking is expected to increase its adsorption capacity in binding heavy metal ions in water. The modified chitosan was later contacted with Cr (VI) to test its adsorption capacity with a variation of pH and contact time. Finally, application of modified chitosan was done in batik industry waste containing Cr (IV). Based on the results, chitosan-ECH 25% (v/v) was the optimum concentration of crosslinker to adsorb Cr (VI) ions. Modified chitosan has a solubility resistance to acids, even though a strong acid. Modification of chitosan also improved its adsorption capacity to Cr (VI) from 74% (pure chitosan) to 89% with contact time 30 min at pH 3. On the application to the batik wastes, the modified chitosan were able to adsorb Cr (IV) up to the level of 5 ppm. Thus, the modified chitosan has a potential to be applied to as an adsorbent of Cr (VI) in batik industry wastes.

  17. Cofilin/Twinstar Phosphorylation Levels Increase in Response to Impaired Coenzyme A Metabolism

    PubMed Central

    Siudeja, Katarzyna; Grzeschik, Nicola A.; Rana, Anil; de Jong, Jannie; Sibon, Ody C. M.

    2012-01-01

    Coenzyme A (CoA) is a pantothenic acid-derived metabolite essential for many fundamental cellular processes including energy, lipid and amino acid metabolism. Pantothenate kinase (PANK), which catalyses the first step in the conversion of pantothenic acid to CoA, has been associated with a rare neurodegenerative disorder PKAN. However, the consequences of impaired PANK activity are poorly understood. Here we use Drosophila and human neuronal cell cultures to show how PANK deficiency leads to abnormalities in F-actin organization. Cells with reduced PANK activity are characterized by abnormally high levels of phosphorylated cofilin, a conserved actin filament severing protein. The increased levels of phospho-cofilin coincide with morphological changes of PANK-deficient Drosophila S2 cells and human neuronal SHSY-5Y cells. The latter exhibit also markedly reduced ability to form neurites in culture – a process that is strongly dependent on actin remodeling. Our results reveal a novel and conserved link between a metabolic biosynthesis pathway, and regulation of cellular actin dynamics. PMID:22912811

  18. Mitohormesis: Promoting Health and Lifespan by Increased Levels of Reactive Oxygen Species (ROS)

    PubMed Central

    Ristow, Michael; Schmeisser, Kathrin

    2014-01-01

    Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful. PMID:24910588

  19. Increased Umbilical Cord PAI-1 Levels in Placental Insufficiency Are Associated with Fetal Hypoxia and Angiogenesis

    PubMed Central

    Seferovic, Maxim D.; Gupta, Madhulika B.

    2016-01-01

    In intrauterine growth restriction (IUGR), a subset of pregnancies undergoes placental vascular dysregulation resulting in restricted blood flow and fetal hypoxemia. Altered transcription of hypoxic regulated plasminogen activator inhibitor 1 (PAI-1) has been associated with pregnancy complications and angiogenic regulation. Here we assessed circulating PAI-1 as an indicator of placental insufficiency. Venous umbilical PAI-1 of hypoxemic (VpO2 20 versus 35 mmHg, p < 0.0001) placental insufficient pregnancies (resistance index 0.9 versus 0.63, p < 0.05) (n = 18) was compared to controls (n = 12). PAI-1 was increased (~10-fold, p < 0.001) and had a positive predictive ratio of 6.7. Further, PAI-1 levels correlated to blood oxygen (r = −0.68, p < 0.0001). The plasma's angiogenic potency measured in vitro was associated with umbilical cord blood PAI-1 levels (r = 0.65, p < 0.01). This association was attenuated by PAI-1 inhibiting antibody (p < 0.001). The results demonstrate PAI-1 as a potential marker of placental insufficiency and identify its close association with pathological hypoxia and angiogenesis in a subset of growth restricted pregnancies. PMID:26903689

  20. Enhanced zinc consumption causes memory deficits and increased brain levels of zinc

    USGS Publications Warehouse

    Flinn, J.M.; Hunter, D.; Linkous, D.H.; Lanzirotti, A.; Smith, L.N.; Brightwell, J.; Jones, B.F.

    2005-01-01

    Zinc deficiency has been shown to impair cognitive functioning, but little work has been done on the effects of elevated zinc. This research examined the effect on memory of raising Sprague-Dawley rats on enhanced levels of zinc (10 ppm ZnCO3; 0.153 mM) in the drinking water for periods of 3 or 9 months, both pre- and postnatally. Controls were raised on lab water. Memory was tested in a series of Morris Water Maze (MWM) experiments, and zinc-treated rats were found to have impairments in both reference and working memory. They were significantly slower to find a stationary platform and showed greater thigmotaxicity, a measure of anxiety. On a working memory task, where the platform was moved each day, zinc-treated animals had longer latencies over both trials and days, swam further from the platform, and showed greater thigmotaxicity. On trials using an Atlantis platform, which remained in one place but was lowered on probe trials, the zinc-treated animals had significantly fewer platform crossings, spent less time in the target quadrant, and did not swim as close to the platform position. They had significantly greater latency on nonprobe trials. Microprobe synchrotron X-ray fluorescence (??SXRF) confirmed that brain zinc levels were increased by adding ZnCO 3 to the drinking water. These data show that long-term dietary administration of zinc can lead to impairments in cognitive function. ?? 2004 Elsevier Inc. All rights reserved.

  1. Smelling lavender and rosemary increases free radical scavenging activity and decreases cortisol level in saliva.

    PubMed

    Atsumi, Toshiko; Tonosaki, Keiichi

    2007-02-28

    Free radicals/reactive oxygen species are related to many biological phenomena such as inflammation, aging, and carcinogenesis. The body possesses various antioxidative systems (free radical scavenging activity, FRSA) for preventing oxidative stress, and saliva contains such activity. In the present study, we measured the total salivary FRSA induced after the smelling of lavender and rosemary essential oils that are widely used in aromatherapy. Various physiologically active substances in saliva such as cortisol, secretory IgA, and alpha-amylase activity were found to be correlated with aroma-induced FRSA. The subjects (22 healthy volunteers) sniffed aroma for 5 min, and each subject's saliva was collected immediately. FRSA was measured using 1,1-diphenyl-2-picrylhydrazyl. The FRSA values were increased by stimulation with low concentrations (1000 times dilution) of lavender or by high-concentrations (10 times dilution) of rosemary. In contrast, both lavender and rosemary stimulations decreased cortisol levels. A significant inverse correlation was observed between the FRSA values and the cortisol levels with each concentration of rosemary stimulation. No significant changes were noted in sIgA or alpha-amylase. These findings clarify that lavender and rosemary enhance FRSA and decrease the stress hormone, cortisol, which protects the body from oxidative stress. PMID:17291597

  2. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration.

    PubMed

    Tanito, Masaki; Brush, Richard S; Elliott, Michael H; Wicker, Lea D; Henry, Kimberly R; Anderson, Robert E

    2009-05-01

    The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

  3. Conventional hemofiltration during cardiopulmonary bypass increases the serum lactate level in adult cardiac surgery

    PubMed Central

    Soliman, Rabie; Fouad, Eman; Belghith, Makhlouf; Abdelmageed, Tarek

    2016-01-01

    Objective: To evaluate the effect of hemofiltration during cardiopulmonary bypass on lactate level in adult patients who underwent cardiac surgery. Design: An observational study. Setting: Prince Sultan cardiac center, Riyadh, Saudi Arabia. Participants: The study included 283 patients classified into two groups: Hemofiltration group (n=138), hemofiltration was done during CPB. Control group (n = 145), patients without hemofiltration. Interventions: Hemofiltration during cardiopulmonary bypass. Measurements and Main Results: Monitors included hematocrit, lactate levels, mixed venous oxygen saturation, amount of fluid removal during hemofiltration and urine output. The lactate elevated in group H than group C (P < 0.05), and the PH showed metabolic acidosis in group H (P < 0.05). The mixed venous oxygen saturation decreased in group H than group C (P < 0.05). The number of transfused packed red blood cells was lower in group H than group C (P < 0.05). The hematocrit was higher in group H than group C (P < 0.05). The urine output was lower in group H than group C (P < 0.05). Conclusions: Hemofiltration during cardiopulmonary bypass leads to hemoconcentration, elevated lactate level and increased inotropic support. There are some recommendations for hemofiltration: First; Hemofiltration should be limited for patients with impaired renal function, positive fluid balance, reduced response to diuretics or prolonged bypass time more than 2 hours. Second; Minimal amount of fluids should be administered to maintain adequate cardiac output and reduction of priming volumes is preferable to maintain controlled hemodilution. Third; it should be done before weaning of or after cardiopulmonary bypass and not during the whole time of cardiopulmonary bypass. PMID:26750673

  4. Characterization of glycidyl methacrylate – Crosslinked hyaluronan hydrogel scaffolds incorporating elastogenic hyaluronan oligomers

    PubMed Central

    Ibrahim, S.; Kothapalli, C.R.; Kang, Q.K.; Ramamurthi, A.

    2013-01-01

    Prior studies on two-dimensional cell cultures suggest that hyaluronic acid (HA) stimulates cell-mediated regeneration of extracellular matrix structures, specifically those containing elastin, though such biologic effects are dependent on HA fragment size. Towards being able to regenerate three-dimensional (3-D) elastic tissue constructs, the present paper studies photo-crosslinked hydrogels containing glycidyl methacrylate (GM)-derivatized bio-inert high molecular weight(HMW)HA (1 × 106 Da) and a bioactive HA oligomer mixture (HA-o: MW ~0.75 kDa). The mechanical (rheology, degradation) and physical (apparent crosslinking density, swelling ratio) properties of the gels varied as a function of incorporated HA oligomer content; however, overall, the mechanics of these hydrogels were too weak for vascular applications as stand-alone materials. Upon in vivo subcutaneous implantation, only a few inflammatory cells were evident around GM–HA gels, however their number increased as HA-o content within the gels increased, and the collagen I distribution was uniform. Smooth muscle cells (SMC) were encapsulated into GM hydrogels, and calcein acetoxymethyl detection revealed that the cells were able to endure twofold the level of UV exposure used to crosslink the gels. After 21 days of culture, SMC elastin production, measured by immunofluorescence quantification, showed HA-o to increase cellular deposition of elastic matrix twofold relative to HA-o-free GM–HAgels. These results demonstrate that cell response to HA/HA-o is not altered by their methacrylation and photo-crosslinking into a hydrogel, and that HA-o incorporation into cell-encapsulating hydrogel scaffolds can be useful for enhancing their production of elastic matrix structures in a 3-D space, important for regenerating elastic tissues. PMID:20709199

  5. Characterization of glycidyl methacrylate - crosslinked hyaluronan hydrogel scaffolds incorporating elastogenic hyaluronan oligomers.

    PubMed

    Ibrahim, S; Kothapalli, C R; Kang, Q K; Ramamurthi, A

    2011-02-01

    Prior studies on two-dimensional cell cultures suggest that hyaluronic acid (HA) stimulates cell-mediated regeneration of extracellular matrix structures, specifically those containing elastin, though such biologic effects are dependent on HA fragment size. Towards being able to regenerate three-dimensional (3-D) elastic tissue constructs, the present paper studies photo-crosslinked hydrogels containing glycidyl methacrylate (GM)-derivatized bio-inert high molecular weight (HMW) HA (1 × 10(6)Da) and a bioactive HA oligomer mixture (HA-o: MW ∼0.75 kDa). The mechanical (rheology, degradation) and physical (apparent crosslinking density, swelling ratio) properties of the gels varied as a function of incorporated HA oligomer content; however, overall, the mechanics of these hydrogels were too weak for vascular applications as stand-alone materials. Upon in vivo subcutaneous implantation, only a few inflammatory cells were evident around GM-HA gels, however their number increased as HA-o content within the gels increased, and the collagen I distribution was uniform. Smooth muscle cells (SMC) were encapsulated into GM hydrogels, and calcein acetoxymethyl detection revealed that the cells were able to endure twofold the level of UV exposure used to crosslink the gels. After 21 days of culture, SMC elastin production, measured by immunofluorescence quantification, showed HA-o to increase cellular deposition of elastic matrix twofold relative to HA-o-free GM-HA gels. These results demonstrate that cell response to HA/HA-o is not altered by their methacrylation and photo-crosslinking into a hydrogel, and that HA-o incorporation into cell-encapsulating hydrogel scaffolds can be useful for enhancing their production of elastic matrix structures in a 3-D space, important for regenerating elastic tissues. PMID:20709199

  6. Interleukin-17 SNPs and serum levels increase ulcerative colitis risk: A meta-analysis

    PubMed Central

    Li, Juan; Tian, Hao; Jiang, Hui-Jun; Han, Bin

    2014-01-01

    AIM: To investigate the associations of interleukin-17 (IL-17) genetic polymorphisms and serum levels with ulcerative colitis (UC) risk. METHODS: Relevant articles were identified through a search of the following electronic databases, excluding language restriction: (1) the Cochrane Library Database (Issue 12, 2013); (2) Web of Science (1945-2013); (3) PubMed (1966-2013); (4) CINAHL (1982-2013); (5) EMBASE (1980-2013); and (6) the Chinese Biomedical Database (1982-2013). Meta-analysis was conducted using STATA 12.0 software. Crude odds ratios and standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were calculated. All of the included studies met all of the following five criteria: (1) the study design must be a clinical cohort or a case-control study; (2) the study must relate to the relationship between IL-17A/F genetic polymorphisms or serum IL-17 levels and the risk of UC; (3) all patients must meet the diagnostic criteria for UC; (4) the study must provide sufficient information about single nucleotide polymorphism frequencies or serum IL-17 levels; and (5) the genotype distribution of healthy controls must conform to the Hardy-Weinberg equilibrium (HWE). The Newcastle-Ottawa Scale (NOS) criteria were used to assess the methodological quality of the studies. The NOS criteria included three aspects: (1) subject selection: 0-4; (2) comparability of subjects: 0-2; and (3) clinical outcome: 0-3. NOS scores ranged from 0 to 9, with a score ≥ 7 indicating good quality. RESULTS: Of the initial 177 articles, only 16 case-control studies met all of the inclusion criteria. A total of 1614 UC patients and 2863 healthy controls were included in this study. Fourteen studies were performed on Asian populations, and two studies on Caucasian populations. Results of the meta-analysis revealed that IL-17A and IL-17F genetic polymorphisms potentially increased UC risk under both allele and dominant models (P < 0.001 for all). The results also

  7. Middle Holocene humidity increase in Florida: climate or sea-level?

    NASA Astrophysics Data System (ADS)

    Donders, Timme H.

    2014-11-01

    Florida climate in highly sensitive to both high and low latitude climate perturbations due to its latitudinal position surrounded by water masses that transport heat northward. A well-studied aspect is that middle Holocene conditions became significantly wetter in Florida, initiating widespread peat accumulation in the Everglades. This environmental change has been attributed to various climate forcings, such as migration of the Intertropical Convergence Zone (ITCZ), increases in tropical storm intensity, position of the Bermuda High, intensification of the El Niño Southern Oscillation (ENSO), and post glacial sea level rise (SLR). Discerning between these forcings is only possible with quantitative reconstructions from a transect of sites that are affected differentially. Application of a transfer function on a north-to-south gradient of pollen records from Florida lakes here shows that the pattern of increasing precipitation during the middle Holocene cannot be explained by SLR, but that ENSO intensification is an important contributing factor. Seasonal-resolved proxy records with improved age models are urgently needed to further solve these issues.

  8. Combined atmospheric oxidant capacity and increased levels of exhaled nitric oxide

    NASA Astrophysics Data System (ADS)

    Yang, Changyuan; Li, Huichu; Chen, Renjie; Xu, Wenxi; Wang, Cuicui; Tse, Lap Ah; Zhao, Zhuohui; Kan, Haidong

    2016-07-01

    Nitrogen dioxide and ozone are two interrelated oxidative pollutants in the atmosphere. Few studies have evaluated the health effects of combined oxidant capacity (O x ). We investigated the short-term effects of O x on fractional exhaled nitric oxide (FeNO), a well-established biomarker for airway inflammation, in a group of chronic obstructive pulmonary disease patients. Real-time concentrations of O x were obtained by calculating directly the sum of nitrogen dioxide and ozone. Linear mixed-effect models were applied to explore the acute effects of O x on FeNO levels. Short-term exposure to Ox was significantly associated with elevated FeNO. This effect was strongest in the first 24 h after exposure, and was robust to the adjustment of PM2.5. A 10 μg m‑3 increase in 24 h average concentrations of O x was associated with 4.28% (95% confidence interval: 1.19%, 7.37%) increase in FeNO. The effect estimates were statistically significant only among males, elders, and those with body mass index ≥24 kg m‑2, a comorbidity, higher educational attainment, or moderate airflow limitation. This analysis demonstrated an independent effect of O x on respiratory inflammation, and suggested that a single metric O x might serve as a preferable indicator of atmospheric oxidative capacity in further air pollution epidemiological studies.

  9. Rice Bran Amendment Suppresses Potato Common Scab by Increasing Antagonistic Bacterial Community Levels in the Rhizosphere.

    PubMed

    Tomihama, Tsuyoshi; Nishi, Yatsuka; Mori, Kiyofumi; Shirao, Tsukasa; Iida, Toshiya; Uzuhashi, Shihomi; Ohkuma, Moriya; Ikeda, Seishi

    2016-07-01

    Potato common scab (PCS), caused by pathogenic Streptomyces spp., is a serious disease in potato production worldwide. Cultural practices, such as optimizing the soil pH and irrigation, are recommended but it is often difficult to establish stable disease reductions using these methods. Traditionally, local farmers in southwest Japan have amended soils with rice bran (RB) to suppress PCS. However, the scientific mechanism underlying disease suppression by RB has not been elucidated. The present study showed that RB amendment reduced PCS by repressing the pathogenic Streptomyces population in young tubers. Amplicon sequencing analyses of 16S ribosomal RNA genes from the rhizosphere microbiome revealed that RB amendment dramatically changed bacterial composition and led to an increase in the relative abundance of gram-positive bacteria such as Streptomyces spp., and this was negatively correlated with PCS disease severity. Most actinomycete isolates derived from the RB-amended soil showed antagonistic activity against pathogenic Streptomyces scabiei and S. turgidiscabies on R2A medium. Some of the Streptomyces isolates suppressed PCS when they were inoculated onto potato plants in a field experiment. These results suggest that RB amendment increases the levels of antagonistic bacteria against PCS pathogens in the potato rhizosphere. PMID:27050572

  10. Apolipoprotein AI levels are increased in part as a consequence of reduced catabolism in nephrotic rats.

    PubMed

    Kaysen, G A; Hoye, E; Jones, H

    1995-03-01

    Apolipoprotein AI (apo AI) synthesis, measured as the turnover of 125I-labeled apo AI-labeled high-density lipoprotein (HDL), was increased significantly in rats with Heymann nephritis (HN) vs. control Sprague-Dawley (SD) rats. However, fractional apo AI catabolic rate was also significantly less in HN vs. SD. We used 125I-apo AI tyramine cellobiose HDL, a marker retained at the catabolic site, to establish where apo AI catabolism decreased in six HN rats, seven rats with adriamycin (Adria)-induced nephrosis, and six control SD. Total renal apo AI catabolism, plus urinary losses, were the same in all three groups, despite significant urinary apo AI in HN and Adria rats. Apo AI catabolism was reduced in skin in both nephrotic groups, accounting for approximately 44% of reduced in apo AI catabolism. Thus a significant fraction of apo AI is catabolized in skin of normal male rats. Reduced apo AI catabolism in skin contributes to increased plasma levels in nephrotic rats. PMID:7900854

  11. Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids

    PubMed Central

    Haeusler, Rebecca A.; Astiarraga, Brenno; Camastra, Stefania; Accili, Domenico; Ferrannini, Ele

    2013-01-01

    Bile acids (BAs) exert pleiotropic metabolic effects, and physicochemical properties of different BAs affect their function. In rodents, insulin regulates BA composition, in part by regulating the BA 12α-hydroxylase CYP8B1. However, it is unclear whether a similar effect occurs in humans. To address this question, we examined the relationship between clamp-measured insulin sensitivity and plasma BA composition in a cohort of 200 healthy subjects and 35 type 2 diabetic (T2D) patients. In healthy subjects, insulin resistance (IR) was associated with increased 12α-hydroxylated BAs (cholic acid, deoxycholic acid, and their conjugated forms). Furthermore, ratios of 12α-hydroxylated/non–12α-hydroxylated BAs were associated with key features of IR, including higher insulin, proinsulin, glucose, glucagon, and triglyceride (TG) levels and lower HDL cholesterol. In T2D patients, BAs were nearly twofold elevated, and more hydrophobic, compared with healthy subjects, although we did not observe disproportionate increases in 12α-hydroxylated BAs. In multivariate analysis of the whole dataset, controlling for sex, age, BMI, and glucose tolerance status, higher 12α-hydroxy/non–12α-hydroxy BA ratios were associated with lower insulin sensitivity and higher plasma TGs. These findings suggest a role for 12α-hydroxylated BAs in metabolic abnormalities in the natural history of T2D and raise the possibility of developing insulin-sensitizing therapeutics based on manipulations of BA composition. PMID:23884887

  12. Decreased melatonin levels and increased levels of advanced oxidation protein products in the seminal plasma are related to male infertility.

    PubMed

    Kratz, Ewa Maria; Piwowar, Agnieszka; Zeman, Michal; Stebelová, Katarína; Thalhammer, Theresia

    2016-03-01

    Melatonin, an indolamine secreted by the pineal gland, is known as a powerful free-radical scavenger and wide-spectrum antioxidant. Therefore, the aim of this study was to correlate markers of oxidative protein damage (advanced oxidation protein products, AOPPs) and the total antioxidant capacity (TAC) with melatonin levels in the seminal plasma of men with azoospermia (n=37), theratozoospermia (n=29) and fertile controls (normozoospermia, n=37). Melatonin concentration was measured by radioimmunoassay. The levels of AOPP as well as TAC efficiency (determined by the ferric reducing antioxidant power, FRAP) were estimated by spectrophotometric methods. The concentration of melatonin and AOPP significantly differed in azoospermic (P<0.0001) and theratozoospermic (P<0.0001) patients versus fertile men, and correlated negatively (r=-0.33, P=0.0016). The TAC levels were significantly higher in azoospermia than in theratozoospermia (P=0.0022) and the control group (P=0.00016). In azoospermia, the AOPP concentration was also significantly higher than that observed in theratozoospermia (P=0.00029). Decreased levels of melatonin together with elevated AOPP altered the oxidative-antioxidative balance in the ejaculate, thereby reducing fertility. Therefore, melatonin and AOPP levels may serve as additional diagnostic markers of semen quality and male reproductive potential. PMID:25218686

  13. Fracture Mechanics of Collagen Fibrils: Influence of Natural Cross-Links

    PubMed Central

    Svensson, Rene B.; Mulder, Hindrik; Kovanen, Vuokko; Magnusson, S. Peter

    2013-01-01

    Tendons are important load-bearing structures, which are frequently injured in both sports and work. Type I collagen fibrils are the primary components of tendons and carry most of the mechanical loads experienced by the tissue, however, knowledge of how load is transmitted between and within fibrils is limited. The presence of covalent enzymatic cross-links between collagen molecules is an important factor that has been shown to influence mechanical behavior of the tendons. To improve our understanding of how molecular bonds translate into tendon mechanics, we used an atomic force microscopy technique to measure the mechanical behavior of individual collagen fibrils loaded to failure. Fibrils from human patellar tendons, rat-tail tendons (RTTs), NaBH4 reduced RTTs, and tail tendons of Zucker diabetic fat rats were tested. We found a characteristic three-phase stress-strain behavior in the human collagen fibrils. There was an initial rise in modulus followed by a plateau with reduced modulus, which was finally followed by an even greater increase in stress and modulus before failure. The RTTs also displayed the initial increase and plateau phase, but the third region was virtually absent and the plateau continued until failure. The importance of cross-link lability was investigated by NaBH4 reduction of the rat-tail fibrils, which did not alter their behavior. These findings shed light on the function of cross-links at the fibril level, but further studies will be required to establish the underlying mechanisms. PMID:23746520

  14. Effects of Increased Von Willebrand Factor Levels on Primary Hemostasis in Thrombocytopenic Patients with Liver Cirrhosis

    PubMed Central

    Wannhoff, Andreas; Müller, Oliver J.; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A.; Gotthardt, Daniel N.

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180±62 s with Col-Epi and 160±70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥150/nL and hematocrit ≥27.0%, pathological PFA-100 results were found. In thrombocytopenic (<150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3±235.9% vs. 338.7±151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future. PMID

  15. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future

  16. Effect of vapor-phase glutaraldehyde crosslinking on electrospun starch fibers.

    PubMed

    Wang, Wenyu; Jin, Xin; Zhu, Yonghao; Zhu, Chengzhang; Yang, Jian; Wang, Hongjie; Lin, Tong

    2016-04-20

    In this work, we have proven that starch nanofibrous membranes with high tensile strength, water stability and non-cytotoxicity can be produced by electrospinning of starch solution and post-treatment with GTA in vapor phase. GTA vapor phase crosslinking plays a key role in forming water-stable nanofiber membrane and improving the mechanical properties. Comparing with non-crosslinked starch fibers, the crosslinked fibers are increased by nearly 10 times in tensile strength. The crosslinked starch fibrous membranes are non-cytotoxic. They may find applications in the fields of tissue engineering, pharmaceutical therapy and medical. PMID:26876862

  17. Electrospinning formaldehyde cross-linked zein solutions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In order to develop zein fibers with improved physical properties and solvent resistance, formaldehyde was used as the cross-linking reagent before spinning. The cross-linking reaction was carried out in either acetic acid or ethanolic-HCl where the amount of cross-linking reagent was between 1 and...

  18. Electrospun zein fibers using glutaraldehyde as the cross-linking reagent

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glutaraldehyde was used as a cross-linking reagent for zein (corn protein) to provide fibers with improved physical properties and solvent resistance. Glutaraldehyde was used at levels between 2 - 8%. The cross-linking reaction was carried out in acetic acid for twenty hours at room temperature. ...

  19. High levels of cathepsin D and cystatin B are associated with increased risk of coronary events

    PubMed Central

    Gonçalves, Isabel; Hultman, Karin; Dunér, Pontus; Edsfeldt, Andreas; Hedblad, Bo; Fredrikson, Gunilla Nordin; Björkbacka, Harry; Nilsson, Jan; Bengtsson, Eva

    2016-01-01

    Objective The majority of acute coronary syndromes are caused by plaque ruptures. Proteases secreted by macrophages play an important role in plaque ruptures by degrading extracellular matrix proteins in the fibrous cap. Matrix metalloproteinases have been shown to be markers for cardiovascular disease whereas the members of the cathepsin protease family are less studied. Methods Cathepsin D, cathepsin L and cystatin B were measured in plasma at baseline from 384 individuals who developed coronary events (CEs), and from 409 age-matched and sex-matched controls from the Malmö Diet and Cancer cardiovascular cohort. Results Cathepsin D (180 (142–238) vs 163 (128–210), p<0.001), cathepsin L (55 (44–73) vs 52 (43–67), p<0.05) and cystatin B levels (45 (36–57) vs 42 (33–52), p<0.001) were significantly increased in CE cases compared to controls. In addition, increased cathepsin D (220 (165–313) vs 167 (133–211), p<0.001), cathepsin L (61 (46–80) vs 53 (43–68), p<0.05) and cystatin B (46 (38–58) vs 43 (34–54), p<0.05) were associated with prevalent diabetes. Furthermore, cathepsin D and cystatin B were increased in smokers. The HRs for incident CE comparing the highest to the lowest tertile(s) of cathepsin D and cystatin B were 1.34 (95% CI 1.02 to 1.75) and 1.26 (95% CI 1.01 to 1.57), respectively, after adjusting for age, sex, low-density lipoprotein/high-density lipoprotein ratio, triglycerides, body mass index, hypertension and glucose, but these associations did not remain significant after further addition of smoking to the model. In addition, cathepsin D was increased in incident CE cases among smokers after adjusting for cardiovascular risk factors. Conclusions The associations of cathepsin D and cystatin B with future CE provide clinical support for a role of these factors in cardiovascular disease, which for cathepsin D may be of particular importance for smokers. PMID:26848396

  20. Increased levels of oxidative DNA damage attributable to cooking-oil fumes exposure among cooks.

    PubMed

    Ke, Yuebin; Cheng, Jinquan; Zhang, Zhicheng; Zhang, Renli; Zhang, Zhunzhen; Shuai, Zhihong; Wu, Tangchun

    2009-07-01

    Previous investigations have indicated that cooks are exposed to polycyclic aromatic hydrocarbons (PAHs) from cooking-oil fumes. However, Emission of PAH and their carcinogenic potencies from cooking oil fumes sources have not been investigated among cooks. To investigate the urinary excretion of a marker for oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OHdG), in different groups of cooks and different exposure groups, and to study the association between 8-OHdG and 1-hydroxypyrene(1-OHP), a biological marker for PAH exposure. Urine samples were collected from different groups of cooks (n = 86) and from unexposed controls (n = 36); all were male with similar age and smoking habits. The health status, occupational history, smoking, and alcohol consumption 24 h prior to sampling was estimated from questionnaires. The urine samples were frozen for later analyses of 8-OHdG and 1-OHP levels by high-performance liquid chromatography. Excretion in urine of 8-OHdG was similar for controls (mean 1.2micromol/mol creatinine, n = 36), and for those who had been in the kitchen with an exhaust-hood operating (mean 1.5micromol/mol creatinine, n = 45). Cooks exposed to cooking-oil fumes without exhaust-hood operation had significantly increased excretion of 8-OHdG (mean 2.3micromol/mol creatinine, n = 18), compared with controls. The urinary levels of ln 1-OHP and ln 8-OHdG were still significantly correlated in a multiple regression analysis. The results indicate that exposure to PAH or possibly other compounds in cooking-oil fumes may cause oxidative DNA damage. PMID:19225966

  1. Increased serum HMGB1 levels in patients with Henoch-Schönlein purpura.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Wang, Wen-Ju; Qin, Sha; Cao, Na; Li, Meng-Meng

    2014-06-01

    High-mobility group box-1 (HMGB1) has been implicated as a pro-inflammatory cytokine in the pathogenesis of various inflammatory and autoimmune diseases. However, information about HMGB1 in Henoch-Schönlein purpura (HSP) is still unclear. Herein, we investigated the role of HMGB1 in patients with HSP and the pro-inflammatory effects of HMGB1 on human dermal microvascular endothelial cell line (HMEC-1). Serum HMGB1 levels in patients with HSP together with patients with allergic vasculitis (AV) and urticarial vasculitis (UV) were detected by enzyme-linked immunosorbent assay (ELISA). HMEC-1 cells were treated with HMGB1 at concentrations ranging from 4 ng/ml to 100 ng/ml. Serum HMGB1 levels were significantly increased in patients with HSP, AV and UV, when compared with those in control group. Moreover, abundant cytoplasmic expression of HMGB1 was observed in endothelial cells in lesional skin of HSP patients. Using membrane cytokine antibody array, we indicate that HMGB1 markedly induced TNF-α and IL-6 release in cultured supernatant. Furthermore, by real-time quantitative PCR and ELISA, the effects of HMGB1 on these cytokines production in HMEC-1 cells were established. Finally, Western blot data revealed that HMGB1 can induce phosphorylation of inhibitor of κB-α (IκBα) and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in HMEC-1 cells. In conclusion, this study provides first observations on the association of HMGB1 with HSP. We suggest that HMGB1 may be an important mediator of endothelial inflammation through the induction of TNF-α and IL-6 production and may play a crucial role in the pathogenesis of HSP. PMID:24758390

  2. Synthesis of borate cross-linked rhamnogalacturonan II

    PubMed Central

    Funakawa, Hiroya; Miwa, Kyoko

    2015-01-01

    In the present review, we describe current knowledge about synthesis of borate crosslinked rhamnogalacturonan II (RG-II) and it physiological roles. RG-II is a portion of pectic polysaccharide with high complexity, present in primary cell wall. It is composed of homogalacturonan backbone and four distinct side chains (A–D). Borate forms ester bonds with the apiosyl residues of side chain A of two RG-II monomers to generate borate dimerized RG-II, contributing for the formation of networks of pectic polysaccharides. In plant cell walls, more than 90% of RG-II are dimerized by borate under boron (B) sufficient conditions. Borate crosslinking of RG-II in primary cell walls, to our knowledge, is the only experimentally proven molecular function of B, an essential trace-element. Although abundance of RG-II and B is quite small in cell wall polysaccharides, increasing evidence supports that RG-II and its borate crosslinking are critical for plant growth and development. Significant advancement was made recently on the location and the mechanisms of RG-II synthesis and borate cross-linking. Molecular genetic studies have successfully identified key enzymes for RG-II synthesis and regulators including B transporters required for efficient formation of RG-II crosslinking and consequent normal plant growth. The present article focuses recent advances on (i) RG-II polysaccharide synthesis, (ii) occurrence of borate crosslinking and (iii) B transport for borate supply to RG-II. Molecular mechanisms underlying formation of borate RG-II crosslinking and the physiological impacts are discussed. PMID:25954281

  3. Effects of ionic crosslinking on physical and mechanical properties of alginate mulching films.

    PubMed

    Liling, Guo; Di, Zheng; Jiachao, Xu; Xin, Gao; Xiaoting, Fu; Qing, Zhang

    2016-01-20

    The effect of different ionic crosslinking parameters on the thickness, radiometric profiles, and mechanical and water vapor permeation (WVP) properties of alginate mulching films was investigated. Crosslinking by Mn(2+), Zn(2+), and Ca(2+) (but not Al(3+)) increased the tensile strength and light transmission and decreased the WVP of the films. Among the films, those crosslinked by Ca(2+) had the greatest tensile strength and exhibited the highest elongation and light transmission. Furthermore, the WVP and light transmission decreased gradually with increasing Ca(2+) concentration, and the maximum tensile strength and elongation were obtained for 2% (w/v) of Ca(2+). However, the WVP of the films increased gradually with increasing crosslinking time, and the elongation saturated after 2 min. These results suggest that alginate films crosslinked by 2% (w/v) calcium chloride for 2 min had the best overall performance and therefore have the potential to be used as entirely biodegradable agricultural mulching films. PMID:26572354

  4. Meta-analysis of internet-delivered interventions to increase physical activity levels

    PubMed Central

    2012-01-01

    Many internet-delivered physical activity behaviour change programs have been developed and evaluated. However, further evidence is required to ascertain the overall effectiveness of such interventions. The objective of the present review was to evaluate the effectiveness of internet-delivered interventions to increase physical activity, whilst also examining the effect of intervention moderators. A systematic search strategy identified relevant studies published in the English-language from Pubmed, Proquest, Scopus, PsychINFO, CINHAL, and Sport Discuss (January 1990 – June 2011). Eligible studies were required to include an internet-delivered intervention, target an adult population, measure and target physical activity as an outcome variable, and include a comparison group that did not receive internet-delivered materials. Studies were coded independently by two investigators. Overall effect sizes were combined based on the fixed effect model. Homogeneity and subsequent exploratory moderator analysis was undertaken. A total of 34 articles were identified for inclusion. The overall mean effect of internet-delivered interventions on physical activity was d = 0.14 (p = 0.00). Fixed-effect analysis revealed significant heterogeneity across studies (Q = 73.75; p = 0.00). Moderating variables such as larger sample size, screening for baseline physical activity levels and the inclusion of educational components significantly increased intervention effectiveness. Results of the meta-analysis support the delivery of internet-delivered interventions in producing positive changes in physical activity, however effect sizes were small. The ability of internet-delivered interventions to produce meaningful change in long-term physical activity remains unclear. PMID:22546283

  5. Increased levels of myelin basic protein transcripts in virus-induced demyelination.

    PubMed

    Kristensson, K; Holmes, K V; Duchala, C S; Zeller, N K; Lazzarini, R A; Dubois-Dalcq, M

    In multiple sclerosis, a demyelinating disease of young adults, there is a paucity of myelin repair in the central nervous system (CNS) which is necessary for the restoration of fast saltatory conduction in axons. Consequently, this relapsing disease often causes marked disability. In similar diseases of small rodents, however, remyelination can be quite extensive, as in the demyelinating disease caused by the A59 strain of mouse hepatitis virus (MHV-A59), a coronavirus of mice. To investigate when and where oligodendrocytes are first triggered to repair CNS myelin in such disease, we have used a complementary DNA probe specific for one major myelin protein gene, myelin basic protein (MBP), which hybridizes with the four forms of MBP messenger RNA in rodents. Using Northern blot and in situ hybridization techniques, we previously found that MBP mRNA is first detected at about 5 days after birth, peaks at 18 days and progressively decreases to 25% of the peak levels in the adult. We now report that in spinal cord sections of adult animals with active demyelination and inflammatory cells, in situ hybridization reveals a dramatic increase in probe binding to MBP-specific mRNA at 2-3 weeks after virus inoculation and before remyelination can be detected by morphological methods. This increase of MBP-specific mRNA is found at the edge of the demyelinating area and extends into surrounding areas of normal-appearing white matter. Thus, in situ hybridization with myelin-specific probes appears to be a useful method for detecting the timing, intensity and location of myelin protein gene reactivation preceding remyelination. This method could be used to elucidate whether such a reactivation occurs in multiple sclerosis brain tissue. Our results suggest that in mice, glial cells react to a demyelinating process with widespread MBP mRNA synthesis which may be triggered by a diffusible factor released in the demyelinated areas. PMID:2426599

  6. Controlled sparse and percolating cross-linking in waterborne soft adhesives.

    PubMed

    Deplace, F; Carelli, C; Langenfeld, A; Rabjohns, M A; Foster, A B; Lovell, P A; Creton, C

    2009-09-01

    The effect of low levels of cross-linking on the adhesive and mechanical properties of waterborne pressure-sensitive adhesives was investigated. We have taken advantage of a core-shell latex particle morphology obtained by emulsion polymerization to create a heterogeneous structure of cross-links without major modification of the monomer composition. The latex particles comprise a shell containing cross-linkable diacetone acrylamide (DAAM) repeat units localized on the periphery of a slightly softer core copolymer of very similar composition. Adipic acid dihydrazide was added to the latex prior to film formation to react with DAAM repeat units and affect interfacial cross-linking between particles in the adhesive films. The honeycomb-like structure obtained after drying of the latex results in a good balance between the dissipative properties required for adhesion and the resistance to creep. The characterization of the mechanical properties of the films shows that the chosen cross-linking method creates a percolating lightly cross-linked network, swollen with a nearly un-cross-linked component. With this cross-linking method, the linear viscoelastic properties of the soft films are nearly unaffected by the cross-linking while the nonlinear tensile properties are greatly modified. As a result, the long-term shear resistance of the adhesive film improves very significantly while the peel force remains nearly the same. A simple rheological model is used to interpret qualitatively the changes in the material parameters induced by cross-linking. PMID:20355828

  7. Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice

    PubMed Central

    Pelosi, Laura; Berardinelli, Maria Grazia; Forcina, Laura; Spelta, Elisa; Rizzuto, Emanuele; Nicoletti, Carmine; Camilli, Carlotta; Testa, Erika; Catizone, Angela; De Benedetti, Fabrizio; Musarò, Antonio

    2015-01-01

    Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD. PMID:26251044

  8. Assessing the sensitivity of human skin hyperspectral responses to increasing anemia severity levels

    NASA Astrophysics Data System (ADS)

    Baranoski, Gladimir V. G.; Dey, Ankita; Chen, Tenn F.

    2015-09-01

    Anemia is a prevalent medical condition that seriously affects millions of people all over the world. In many regions, not only its initial detection but also its monitoring are hindered by limited access to laboratory facilities. This situation has motivated the development of a wide range of optical devices and procedures to assist physicians in these tasks. Although noticeable progress has been achieved in this area, the search for reliable, low-cost, and risk-free solutions still continues, and the strengthening of the knowledge base about this disorder and its effects is essential for the success of these initiatives. We contribute to these efforts by closely examining the sensitivity of human skin hyperspectral responses (within and outside the visible region of the light spectrum) to reduced hemoglobin concentrations associated with increasing anemia severity levels. This investigation, which involves skin specimens with distinct biophysical and morphological characteristics, is supported by controlled in silico experiments performed using a predictive light transport model and measured data reported in the biomedical literature. We also propose a noninvasive procedure to be employed in the monitoring of this condition at the point-of-care.

  9. Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke.

    PubMed

    Silva, Bruno; Sousa, Larissa; Miranda, Aline; Vasconcelos, Anilton; Reis, Helton; Barcelos, Lucíola; Arantes, Rosa; Teixeira, Antonio; Rachid, Milene Alvarenga

    2015-08-01

    The present study aimed to investigate behavioral changes and neuroinflammatory process following left unilateral common carotid artery occlusion (UCCAO), a model of cerebral ischemia. Post-ischemic behavioral changes following 15 min UCCAO were recorded 24 hours after reperfusion. The novel object recognition task was used to assess learning and memory. After behavioral test, brains from sham and ischemic mice were removed and processed to evaluate central nervous system pathology by TTC and H&E techniques as well as inflammatory mediators by ELISA. UCCAO promoted long-term memory impairment after reperfusion. Infarct areas were observed in the cerebrum by TTC stain. Moreover, the histopathological analysis revealed cerebral necrotic cavities surrounded by ischemic neurons and hippocampal neurodegeneration. In parallel with memory dysfunction, brain levels of TNF-a, IL-1b and CXCL1 were increased post ischemia compared with sham-operated group. These findings suggest an involvement of central nervous system inflammatory mediators and brain damage in cognitive impairment following unilateral acute ischemia. PMID:26222355

  10. Metabolic engineering of Corynebacterium glutamicum for methionine production by removing feedback inhibition and increasing NADPH level.

    PubMed

    Li, Ying; Cong, Hua; Liu, Bingnan; Song, Jinzhu; Sun, Xueying; Zhang, Junzheng; Yang, Qian

    2016-09-01

    Relieving the feedback inhibition of key enzymes in a metabolic pathway is frequently the first step of producer-strain construction by genetic engineering. However, the strict feedback regulation exercised by microorganisms in methionine biosynthesis often makes it difficult to produce methionine at a high level. In this study, Corynebacterium glutamicum ATCC 13032 was metabolically engineered for methionine production. First, the metD gene encoding the methionine uptake system was deleted to achieve extracellular accumulation of methionine. Then, random mutagenesis was performed to remove feedback inhibition by metabolic end-products. The resulting strain C. glutamicum ENM-16 was further engineered to block or decrease competitive branch pathways by deleting the thrB gene and changing the start codon of the dapA gene, followed by point mutations of lysC (C932T) and pyc (G1A, C1372T) to increase methionine precursor supply. To enrich the NADPH pool, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase in the pentose phosphate pathway were mutated to reduce their sensitivity to inhibition by intracellular metabolites. The resultant strain C. glutamicum LY-5 produced 6.85 ± 0.23 g methionine l(-1) with substrate-specific yield (Y P/S) of 0.08 mol per mol of glucose after 72 h fed-batch fermentation. The strategies described here will be useful for construction of methionine engineering strains. PMID:27255137

  11. Performance of growing rabbits fed increasing levels of discarded Salvia hispanica L. (chia) seed.

    PubMed

    Rodríguez-Abello, Diana; Ramírez-Avilés, Luis; Navarro-Alberto, Jorge; Zamora-Bustillos, Roberto

    2016-06-01

    This experiment was carried out to evaluate the effect of including five levels of discarded chia seed (DCS) on growth, energy, and economic efficiency in rabbits. Fifty crossbred (New Zealand × Californian) weaning rabbits, weighing 798 ± 170 g, were randomly assigned to the following treatments: 0 % (control), 10 % (Ch10), 20 % (Ch20), 30 % (Ch30), and 40 % (Ch40) of DCS. Ten unsexed rabbits were allocated to each treatment and housed individually in cages; the experimental period was 6 weeks. There were no statistically significant differences between treatments in final body weight (2050 g), body weight gain (30 g/rabbit/day), and carcass weight (1010 g); however, feed intake (91 g/rabbit/day in Ch20 vs. 80 g/rabbit/day in Ch40), feed conversion ratio (2.77 in control and Ch40 vs. 2.95 in Ch10, Ch20, and Ch30), energy conversion ratio (32 MJ/kg in Ch20 vs. 29 MJ/kg on average in control, Ch10, Ch20, Ch30, and Ch40), and economic efficiency (358 % in control vs. 433 % in Ch40) showed differences (P < 0.05) between treatments. Discarded chia seed can be included up to 40 % in growing rabbit diets without any adverse effects on growth and carcass weight, and increased economic efficiency. PMID:26992735

  12. Increased harbor porpoise mortality in the Pacific Northwest, USA: understanding when higher levels may be normal.

    PubMed

    Huggins, Jessica L; Raverty, Stephen A; Norman, Stephanie A; Calambokidis, John; Gaydos, Joseph K; Duffield, Deborah A; Lambourn, Dyanna M; Rice, James M; Hanson, Brad; Wilkinson, Kristin; Jeffries, Steven J; Norberg, Brent; Barre, Lynne

    2015-07-23

    In 2006, a marked increase in harbor porpoise Phocoena phocoena strandings were reported in the Pacific Northwest of the USA, resulting in the declaration of an unusual mortality event (UME) for Washington and Oregon to facilitate investigation into potential causes. The UME was in place during all of 2006 and 2007, and a total of 114 porpoises stranded during this period. Responders examined 95 porpoises; of these, detailed necropsies were conducted on 75 animals. Here we review the findings related to this event and how these compared to the years immediately before and after the UME. Relatively equal numbers among sexes and age classes were represented, and mortalities were attributed to a variety of specific causes, most of which were categorized as trauma or infectious disease. Continued monitoring of strandings during 4 yr following the UME showed no decrease in occurrence. The lack of a single major cause of mortality or evidence of a significant change or event, combined with high levels of strandings over several post-UME years, demonstrated that this was not an actual mortality event but was likely the result of a combination of factors, including: (1) a growing population of harbor porpoises; (2) expansion of harbor porpoises into previously sparsely populated areas in Washington's inland waters; and (3) a more well established stranding network that resulted in better reporting and response. This finding would not have been possible without the integrated response and investigation undertaken by the stranding network. PMID:26203880

  13. Nanovoid formation in cross-linked epoxy and poly(dicyclopentadiene) networks during high strain rate deformation

    NASA Astrophysics Data System (ADS)

    Elder, Robert M.; Knorr, Daniel B., Jr.; Lenhart, Joseph L.; Andzelm, Jan W.; Sirk, Timothy W.

    2015-03-01

    Cross-linked polymer networks are widely used as structural and protective materials under extremes of temperature, pressure, or strain rate. In particular, substantial effort has been devoted to improving the high strain rate impact resistance of epoxy resins. Although epoxy resins are widely used in applications requiring impact resistance, epoxy resins with the strength and stiffness necessary in structural applications typically have poor toughness. Recent work showed that other chemistries in cross-linked polymers can overcome this trade-off between strength and toughness. Specifically, cross-linked polydicyclopentadiene (pDCPD) was found to have exceptional performance compared to epoxy resins, which is related to the high toughness of pDCPD. Based on the physicochemical properties of epoxy and pDCPD, it was hypothesized that the excellent toughness of pDCPD was due to the formation and growth of nanovoids during impact events. Void growth dissipates energy that otherwise would contribute to failure. We use atomistic molecular dynamics simulations to quantify void formation in these cross-linked polymer networks and to examine the molecular-level properties of the voids. Our findings suggest methods to increase void formation and growth, which may improve toughness.

  14. Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel.

    PubMed

    Dong, Yixiao; Hassan, Waqar; Zheng, Yu; Saeed, Aram Omer; Cao, Hongliang; Tai, Hongyun; Pandit, Abhay; Wang, Wenxin

    2012-01-01

    Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an 'one pot and one step' in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M(n) = 258 g mol(-1)), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M(n )= 475 g mol(-1)) and (2-methoxyethoxy) ethyl methacrylate (MEO(2)MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models. PMID:22143908

  15. Friedel–Crafts Crosslinked Highly Sulfonated Polyether Ether Ketone (SPEEK) Membranes for a Vanadium/Air Redox Flow Battery

    PubMed Central

    Merle, Géraldine; Ioana, Filipoi Carmen; Demco, Dan Eugen; Saakes, Michel; Hosseiny, Seyed Schwan

    2014-01-01

    Highly conductive and low vanadium permeable crosslinked sulfonated poly(ether ether ketone) (cSPEEK) membranes were prepared by electrophilic aromatic substitution for a Vanadium/Air Redox Flow Battery (Vanadium/Air-RFB) application. Membranes were synthesized from ethanol solution and crosslinked under different temperatures with 1,4-benzenedimethanol and ZnCl2 via the Friedel–Crafts crosslinking route. The crosslinking mechanism under different temperatures indicated two crosslinking pathways: (a) crosslinking on the sulfonic acid groups; and (b) crosslinking on the backbone. It was observed that membranes crosslinked at a temperature of 150 °C lead to low proton conductive membranes, whereas an increase in crosslinking temperature and time would lead to high proton conductive membranes. High temperature crosslinking also resulted in an increase in anisotropy and water diffusion. Furthermore, the membranes were investigated for a Vanadium/Air Redox Flow Battery application. Membranes crosslinked at 200 °C for 30 min with a molar ratio between 2:1 (mol repeat unit:mol benzenedimethanol) showed a proton conductivity of 27.9 mS/cm and a 100 times lower VO2+ crossover compared to Nafion. PMID:24957118

  16. Cross-Linking Electrochemical Mass Spectrometry for Probing Protein Three-Dimensional Structures

    PubMed Central

    2015-01-01

    Chemical cross-linking combined with mass spectrometry (MS) is powerful to provide protein three-dimensional structure information but difficulties in identifying cross-linked peptides and elucidating their structures limit its usefulness. To tackle these challenges, this study presents a novel cross-linking MS in conjunction with electrochemistry using disulfide-bond-containing dithiobis[succinimidyl propionate] (DSP) as the cross-linker. In our approach, electrolysis of DSP-bridged protein/peptide products, as online monitored by desorption electrospray ionization mass spectrometry is highly informative. First, as disulfide bonds are electrochemically reducible, the cross-links are subject to pronounced intensity decrease upon electrolytic reduction, suggesting a new way to identify cross-links. Also, mass shift before and after electrolysis suggests the linkage pattern of cross-links. Electrochemical reduction removes disulfide bond constraints, possibly increasing sequence coverage for tandem MS analysis and yielding linear peptides whose structures are more easily determined than their cross-linked precursor peptides. Furthermore, this cross-linking electrochemical MS method is rapid, due to the fast nature of electrochemical conversion (much faster than traditional chemical reduction) and no need for chromatographic separation, which would be of high value for structural proteomics research. PMID:25141260

  17. Effects of Crosslinking on the Mechanical Properties Drug Release, and Cytocompatibility of Protein Polymers

    PubMed Central

    Martinez, Adam W.; Caves, Jeffrey M.; Ravi, Swathi; Li, Wehnsheng; Chaikof, Elliot L.

    2013-01-01

    Recombinant elastin-like protein polymers are increasingly being investigated as component materials of a variety of implantable medical devices. This is chiefly a result of their favorable biological properties and the ability to tailor their physical and mechanical properties. In this report, we explore the potential of modulating the water content, mechanical properties, and drug release profiles of protein films through the selection of different crosslinking schemes and processing strategies. We find that the selection of crosslinking scheme and processing strategy has a significant influence on all aspects of protein polymer films. Significantly, utilization of a confined, fixed volume, as well as vapor phase crosslinking strategies decreased protein polymer equilibrium water content. Specifically, as compared to uncrosslinked protein gels, water content was reduced for genipin (15.5%), glutaraldehyde (GTA) (24.5%), GTA vapor crosslinking (31.6%), disulfide (SS) (18.2%), and SS vapor crosslinking (25.5%) (p <0.05). Distinct crosslinking strategies modulated protein polymer stiffness, strain at failure, and ultimate tensile strength (UTS). In all cases, vapor phase crosslinking produced the stiffest films with the highest UTS. Moreover, both confined, fixed volume and vapor phase approaches influenced drug delivery rates; with decreased initial drug burst and release rates as compared to solution phase crosslinking. Tailored crosslinking strategies provide an important option for modulating the physical, mechanical, and drug delivery properties of protein polymers. PMID:23993944

  18. Tea derived galloylated polyphenols cross-link purified gastrointestinal mucins.

    PubMed

    Georgiades, Pantelis; Pudney, Paul D A; Rogers, Sarah; Thornton, David J; Waigh, Thomas A

    2014-01-01

    Polyphenols derived from tea are thought to be important for human health. We show using a combination of particle tracking microrheology and small-angle neutron scattering that polyphenols acts as cross-linkers for purified gastrointestinal mucin, derived from the stomach and the duodenum. Both naturally derived purified polyphenols, and green and black tea extracts are shown to act as cross-linkers. The main active cross-linking component is found to be the galloylated forms of catechins. The viscosity, elasticity and relaxation time of the mucin solutions experience an order of magnitude change in value upon addition of the polyphenol cross-linkers. Similarly small-angle neutron scattering experiments demonstrate a sol-gel transition with the addition of polyphenols, with a large increase in the scattering at low angles, which is attributed to the formation of large scale (>10 nm) heterogeneities during gelation. Cross-linking of mucins by polyphenols is thus expected to have an impact on the physicochemical environment of both the stomach and duodenum; polyphenols are expected to modulate the barrier properties of mucus, nutrient absorption through mucus and the viscoelastic microenvironments of intestinal bacteria. PMID:25162539

  19. Adsorption of allura red dye by cross-linked chitosan from shrimp waste.

    PubMed

    Sánchez-Duarte, Reyna G; Sánchez-Machado, Dalia I; López-Cervantes, Jaime; Correa-Murrieta, Ma A

    2012-01-01

    The present study was designed to evaluate the chitosan, which has been obtained by deacetylation of chitin, as a biosorbent. The chitin was isolated from fermented shrimp waste by an important local industrial food biopolymer. The aim of this work was the characterization of chitosan and preparation of cross-linked chitosan- tripolyphosphate (chitosan-TPP) beads for the removal of allura red food dye from aqueous solutions. Conditions of batch adsorption such as pH, time and adsorbent dose were examined. The effectiveness of cross-linked chitosan beads for dye removal was found to be higher for pH 2 (98%, percentage of dye removal) and tends to decrease at pHs of 3 to 11 (up to 49%). The values of percentage removal show that the adsorption capacity increases with time of contact and dosage of chitosan-TPP, but red dye adsorption is mainly influenced by pH level. The cross-linked chitosan-TPP beads can significantly adsorb allura red monoazo dye from aqueous solutions even at acidic pHs unlike raw chitosan beads that tend to dissolve in acidic solutions. Consequently, this modified chitosan has characteristics that allow minimization of environmental pollution and widening the valorization of shrimp waste. PMID:22277220

  20. Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking.

    PubMed

    Cohen, Todd J; Hwang, Andrew W; Unger, Travis; Trojanowski, John Q; Lee, Virginia M Y

    2012-03-01

    TDP-43 is the major disease protein in ubiquitin-positive inclusions of amyotrophic lateral sclerosis and frontotemporal lobar degeneration (FTLD) characterized by TDP-43 pathology (FTLD-TDP). Accumulation of insoluble TDP-43 aggregates could impair normal TDP-43 functions and initiate disease progression. Thus, it is critical to define the signalling mechanisms regulating TDP-43 since this could open up new avenues for therapeutic interventions. Here, we have identified a redox-mediated signalling mechanism directly regulating TDP-43. Using in vitro and cell-based studies, we demonstrate that oxidative stress promotes TDP-43 cross-linking via cysteine oxidation and disulphide bond formation leading to decreased TDP-43 solubility. Biochemical analysis identified several cysteine residues located within and adjacent to the second RNA-recognition motif that contribute to both intra- and inter-molecular interactions, supporting TDP-43 as a target of redox signalling. Moreover, increased levels of cross-linked TDP-43 species are found in FTLD-TDP brains, indicating that aberrant TDP-43 cross-linking is a prominent pathological feature of this disease. Thus, TDP-43 is dynamically regulated by a redox regulatory switch that links oxidative stress to the modulation of TDP-43 and its downstream targets. PMID:22193716

  1. Redox signalling directly regulates TDP-43 via cysteine oxidation and disulphide cross-linking

    PubMed Central

    Cohen, Todd J; Hwang, Andrew W; Unger, Travis; Trojanowski, John Q; Lee, Virginia M Y

    2012-01-01

    TDP-43 is the major disease protein in ubiquitin-positive inclusions of amyotrophic lateral sclerosis and frontotemporal lobar degeneration (FTLD) characterized by TDP-43 pathology (FTLD-TDP). Accumulation of insoluble TDP-43 aggregates could impair normal TDP-43 functions and initiate disease progression. Thus, it is critical to define the signalling mechanisms regulating TDP-43 since this could open up new avenues for therapeutic interventions. Here, we have identified a redox-mediated signalling mechanism directly regulating TDP-43. Using in vitro and cell-based studies, we demonstrate that oxidative stress promotes TDP-43 cross-linking via cysteine oxidation and disulphide bond formation leading to decreased TDP-43 solubility. Biochemical analysis identified several cysteine residues located within and adjacent to the second RNA-recognition motif that contribute to both intra- and inter-molecular interactions, supporting TDP-43 as a target of redox signalling. Moreover, increased levels of cross-linked TDP-43 species are found in FTLD-TDP brains, indicating that aberrant TDP-43 cross-linking is a prominent pathological feature of this disease. Thus, TDP-43 is dynamically regulated by a redox regulatory switch that links oxidative stress to the modulation of TDP-43 and its downstream targets. PMID:22193716

  2. Increased viability of odontoblast-like cells subjected to low-level laser irradiation

    NASA Astrophysics Data System (ADS)

    Oliveira, C. F.; Basso, F. G.; Lins, E. C.; Kurachi, C.; Hebling, J.; Bagnato, V. S.; de Souza Costa, C. A.

    2010-07-01

    Studies have shown that the increase of cell metabolism depends on the low level laser therapy (LLLT) parameters used to irradiate the cells. However, the optimal laser dose to up-regulate pulp cell activity remains unknown. Consequently, the aim of this study was to evaluate the metabolic response of odontoblast-like cells (MDPC-23) exposed to different LLLT doses. Cells at 20000 cells/cm2 were seeded in 24-well plates using plain culture medium (DMEM) and were incubated in a humidified incubator with 5% CO2 at 37°C. After 24 h, the culture medium was replaced by fresh DMEM supplemented with 5% (stress by nutritional deficit) or 10% fetal bovine serum (FBS). The cells were exposed to different laser doses from a near infrared diode laser prototype designed to provide a uniform irradiation of the wells. The experimental groups were: G1: 1.5 J/cm2 + 5% FBS; G2: 1.5 J/cm2 + 10% FBS; G3: 5 J/cm2 + 5% FBS; G4: 5 J/cm2 + 10% FBS; G5: 19 J/cm2 + 5% FBS; G6: 19 J/cm2 + 10% FBS. LLLT was performed in 3 consecutive irradiation cycles with a 24-hour interval. Non-irradiated cells cultured in DMEM supplemented with either 5 or 10% FBS served as control groups. The analysis of the metabolic response was performed by the MTT assay 3 h after the last irradiation. G1 presented an increase in SDH enzyme activity and differed significantly (Mann-Whitney test, p < 0.05) from the other groups. Analysis by scanning electron microscopy showed normal cell morphology in all groups. Under the tested conditions, LLLT stimulated the metabolic activity of MDPC-23 cultured in DMEM supplemented with 5% FBS and exposed to a laser dose of 1.5 J/cm2. These findings are relevant for further studies on the action of near infrared lasers on cells with odontoblast phenotype.

  3. Glucosepane is a major protein cross-link of the senescent human extracellular matrix. Relationship with diabetes.

    PubMed

    Sell, David R; Biemel, Klaus M; Reihl, Oliver; Lederer, Markus O; Strauch, Christopher M; Monnier, Vincent M

    2005-04-01

    The extracellular matrix in most tissues is characterized by progressive age-related stiffening and loss of proteolytic digestibility that are accelerated in diabetes and can be duplicated by the nonenzymatic reaction of reducing sugars and extracellular matrix proteins. However, most cross-links of the Maillard reaction described so far are present in quantities too low to account for these changes. Here we have determined in human skin and glomerular basement membrane (GBM) collagen the levels of the recently discovered lysine-arginine cross-links derived from glucose, methylglyoxal, glyoxal, and 3-deoxyglucosone, i.e. glucosepane, MODIC, GODIC, and DOGDIC, respectively. Insoluble preparations of skin collagen (n = 110) and glomerular basement membrane (GBM, n = 28) were enzymatically digested, and levels were measured by isotope dilution technique using liquid chromatography/mass spectrometry. In skin, all cross-links increased with age (p < 0.0001) except DOGDIC (p = 0.34). In nondiabetic controls, levels at 90 years were 2000, 30, and 15 pmol/mg for glucosepane, MODIC, and GODIC, respectively. Diabetes, but not renal failure, increased glucosepane to 5000 pmol/mg (p < 0.0001), and for all others, increased it to <60 pmol/mg (p < 0.01). In GBMs, glucosepane reached up to 500 pmol/mg of collagen and was increased in diabetes (p < 0.0001) but not old age. In conclusion, glucosepane is the single major cross-link of the senescent extracellular matrix discovered so far, accounting for up to >120 mole% of triple helical collagen modification in diabetes. Its presence in high quantities may contribute to a number of structural and cell matrix dysfunctions observed in aging and diabetes. PMID:15677467

  4. Bioaugmentation of Syntrophic Acetate-Oxidizing Culture in Biogas Reactors Exposed to Increasing Levels of Ammonia

    PubMed Central

    Westerholm, Maria; Levén, Lotta

    2012-01-01

    The importance of syntrophic acetate oxidation for process stability in methanogenic systems operating at high ammonia concentrations has previously been emphasized. In this study we investigated bioaugmentation of syntrophic acetate-oxidizing (SAO) cultures as a possible method for decreasing the adaptation period of biogas reactors operating at gradually increased ammonia concentrations (1.5 to 11 g NH4+-N/liter). Whole stillage and cattle manure were codigested semicontinuously for about 460 days in four mesophilic anaerobic laboratory-scale reactors, and a fixed volume of SAO culture was added daily to two of the reactors. Reactor performance was evaluated in terms of biogas productivity, methane content, pH, alkalinity, and volatile fatty acid (VFA) content. The decomposition pathway of acetate was analyzed by isotopic tracer experiments, and population dynamics were monitored by quantitative PCR analyses. A shift in dominance from aceticlastic methanogenesis to SAO occurred simultaneously in all reactors, indicating no influence by bioaugmentation on the prevailing pathway. Higher abundances of Clostridium ultunense and Tepidanaerobacter acetatoxydans were associated with bioaugmentation, but no influence on Syntrophaceticus schinkii or the methanogenic population was distinguished. Overloading or accumulation of VFA did not cause notable dynamic effects on the population. Instead, the ammonia concentration had a substantial impact on the abundance level of the microorganisms surveyed. The addition of SAO culture did not affect process performance or stability against ammonia inhibition, and all four reactors deteriorated at high ammonia concentrations. Consequently, these findings further demonstrate the strong influence of ammonia on the methane-producing consortia and on the representative methanization pathway in mesophilic biogas reactors. PMID:22923397

  5. Increased HO-1 Levels Ameliorate Fatty Liver Development Through a Reduction of Heme and Recruitment of FGF21

    PubMed Central

    Hinds, Terry D.; Sodhi, Komal; Meadows, Charles; Fedorova, Larisa; Puri, Nitin; Kim, Dong Hyun; Peterson, Stephen J.; Shapiro, Joseph; Abraham, Nader G.; Kappas, Attallah

    2013-01-01

    Objective Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development. Design and Methods Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO-1, HO activity, PGC1α, FGF21, glycogen content and lipogenesis were assessed. Results CoPP administration increased hepatic HO-1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels and resulted in decreased steatosis. Increased levels of HO-1 produced a decrease in lipid droplet size, FAS levels involving recruitment of FGF21, PPARα and Glut 1. These beneficial effects were reversed by inhibition of HO activity. Conclusion Increased levels of HO-1 and HO activity reduced the levels of obesity by reducing hepatic heme and lipid accumulation. These changes were manifested by decreases in cellular heme, increases in FGF21, glycogen content and fatty liver. The beneficial effect of HO-1 induction results from an increase in PPARα and FGF21 levels and a decrease in PGC1α, levels they were reversed by SnMP. Low levels of HO-1 and HO activity are responsible for fatty liver. PMID:23839791

  6. Bifunctional crosslinking ligands for transthyretin

    PubMed Central

    Mangione, P. Patrizia; Deroo, Stéphanie; Ellmerich, Stephan; Bellotti, Vittorio; Kolstoe, Simon; Wood, Stephen P.; Robinson, Carol V.; Smith, Martin D.; Tennent, Glenys A.; Broadbridge, Robert J.; Council, Claire E.; Thurston, Joanne R.; Steadman, Victoria A.; Vong, Antonio K.; Swain, Christopher J.; Pepys, Mark B.; Taylor, Graham W.

    2015-01-01

    Wild-type and variant forms of transthyretin (TTR), a normal plasma protein, are amyloidogenic and can be deposited in the tissues as amyloid fibrils causing acquired and hereditary systemic TTR amyloidosis, a debilitating and usually fatal disease. Reduction in the abundance of amyloid fibril precursor proteins arrests amyloid deposition and halts disease progression in all forms of amyloidosis including TTR type. Our previous demonstration that circulating serum amyloid P component (SAP) is efficiently depleted by administration of a specific small molecule ligand compound, that non-covalently crosslinks pairs of SAP molecules, suggested that TTR may be also amenable to this approach. We first confirmed that chemically crosslinked human TTR is rapidly cleared from the circulation in mice. In order to crosslink pairs of TTR molecules, promote their accelerated clearance and thus therapeutically deplete plasma TTR, we prepared a range of bivalent specific ligands for the thyroxine binding sites of TTR. Non-covalently bound human TTR–ligand complexes were formed that were stable in vitro and in vivo, but they were not cleared from the plasma of mice in vivo more rapidly than native uncomplexed TTR. Therapeutic depletion of circulating TTR will require additional mechanisms. PMID:26400472

  7. Corneal collagen cross-linking: a review.

    PubMed

    O'Brart, David P S

    2014-01-01

    The aim was to review the published literature on corneal collagen cross-linking. The emphasis was on the seminal publications, systemic reviews, meta-analyses and randomized controlled trials. Where such an evidence did not exist, selective large series cohort studies, case controlled studies and case series with follow-up preferably greater than 12 months were included. Riboflavin/Ultraviolet A (UVA) corneal collagen cross-linking appears to be the first treatment modality to halt the progression of keratoconus and other corneal ectatic disorders with improvement in visual, keratometric and topographic parameters documented by most investigators. Its precise mechanism of action at a molecular level is as yet not fully determined. Follow-up is limited to 4-6 years at present but suggests continued stability and improvement in corneal shape with time. Most published data are with epithelium-off techniques. Epithelium-on studies suggest some efficacy but less than with the epithelium-off procedures and long-term data are not currently available. The use of Riboflavin/UVA CXL for the management of infectious and non-infectious keratitis appears very promising. Its use in the management of bullous keratopathy is equivocal. Investigation of other methodologies for CXL are under investigation. PMID:25000866

  8. Corneal collagen cross-linking: A review

    PubMed Central

    O’Brart, David P.S.

    2014-01-01

    The aim was to review the published literature on corneal collagen cross-linking. The emphasis was on the seminal publications, systemic reviews, meta-analyses and randomized controlled trials. Where such an evidence did not exist, selective large series cohort studies, case controlled studies and case series with follow-up preferably greater than 12 months were included. Riboflavin/Ultraviolet A (UVA) corneal collagen cross-linking appears to be the first treatment modality to halt the progression of keratoconus and other corneal ectatic disorders with improvement in visual, keratometric and topographic parameters documented by most investigators. Its precise mechanism of action at a molecular level is as yet not fully determined. Follow-up is limited to 4–6 years at present but suggests continued stability and improvement in corneal shape with time. Most published data are with epithelium-off techniques. Epithelium-on studies suggest some efficacy but less than with the epithelium-off procedures and long-term data are not currently available. The use of Riboflavin/UVA CXL for the management of infectious and non-infectious keratitis appears very promising. Its use in the management of bullous keratopathy is equivocal. Investigation of other methodologies for CXL are under investigation. PMID:25000866

  9. Increased chromosome fragility as a consequence of blood folate levels, smoking status, and coffee consumption

    SciTech Connect

    Chen, A.T.L.; Reidy, J.A.; Annest, J.L.; Welty, T.K.; Zhou, H. )

    1989-01-01

    Chromosome fragility in 96 h, low-folate cultures was found to be associated with smoking status, coffee consumption, and blood folate level. The higher proportion of cells with chromosome aberrations in cigarette smokers was attributable to lower red cell folate levels in smokers compared with nonsmokers. There was a positive linear relationship between the average cups of coffee consumed per day and the proportion of cells with aberrations. This association was independent of the effects of smoking and red cell folate level. These data suggest that smoking history, coffee consumption, and red cell folate level are important considerations for the design and interpretation of fragile site studies in cancer cytogenetics.

  10. Intra-molecular cross-linking of acidic residues for protein structure studies.

    SciTech Connect

    Kruppa, Gary Hermann; Young, Malin M.; Novak, Petr; Schoeniger, Joseph S.

    2005-03-01

    can be obtained by exploiting new cross-linker chemistry, increasing the probability that the protein target of choice will yield sufficient distance constraints to develop a structural model.

  11. Early life stress increases anxiety-like behavior in Balbc mice despite a compensatory increase in levels of postnatal maternal care

    PubMed Central

    Wei, Lan; David, Aisha; Duman, Ron S.; Anisman, Hymie; Kaffman, Arie

    2010-01-01

    A better understanding of the molecular and cellular mechanisms by which early life stress (ELS) modifies brain development and adult behavior is necessary for diagnosing and treating psychopathology associated with exposure to ELS. For historical reasons most of the work in rodents has been done in rats and attempts to establish robust and reproducible paradigms in the mouse have proven to be challenging. Here we show that under normal rearing conditions, increased levels of postnatal maternal care are associated with a decrease in anxiety-like behavior in BALB/cByj offspring. Brief daily pup-dam separation (BDS) during the postnatal period was associated with increased postnatal maternal care but was surprisingly associated with increased anxiety-like behavior in adult offspring, providing the first example in which offspring receiving higher levels of postnatal maternal care are more anxious in adulthood. Plasma corticosterone levels were elevated in BDS pups even three hours after the pups were reunited with the dam, suggesting that this paradigm represents a form of early life stress. We also show that levels of total RNA and DNA in the hippocampus reach a peak at postnatal day 14 and that exposure to BDS seems to inhibit this developmental growth spurt. We propose that exposure to stress during the postnatal period overrides the ability of high levels of postnatal maternal care to program anxiety-like behavior by inhibiting the normal growth spurt that characterizes this period. PMID:20096699

  12. Increasing the Validity of Angoff Standards through Analysis of Judge-Level Internal Consistency

    ERIC Educational Resources Information Center

    Clauser, Jerome C.; Clauser, Brian E.; Hambleton, Ronald K.

    2014-01-01

    The purpose of the present study was to extend past work with the Angoff method for setting standards by examining judgments at the judge level rather than the panel level. The focus was on investigating the relationship between observed Angoff standard setting judgments and empirical conditional probabilities. This relationship has been used as a…

  13. Six Increasingly Higher Levels of Wellness Based on Holistic Principles and Risk Factor Science.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1987-01-01

    Describes program for achievement of higher wellness levels based on holistic principles and risk factor science. Levels focus on (1) heart disease risk factors and how to reverse them; (2) unconscious needs at conflict with one's conscious goals; (3) identity status, meaning to love and to be loved; (4) autogenics; and (5) full ego development…

  14. Smokers Beware: Study Shows Increased Cadmium Levels in the Brain May Cause Severe Neurological Disorders

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Tobacco is one crop that accumulates cadmium, making smokers susceptible to higher levels of the metal in their bodies. The findings suggest that even a low-level exposure to a heavy metal like cadmium is likely to cause a change in the functions of neurons in the brain and the behavioral response to drugs of abuse.

  15. Gas-phase intramolecular protein crosslinking via ion/ion reactions: ubiquitin and a homobifunctional sulfo-NHS ester.

    PubMed

    Webb, Ian K; Mentinova, Marija; McGee, William M; McLuckey, Scott A

    2013-05-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge-reduced complex. Covalent crosslinking is indicated by the consecutive loss of 2 molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is, therefore, sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended because of intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for 'electrostatic crosslinking' in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions. PMID:23463545

  16. Corneal Collagen Cross-Linking Outcomes: Review

    PubMed Central

    Jankov II, Mirko R; Jovanovic, Vesna; Delevic, Sladjana; Coskunseven, Efekan

    2011-01-01

    Keratoconus is a condition characterized by biomechanical instability of the cornea, presenting in a progressive, asymmetric and bilateral way. Corneal collagen cross-linking with riboflavin and UVA (CXL) is a new technique of corneal tissue strengthening that combines the use of riboflavin as a photo sensitizer and UVA irradiation. The studies showed that CXL was effective in halting the progression of keratoconus over a period of up to four years. The published studies also revealed a reduction of max K readings by more than 2 D, while the postoperative SEQ was reduced by an average of more than 1 D, and refractive cylinder decreased by about 1 D. No eyes lost any line of BCDVA. Moreover, there was no significant decrease in endothelial cell density. It was also found that CXL treatment was effective with reducing corneal and total wavefront aberrations. Corneal cross-linking has also led to an arrest and/or even a partial reversal of keratectasia in the treatment of iatrogenic ectasia after excimer laser ablation. A primary intervention such as CXL should be considered to potentially increase the biomechanical stability of the corneal tissue and postpone the need of lamellar or penetrating keratoplasty. PMID:21448301

  17. Mitigating crosslinking reactions through preconversion strategies

    SciTech Connect

    Not Available

    1992-03-01

    The ultimate goal of this research is to develop preconversion techniques that will mitigate crosslinking reactions and thereby substantially increase liquid yields during subsequent liquefaction. The immediate objective is to explore the effect of several pretreatments on the evolution of oxygen functions, crosslinking, and conversion in laboratory studies. The pretreatments to be explored include several that hold promise for effecting deoxygenation or other reduction, for example, treatment with CO/water/base and hydroquinones, either alone or in conjunction. The effects of these pretreatments on functional group distribution, macromoleculer structure, and liquefaction will be compared with those that have shown promise in the past for improved conversions, such as simple hydrothermal pretreatment, mild hydrogenation with dispersed catalysts, and demineralization. A second objective is to develop suitable test procedures for assessing the effect of the pretreatment on subsequent liquefaction and achieve also an understanding the chemical origin of the effect. These test procedures will include the use of proton magnetic resonance thermal analysis (PMRTA) for determining the effect of pretreatment on fluidity as liquefaction conditions (temperature, pressure) are approached. They will also involve the use of simpler and more pertinent laboratory measures of volatile product yields following the batch liquefactions that will be run to test the susceptibility of pretreated coals to subsequent liquefaction.

  18. Increased Interleukin-17 and decreased BAFF serum levels in drug-free acute schizophrenia.

    PubMed

    El Kissi, Yousri; Samoud, Samar; Mtiraoui, Ahlem; Letaief, Leila; Hannachi, Neila; Ayachi, Mouna; Ali, Bechir Ben Hadj; Boukadida, Jalel

    2015-01-30

    Hypotheses regarding an immune-cytokine basis of schizophrenia have been postulated with controversial findings and a lack of data related to many cytokines. The aim of this study was to assess serum levels of Interferon-γ (IFN-γ), Interleukin-4 (IL-4), Transforming Growth Factor-β (TGF-β), Interleukin-17 (IL-17) and B-cell Activating Factor (BAFF) in schizophrenic patients and to determine correlations between cytokine levels and clinical parameters. Serum cytokine levels were measured with ELISA techniques in 60 neuroleptic-free patients on acute phase of the disease (BPRS≥40) and 28 healthy controls matched for age and sex. Current symptoms were assessed with Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). No significant difference was found between patients and controls regarding IFN-γ serum levels. IL-4 was not detected in both groups. Patients exhibited significantly higher IL-17 and lower BAFF serum levels. IL-17 and BAFF levels were negatively correlated in schizophrenic patients. SANS global score was negatively correlated with IL-17 and positively correlated with IFN-γ serum levels. These results argue against the involvement of Th1 or Th2 population cells in schizophrenia. IL-17 and BAFF could be valuable markers for schizophrenia. PMID:25453636

  19. Synthesis, characterization and application of biodegradable crosslinked carboxymethyl chitosan/poly(vinyl alcohol) clay nanocomposites.

    PubMed

    Sabaa, Magdy W; Abdallah, Heba M; Mohamed, Nadia A; Mohamed, Riham R

    2015-11-01

    Crosslinked poly(vinyl alcohol) (PVA)/carboxymethyl chitosan (CMCh) nanocomposites were synthesized using terephthaloyl diisothiocyanate crosslinker, in the presence of montmorillonite (MMT), in different ratios of the two matrices. Characterization of nanocomposites was performed using different analyses. Swelling behavior was studied in different buffered solutions. It was found that formation of crosslinked CMCh/PVA hydrogels increased the swellability. Metal ion adsorption has also been investigated. The results indicated that crosslinked CMCh adsorbs various metal ions much more than non crosslinked CMCh. Antimicrobial activity was examined against Gram positive bacteria, against Gram negative bacteria, and also against fungi. Results indicated that most of these nanocomposites exhibited good antimicrobial potency. Degradation study was carried out in Simulated Body Fluid (SBF) for different time periods in order to find out degradation index (Di). Results showed that weight loss of most of the nanocomposites increased as a function of incubation time. PMID:26249602

  20. Peanut consumption increases levels of plasma very long chain fatty acids in humans.

    PubMed

    Lam, Christina; Wong, Derek; Cederbaum, Stephen; Lim, Bennie; Qu, Yong

    2012-11-01

    Peanut consumption has been suspected of raising plasma very long chain fatty acid (VLCFA) levels in humans. The effect of peanut consumption on VLCFAs was studied in six human subjects. After 3 to 4h of peanut butter ingestion, plasma C26:0 and C26:0/C22:0 were found to be significantly elevated to levels seen in patients with peroxisomal disorders. These levels returned to normal within 12h. Peanut consumption needs to be accounted for when interpreting VLCFAs. PMID:22864056

  1. High blood glucose level and increased risk of mortality in critically ill patients.

    PubMed

    Dhungel, Sanjib; Bista, Sukirti

    2007-03-01

    102 patients, 38 from ICU and 64 from postoperative ward were evaluated. Out of these, 49 of the patients had random blood glucose level < 100 mg/dl, 46 had in the range 100 to 140 mg/dl and 7 had > 140 mg/dl. The mean random blood glucose level in medical patients was 146 mg/dl with a standard deviation of 20 and that in the post operative patients was 94.3 mg/dl with a standard deviation of 10. There was an overall mortality of 13.7% (14 patients), of which medical patients were 78.6% (11 patients) and surgical patients were 21.4% (3 patients). Amongst the dead, 81.8% had random blood glucose level > 110 mg/dl and all were medical patients. However all 3 deaths (18.2%) in surgical patients had their random blood glucose level < 110 mg/dl. Higher blood glucose level was observed in critically ill medical patients and mortality was higher among patients with random blood glucose level > 110 mg/dl. PMID:17593678

  2. County-level analysis of the impact of temperature and population increases on California wildfire data

    USGS Publications Warehouse

    Baltar, M.; Keeley, Jon E.; Schoenberg, F.P.

    2013-01-01

    The extent to which the apparent increase in wildfire incidence and burn area in California from 1990 to 2006 is affected by population and temperature increases is examined. Using generalized linear models with random effects, we focus on the estimated impacts of increases in mean daily temperatures and populations in different counties on wildfire in those counties, after essentially controlling for the overall differences between counties in their overall mean temperatures and populations. We find that temperature increase appears to have a significant positive impact on both total burn area and number of observed wildfires. Population growth appears to have a much less pronounced impact on total burn area than do annual temperature increases, and population growth appears to be negatively correlated with the total number of observed wildfires. These effects are especially pronounced in the winter season and in Southern California counties.

  3. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

    PubMed

    Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; Pereira, Michelly Cristiny; Gonçalves, Rafaela Silva Guimarães; Marques, Cláudia Diniz Lopes; Rego, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-09-01

    The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc. PMID:26160266

  4. Group-Level Selection Increases Cooperation in the Public Goods Game.

    PubMed

    Eckel, Catherine C; Fatas, Enrique; Godoy, Sara; Wilson, Rick K

    2016-01-01

    When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation. PMID:27574971

  5. Group-Level Selection Increases Cooperation in the Public Goods Game

    PubMed Central

    Eckel, Catherine C.; Fatas, Enrique; Godoy, Sara

    2016-01-01

    When groups compete for resources, some groups will be more successful than others, forcing out less successful groups. Group-level selection is the most extreme form of group competition, where the weaker group ceases to exist, becoming extinct. We implement group-level selection in a controlled laboratory experiment in order to study its impact on human cooperation. The experiment uses variations on the standard linear public goods game. Group-level selection operates through competition for survival: the least successful, lowest-earning groups become extinct, in the sense that they no longer are able to play the game. Additional control treatments include group comparison without extinction, and extinction of the least successful individuals across groups. We find that group-level extinction produces very high contributions to the provision of the public good, while group comparison alone or individual extinction fail to cause higher contributions. Our results provide stark evidence that group-level selection enhances within-group cooperation. PMID:27574971

  6. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI. PMID:27003900

  7. Characterization of crosslinked polystyrene(PS) beads in SBR matrix

    SciTech Connect

    Cha, Yoon-Jong; Choe, Soonja

    1995-12-01

    Monodisperse sized crosslinked polystyrene(PS) beads were prepared by a reaction of semibatch emulsion polymerization with styrene monomer, divinylbenzene(DVB) crosslinking agent and potassium persulfate(K{sub 2}S{sub 2}O{sub 9}) initiator in the absence of emulsifier. The glass transition temperature(T{sub g}) and the mean diameter of the beads were increased from 100{degrees}C to 135{degrees}C and from 402 nm to 532 nm, respectively, for an incorporation of 2 to 10 mol% DVB. Crosslinking density was also linearly increased with DVB content. SEM microphotographs of SBR composite filled with various contents of PS beads revealed that PS beads are relatively well dispersed without changing the spherical shape of the beads in all range of compositions. In stress-strain analysis, elongation at break and tensile strength of SBR composite were increased with the bead content. Applicability of the PS beads as a filler in SBR matrix is tested by plotting Mooney-Rivlin or Guth-Smallwood equations. However, mechanical properties of the composite with the beads were not so excellent as those of the composite with carbon black. Crosslinked PS beads are still tentative as a white color reinforcing filler on SBR matrix.

  8. Order-Disorder Transitions in Cross-Linked Block Copolymer Solids

    SciTech Connect

    Das, J.

    2005-01-12

    With a view toward creating solid block copolymers wherein the order-disorder transition can be accessed many times they investigated the nature of order-disorder transitions in cross-linked diblock copolymer melts using synergistic theory and experiment. A mean-field theory based on a coarse grained free-energy and the Random Phase Approximation (RPA) is developed for the system of interest. The quenched distribution of cross-links is averaged using the replica method. The phase behavior of a particular A-B block copolymer melt with a randomly cross-linked B-Block is determined as a function of the Florry-Huggins interaction parameter ({chi}) and the average number of cross-links per chain N{sub c}. They find for a cross-link density greater than N*{sub c} the B monomers are localized within a region of size {zeta} {approx} (N{sub c} - N*{sub c}){sup -1/2}. The cross-links strongly oppose ordering in the system as {zeta} becomes comparable to the radius of gyration of the block copolymer chain. As such the order-disorder transition temperature T{sub ODT} decreases precipitously when N{sub c} > N*{sub c}. When N{sub c} < N*{sub c}, T{sub ODT} increases weakly with N{sub c}. Experiments were conducted on cross-linked polystyrene-block-polyisoprene copolymer samples wherein the polyisoprene block was selectively cross-linked at a temperature well above the order-disorder transition temperature of the pure block copolymer. Small angle X-ray scattering (SAXS) and birefringence measurements on the cross-linked samples are consistent with the theoretical prediction. T{sub ODT} decreases rapidly when the cross-linking density exceeds the critical cross-linking density.

  9. Exogenous Supply of Pantoyl Lactone to Excised Leaves Increases their Pantothenate Levels

    PubMed Central

    RATHINASABAPATHI, BALA; RAMAN, SURESH BABU

    2005-01-01

    • Background and Aims All plants synthesize pantothenate but its synthesis and regulation are not well understood. The aim of this work is to study the effect of exogenous supply of precursor compounds on pantothenate levels in leaves. • Methods Precursor compounds were supplied in solution to excised leaves and the pantothenate content was measured using a microbial method. • Key Results Pantothenate levels in excised leaves of Limonium latifolium, tomato (Lycopersicon esculentum), bean (Phaseolus vulgaris) and grapefruit (Citrus × paradisi) were examined following an exogenous supply of the precursor compounds pantoyl lactone or β-alanine. Significantly higher levels of extractable pantothenate were found when pantoyl lactone was supplied, but not when β-alanine was supplied despite a measurable uptake of β-alanine into the leaf. • Conclusions The results suggested that the pantoate supply may be rate-limiting or regulating pantothenate synthesis in leaves. PMID:15767268

  10. Increased IL6 plasma levels in indolent systemic mastocytosis patients are associated with high risk of disease progression.

    PubMed

    Mayado, A; Teodosio, C; Garcia-Montero, A C; Matito, A; Rodriguez-Caballero, A; Morgado, J M; Muñiz, C; Jara-Acevedo, M; Álvarez-Twose, I; Sanchez-Muñoz, L; Matarraz, S; Caldas, C; Muñoz-González, J I; Escribano, L; Orfao, A

    2016-01-01

    Systemic mastocytosis (SM) is a heterogeneous disease with altered interleukin (IL)-6 and IL13 plasma levels. However, no study has simultaneously investigated the plasma levels of IL1β, IL6, IL13, CCL23 and clusterin in SM at diagnosis and correlated them with disease outcome. Here we investigated IL1β, IL6, IL13, CCL23 and clusterin plasma levels in 75 SM patients--66 indolent SM (ISM) and 9 aggressive SM--and analyzed their prognostic impact among ISM cases grouped according to the extent of hematopoietic involvement of the bone marrow cells by the KIT D816V mutation. Although increased IL1β, IL6 and CCL23 levels were detected in SM patients versus healthy controls, only IL6 and CCL23 levels gradually increased with disease severity. Moreover, increased IL6 plasma levels were associated with ISM progression to more aggressive disease, in particular among ISM patients with multilineal KIT mutation (ISM-ML), these patients also showing a higher frequency of organomegalies, versus other ISM-ML patients. Of note, all ISM patients who progressed had increased IL6 plasma levels already at diagnosis. Our results indicate that SM patients display an altered plasma cytokine profile already at diagnosis, increased IL6 plasma levels emerging as an early marker for disease progression among ISM cases, in particular among high-risk ISM patients who carry multilineage KIT mutation. PMID:26153655

  11. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and γ-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and γ-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  12. Increased Levels of 8-Hydroxy-2′-Deoxyguanosine Attributable to Carcinogenic Metal Exposure among Schoolchildren

    PubMed Central

    Wong, Ruey-Hong; Kuo, Chung-Yih; Hsu, Ming-Lin; Wang, Tsun-Yen; Chang, Pi-I; Wu, Tsung-Hsun; Huang, Shuai

    2005-01-01

    Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer. However, the health effects of arsenic, chromium, and nickel exposures are equivocal for children. Therefore, we performed a cross-sectional study to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress to DNA in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking children using atomic absorption spectrometry. As a biomarker for oxidative stress, urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine. No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean ± SE, 16.0 ± 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 ± 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 ± 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 ± 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children. PMID:16203252

  13. Increased level/dose ratio of amphotericin-B in premature infants with renal failure.

    PubMed

    Higuchi, R; Kusumoto, S; Ban, H; Iwahashi, S; Kobayashi, M; Sumiyama, K; Koike, M

    1993-06-01

    We introduced continuous intravenous infusion of amphotericin-B (AMPH-B) to extremely low birthweight (ELBW) infants (< 1000 g) with or without renal failure as a single agent for treating definite or probable systemic candidiasis. The species of Candida isolated from blood or tracheal aspirate or urine were C. albicans in seven infants, C glabrata in two, C. tropicalis in one and C. parapsilosis in one. The minimal inhibitory concentrations (MIC) of AMPH-B required against these isolates were less than 0.2 micrograms/mL except for that against one strain of C. albicans (0.78 microgram/mL). Serum AMPH-B levels were 0.31-0.78 (0.51 +/- 0.14) micrograms/mL when doses of 0.2-0.55 (0.32 +/- 0.11) mg/kg per day were being administered. The serum level was higher than the MIC of each isolate in all but one infant who died of disseminated intravascular coagulation and Candida pneumonia. Another infant died of congenital heart disease. The other nine infants survived. The serum level showed no correlation with the daily dose. The ratio of the serum level to the daily dose (L/D ratio) showed a significant correlation to serum creatinine (r = 0.787) and the linear regression curve followed the equation: L/D ratio = 0.223 x serum creatinine + 1.11 (P < 0.01). Few adverse effects due to AMPH-B were noted. Our data may give a simple reference to serum AMPH-B levels during continuous intravenous infusion from the dose and the serum creatinine level. PMID:8351992

  14. Preliminary efficacy of prize-based contingency management to increase activity levels in healthy adults.

    PubMed

    Washington, Wendy Donlin; Banna, Kelly M; Gibson, Amanda L

    2014-01-01

    An estimated 30% of Americans meet the criteria for obesity. Effective, low-cost interventions to increase physical activity are needed to prevent and treat obesity. In this study, 11 healthy adults wore Fitbit accelerometers for 3 weeks. During the initial baseline, subjects earned prize draws for wearing the Fitbit. During intervention, percentile schedules were used to calculate individual prize-draw criteria. The final week was a return to baseline. Four subjects increased step counts as a result of the intervention. A bout analysis of interresponse times revealed that subjects increased overall step counts by increasing daily minutes active and within-bout response rates and decreasing pauses between bouts of activity. Strategies to improve effectiveness are suggested, such as modification of reinforcement probability and amount and identification of the function of periods of inactivity. PMID:24740477

  15. A recent increase in the rate of Indian Ocean sea level change

    NASA Astrophysics Data System (ADS)

    Thompson, P. R.; Merrifield, M. A.

    2014-12-01

    Decadal rates of sea surface height (SSH) change measured by satellites (1993-present) north of 20°S in the Indian Ocean increase substantially after the turn of the century. In contrast, the increase in the sea surface temperature of the region is approximately linear. This increase in Indian Ocean rates of SSH change appears to be thermosteric in origin, but it is not accounted for variability in Pacific climate indices. We find the GECCO2 simulation (1948-2011) reproduces the SSH variability in this region to good approximation, and we use the model fields to diagnose the origin of the increase in the rate of Indian Ocean SSH change and to place the recent variability in historical context.

  16. Intra-molecular cross-linking of acidic residues for protein structure studies.

    PubMed

    Novak, Petr; Kruppa, Gary H

    2008-01-01

    Intra-molecular cross-linking has been suggested as a method of obtaining distance constraints that would help to develop structural models of proteins. Recent work published on intra-molecular cross-linking for protein structural studies has employed commercially available primary amine (lysine, the amino terminus) selective reagents. Previous work using these cross-linkers has shown that for several proteins of known structure, the number of cross-links that can be obtained experimentally may be small compared to what would be expected from the known structure, due to the relative reactivity, distribution and solvent accessibility of the lysines in the protein sequence. To overcome these limitations, we have investigated the use of cross-linking reagents that can react with other reactive side chains in proteins. We used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) to activate the carboxylic acid containing residues, aspartic acid (D), glutamic acid (E) and the carboxy terminus (O), for cross-linking reactions. Once activated, the DEO side chains can react to form "zero-length" cross-links with nearby primary amine containing residues, lysines (K) and the amino terminus (X), via the formation of a new amide bond. We also show that the EDC-activated DEO side chains can be cross-linked to each other using dihydrazides, two hydrazide moieties connected by an alkyl cross-linker arm of variable length. Using these reagents, we have found three new "zero-length" cross-links in ubiquitin consistent with its known structure (M1-E16, M1-E18 and K63-E64). Using the dihydrazide cross-linkers, we have identified two new cross-links (D21-D32 and E24-D32) unambiguously. Using a library of dihydrazide cross-linkers with varying arm length, we have shown that there is a minimum arm length required for the DEO-DEO cross-links of 5.8 A. These results show that additional structural information can be obtained by exploiting new cross-linker chemistry

  17. INCREASING SAFETY AND REDUCING ENVIRONMENTAL DAMAGE RISK FROM AGING HIGH-LEVEL RADIOACTIVE WASTE TANKS

    EPA Science Inventory

    There exists a paramount need for improved understanding of the behavior of high-level nuclear waste containers and the impact on structural integrity in terms of leak tightness and mechanical stability. The current program, which at the time of this writing is in its early stage...

  18. Increased Circulating Levels of Vitamin D Binding Protein in MS Patients

    PubMed Central

    Rinaldi, Arturo Ottavio; Sanseverino, Isabella; Purificato, Cristina; Cortese, Antonio; Mechelli, Rosella; Francisci, Silvia; Salvetti, Marco; Millefiorini, Enrico; Gessani, Sandra; Gauzzi, Maria Cristina

    2015-01-01

    Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS. PMID:25590278

  19. Increased Endothelial Progenitor Cell Levels are Associated with Good Outcome in Intracerebral Hemorrhage.

    PubMed

    Pías-Peleteiro, Juan; Pérez-Mato, María; López-Arias, Esteban; Rodríguez-Yáñez, Manuel; Blanco, Miguel; Campos, Francisco; Castillo, José; Sobrino, Tomás

    2016-01-01

    Circulating endothelial progenitor cells (EPCs) play a role in the regeneration of damaged brain tissue. However, the relationship between circulating EPC levels and functional recovery in intracerebral hemorrhage (ICH) has not yet been tested. Therefore, our aim was to study the influence of circulating EPCs on the outcome of ICH. Forty-six patients with primary ICH (males, 71.7%; age, 72.7 ± 10.8 years) were prospectively included in the study within 12 hours of symptom onset. The main outcome variable was good functional outcome at 12 months (modified Rankin scale ≤2), considering residual volume at 6 months as a secondary variable. Circulating EPC (CD34(+)/CD133(+)/KDR(+)) levels were measured by flow cytometry from blood samples obtained at admission, 72 hours and day 7. Our results indicate that patients with good outcome show higher EPC numbers at 72 hours and day 7 (all p < 0.001). However, only EPC levels at day 7 were independently associated with good functional outcome at 12 months (OR, 1.15; CI95%, 1.01-1.35) after adjustment by age, baseline stroke severity and ICH volume. Moreover, EPC levels at day 7 were negatively correlated to residual volume (r = -0.525; p = 0.005). In conclusion, these findings suggest that EPCs may play a role in the functional recovery of ICH patients. PMID:27346699

  20. Increased Endothelial Progenitor Cell Levels are Associated with Good Outcome in Intracerebral Hemorrhage

    PubMed Central

    Pías-Peleteiro, Juan; Pérez-Mato, María; López-Arias, Esteban; Rodríguez-Yáñez, Manuel; Blanco, Miguel; Campos, Francisco; Castillo, José; Sobrino, Tomás

    2016-01-01

    Circulating endothelial progenitor cells (EPCs) play a role in the regeneration of damaged brain tissue. However, the relationship between circulating EPC levels and functional recovery in intracerebral hemorrhage (ICH) has not yet been tested. Therefore, our aim was to study the influence of circulating EPCs on the outcome of ICH. Forty-six patients with primary ICH (males, 71.7%; age, 72.7 ± 10.8 years) were prospectively included in the study within 12 hours of symptom onset. The main outcome variable was good functional outcome at 12 months (modified Rankin scale ≤2), considering residual volume at 6 months as a secondary variable. Circulating EPC (CD34+/CD133+/KDR+) levels were measured by flow cytometry from blood samples obtained at admission, 72 hours and day 7. Our results indicate that patients with good outcome show higher EPC numbers at 72 hours and day 7 (all p < 0.001). However, only EPC levels at day 7 were independently associated with good functional outcome at 12 months (OR, 1.15; CI95%, 1.01–1.35) after adjustment by age, baseline stroke severity and ICH volume. Moreover, EPC levels at day 7 were negatively correlated to residual volume (r = −0.525; p = 0.005). In conclusion, these findings suggest that EPCs may play a role in the functional recovery of ICH patients. PMID:27346699

  1. Circulating T helper 9 cells and increased serum interleukin-9 levels in patients with knee osteoarthritis.

    PubMed

    Qi, Changlin; Shan, Yuxing; Wang, Jing; Ding, Fupeng; Zhao, Ding; Yang, Teng; Jiang, Yanfang

    2016-05-01

    The purpose of this study was to examine the roles of T helper 9 (Th9) cells and the serum interleukin (IL)-9 level in the pathogenesis of osteoarthritis (OA). The numbers of IL-9(+)  CD4(+)  CD8(-) T cells, interferon (IFN)-γ+ CD4(+)  CD8(-) T cells, IL-4(+) CD4(+)  CD8(-) T cells, and IL-17A(+ ) CD4(+ ) CD8(-) T cells in 25 OA patients and 13 healthy controls (HC) were examined by flow cytometry. The serum concentrations of IL-9, IL-4, IL-17A, and IFN-γ were also determined. The numbers of CD4(+) CD45RO(+) T cells, Th9 cells, Th1 cells, and Th17 cells in OA patients were significantly higher than those in HCs. Furthermore, serum IL-9, IL-17A, and IFN-γ levels in OA patients were higher than those in HCs. The number of Th9 cells was positively correlated with the number of Th17 cells in OA patients. Furthermore, greater numbers of Th9 cells were positively associated with elevated C-reactive protein, and both Th9 cells and IL-9 levels were positively correlated with the Western Ontario and McMaster Universities Osteoarthritis index in OA patients. Th9 cell numbers and IL-9 levels are correlated with OA patient symptoms and joint functionality and may be a marker of disease activity. PMID:26926842

  2. Insoluble Fiber in Young Barley Leaf Suppresses the Increment of Postprandial Blood Glucose Level by Increasing the Digesta Viscosity

    PubMed Central

    Kamiya, Tomoyasu; Tomozawa, Hiroshi; Ueno, Shiori; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Okushima, Ayaka; Miyata, Yu; Tamaru, Shizuka; Tanaka, Kazunari; Takahashi, Toru

    2013-01-01

    Barley (Hordeum vulgare L.) is a well-known cereal plant. Young barley leaf is consumed as a popular green-colored drink, which is named “Aojiru” in Japan. We examined the effects of barley leaf powder (BLP) and insoluble fibers derived from BLP on postprandial blood glucose in rats and healthy Japanese volunteers. BLP and insoluble fibers derived from BLP suppressed the increment of postprandial blood glucose levels in rats (P < 0.01), and increased the viscosity of their digesta. The insoluble fibers present in BLP might play a role in controlling blood glucose level by increasing digesta viscosity. In human, BLP suppressed the increment of postprandial blood glucose level only in those which exhibited higher blood glucose levels after meals (P < 0.01). BLP might suppress the increment of postprandial blood glucose level by increasing digesta viscosity in both of rats and humans who require blood glucose monitoring. PMID:24348688

  3. Lipofundin® MCT/LCT 20% increase left ventricular systolic pressure in an ex vivo rat heart model via increase of intracellular calcium level

    PubMed Central

    Kim, Yeon A; Han, Jeong Yeol; Jin, Sangkyu; Ok, Seong-Ho; Lee, Heon-Keun; Chung, Young-Kyun

    2016-01-01

    Background Lipid emulsions have been used to treat various drug toxicities and for total parenteral nutrition therapy. Their usefulness has also been confirmed in patients with local anesthetic-induced cardiac toxicity. The purpose of this study was to measure the hemodynamic and composition effects of lipid emulsions and to elucidate the mechanism associated with changes in intracellular calcium levels in myocardiocytes. Methods We measured hemodynamic effects using a digital analysis system after Intralipid® and Lipofundin® MCT/LCT were infused into hearts hanging in a Langendorff perfusion system. We measured the effects of the lipid emulsions on intracellular calcium levels in H9c2 cells by confocal microscopy. Results Infusion of Lipofundin® MCT/LCT 20% (1 ml/kg) resulted in a significant increase in left ventricular systolic pressure compared to that after infusing modified Krebs-Henseleit solution (1 ml/kg) (P = 0.003, 95% confidence interval [CI], 2.4–12.5). Lipofundin® MCT/LCT 20% had a more positive inotropic effect than that of Intralipid® 20% (P = 0.009, 95% CI, 1.4–11.6). Both lipid emulsion treatments increased intracellular calcium levels. Lipofundin® MCT/LCT (0.01%) increased intracellular calcium level more than that of 0.01% Intralipid® (P < 0.05, 95% CI, 0.0–1.9). Conclusions These two lipid emulsions had different inotropic effects depending on their triglyceride component. The inotropic effect of lipid emulsions could be related with intracellular calcium level. PMID:26885303

  4. Childhood abuse is associated with increased hair cortisol levels among urban pregnant women

    PubMed Central

    Schreier, Hannah M C; Enlow, Michelle Bosquet; Ritz, Thomas; Gennings, Chris; Wright, Rosalind J

    2015-01-01

    Background Hypothalamic–pituitary–adrenal (HPA) axis activity is known to be altered following events such as childhood abuse. However, despite potential adverse consequences for the offspring of women who have experienced abuse, very little is known about altered HPA axis activity during pregnancy. Methods During pregnancy, 180 women from diverse racial/ethnic backgrounds reported on their exposure to emotional, physical and/or sexual abuse before the age of 11, and general post-traumatic stress symptoms (ie, not limited to childhood years or abuse experiences). Around delivery, they provided hair samples for the assessment of cortisol levels during pregnancy. Hair cortisol was assessed for each pregnancy trimester. The effect of childhood abuse on hair cortisol was assessed using mixed-effects analyses of covariance models allowing for within-subject correlated observations, and were first performed in the entire sample and subsequently stratified by race/ethnicity. Results Controlling for post-traumatic stress symptoms, hair cortisol levels varied by history of child abuse, F(2,166)=3.66, p=0.028. Childhood physical and/or sexual abuse was associated with greater hair cortisol levels, t(166)=2.65, p=0.009, compared with no history of abuse. Because childhood rates of abuse and hair cortisol levels varied by race/ethnicity, analyses were stratified by race/ethnicity. The associations between history of abuse and cortisol levels were only significant among black women, F(2,23)=5.37, p=0.012. Conclusions Childhood abuse, especially physical and/or sexual abuse, is associated with differences in cortisol production during pregnancy, particularly among black women. Future research should investigate how these differences impact physical and mental health outcomes among offspring of affected women. PMID:26219886

  5. Autophagy promotes DNA-protein crosslink clearance.

    PubMed

    Mu, Haibo; Liu, Qianjin; Niu, Hong; Wang, Dongdong; Tang, Jiangjiang; Duan, Jinyou

    2016-02-01

    Toxic DNA-protein crosslinks (DPCs) can result from exposure to radiation or chemotherapeutic agents. DPCs can also accumulate during aging or stress. However, the cellular mechanisms underlying clearance of DPCs remain largely unknown. Here, we have identified an important role of autophagy in the processing of DPCs induced by three representative agents: formaldehyde, a chemical used widely in industry; UV light; and camptothecin, a cytotoxic anticancer drug. Autophagy inhibitors, 3-methyladenine (3-MA) or chloroquine (CQ), promoted the accumulation of DPCs in damaged cells and injured organs. siRNA-mediated silencing of Atg5 or Atg7, two essential components for the formation of the autophagosome, gave similar results. In contrast, the autophagy inducer rapamycin (RAP) attenuated DPCs in vitro and in vivo. Our findings reveal the importance of autophagy in controlling the level of DPCs, and may open up a new avenue for understanding the formation and clearance of this detrimental DNA adduct. PMID:26921017

  6. Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro.

    PubMed

    Uzawa, K; Grzesik, W J; Nishiura, T; Kuznetsov, S A; Robey, P G; Brenner, D A; Yamauchi, M

    1999-08-01

    The pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]). In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs). In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen alpha chains and collagen cross-linking chemistries have been characterized. High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA. This increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of alpha chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern. PMID:10457259

  7. Differential expression of human lysyl hydroxylase genes, lysine hydroxylation, and cross-linking of type I collagen during osteoblastic differentiation in vitro

    NASA Technical Reports Server (NTRS)

    Uzawa, K.; Grzesik, W. J.; Nishiura, T.; Kuznetsov, S. A.; Robey, P. G.; Brenner, D. A.; Yamauchi, M.

    1999-01-01

    The pattern of lysyl hydroxylation in the nontriple helical domains of collagen is critical in determining the cross-linking pathways that are tissue specific. We hypothesized that the tissue specificity of type I collagen cross-linking is, in part, due to the differential expression of lysyl hydroxylase genes (Procollagen-lysine,2-oxyglutarate,5-dioxygenase 1, 2, and 3 [PLOD1, PLOD2, and PLOD3]). In this study, we have examined the expression patterns of these three genes during the course of in vitro differentiation of human osteoprogenitor cells (bone marrow stromal cells [BMSCs]) and normal skin fibroblasts (NSFs). In addition, using the medium and cell layer/matrix fractions in these cultures, lysine hydroxylation of type I collagen alpha chains and collagen cross-linking chemistries have been characterized. High levels of PLOD1 and PLOD3 genes were expressed in both BMSCs and NSFs, and the expression levels did not change in the course of differentiation. In contrast to the PLOD1 and PLOD3 genes, both cell types showed low PLOD2 gene expression in undifferentiated and early differentiated conditions. However, fully differentiated BMSCs, but not NSFs, exhibited a significantly elevated level (6-fold increase) of PLOD2 mRNA. This increase coincided with the onset of matrix mineralization and with the increase in lysyl hydroxylation in the nontriple helical domains of alpha chains of type I collagen molecule. Furthermore, the collagen cross-links that are derived from the nontriple helical hydroxylysine-aldehyde were found only in fully differentiated BMSC cultures. The data suggests that PLOD2 expression is associated with lysine hydroxylation in the nontriple helical domains of collagen and, thus, could be partially responsible for the tissue-specific collagen cross-linking pattern.

  8. Synthesis, self-assembly, and pH-responsive behavior of (photo-crosslinked) star amphiphilic triblock copolymer.

    PubMed

    Bian, Qingqing; Xiao, Yan; Zhou, Chen; Lang, Meidong

    2013-02-15

    Conventional polymeric micelles employed as drug carriers suffer from the drawback of disaggregation when diluted into body fluids, giving rise to premature release of drugs. In this work, cinnamate was chosen as a crosslinker to overcome this issue and regulate pH response. A series of photo-crosslinkable star amphiphilic triblock copolymers, star poly(ε-caprolactone)-b-poly(2-cinnamoyloxyethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (SPCL-b-PCEMA-b-PDMAEMA), were prepared by combination of stepwise reversible addition-fragment chain transfer (RAFT) polymerization and carbodiimide-mediated coupling reaction. These star amphiphilic copolymers could self-assemble into core-shell-corona micelles. Facile photo crosslinking of the micelles was carried out via UV irradiation. The crosslinked micelles showed an improved stability determined by critical micelle concentration (CMC). The degree of photo crosslinking was easily regulated by tuning UV irradiation time, and the hydrodynamic diameters (D(h)) decreased with increasing degree of photo crosslinking. The pH responses of micelles were investigated by dynamic light scattering (DLS), indicating pH-induced swelling-shrinking behavior. For photo-crosslinked micelle, its capability of swelling-shrinking weakened with increasing crosslinking degree, suggesting that pH response was controlled by crosslinking density. This novel photo-crosslinked micelle system with adjustable pH response was expected to have potential as drug carriers for controlled release. PMID:23127872

  9. Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

    PubMed Central

    Aydin, Erdinc; Sahin, Semsettin

    2016-01-01

    AIM To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. CONCLUSION Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity. PMID:27275429

  10. Modelling the increased frequency of extreme sea levels in the Ganges-Brahmaputra-Meghna delta due to sea level rise and other effects of climate change.

    PubMed

    Kay, S; Caesar, J; Wolf, J; Bricheno, L; Nicholls, R J; Saiful Islam, A K M; Haque, A; Pardaens, A; Lowe, J A

    2015-07-01

    Coastal flooding due to storm surge and high tides is a serious risk for inhabitants of the Ganges-Brahmaputra-Meghna (GBM) delta, as much of the land is close to sea level. Climate change could lead to large areas of land being subject to increased flooding, salinization and ultimate abandonment in West Bengal, India, and Bangladesh. IPCC 5th assessment modelling of sea level rise and estimates of subsidence rates from the EU IMPACT2C project suggest that sea level in the GBM delta region may rise by 0.63 to 0.88 m by 2090, with some studies suggesting this could be up to 0.5 m higher if potential substantial melting of the West Antarctic ice sheet is included. These sea level rise scenarios lead to increased frequency of high water coastal events. Any effect of climate change on the frequency and severity of storms can also have an effect on extreme sea levels. A shelf-sea model of the Bay of Bengal has been used to investigate how the combined effect of sea level rise and changes in other environmental conditions under climate change may alter the frequency of extreme sea level events for the period 1971 to 2099. The model was forced using atmospheric and oceanic boundary conditions derived from climate model projections and the future scenario increase in sea level was applied at its ocean boundary. The model results show an increased likelihood of extreme sea level events through the 21st century, with the frequency of events increasing greatly in the second half of the century: water levels that occurred at decadal time intervals under present-day model conditions occurred in most years by the middle of the 21st century and 3-15 times per year by 2100. The heights of the most extreme events tend to increase more in the first half of the century than the second. The modelled scenarios provide a case study of how sea level rise and other effects of climate change may combine to produce a greatly increased threat to life and property in the GBM delta by the end

  11. UV dosage levels in summer: increased risk of ozone loss from convectively injected water vapor.

    PubMed

    Anderson, James G; Wilmouth, David M; Smith, Jessica B; Sayres, David S

    2012-08-17

    The observed presence of water vapor convectively injected deep into the stratosphere over the United States can fundamentally change the catalytic chlorine/bromine free-radical chemistry of the lower stratosphere by shifting total available inorganic chlorine into the catalytically active free-radical form, ClO. This chemical shift markedly affects total ozone loss rates and makes the catalytic system extraordinarily sensitive to convective injection into the mid-latitude lower stratosphere in summer. Were the intensity and frequency of convective injection to increase as a result of climate forcing by the continued addition of CO(2) and CH(4) to the atmosphere, increased risk of ozone loss and associated increases in ultraviolet dosage would follow. PMID:22837384

  12. Cross-Linking the Surface of Cured Polydimethylsiloxane via Hyperthemal Hydrogen Projectile Bombardment.

    PubMed

    Bao, Chao; Xu, Ke-Qin; Tang, Chang-Yu; Lau, Woon-ming; Yin, Cong-Bin; Zhu, Yan; Mei, Jun; Lee, Jonathan; Hui, David; Nie, Heng-Yong; Liu, Yu

    2015-04-29

    Cross-linking of polydimethylsiloxane (PDMS) is increasingly important with recent focus on its top surface stiffness. In this paper, we demonstrate that hyperthermal hydrogen projectile bombardment, a surface sensitive cross-linking technology, is superior in enhancing the mechanical properties of a cured PDMS surface without significantly degrading its hydrophobicity. Both water contact angle measurements and time-of-flight secondary ion mass spectrometry are used to investigate the variations in surface chemistry and structure upon cross-linking. Using nanoindentation and atomic force microscopy, we confirm that the thickness of the cross-linked PDMS is controllable by the bombardment time, which opens opportunities for tuning cross-linking degree in compliance with arising requirements from the practice. PMID:25849306

  13. Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Yamauchi, M.

    1992-01-01

    Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.

  14. Jujube promotes learning and memory in a rat model by increasing estrogen levels in the blood and nitric oxide and acetylcholine levels in the brain

    PubMed Central

    LI, BAOLI; WANG, LU; LIU, YONGXIAN; CHEN, YAHUI; ZHANG, ZHENGXIANG; ZHANG, JING

    2013-01-01

    The aim of this study was to observe the effects of jujube on learning and memory in ovariectomized rats. The effects of jujube on learning and memory in ovariectomized rats were observed using the Morris water maze method. The serum follicle-stimulating hormone (FSH), estrogen and luteinizing hormone (LH) levels, and the brain nitric oxide synthase (NOS) and acetylcholinesterase (AChE) levels of the rats were determined. The results indicated that jujube reduced the latency period and increased the number of crossings made by the ovariectomized rats in the Morris water maze test. Jujube also increased the serum estrogen level, reduced the serum FSH and corpus luteum LH levels, increased brain NOS activity and reduced AChE activity. The results indicate that jujube promoted the learning and memory of the ovariectomized rats. This effect may be correlated with the increase in the estrogen level in the blood, and the changes in the nitric oxide and acetylcholine levels in the brain. PMID:23837068

  15. Level I trauma center internal campaign to increase safe driving by staff.

    PubMed

    Melton, Thomas Jerome; Couillard, Deborah J; Ferguson, Pamela L; Power, Stephanie; Norcross, E Douglass; Fakhry, Samir M

    2012-01-01

    A 3-month internal campaign at our trauma center was conducted to improve employee motor vehicle safety and have employees serve as community role models. The injury-prevention coordinator and trauma program manager developed and implemented a campaign of high-visibility events. Effectiveness was evaluated through pre- and postcampaign surveys and seat belt-use observation and observation at 1 year. Although survey responses did not change, observed seat belt use increased significantly from 79% to 87%, with maintenance at 1 year (89%). No direct causal effect can be proven, but the campaign appears to have increased employee seat belt use. PMID:23222402

  16. Tissue plasminogen activator inhibits NMDA-receptor-mediated increases in calcium levels in cultured hippocampal neurons

    PubMed Central

    Robinson, Samuel D.; Lee, Tet Woo; Christie, David L.; Birch, Nigel P.

    2015-01-01

    NMDA receptors (NMDARs) play a critical role in neurotransmission, acting as essential mediators of many forms of synaptic plasticity, and also modulating aspects of development, synaptic transmission and cell death. NMDAR-induced responses are dependent on a range of factors including subunit composition and receptor location. Tissue-type plasminogen activator (tPA) is a serine protease that has been reported to interact with NMDARs and modulate NMDAR activity. In this study we report that tPA inhibits NMDAR-mediated changes in intracellular calcium levels in cultures of primary hippocampal neurons stimulated by low (5 μM) but not high (50 μM) concentrations of NMDA. tPA also inhibited changes in calcium levels stimulated by presynaptic release of glutamate following treatment with bicucculine/4-aminopyridine (4-AP). Inhibition was dependent on the proteolytic activity of tPA but was unaffected by α2-antiplasmin, an inhibitor of the tPA substrate plasmin, and receptor-associated protein (RAP), a pan-ligand blocker of the low-density lipoprotein receptor, two proteins previously reported to modulate NMDAR activity. These findings suggest that tPA can modulate changes in intracellular calcium levels in a subset of NMDARs expressed in cultured embryonic hippocampal neurons through a mechanism that involves the proteolytic activity of tPA and synaptic NMDARs. PMID:26500501

  17. The response of lactating dairy cows to increasing levels of whole roasted soybeans.

    PubMed

    Knapp, D M; Grummer, R R; Dentine, M R

    1991-08-01

    Twenty-four Holstein cows, including four primiparous and four ruminally cannulated, were in replicated 4 x 4 Latin squares with 21-d periods to determine the effects of feeding level of whole roasted soybeans on lactation performance and rumen function. Cows were fed rations containing a 50:50 forage:concentrate ratio with 0, 12, 18, or 24% of diet DM as whole roasted soybeans. Rations contained 16.8, 16.9, 18.6, and 19.7% CP and 1.68, 1.71, 1.72, and 1.74 Mcal NEL/kg DM, respectively. Milk production and milk fat percentages for diets containing 0, 12, 18, or 24% whole roasted soybeans were 34.9, 37.5, 38.5, and 38.8 kg/d and 3.23, 3.20, 3.32, and 3.37%, respectively. Milk protein percentage was depressed at all levels of whole roasted soybeans. Ruminal pH, VFA molar percentages except valerate, and DM disappearance of forage from dacron bags did not differ among treatments. Responses were similar among primiparous and multiparous cows. Results suggest benefit from feeding whole roasted soybeans at levels up to 18% of ration DM without adversely affecting DMI, milk fat, or rumen fermentation. PMID:1918534

  18. The TGFβ pathway stimulates ovarian cancer cell proliferation by increasing IGF1R levels.

    PubMed

    Alsina-Sanchis, Elisenda; Figueras, Agnès; Lahiguera, Álvaro; Vidal, August; Casanovas, Oriol; Graupera, Mariona; Villanueva, Alberto; Viñals, Francesc

    2016-10-15

    In a search for new therapeutic targets for treating epithelial ovarian cancer, we analyzed the Transforming Growth Factor Beta (TGFβ) signaling pathway in these tumors. Using a TMA with patient samples we found high Smad2 phosphorylation in ovarian cancer tumoral cells, independently of tumor subtype (high-grade serous or endometrioid). To evaluate the impact of TGFβ receptor inhibition on tumoral growth, we used different models of human ovarian cancer orthotopically grown in nude mice (OVAs). Treatment with a TGFβRI&II dual inhibitor, LY2109761, caused a significant reduction in tumor size in all these models, affecting cell proliferation rate. We identified Insulin Growth Factor (IGF)1 receptor as the signal positively regulated by TGFβ implicated in ovarian tumor cell proliferation. Inhibition of IGF1R activity by treatment with a blocker antibody (IMC-A12) or with a tyrosine kinase inhibitor (linsitinib) inhibited ovarian tumoral growth in vivo. When IGF1R levels were decreased by shRNA treatment, LY2109761 lost its capacity to block tumoral ovarian cell proliferation. At the molecular level TGFβ induced mRNA IGF1R levels. Overall, our results suggest an important role for the TGFβ signaling pathway in ovarian tumor cell growth through the control of IGF1R signaling pathway. Moreover, it identifies anti-TGFβ inhibitors as being of potential use in new therapies for ovarian cancer patients as an alternative to IGF1R inhibition. PMID:27299695

  19. Using a High-Performance Planning Model to Increase Levels of Functional Effectiveness Within Professional Development.

    PubMed

    Winter, Peggi

    2016-01-01

    Nursing professional practice models continue to shape how we practice nursing by putting families and members at the heart of everything we do. Faced with enormous challenges around healthcare reform, models create frameworks for practice by unifying, uniting, and guiding our nurses. The Kaiser Permanente Practice model was developed to ensure consistency for nursing practice across the continuum. Four key pillars support this practice model and the work of nursing: quality and safety, leadership, professional development, and research/evidence-based practice. These four pillars form the foundation that makes transformational practice possible and aligns nursing with Kaiser Permanente's mission. The purpose of this article is to discuss the pillar of professional development and the components of the Nursing Professional Development: Scope and Standards of Practice model (American Nurses Association & National Nursing Staff Development Organization, 2010) and place them in a five-level development framework. This process allowed us to identify the current organizational level of practice, prioritize each nursing professional development component, and design an operational strategy to move nursing professional development toward a level of high performance. This process is suggested for nursing professional development specialists. PMID:26457816

  20. A surface crosslinked UHMWPE stabilized by vitamin E with low wear and high fatigue strength.

    PubMed

    Oral, Ebru; Ghali, Bassem W; Rowell, Shannon L; Micheli, Brad R; Lozynsky, Andrew J; Muratoglu, Orhun K

    2010-09-01

    Wear particle-induced periprosthetic osteolysis has been a clinical problem driving the development of wear resistant ultrahigh molecular weight polyethylene (UHMWPE) for total joint replacement. Radiation crosslinking has been used to decrease wear through decreased plastic deformation; but crosslinking also reduces mechanical properties including fatigue resistance, a major factor limiting the longevity of joint implants. Reducing UHMWPE wear with minimal detriment to mechanical properties is an unaddressed need for articular bearing surface development. Here we report a novel approach to achieve this by limiting crosslinking to the articular surface. The antioxidant vitamin E reduces crosslinking efficiency in UHMWPE during irradiation with increasing concentration, thus we propose to spatially control the crosslink density distribution by controlling the vitamin E concentration profile. Surface crosslinking UHMWPE prepared using this approach had high wear resistance and decreased crosslinking in the bulk resulting in high fatigue crack propagation resistance. The interface region did not represent a weakness in the material due to the gradual change in the crosslink density. Such an implant has the potential of decreasing risk of fatigue fracture of total joint implants as well as expanding the use of UHMWPE to younger and more active patients. PMID:20579730

  1. Load transfer mechanisms in cross-linked DWNT fibers

    NASA Astrophysics Data System (ADS)

    Filleter, T.; Naraghi, M.; Moravsky, A.; Bernal, R.; Loutfy, R. O.; Espinosa, H. D.

    2011-03-01

    The application of carbon nanotubes (CNT) to macroscopic composite fibers has been limited by weak shear interfaces between adjacent CNT shells and composite matrix elements. A fundamental understanding of load transfer at multiple length-scales is needed to identify how the exceptional mechanical properties of CNTs can be scaled to produce high-performance fibers. Through in-situ electron microscopy tensile testing we have elucidated load transfer mechanisms across multiple scales of cross-linked double-walled nanotube (DWNT) fibers. A low density of polymer cross-links is found to increase the total energy dissipated at failure and ductility of fibers by 5 and 10X, respectively, without reducing strength. This mutiscale approach has identified a need to enhance shear interactions between individual DWNTs within the hierarchical DWNT fiber structures. Through in-situ TEM electron irradiation studies we have shown that load can be effectively transferred to inner DWNTs within bundles by covalently cross-linking the interfaces of adjacent DWNTs and shells. We have observed order of magnitude increases in strength and modulus and identified their dependence on irradiation dose. In future a combined approach of irradiation induced covalent and polymer cross-linking may lead to high-performance DWNT-based fibers and composites with tunable mechanical properties.

  2. Molecular mechanisms in deformation of cross-linked hydrogel nanocomposite.

    PubMed

    Mathesan, Santhosh; Rath, Amrita; Ghosh, Pijush

    2016-02-01

    The self-folding behavior in response to external stimuli observed in hydrogels is potentially used in biomedical applications. However, the use of hydrogels is limited because of its reduced mechanical properties. These properties are enhanced when the hydrogels are cross-linked and reinforced with nanoparticles. In this work, molecular dynamics (MD) simulation is applied to perform uniaxial tension and pull out tests to understand the mechanism contributing towards the enhanced mechanical properties. Also, nanomechanical characterization is performed using quasi static nanoindentation experiments to determine the Young's modulus of hydrogels in the presence of nanoparticles. The stress-strain responses for chitosan (CS), chitosan reinforced with hydroxyapatite (HAP) and cross-linked chitosan are obtained from uniaxial tension test. It is observed that the Young's modulus and maximum stress increase as the HAP content increases and also with cross-linking process. Load displacement plot from pullout test is compared for uncross-linked and cross-linked chitosan chains on hydroxyapatite surface. MD simulation reveals that the variation in the dihedral conformation of chitosan chains and the evolution of internal structural variables are associated with mechanical properties. Additional results reveal that the formation of hydrogen bonds and electrostatic interactions is responsible for the above variations in different systems. PMID:26652360

  3. Optimization model for UV-Riboflavin corneal cross-linking

    NASA Astrophysics Data System (ADS)

    Schumacher, S.; Wernli, J.; Scherrer, S.; Bueehler, M.; Seiler, T.; Mrochen, M.

    2011-03-01

    Nowadays UV-cross-linking is an established method for the treatment of keraectasia. Currently a standardized protocol is used for the cross-linking treatment. We will now present a theoretical model which predicts the number of induced crosslinks in the corneal tissue, in dependence of the Riboflavin concentration, the radiation intensity, the pre-treatment time and the treatment time. The model is developed by merging the difussion equation, the equation for the light distribution in dependence on the absorbers in the tissue and a rate equation for the polymerization process. A higher concentration of Riboflavin solution as well as a higher irradiation intensity will increase the number of induced crosslinks. However, performed stress-strain experiments which support the model showed that higher Riboflavin concentrations (> 0.125%) do not result in a further increase in stability of the corneal tissue. This is caused by the inhomogeneous distribution of induced crosslinks throughout the cornea due to the uneven absorption of the UV-light. The new model offers the possibility to optimize the treatment individually for every patient depending on their corneal thickness in terms of efficiency, saftey and treatment time.

  4. Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease

    PubMed Central

    Wang, Xiao-ru; Li, Yong-pu; Gao, Shui; Xia, Wei; Gao, Kun; Kong, Qing-hua; Qi, Hui; Wu, Ling; Zhang, Jing; Qu, Jie-ming; Bai, Chun-xue

    2014-01-01

    Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD), only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs) might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58) and healthy controls (n=29). Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P<0.001) and LCN2 (11.29±3.92 ng/mL versus 6.09±5.13 ng/mL, P<0.001) were both elevated in subjects with COPD after adjusting for age, sex, smoking habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as quantified by pack-year, had no impact on systemic expressions of LCN1 and LCN2 in our study. Blood levels of LCN1 and LCN2, respectively, were negatively correlated to COPD Assessment Test and Modified Medical British Research Council score (P<0.001). Disease category by Global Initiative for Chronic Obstructive Lung Disease grade 1–4 or group A–D was not associated with levels of LCNs. Patient-reported exacerbations and body mass index were also tested, but no relationship with LCNs was found. In summary, serum concentrations of LCN1 and LCN2 were both elevated in patients with COPD, with their levels correlating to COPD Assessment Test and

  5. Supercooling Capacity Increases from Sea Level to Tree Line in the Hawaiian Tree Species Metrosideros polymorpha.

    PubMed

    Melcher; Cordell; Jones; Scowcroft; Niemczura; Giambelluca; Goldstein

    2000-05-01

    Population-specific differences in the freezing resistance of Metrosideros polymorpha leaves were studied along an elevational gradient from sea level to tree line (located at ca. 2500 m above sea level) on the east flank of the Mauna Loa volcano in Hawaii. In addition, we also studied 8-yr-old saplings grown in a common garden from seeds collected from the same field populations. Leaves of low-elevation field plants exhibited damage at -2 degrees C, before the onset of ice formation, which occurred at -5.7 degrees C. Leaves of high-elevation plants exhibited damage at ca. -8.5 degrees C, concurrent with ice formation in the leaf tissue, which is typical of plants that avoid freezing in their natural environment by supercooling. Nuclear magnetic resonance studies revealed that water molecules of both extra- and intracellular leaf water fractions from high-elevation plants had restricted mobility, which is consistent with their low water content and their high levels of osmotically active solutes. Decreased mobility of water molecules may delay ice nucleation and/or ice growth and may therefore enhance the ability of plant tissues to supercool. Leaf traits that correlated with specific differences in supercooling capacity were in part genetically determined and in part environmentally induced. Evidence indicated that lower apoplastic water content and smaller intercellular spaces were associated with the larger supercooling capacity of the plant's foliage at tree line. The irreversible tissue-damage temperature decreased by ca. 7 degrees C from sea level to tree line in leaves of field populations. However, this decrease appears to be only large enough to allow M. polymorpha trees to avoid leaf tissue damage from freezing up to a level of ca. 2500 m elevation, which is also the current tree line location on the east flank of Mauna Loa. The limited freezing resistance of M. polymorpha leaves may be partially responsible for the occurrence of tree line at a relatively

  6. Zebra chip symptoms are associated with increased phenolic, pathogenesis-related protein, and amino acid levels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Zebra chip disease (ZC) is an emerging problem for the potato industry as it causes undesirable symptoms such as increased browning of freshly-cut tubers and brown-striping of fried tuber slices. ZC is putatively caused by infection of the bacterium ‘Candidatus Liberibacter solanacearum’ (CLso). Thi...

  7. Holistic Goal Attainment To Increase Levels of Self-Help. Teacher's Guide and Learner's Manual.

    ERIC Educational Resources Information Center

    Bosler, Shirley

    This guide demonstrates a holistic approach to goal attainment in adult education, welfare, and work force program. Holistic goal attainment treats the roots of illiteracy, measuring impact on learning and job readiness that increases teachable/reachable moments for instructors and builds self-esteem within the learner. The teacher's guide…

  8. Effect of Cues to Increase Sound Pressure Level on Respiratory Kinematic Patterns during Connected Speech

    ERIC Educational Resources Information Center

    Huber, Jessica E.

    2007-01-01

    Purpose: This study examined the response of the respiratory system to 3 cues used to elicit increased vocal loudness to determine whether the effects of cueing, shown previously in sentence tasks, were present in connected speech tasks and to describe differences among tasks. Method: Fifteen young men and 15 young women produced a 2-paragraph…

  9. Increasing within-School Competition: A Case for Department Level Performance Indicators?

    ERIC Educational Resources Information Center

    Telhaj, Shqiponja; Adnett, Nick; Davies, Peter; Hutton, David; Coe, Robert

    2009-01-01

    The authors investigate the size and stability of departmental effects in English secondary schooling during a period in which extensions to parental choice and annual publication of school performance tables had significantly increased competitive pressures on schools. Their database of nearly 450 English secondary schools enables them to…

  10. Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides

    PubMed Central

    Hatami, Zahra M.; Gherekhloo, Javid; Rojano-Delgado, Antonia M.; Osuna, Maria D.; Alcántara, Ricardo; Fernández, Pablo; Sadeghipour, Hamid R.; De Prado, Rafael

    2016-01-01

    Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5–6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM. PMID:26941749

  11. Multiple Mechanisms Increase Levels of Resistance in Rapistrum rugosum to ALS Herbicides.

    PubMed

    Hatami, Zahra M; Gherekhloo, Javid; Rojano-Delgado, Antonia M; Osuna, Maria D; Alcántara, Ricardo; Fernández, Pablo; Sadeghipour, Hamid R; De Prado, Rafael

    2016-01-01

    Rapistrum rugosum (turnip weed) is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM), a sulfonylurea (SU) belonging to the acetolactate synthase (ALS) inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose-response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF) for resistant (R) populations was 2.5-6.6 fold higher than susceptible (S) plant. Neither foliar retention, nor (14)C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1), in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (RFs were from 28 to 38) and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT), pyrimidinyl-thiobenzoate (PTB) and triazolopyrimidine (TP), with no cross-resistance to imidazolinone (IMI). Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB, and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM. PMID:26941749

  12. Increasing Safety and Reducing Environmental Damage Risk from Aging High-Level Radioactive Waste Tanks

    SciTech Connect

    Steffler, Eric D.; McClintock, Frank A.; Lloyd, W. Randolph; Rashid, Mark M.; Williamson, Richard L.

    2005-06-01

    Cracks of various shapes and sizes exist in large high-level waste (HLW) tanks at several DOE sites. There is justifiable concern that these cracks could grow to become unstable causing a substantial release of liquid contaminants to the environment. Accurate prediction of crack growth behavior in the tanks, especially during accident scenarios, is not possible with existing analysis methodologies. This research project responds to this problem by developing an improved ability to predict crack growth in material structure combinations that are ductile (Fig. 1). This new model not only addresses the problem for these tanks, but also has applicability to any crack in any ductile structure.

  13. Cisplatin-resistant cells express increased levels of a factor that recognizes damaged DNA

    SciTech Connect

    Chu, G.; Chang, E. )

    1990-05-01

    Cancer treatment with the drug cisplatin is often thwarted by the emergence of drug-resistant cells. To study this phenomenon, the authors identified two independent cellular factors that recognize cisplatin-damaged DNA. One of the two factors, designated XPE binding factor, is deficient in complementation group E of xeroderma pigmentosum, an inherited disease characterized by defective repair of DNA damaged by ultraviolet radiation, cisplatin, and other agents. Human tumor cell lines selected for resistance to cisplatin showed more efficient DNA repair and increased expression of XPE binding factor. These results suggest that XPE binding factor may be responsible, at least in part, for the development of cisplatin resistance in human tumors and that the mechanism may be increased DNA repair.

  14. Mechanisms of an increased level of serum iron in gamma-irradiated mice.

    PubMed

    Xie, Li-hua; Zhang, Xiao-hong; Hu, Xiao-dan; Min, Xuan-yu; Zhou, Qi-fu; Zhang, Hai-qian

    2016-03-01

    The potential mechanisms underlying the increase in serum iron concentration in gamma-irradiated mice were studied. The gamma irradiation dose used was 4 Gy, and cobalt-60 ((60)Co) source was used for the irradiation. The dose rate was 0.25 Gy/min. In the serum of irradiated mice, the concentration of ferrous ions decreased, whereas the serum iron concentration increased. The concentration of ferrous ions in irradiated mice returned to normal at 21 day post-exposure. The concentration of reactive oxygen species in irradiated mice increased immediately following irradiation but returned to normal at 7 day post-exposure. Serum iron concentration in gamma-irradiated mice that were pretreated with reduced glutathione was significant lower (p < 0.01) than that in mice exposed to gamma radiation only. However, the serum iron concentration was still higher than that in normal mice (p < 0.01). This change was biphasic, characterized by a maximal decrease phase occurring immediately after gamma irradiation (relative to the irradiated mice) and a recovery plateau observed during the 7th and 21st day post-irradiation, but serum iron recovery was still less than that in the gamma-irradiated mice (4 Gy). In gamma-irradiated mice, ceruloplasmin activity increased and serum copper concentration decreased immediately after irradiation, and both of them were constant during the 7th and 21st day post-irradiation. It was concluded that ferrous ions in irradiated mice were oxidized to ferric ions by ionizing radiation. Free radicals induced by gamma radiation and ceruloplasmin mutually participated in this oxidation process. The ferroxidase effect of ceruloplasmin was achieved by transfer of electrons from ferrous ions to cupric ions. PMID:26511140

  15. Methamphetamine induces a rapid increase of intracellular Ca(++) levels in neurons overexpressing GCaMP5.

    PubMed

    Yu, Seong-Jin; Wu, Kou-Jen; Bae, Eun K; Hsu, Man-Jung; Richie, Christopher T; Harvey, Brandon K; Wang, Yun

    2016-03-01

    In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca(++) (Ca(++) i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca(++) probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca(++) to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++) i, which was blocked by MK801, suggesting that Meth enhanced Ca(++) i through Glu receptor in neurons. The Meth-mediated Ca(++) signal was also blocked by Mg(++) , low Ca(++) or the L-type Ca(++) channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca(++) influx but partially reduced the peak of Ca(++) i. These data suggest that Meth enhanced Ca(++) influx through membrane Ca(++) channels, which then triggered the release of Ca(++) from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca(++) in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca(++) i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca(++) i, modulation of Ca(++) i may be useful to reduce Meth-related reactions. PMID:25377775

  16. Hemostatic efficacy evaluation of radiation crosslinked carboxymethyl kappa-carrageenan and chitosan with varying degrees of substitution

    NASA Astrophysics Data System (ADS)

    Tranquilan-Aranilla, Charito; Barba, Bin Jeremiah D.; Vista, Jeanina Richelle M.; Abad, Lucille V.

    2016-07-01

    Carboxymethyl derivatives of kappa-carrageenan and chitosan, with varying degrees of substitution, were synthesized by multi-step reaction technique and evaluated for hemostatic efficacy through in vitro assays. FTIR analysis confirmed the presence of carboxymethyl group while 1H NMR spectroscopy indicated degrees of substitution ranging from 1.15-1.58 and 0.45-0.51 for carboxymethyl-κ-carrageenan and carboxymethylchitosan, respectively. Derivatives formed into paste consistency (30% w/v) were successfully crosslinked by gamma irradiation at 30 kGy. The data obtained from whole blood clotting and platelet adhesion assays showed a significant increase in hemostatic capability of κ-carrageenan and chitosan as a consequence of carboxymethylation and crosslinking modifications. In addition, the level of efficacy was comparable to that of a chitosan-based commercial product. These results suggest the potential of κ-carrageenan and chitosan derivatives for development into hemostatic agents.

  17. Loss of FANCC function is associated with failure to inhibit late firing replication origins after DNA cross-linking

    SciTech Connect

    Phelps, Randall A.; Gingras, Helene; Hockenbery, David M. . E-mail: dhockenb@fhcrc.org

    2007-07-01

    Fanconi anemia (FA) cells are abnormally sensitive to DNA cross-linking agents with increased levels of apoptosis and chromosomal instability. Defects in eight FA complementation groups inhibit monoubiquitination of FANCD2, and subsequent recruitment of FANCD2 to DNA damage and S-phase-associated nuclear foci. The specific functional defect in repair or response to DNA damage in FA cells remains unknown. Damage-resistant DNA synthesis is present 2.5-5 h after cross-linker treatment of FANCC, FANCA and FANCD2-deficient cells. Analysis of the size distribution of labeled DNA replication strands revealed that diepoxybutane treatment suppressed labeling of early but not late-firing replicons in FANCC-deficient cells. In contrast, normal responses to ionizing radiation were observed in FANCC-deficient cells. Absence of this late S-phase response in FANCC-deficient cells leads to activation of secondary checkpoint responses.

  18. Making cities resilient: Increasing resilience to disasters at the local level.

    PubMed

    Albrito, Paola

    2012-01-01

    Half of humanity is now living in cities, according to the United Nations Population Division. The urban population exceeded the rural for the first time in 2008, and by 2050 urbanisation will rise to 70 per cent with increased urban risk. 'Today, 100 cities are in control of 30 per cent of the world's economy.' The need for maintenance and upkeep of these cities makes safety measures for their citizens crucial. In this context, urban risk, city planning and the role of local governments in dealing with risk reduction have been recognised as key factors to build communities resilient to disasters. While many local governments have taken action to reduce vulnerability, especially when it comes to government organising capacity to deal with disasters, much remains to be done. Disaster risk has become an acute and increasingly urban issue. Poorly-planned urban environments, weak urban governance, an old and fragile infrastructure, and rapid population growth have increased pressure on the urban environment and triggered exposure to disaster risk. More and more people are settling in potential danger zones such as flood plains, volcanic flanks or earthquake faults and coastal areas. They do so because planners and local governments fail to provide alternatives, or because they cannot afford safer land. Local government officials are confronted with the threat of disasters daily, and need improved access to policies and tools to cope with them effectively. PMID:22576134

  19. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability. PMID:17652829

  20. Thinking Concretely Increases the Perceived Likelihood of Risks: The Effect of Construal Level on Risk Estimation.

    PubMed

    Lermer, Eva; Streicher, Bernhard; Sachs, Rainer; Raue, Martina; Frey, Dieter

    2016-03-01

    Recent findings on construal level theory (CLT) suggest that abstract thinking leads to a lower estimated probability of an event occurring compared to concrete thinking. We applied this idea to the risk context and explored the influence of construal level (CL) on the overestimation of small and underestimation of large probabilities for risk estimates concerning a vague target person (Study 1 and Study 3) and personal risk estimates (Study 2). We were specifically interested in whether the often-found overestimation of small probabilities could be reduced with abstract thinking, and the often-found underestimation of large probabilities was reduced with concrete thinking. The results showed that CL influenced risk estimates. In particular, a concrete mindset led to higher risk estimates compared to an abstract mindset for several adverse events, including events with small and large probabilities. This suggests that CL manipulation can indeed be used for improving the accuracy of lay people's estimates of small and large probabilities. Moreover, the results suggest that professional risk managers' risk estimates of common events (thus with a relatively high probability) could be improved by adopting a concrete mindset. However, the abstract manipulation did not lead managers to estimate extremely unlikely events more accurately. Potential reasons for different CL manipulation effects on risk estimates' accuracy between lay people and risk managers are discussed. PMID:26111548

  1. Increased levels of hyper-stable protein aggregates in plasma of older adults.

    PubMed

    Xia, Ke; Trasatti, Hannah; Wymer, James P; Colón, Wilfredo

    2016-06-01

    Proteins that misfold into hyper-stable/degradation-resistant species during aging may accumulate and disrupt protein homeostasis (i.e., proteostasis), thereby posing a survival risk to any organism. Using the method diagonal two-dimensional (D2D) SDS-PAGE, which separates hyper-stable SDS-resistant proteins at a proteomics level, we analyzed the plasma of healthy young (<30 years) and older (60-80 years) adults. We discovered the presence of soluble SDS-resistant protein aggregates in the plasma of older adults, but found significantly lower levels in the plasma of young adults. We identified the inflammation-related chaperone protein haptoglobin as the main component of the hyper-stable aggregates. This observation is consistent with the growing link between accumulations of protein aggregates and aging across many organisms. It is plausible higher amounts of SDS-resistant protein aggregates in the plasma of older adults may reflect a compromise in proteostasis that may potentially indicate cellular aging and/or disease risk. The results of this study have implications for further understanding the link between aging and the accumulation of protein aggregates, as well as potential for the development of aging-related biomarkers. More broadly, this novel application of D2D SDS-PAGE may be used to identify, quantify, and characterize the degradation-resistant protein aggregates in human plasma or any biological system. PMID:27179971

  2. Highly Dynamic Cellular-Level Response of Symbiotic Coral to a Sudden Increase in Environmental Nitrogen

    PubMed Central

    Kopp, C.; Pernice, M.; Domart-Coulon, I.; Djediat, C.; Spangenberg, J. E.; Alexander, D. T. L.; Hignette, M.; Meziane, T.; Meibom, A.

    2013-01-01

    ABSTRACT Metabolic interactions with endosymbiotic photosynthetic dinoflagellate Symbiodinium spp. are fundamental to reef-building corals (Scleractinia) thriving in nutrient-poor tropical seas. Yet, detailed understanding at the single-cell level of nutrient assimilation, translocation, and utilization within this fundamental symbiosis is lacking. Using pulse-chase 15N labeling and quantitative ion microprobe isotopic imaging (NanoSIMS; nanoscale secondary-ion mass spectrometry), we visualized these dynamic processes in tissues of the symbiotic coral Pocillopora damicornis at the subcellular level. Assimilation of ammonium, nitrate, and aspartic acid resulted in rapid incorporation of nitrogen into uric acid crystals (after ~45 min), forming temporary N storage sites within the dinoflagellate endosymbionts. Subsequent intracellular remobilization of this metabolite was accompanied by translocation of nitrogenous compounds to the coral host, starting at ~6 h. Within the coral tissue, nitrogen is utilized in specific cellular compartments in all four epithelia, including mucus chambers, Golgi bodies, and vesicles in calicoblastic cells. Our study shows how nitrogen-limited symbiotic corals take advantage of sudden changes in nitrogen availability; this opens new perspectives for functional studies of nutrient storage and remobilization in microbial symbioses in changing reef environments. PMID:23674611

  3. Evaluation of epigallocatechin-3-gallate (EGCG) cross-linked collagen membranes and concerns on osteoblasts.

    PubMed

    Chu, Chenyu; Deng, Jia; Xiang, Lin; Wu, Yingying; Wei, Xiawei; Qu, Yili; Man, Yi

    2016-10-01

    Collagen membranes have ideal biological and mechanical properties for supporting infiltration and proliferation of osteoblasts and play a vital role in guided bone regeneration (GBR). However, pure collagen can lead to inflammation, resulting in progressive bone resorption. Therefore, a method for regulating the level of inflammatory cytokines at surgical sites is paramount for the healing process. Epigallocatechin-3-gallate (EGCG) is a component extracted from green tea with numerous biological activities including an anti-inflammatory effect. Herein, we present a novel cross-linked collagen membrane containing different concentrations of EGCG (0.0064%, 0.064%, and 0.64%) to regulate the level of inflammatory factors secreted by pre-osteoblast cells; improve cell proliferation; and increase the tensile strength, wettability, and thermal stability of collagen membranes. Scanning electron microscope images show that the surfaces of collagen membranes became smoother and the collagen fiber diameters became larger with EGCG treatment. Measurement of the water contact angle demonstrated that introducing EGCG improved membrane wettability. Fourier transform infrared spectroscopy analyses indicated that the backbone of collagen was intact, and the thermal stability was significant improved in differential scanning calorimetry. The mechanical properties of 0.064% and 0.64% EGCG-treated collagen membranes were 1.5-fold greater than those of the control. The extent of cross-linking was significantly increased, as determined by a 2,4,6-trinitrobenzenesulfonic acid solution assay. The Cell Counting Kit-8 (CCK-8) and live/dead assays revealed that collagen membrane cross-linked by 0.0064% EGCG induced greater cell proliferation than pure collagen membranes. Additionally, real-time polymerase chain reaction and enzyme-linked immunosorbent assay results showed that EGCG significantly affected the production of inflammatory factors secreted by MC3T3-E1 cells. Taken together, our

  4. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis

    PubMed Central

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  5. TREM-2 Receptor Expression Increases with 25(OH)D Vitamin Serum Levels in Patients with Pulmonary Sarcoidosis.

    PubMed

    Bucova, Maria; Suchankova, Magda; Tibenska, Elena; Tedlova, Eva; Demian, Juraj; Majer, Ivan; Novosadova, Helena; Tedla, Miroslav

    2015-01-01

    TREM-1 and TREM-2 molecules are members of the TREM transmembrane glycoproteins. In our previous study we identified increased expressions of TREM-1 and TREM-2 receptors in pulmonary sarcoidosis (PS). Only a few studies concerning the association between vitamin D and TREM receptor expression can be found. The aim of our current study was to determine the association between the levels of an inactive form of 25(OH)D vitamin and TREM-1 and TREM-2 receptor expressions. We have detected low levels of 25(OH)D vitamin in 79% of PS patients. Only 21% of patients had normal serum level of 25(OH)D vitamin with values clustered within the low-normal range. The most striking findings were the increased TREM-2 expressions on myeloid cells surfaces in BALF of PS patients with normal 25(OH)D vitamin serum levels compared with those with its decreased levels. The total number of TREM-2 positive cells was 5.7 times higher and the percentage of TREM-2 positive cells was also significantly increased in BALF of PS patients with normal compared to PS patients with low 25(OH)D vitamin serum levels. A significant correlation between total TREM-2 expression and vitamin D levels has been detected too. However, we have not detected similar differences in TREM-1expression and 25(OH)D vitamin serum levels. PMID:26166951

  6. Interleukin-1β (IL-1β) increases pain behavior and the blood glucose level: possible involvement of glucocorticoid system.

    PubMed

    Sim, Yun-Beom; Park, Soo-Hyun; Kang, Yu-Jung; Jung, Jun-Sub; Ryu, Ohk-Hyun; Choi, Moon-Gi; Choi, Seong-Soo; Suh, Hong-Won

    2013-10-01

    The possible involvement of glucocorticoid system in interleukin-1β (IL-1β)-induced nociception and the blood glucose level was studied in ICR mice. In the first experiment, mice were treated intrathecally (i.t.) with IL-1β (100 pg). Corticotrophin releasing hormone (CRH) mRNA (hypothalamus) and c-Fos mRNA (pituitary gland, spinal cord, and the adrenal gland) levels were measured at 30, 60 and 120 min after IL-1β administration. We found that i.t. injection with IL-1β increased CRH mRNA level in the hypothalamus. The IL-1β administered i.t. elevated c-Fos mRNA levels in the spinal cord, pituitary and adrenal glands. Furthermore, i.t. administration of IL-1β significantly increased the plasma corticosterone level up to 60 min. In addition, the adrenalectomy caused the reductions of the blood glucose level and pain behavior induced by IL-1β injected i.t. in normal and D-glucose-fed groups. Furthermore, intraperitoneal (i.p.) pretreatment with RU486 (100mg/kg) attenuated the blood glucose level and pain behavior induced by IL-1β administered i.t. in normal and D-glucose-fed groups. Our results suggest that IL-1β administered i.t. increases the blood glucose level and pain behavior via an activation of the glucocorticoid system. PMID:23773309

  7. Increased level of soluble adenosine deaminase in bone marrow of visceral leishmaniasis patients: an inverse relation with parasite load.

    PubMed

    Rai, Ambak K; Kumar, Prabin; Saini, Sheetal; Thakur, Chandreshwar P; Seth, Tulika; Mitra, Dipendra K

    2016-09-01

    Adenosine deaminase (ADA) which degrades adenosine to inosine, is known to be pro-inflammatory molecule in many diseases. Adenosine suppresses the functioning of the immune system and thus promotes dissemination of the parasite. In our previous finding, the level of soluble ADA in serum of visceral leishmaniasis (VL) was found to be increased as compared to healthy controls. However, it cannot be fairly interpreted unless their level is demonstrated at the disease site, where the parasite resides. We designed this study to correlate the level of soluble ADA (sADA) with parasitic load at the disease site i.e. bone marrow (BM). We found increased levels of sADA in BM as compared to the unaffected BM. Furthermore, a significant inverse correlation is observed between the parasite load and level of sADA at the disease site. PMID:27447233

  8. Increased serum hepcidin-25 level and increased tumor expression of hepcidin mRNA are associated with metastasis of renal cell carcinoma

    PubMed Central

    2009-01-01

    Background Hepcidin has an important role in iron metabolism. We investigated whether hepcidin was involved in renal cell carcinoma (RCC). Methods We measured serum hepcidin-25 levels in 32 patients by liquid chromatograpy (LC)-mass spectrometry (MS)/MS, and assessed hepcidin mRNA expression in paired tumor and non-tumor tissue samples from the surgical specimens of 53 consecutive patients with RCC by real-time reverse transcription polymerase chain reaction. Results The serum hepcidin-25 level was higher in patients with metastatic RCC than nonmetastatic RCC (P < 0.0001), and was positively correlated with the serum interleukin-6 and C-reactive protein levels (P < 0.001). Expression of hepcidin mRNA was lower in tumor tissues than in non-tumor tissues (P < 0.0001). The serum hepcidin-25 level was not correlated with the expression of hepcidin mRNA in the corresponding tumor tissue specimens from 32 patients. Hepcidin mRNA expression in tumor tissue was correlated with metastatic potential, but not with histological differentiation or tumor stage. Kaplan-Meier analysis showed that over expression of hepcidin mRNA was related to shorter overall survival in RCC patients. Univariate analysis (Cox proportional hazards model) showed that the hepcidin mRNA level was an independent prognostic factor for overall survival. Conclusion Our findings suggest that a high serum hepcidin-25 level may indicate the progression of RCC, and that upregulation of hepcidin mRNA expression in tumor tissue may be related to increased metastatic potential. PMID:19656379

  9. Increased levels of platelet-activating factor in blood following intestinal ischemia in the dog.

    PubMed

    Filep, J; Hermán, F; Braquet, P; Mózes, T

    1989-01-31

    The possible role of platelet-activating factor (PAF) in superior mesenteric artery occlusion induced circulatory collapse was studied in anesthetized dogs. PAF was measured by platelet aggregation assay. Identity of PAF-like product in blood was ascertained by thin layer chromatography, high pressure liquid chromatography and alkaline treatment. Low amount of PAF was detected in the mesenteric blood under normal conditions, during reperfusion PAF levels were significantly higher. Pretreatment of the animals with BN 52021, a specific PAF receptor antagonist abolished the fall in mean arterial pressure and the rise in hematocrit due to ischemia/reperfusion. These findings suggest that PAF may play an important role in mesenteric ischemia-induced circulatory collapse. PMID:2916986

  10. Increasing physical activity levels in primary school physical education: The SHARP Principles Model

    PubMed Central

    Powell, Emma; Woodfield, Lorayne A.; Nevill, Alan M.

    2015-01-01

    Objectives: To evaluate the effectiveness of a one-year teaching intervention to increase moderate to vigorous physical activity (MVPA) during primary school physical education (PE). Methods: A quasi-experimental, non-equivalent group design involving four classes from two primary schools in the West Midlands, UK. In March 2014 schools were selected through purposive sampling to match schools in terms of size and demographics (baseline, n = 111: post-intervention, n = 95); data were collected from children in school years 3 and 4 (aged 7 to 9 years). The intervention involved developing teacher effectiveness through the SHARP Principles Model which was grounded in the Self Determination Theory (SDT), the Social Ecological Model (SEM) and three key ingredients from the Behaviour Change Taxonomy (BCT). MVPA was assessed at baseline and four weeks post-intervention using the System for Observing Fitness and Instruction Time (SOFIT). Four individual teacher interviews were conducted with the intervention school, to explore teachers' perceptions of the intervention. Results: A two-way ANOVA (Analysis of Variance) indicated large interaction effect sizes for time spent in MVPA (F(1, 27) = 11.07, p = 0.003, ηp2 = .316) and vigorous activity (VPA) (F = (1,27) = 8.557, p = .007, ηp2 = .263). PA in the intervention school increased significantly whereas in the control school MVPA remained relatively constant and VPA decreased. The qualitative findings revealed two main emergent themes: a paradigm shift and teacher's developing pedagogy. Conclusions: The intervention was effective in increasing MVPA in PE. Recommendations based on this evaluation would be for the SHARP Principles Model to be replicated and evaluated on a wider scale across a variety of contexts. PMID:26844179

  11. Gas-Phase Intramolecular Protein Crosslinking via Ion/Ion Reactions: Ubiquitin and a Homobifunctional sulfo-NHS Ester

    PubMed Central

    Webb, Ian K.; Mentinova, Marija; McGee, William M.; McLuckey, Scott A.

    2013-01-01

    Gas-phase intra-molecular crosslinking of protein ubiquitin cations has been demonstrated via ion/ion reactions with anions of a homobifunctional N-hydroxysulfosuccinimide (sulfo-NHS) ester reagent. The ion/ion reaction between multiply-protonated ubiquitin and crosslinker monoanions produces a stable, charge reduced complex. Covalent crosslinking is indicated by the consecutive loss of two molecules of sulfo-NHS under ion trap collisional activation conditions. Covalent modification is verified by the presence of covalently crosslinked sequence ions produced by ion-trap collision-induced dissociation of the ion generated from the losses of sulfo-NHS. Analysis of the crosslinked sequence fragments allows for the localization of crosslinked primary amines, enabling proximity mapping of the gas-phase 3-D structures. The presence of two unprotonated reactive sites within the distance constraint of the crosslinker is required for successful crosslinking. The ability to covalently crosslink is therefore sensitive to protein charge state. As the charge state increases, fewer reactive sites are available and protein structure is more likely to become extended due to intramolecular electrostatic repulsion. At high charge states, the reagent shows little evidence for covalent crosslinking but does show evidence for ‘electrostatic crosslinking’ in that the binding of the sulfonate groups to the protein is sufficiently strong that backbone cleavages are favored over reagent detachment under ion trap collisional activation conditions. PMID:23463545

  12. Increased levels of chromosomal aberrations and DNA damage in a group of workers exposed to formaldehyde.

    PubMed

    Costa, Solange; Carvalho, Sandra; Costa, Carla; Coelho, Patrícia; Silva, Susana; Santos, Luís S; Gaspar, Jorge F; Porto, Beatriz; Laffon, Blanca; Teixeira, João P

    2015-07-01

    Formaldehyde (FA) is a commonly used chemical in anatomy and pathology laboratories as a tissue preservative and fixative. Because of its sensitising properties, irritating effects and cancer implication, FA accounts probably for the most important chemical-exposure hazard concerning this professional group. Evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting, particularly in regard to the ability of inhaled FA to induce toxicity on other cells besides first contact tissues, such as buccal and nasal cells. To evaluate the effects of exposure to FA in human peripheral blood lymphocytes, a group of 84 anatomy pathology laboratory workers exposed occupationally to FA and 87 control subjects were tested for chromosomal aberrations (CAs) and DNA damage (comet assay). The level of exposure to FA in the workplace air was evaluated. The association between genotoxicity biomarkers and polymorphic genes of xenobiotic-metabolising and DNA repair enzymes were also assessed. The estimated mean level of FA exposure was 0.38±0.03 ppm. All cytogenetic endpoints assessed by CAs test and comet assay % tail DNA (%TDNA) were significantly higher in FA-exposed workers compared with controls. Regarding the effect of susceptibility biomarkers, results suggest that polymorphisms in CYP2E1 and GSTP1 metabolic genes, as well as, XRCC1 and PARP1 polymorphic genes involved in DNA repair pathways are associated with higher genetic damage in FA-exposed subjects. Data obtained in this study show a potential health risk situation of anatomy pathology laboratory workers exposed to FA (0.38 ppm). Implementation of security and hygiene measures may be crucial to decrease risk. The obtained information may also provide new important data to be used by health care programs and by governmental agencies responsible for occupational health and safety. PMID:25711496

  13. Comparison of two methods of assessing total body water at sea level and increasing high altitude.

    PubMed

    Boos, C J; Holdsworth, D A; Hall, D P; Mellor, A; O'Hara, J; Woods, D R

    2014-11-01

    Fluid retention is a recognized feature of acute mountain sickness. However, accurate assessment of hydration, including the quantification of body water, has traditionally relied on expensive and non-portable equipment limiting its utility in the field setting. We compared the assessment of total body water (TBW) and their relationship to total body weight using two non-invasive methods using the NICas single-frequency bioimpedance analysis (SF-BIA) system and the BodyStat QuadScan 4000 multifrequency BIA system (MF-BIA). TBW measurements were performed at rest at sea level and at high altitude (HA) at 3833 m postexercise and at rest and thereafter at rest at 4450 m and 5129 m on 47 subjects. The average age was 34.5 ± 9.3 years with an age range of 21-54 years (70.2% male). There were strong correlations between TBW assessment with both methods at sea level (r = 0.90; 95% CI 0.78-0.95: P<0.0001) and at HA (r = 0.92; 0.89-0.94: P<0.0001), however, TBW readings were 0.2 l and 1.91 l lower, respectively, with the NICaS. There was a stronger correlation between TBW and body weight with the QuadScan (r = 0.91; P<0.0001) than with the NICaS (r = 0.83; P<0.0001). The overall agreement between the two TBW methods was good, but the 95% confidence intervals around these agreements were relatively wide. We conclude that there was reasonable agreement between the two methods of BIA for TBW, but this agreement was lower at HA. PMID:24797153

  14. Dietary selenium increases the antioxidant levels and ATPase activity in the arteries and veins of poultry.

    PubMed

    Cao, Changyu; Zhao, Xia; Fan, Ruifeng; Zhao, Jinxin; Luan, Yilin; Zhang, Ziwei; Xu, Shiwen

    2016-07-01

    Selenium (Se) deficiency is associated with the pathogenesis of vascular diseases. It has been shown that oxidative levels and ATPase activity were involved in Se deficiency diseases in humans and mammals; however, the mechanism by how Se influences the oxidative levels and ATPase activity in the poultry vasculature is unclear. We assessed the effects of dietary Se deficiency on the oxidative stress parameters (superoxide dismutase, catalase, and hydroxyl radical) and ATPase (Na(+)K(+)-ATPase, Ca(++)-ATPase, Mg(++)-ATPase, and Ca(++)Mg(++)-ATPase) activity in broiler poultry. A total of 40 broilers (1-day old) were randomly divided into a Se-deficient group (L group, fed a Se-deficient diet containing 0.08 mg/kg Se) and a control group (C group, fed a diet containing sodium selenite at 0.20 mg/kg Se). Then, arteries and veins were collected following euthanasia when typical symptoms of Se deficiency appeared. Antioxidant indexes and ATPase activity were evaluated using standard assays in arteries and veins. The results indicated that superoxide dismutase activity in the artery according to dietary Se deficiency was significantly lower (p < 0.05) compared with the C group. The catalase activity in the veins and hydroxyl radical inhibition in the arteries and veins by dietary Se deficiency were significantly higher (p < 0.05) compared with the C group. The Se-deficient group showed a significantly lower (p < 0.05) tendency in Na(+)K(+)-ATPase activity, Ca(++)-ATPase activity, and Ca(++)Mg(++)-ATPase activity. There were strong correlations between antioxidant indexes and Ca(++)-ATPase activity. Thus, these results indicate that antioxidant indexes and ATPases may have special roles in broiler artery and vein injuries under Se deficiency. PMID:26637493

  15. Evolution of Wholesale Electricity Market Design with Increasing Levels of Renewable Generation

    SciTech Connect

    Ela, E.; Milligan, M.; Bloom, A.; Botterud, A.; Townsend, A.; Levin, T.

    2014-09-01

    Variable generation such as wind and photovoltaic solar power has increased substantially in recent years. Variable generation has unique characteristics compared to the traditional technologies that supply energy in the wholesale electricity markets. These characteristics create unique challenges in planning and operating the power system, and they can also influence the performance and outcomes from electricity markets. This report focuses on two particular issues related to market design: revenue sufficiency for long-term reliability and incentivizing flexibility in short-term operations. The report provides an overview of current design and some designs that have been proposed by industry or researchers.

  16. Anomalous increases in piezometric levels in advance of longwall mining subsidence

    USGS Publications Warehouse

    Booth, C.J.; Curtiss, A.M.; DeMaris, P.J.; Van Roosendaal, D. J.

    1999-01-01

    The typical initial piezometric response to longwall undermining is a decline in head due to the opening of fractures and bedding planes during early subsidence. However, in studies over two active longwall mines in southern Illinois, temporary rises in head just before subsidence were observed in piezometers constructed in low-permeability units. Although the initial phase of subsidence is considered dilational, these head increases indicate compressional effects that raise pore-water pressures. Possible mechanisms are shear stresses at the leading edge of subsidence or transmission of stress related to dewatering of underlying permeable units.

  17. Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors.

    PubMed

    Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

    2016-01-01

    Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287

  18. Defects in interstrand cross-link uncoupling do not account for the extreme sensitivity of ERCC1 and XPF cells to cisplatin.

    PubMed

    De Silva, Inusha U; McHugh, Peter J; Clingen, Peter H; Hartley, John A

    2002-09-01

    The anticancer drug cisplatin reacts with DNA leading to the formation of interstrand and intrastrand cross-links that are the critical cytotoxic lesions. In contrast to cells bearing mutations in other components of the nucleotide excision repair apparatus (XPB, XPD, XPG and CSB), cells defective for the ERCC1-XPF structure-specific nuclease are highly sensitive to cisplatin. To determine if the extreme sensitivity of XPF and ERCC1 cells to cisplatin results from specific defects in the repair of either intrastrand or interstrand cross-links we measured the elimination of both lesions in a range of nucleotide excision repair Chinese hamster mutant cell lines, including XPF- and ERCC1-defective cells. Compared to the parental, repair-proficient cell line all the mutants tested were defective in the elimination of both classes of adduct despite their very different levels of increased sensitivity. Consequently, there is no clear relationship between initial incisions at interstrand cross-links or removal of intrastrand adducts and cellular sensitivity. These results demonstrate that the high cisplatin sensitivity of ERCC1 and XPF cells likely results from a defect other than in excision repair. In contrast to other conventional DNA cross-linking agents, we found that the repair of cisplatin adducts does not involve the formation of DNA double-strand breaks. Surprisingly, XRCC2 and XRCC3 cells are defective in the uncoupling step of cisplatin interstrand cross-link repair, suggesting that homologous recombination might be initiated prior to excision of this type of cross-link. PMID:12202770

  19. Folic acid-targeted disulfide-based cross-linking micelle for enhanced drug encapsulation stability and site-specific drug delivery against tumors

    PubMed Central

    Zhang, Yumin; Zhou, Junhui; Yang, Cuihong; Wang, Weiwei; Chu, Liping; Huang, Fan; Liu, Qiang; Deng, Liandong; Kong, Deling; Liu, Jianfeng; Liu, Jinjian

    2016-01-01

    Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation. PMID:27051287