Self-assembly of Fmoc-tetrapeptides based on the RGDS cell adhesion motif

Self-assembly in aqueous solution has been investigated for two Fmoc [Fmoc ¼ N-(fluorenyl)-9-methoxycarbonyl] tetrapeptides comprising the RGDS cell adhesion motif from fibronectin or the scrambled sequence GRDS. The hydrophobic Fmoc unit confers amphiphilicity on the molecules, and introduces aromatic stacking interactions. Circular dichroism and FTIR spectroscopy show that the self-assembly of both peptides at low concentration is dominated by interactions among Fmoc units, although Fmoc-GRDS shows b-sheet features, at lower concentration than Fmoc-RGDS. Fibre X-ray diffraction indicates b-sheet formation by both peptides at sufficiently high concentration. Strong alignment effects are revealed by linear dichroism experiments for Fmoc-GRDS. Cryo-TEM and smallangle X-ray scattering (SAXS) reveal that both samples form fibrils with a diameter of approximately 10 nm. Both Fmoc-tetrapeptides form self-supporting hydrogels at sufficiently high concentration. Dynamic shear rheometry enabled measurements of the moduli for the Fmoc-GRDS hydrogel, however syneresis was observed for the Fmoc-RGDS hydrogel which was significantly less stable to shear. Molecular dynamics computer simulations were carried out considering parallel and antiparallel b-sheet configurations of systems containing 7 and 21 molecules of Fmoc-RGDS or Fmoc-GRDS, the results being analyzed in terms of both intermolecular structural parameters and energy contributions.

Mapping Educational Specialist knowHow (MESH): the building of a knowledge management system for research informed practice

In this invited article the authors present an evaluative report on the development of the MESHGuides project (http://www.meshguides.org/). MESHGuides’ objective is to provide education with an international knowledge management system. MESHGuides were conceived as research summaries for supporting teachers’ in developing evidence-based practice. Their aim is to enhance teachers’ capacity to engage actively with research in their own classrooms. The original thinking for MESH arose from the work of UK-based academics Professor Marilyn Leask and Dr Sarah Younie in response to a desire, which has recently gathered momentum in the UK, for the development of a more research-informed teaching profession and for the establishment of an on-line platform to support evidence-based practice (DfE, 2015; Leask and Younie 2001; OECD 2009). The focus of this article is on how the MESHGuides project was conceived and structured, the technical systems supporting it and the practical reality for academics and teachers of composing and using MESHGuides. The project and the guides are in the early stages of development, and discussion indicates future possibilities for more global engagement with this knowledge management system.

Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes

Aims Thyroid hormone (TH) rapidly relaxes vascular smooth muscle cells (VSMCs). However, the mechanisms involved in this effect remain unclear. We hypothesize that TH-induced rapid vascular relaxation is mediated by VSMC-derived nitric oxide (NO) production and is associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signalling pathway. Methods and results NO levels were determined using a NO-specific fluorescent dye (DAF-2) and nitrite (NO(2)) levels. Expression of NO synthase (NOS) isoforms and proteins of the PI3K/Akt pathway was determined by both western blotting and immunocytochemistry. Myosin light chain (MLC) phosphorylation levels were also investigated by western blotting. Exposure of cultured VSMCs from rat thoracic aortas to triiodothyronine (T3) resulted in a significant decrease of MLC phosphorylation levels. T3 also induced a rapid increase in Akt phosphorylation and increased NO production in a dose-dependent manner (0.001-1 mu M). VSMCs stimulated with T3 for 30 min showed an increase in the expression of all three NOS isoforms and augmented NO production, effects that were prevented by inhibitors of PI3K. Vascular reactivity studies showed that vessels treated with T3 displayed a decreased response to phenylephrine, which was reversed by NOS inhibition. These data suggest that T3 treatment induces greater generation of NO both in aorta and VSMCs and that this phenomenon is endothelium independent. In addition, these findings show for the first time that the PI3K/Akt signalling pathway is involved in T3-induced NO production by VSMCs, which occurs with expressive participation of inducible and neuronal NOS. Conclusion Our data strongly indicate that T3 causes NO-dependent rapid relaxation of VSMC and that this effect is mediated by the PI3K/Akt signalling pathway.

Jämförelsestudie avseende stomsystem : Ramverk eller fackverk/balk/pelar-system

Projektet omfattade en jämförelsestudie avseende stomsystem. Studien undersökte ramverk och fackverk/balk/pelar-system och genomfördes självständigt med stöttning av Ramböll AB´s kontor i Falun. Syftet var främst att undersöka vilka skillnader det finns mellan tvåledsramar och fackverk/balk/pelar-system för lätta hallbyggnader och försöka få klarhet i varför fackverk/balk/pelar-system är det dominerande systemet i Sverige eftersom övriga Europa har tagit en annan utveckling och domineras av tvåledsramar. Studien undersöker skillnaderna mellan systemen i en hallbyggnad med förutbestämda mått i stål.Inledningsvis gjordes en litteraturstudie för att få en bredare bakgrund av systemen och en bättre förståelse om förutsättningarna för varje system. Efter litteraturstudien kunde sedan ett typhus och beräkningsunderlag för jämförelsestudien tas fram. Även en enkätstudie gjordes med syftet att skapa en tydlig bild av vilket stomsystem konstruktörer i Sverige oftast väljer och varför. Resultatet av studien visade att tvåledsramar ger en ökad kostnad jämfört med fackverk/balk/pelar-system i materialåtgång och framställning samt att beräkningarna blir mer komplicerade. Skulle fortsatta studier göras med dessa system i byggnader med andra mått skulle det kanske gå att få fram speciella mått på byggnader där kostnaden för tvåledsramar blir densamma som för fackverk/balk/pelar-system och därför är ett likvärdigt alternativ som stomsystem.En viktig slutsats från projektet är att tvåledsramar används mycket mer sällan än fackverk/balk/pelar-system som stomsystem i lätta hallbyggnader i Sverige på grund av att kostnaderna blir mycket högre med tvåledsramar och att det är ett mer komplicerat system i beräkningsarbetet. De viktigaste slutsatserna från jämförelsestudien går att sammafatta som följande: Tvåledsramar är dyrare att använda. Tvåledsramar är ett mer komplicerat system beräkningsmässigt. Traditionen av att använda tvåledsramar finns inte och därför används inte systemet.

Efficacy of linear and convex transducers for ultrasound-guided transvaginal follicle aspiration

A new device was developed to hold linear transducers for transvaginal follicle aspiration. Efficacy of follicle aspiration was compared using a linear 6 MHz and a convex 5 MHz transducer. Fifty-five cows were submitted to follicle aspiration at random days of the estrous cycle. Aspirations were conducted with linear (n = 28) and convex (n = 38) transducers with 18 G needles at a negative pressure corresponding to 13 ml H2O/min. A greater number of follicles were aspirated using convex than to linear probe (12.4 versus 7.8, respectively, P < 0.05). Mean number of oocytes and recovery rates were similar for convex (5.4 and 48.6%) and linear (4.6 and 59.3%) transducers. Limited space between the linear transducer and needle guide restricted access to some portions of the ovary, reducing the number of follicles aspirated using a linear transducer. The newly developed adaptor allowed greater stability, holding the ovaries firmly against the linear transducer. This diminished mobility permitted a similar number of oocytes to be recovered with both transducers. In conclusion, this new adaptor provided a low cost alternative for routine follicle aspiration and oocyte recovery in cattle. (C) 2002 Elsevier B.V. All rights reserved.

Construction of an alkaline phosphatase-liposome system: a tool for biomineralization study

Alkaline phosphatase is required for the mineralization of bone and cartilage. This enzyme is localized in the matrix vesicle, which plays a role key in calcifying cartilage. In this paper. we standardize a method for construction an alkaline phosphatase liposome system to mimic matrix vesicles and examine a some kinetic behavior of the incorporated enzyme. Polidocanol-solubilized alkaline phosphatase, free of detergent, was incorporated into liposomes constituted from dimyristoylphosphatidylcholine (DMPC), dilaurilphosphatidylcholine (DLPC) or dipalmitoylphosphatidylcholine (DPPC). This process was time-dependent and >95% of the enzyme was incorporated into the liposome after 4 h of incubation at 25 degreesC. Although, incorporation was more rapid when vesicles constituted from DPPC were used, the incorporation was more efficient using vesicles constituted from DMPC. The 395 nm diameter of the alkaline phosphatase-liposome system was relatively homogeneous and more stable when stored at 4 degreesC.Alkaline phosphatase was completely released from liposome system only using purified phosphatidylinositol-specific phospholipase C (PIPLC). These experiments confirm that the interaction between alkaline phosphatase and lipid bilayer of liposome is via GPI anchor of the enzyme, alone. An important point shown is that an enzyme bound to liposome does not lose the ability to hydrolyze ATP, pyrophosphate and p-nitrophenyl phosphate (PNPP), but a liposome environment affects its kinetic properties, specifically for pyrophosphate.The standardization of such system allows the study of the effect of phospholipids and the enzyme in in vitro and in vivo mineralization, since it reproduces many essential features of the matrix vesicle. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

The dorsal raphe nucleus exerts opposed control on generalized anxiety and panic-related defensive responses in rats

It has been proposed that the ascending dorsal raphe (DR)-serotonergic (5-HT) pathway facilitates conditioned avoidance responses to potential or distal threat, while the DR-periventricular 5-HT pathway inhibits unconditioned flight reactions to proximal danger. Dysfunction on these pathways would be, respectively, related to generalized anxiety (GAD) and panic disorder (PD). To investigate this hypothesis, we microinjected into the rat DR the benzodiazepine inverse receptor agonist FG 7142, the 5-HT1A receptor agonist 8-OH-DPAT or the GABA(A) receptor agonist muscimol. Animals were evaluated in the elevated T-maze (ETM) and light/dark transition test. These models generate defensive responses that have been related to GAD and PD. Experiments were also conducted in the ETM 14 days after the selective lesion of DR serotonergic neurons by 5,7-dihydroxytriptamine (DHT). In all cases, rats were pre-exposed to one of the open arms of the ETM 1 day before testing. The results showed that FG 7142 facilitated inhibitory avoidance, an anxiogenic effect, while impairing one-way escape, an anxiolytic effect. 8-OH-DPAT, muscimol, and 5,7-DHT-induced lesions acted in the opposite direction, impairing inhibitory avoidance while facilitating one-way escape from the open arm. In the light/dark transition, 8-OH-DPAT and muscimol increased the time spent in the lighted compartment, an anxiolytic effect. The data supports the view that distinct DR-5-HT pathways regulate neural mechanisms underlying GAD and PD. (C) 2002 Elsevier B.V. B.V. All rights reserved.

Effects of environrnental conditions on the radon daughters spatial distribution

The influence of environmental conditions on the indoor radon daughters spatial distribution is studied both theoretically and experimentally. Simple theoretical calculations indicate that ventilation and variation in the size distribution of aerosols should play an important role influencing the spatial distribution of indoor radon decay products, but experimental results indicate that these environmental factors have little influence on the spatial distribution of radon daughters near the walls of indoor environments. We have observed that the maximum effective range of the plate-out effect varies only between I and 3 cm in typical dwellings. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Structural and electrochemical properties of LiCoO2 prepared by combustion synthesis

LiCoO2 powders were prepared by combustion synthesis, using metallic nitrates as the oxidant and metal sources and urea as fuel. A small amount of the LiCoO2 phase was obtained directly from the combustion reaction, however, a heat treatment was necessary for the phase crystallization. The heat treatment was performed at the temperature range from 400 up to 700 degreesC for 12 h. The powders were characterized by X-ray diffraction (XRD), X ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and specific surface area values were obtained by BET isotherms. Composite electrodes were prepared using a mixture of LiCoO2, carbon black and poly(vinylidene fluoride) (PVDF) in the 85:10:5% w/w ratio. The electrochemical behavior of these composites was evaluated in ethylene carbonate/dimethylcarbonate solution, using lithium perchlorate as supporting electrolyte. Cyclic voltammograms showed one reversible redox process at 4.0/3.85 V and one irreversible redox process at 3.3 V for the LiCoO2 obtained after a post-heat treatment at 400 and 500 degreesC.Raman spectroscopy showed the possible presence of LiCoO2 with cubic structure for the material obtained at 400 and 500 degreesC. This result is in agreement with X-ray data with structural refinement for the LiCoO2 powders obtained at different temperatures using the Rietveld method. Data from this method showed the coexistence of cubic LiCoO2 (spinel) and rhombohedral (layered) structures when LiCoO2 was obtained at lower temperatures (400 and 500 degreesC). The single rhombohedral structure for LiCoO2 was obtained after post-heat treatment at 600 degreesC. The maximum energy capacity in the first discharge was 136 mA g(-1) for the composite electrode based on LiCoO2 obtained after heat treatment at 700 degreesC. (C) 2002 Elsevier B.V. B.V. All rights reserved.