260 research outputs found
A catalytic approach via retro-aldol condensation of glucose to furanic compounds
The synthesis of new types of furan-based compounds other than 5-hydroxymethylfurfural from glucose is a very attractive yet underexploited strategy. We report here a catalytic conversion of glucose with acetylacetone (acac) to furan-centered chemicals, 2-methyl-3-acetylfuran (MAF) and 1-(5-(1,2-dihydroxyethyl)-2-methylfuran-3-yl)ethan-1-one (DMAF), which are potential building blocks for the synthesis of fine chemicals. The experimentally supported reaction mechanism is cascade-type, including glycolaldehyde (GA) formation by H2MoO4-catalysed retro-aldol condensation (C2 + C4) of glucose and immediate capture of transient C2 and C4 intermediates by acac to yield MAF and DMAF. To the best of our knowledge, this is the first report on the straightforward synthesis of MAF and DMAF from glucose, providing a new but generic synthesis strategy for GA-based C2 and erythrose-based C4 chemistry in biorefining.Peer reviewe
The snow must go on: Ground ice encasement, snow compaction and absence of snow differently cause soil hypoxia, CO2 accumulation and tree seedling damage in boreal forest
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Matrix metalloproteinases and their tissue inhibitors after selective laser trabeculoplasty in pseudoexfoliative secondary glaucoma
<p>Abstract</p> <p>Background</p> <p>The aim of this study was to assess changes in metalloproteinases (MMP-2) and tissue inhibitor of metalloproteinases (TIMP-2) following selective laser trabeculoplasty (SLT) in patients with pseudoexfoliative glaucoma (PEXG).</p> <p>Methods</p> <p>We enrolled 15 patients with PEXG and cataracts (PEXG-C group) and good intraocular pressure (IOP) controlled with β-blockers and dorzolamide eye drops who were treated by cataract phacoemulsification and 15 patients with pseudoexfoliative glaucoma (PEXG-SLT group). The PEXG-SLT patients underwent a trabeculectomy for uncontrolled IOP in the eye that showed increased IOP despite the maximum drug treatment with β-blockers and dorzolamide eye drops and after ineffective selective laser trabeculoplasty (SLT). The control group consisted of 15 subjects with cataracts. Aqueous humor was aspirated during surgery from patients with PEXG-C, PEXG-SLT and from matched control patients with cataracts during cataract surgery or trabeculectomy. The concentrations of MMP-2 and TIMP-2 in the aqueous humor were assessed with commercially available ELISA kits.</p> <p>Results</p> <p>In PEXG-SLT group in the first 10 days after SLT treatment a significant reduction in IOP was observed: 25.8 ± 1.9 vs 18.1.0 ± 1.4 mm/Hg (p < 0.001), but after a mean time of 31.5 ± 7.6 days IOP increased and returned to pretreatment levels: 25.4 ± 1.6 mm/Hg (p < 0.591). Therefore a trabeculectomy was considered necessary.</p> <p>The MMP-2 in PEXG-C was 57.77 ± 9.25 μg/ml and in PEXG-SLT was 58.52 ± 9.66 μg/ml (p < 0.066). TIMP-2 was 105.19 ± 28.53 μg/ml in PEXG-C and 105.96 ± 27.65 μg/ml in PEXG-SLT (p < 0.202). The MMP-2/TIMP-2 ratio in the normal subjects was 1.11 ± 0.44. This ratio increase to 1.88 ± 0.65 in PEXG-C (p < 0.001) and to 1.87 ± 0.64 in PEXG-SLT (p < 0.001). There was no statistically significant difference between the PEXG-C and PEXG-SLT ratios (p < 0.671).</p> <p>Conclusion</p> <p>This case series suggest that IOP elevation after SLT can be a serious adverse event in some PEXG patients. The IOP increase in these cases would be correlated to the failure to decrease the TIMP-2/MMP-2 ratio.</p> <p>Trial registration</p> <p>Current Controlled Trials <b>ISRCTN79745214</b></p
Palmitoylation of human proteinase-activated receptor-2 differentially regulates receptor-triggered ERK1/2 activation, calcium signalling and endocytosis
hPAR2 (human proteinase-activated receptor-2) is a member of the novel family of proteolytically activated GPCRs (G-protein-coupled receptors) termed PARs (proteinase-activated receptors). Previous pharmacological studies have found that activation of hPAR2 by mast cell tryptase can be regulated by receptor N-terminal glycosylation. In order to elucidate other post-translational modifications of hPAR2 that can regulate function, we have explored the functional role of the intracellular cysteine residue Cys361. We have demonstrated, using autoradiography, that Cys361 is the primary palmitoylation site of hPAR2. The hPAR2C361A mutant cell line displayed greater cell-surface expression compared with the wt (wild-type)-hPAR2-expressing cell line. hPAR2C361A also showed a decreased sensitivity and efficacy (intracellular calcium signalling) towards both trypsin and SLIGKV. In stark contrast, hPAR2C361A triggered greater and more prolonged ERK (extracellular-signal-regulated kinase) phosphorylation compared with that of wt-hPAR2 possibly through Gi, since pertussis toxin inhibited the ability of this receptor to activate ERK. Finally, flow cytometry was utilized to assess the rate and extent of receptor internalization following agonist challenge. hPAR2C361A displayed faster internalization kinetics following trypsin activation compared with wt-hPAR2, whereas SLIGKV had a negligible effect on internalization for either receptor. In conclusion, palmitoylation plays an important role in the regulation of PAR2 expression, agonist sensitivity, desensitization and internalization
2010 update of the ASAS/EULAR recommendations for the management of ankylosing spondylitis
This first update of the ASAS/EULAR recommendations on the management of ankylosing spondylitis (AS) is based on the original paper, a systematic review of existing recommendations and the literature since 2005 and the discussion and agreement among 21 international experts, 2 patients and 2 physiotherapists in a meeting in February 2010. Each original bullet point was discussed in detail and reworded if necessary. Decisions on new recommendations were made — if necessary after voting. The strength of the recommendations (SOR) was scored on an 11-point numerical rating scale after the meeting by email. These recommendations apply to patients of all ages that fulfill the modified NY criteria for AS, independent of extra-articular manifestations, and they take into account all drug and non-drug interventions related to AS. Four overarching principles were introduced, implying that one bullet has been moved to this section. There are now 11 bullet points including 2 new ones, one related to extra-articular manifestations and one to changes in the disease course. With a mean score of 9.1 (range 8-10) the SOR was generally very good
A comparison of the physical and chemical differences between cancellous and cortical bovine bone mineral at two ages
To assess possible differences between the mineral phases of cortical and cancellous bone, the structure and composition of isolated bovine mineral crystals from young (1–3 months) and old (4–5 years) postnatal bovine animals were analyzed by a variety of complementary techniques: chemical analyses, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and 31P solid-state magic angle spinning nuclear magnetic resonance spectroscopy (NMR). This combination of methods represents the most complete physicochemical characterization of cancellous and cortical bone mineral completed thus far. Spectra obtained from XRD, FTIR, and 31P NMR all confirmed that the mineral was calcium phosphate in the form of carbonated apatite; however, a crystal maturation process was evident between the young and old and between cancellous and cortical mineral crystals. Two-way analyses of variance showed larger
increases of crystal size and Ca/P ratio for the cortical vs. cancellous bone of 1–3 month than the 4–5 year animals.
The Ca/(P + CO3) remained nearly constant within a given
bone type and in both bone types at 4–5 years. The carbonate
and phosphate FTIR band ratios revealed a decrease of labile ions with age and in cortical, relative to cancellous, bone. Overall, the same aging or maturation trends were observed for young vs. old and cancellous vs. cortical. Based on the larger proportion of newly formed bone in cancellous bone relative to cortical bone, the major differences between the cancellous and cortical mineral crystals must be ascribed to differences in average age of the crystals
Effects of soil warming and nitrogen foliar applications on bud burst of black spruce
Key message: In mature black spruce, bud burst process is anticipated by soil warming, while delayed by foliar applications of nitrogen; however, the effects depend on growth conditions at the site.
Abstract: The observation of phenological events can be used as biological indicator of environmental changes, especially from the perspective of climate change. In boreal forests, the onset of the bud burst is a key factor in the length of the growing season. With current climate change, the major factors limiting the growth of boreal trees (i.e., temperature and nitrogen availability) are changing and studies on mature trees are limited. The aim of this study was to investigate the effects of soil warming and increased nitrogen (N) deposition on bud burst of mature black spruce [Picea mariana (Mill.) BSP]. From 2008 onwards, an experimental manipulation of these environmental growth conditions was conducted in two stands (BER and SIM) at different altitudes in the boreal forest of Quebec, Canada. An increase in soil temperature (H treatment) and a canopy application of artificial rain enriched with nitrogen (N treatment) were performed. Observations of bud phenology were made during May–July 2012 and 2013. In BER, H treatment caused an anticipation (estimated as 1–3 days); while N treatment, a delay (estimated as 1–2 days but only in 2012) in bud burst. No treatments effect was significant in SIM. It has been demonstrated that soil temperature and N availability can play an important role in affecting bud burst in black spruce but the effects of these environmental factors on growth are closely linked with site conditions
The Human Gonadotropin Releasing Hormone Type I Receptor Is a Functional Intracellular GPCR Expressed on the Nuclear Membrane
The mammalian type I gonadotropin releasing hormone receptor (GnRH-R) is a structurally unique G protein-coupled receptor (GPCR) that lacks cytoplasmic tail sequences and displays inefficient plasma membrane expression (PME). Compared to its murine counterparts, the primate type I receptor is inefficiently folded and retained in the endoplasmic reticulum (ER) leading to a further reduction in PME. The decrease in PME and concomitant increase in intracellular localization of the mammalian GnRH-RI led us to characterize the spatial distribution of the human and mouse GnRH receptors in two human cell lines, HEK 293 and HTR-8/SVneo. In both human cell lines we found the receptors were expressed in the cytoplasm and were associated with the ER and nuclear membrane. A molecular analysis of the receptor protein sequence led us to identify a putative monopartite nuclear localization sequence (NLS) in the first intracellular loop of GnRH-RI. Surprisingly, however, neither the deletion of the NLS nor the addition of the Xenopus GnRH-R cytoplasmic tail sequences to the human receptor altered its spatial distribution. Finally, we demonstrate that GnRH treatment of nuclei isolated from HEK 293 cells expressing exogenous GnRH-RI triggers a significant increase in the acetylation and phosphorylation of histone H3, thereby revealing that the nuclear-localized receptor is functional. Based on our findings, we conclude that the mammalian GnRH-RI is an intracellular GPCR that is expressed on the nuclear membrane. This major and novel discovery causes us to reassess the signaling potential of this physiologically and clinically important receptor
G protein-coupled receptors: what a difference a 'partner' makes
G protein-coupled receptors (GPCRs) are important cell signaling mediators, involved in essential physiological processes. GPCRs respond to a wide variety of ligands from light to large macromolecules, including hormones and small peptides. Unfortunately, mutations and dysregulation of GPCRs that induce a loss of function or alter expression can lead to disorders that are sometimes lethal. Therefore, the expression, trafficking, signaling and desensitization of GPCRs must be tightly regulated by different cellular systems to prevent disease. Although there is substantial knowledge regarding the mechanisms that regulate the desensitization and down-regulation of GPCRs, less is known about the mechanisms that regulate the trafficking and cell-surface expression of newly synthesized GPCRs. More recently, there is accumulating evidence that suggests certain GPCRs are able to interact with specific proteins that can completely change their fate and function. These interactions add on another level of regulation and flexibility between different tissue/cell-types. Here, we review some of the main interacting proteins of GPCRs. A greater understanding of the mechanisms regulating their interactions may lead to the discovery of new drug targets for therapy
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