Role of the synthesis route on the properties of hybrid LDH-graphene as basic catalysts

Layered double hydroxides (LDH or HT) or their derived mixed oxides present marked acid-base properties useful in catalysis, but they lead to agglomerate inducing a weak accessibility to the active sites. In this study we report the preparation and characterization of HT/Graphene (HT/rGO) nanocomposites as active and selective basic catalysts for the acetone condensation reaction. The graphene high specific surface area and structural compatibility with the HT allowed increasing the number and accessibility of the active sites and activity of this later. Two series of HT/rGO nanocomposites with 0.5 = HT/rGO = 10 mass ratio were prepared by: i) direct HT coprecipitation in the presence of GO; ii) self-assembly of preformed HT with GO. The prepared HT/rGO nanocomposites were dried either in air at 80 °C or freeze-dried. A series of characterizations showed the great influence of the preparation method and HT/rGO mass ratio on both the nanocomposite structure and catalytic activity. An optimum activity was observed for a HT/rGO = 10 catalyst. Particularly, the highest catalytic activity was found in those nanocomposites obtained by coprecipitation and freeze dried (3 times more active than bulk HT) which can be connected to their structure with a better accessibility to the basic sites.Postprint (author's final draft

5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

Comparison of Blood Pressure and Blood Glucose Level Among Elderly with Non-communicable Disease

Due to increasing age, elderly are prone to non-communicable diseases (NCD), such as hypertension (HT) and diabetes mellitus (DM). Easy physical condition monitoring of people with HT and/or DM is by measuring their blood pressure (BP) and/or blood glucose level (BGL) periodically. This study aimed to compare and analyze the differences of BP and BGL among elderly with HT and/or DM in Bangkok and Surabaya. This cross-sectional study involved 100 and 96 elderly with HT and/or DM in communities of Bangkok and Surabaya respectively (n=196). There were three groups of samples which consisted of 60 DM, 68 HT, and 68 DM&HT cases. Instruments used were demography questionnaire, sphygmomanometer, and glucometer. Test of one-way ANOVA, Least Significant Difference (LSD), Kruskal-Wallis, and Mann-Whitney U were used for data analysis (α<.05). There was a significant difference of systolic and diastolic BP found between groups (p=.000 and p=.011 respectively), but no difference found between the groups of HT and DM&HT (p=.657 and p=.330 respectively). There was a significant difference of BGL found between groups (p=.002), but no difference found between the groups of HT and DM (p=.075) and between the groups of DM and DM&HT (p=.066). BP is significantly different between the group of HT and DM in term of systole and diastole, especially in elderly, but BGL is similar. The risk of being HT for elderly with DM is very high. Elderly with DM&HT have high BP and BGL similarly to those with single disease of HT or DM

The Effects of Serotonin on Functionally Diverse Isolated Lamprey Spinal Cord Neurons

The experiments reported here showed that application of serotonin (5-hydroxytryptamine, 5-HT) (100 µ M) did not induce any significant current through the membranes of any of the spinal neurons studied (n = 62). At the same time, the membranes of most motoneurons and interneurons (15 of 18) underwent slight depolarization (2–6 mV) in the presence of 5-HT, which was not accompanied by any change in the input resistance of the cells. Depolarization to 10–20 mV occurred in some cells (3 of 18) of these functional groups, this being accompanied by 20–60% decreases in input resistance. The same concentration of 5-HT induced transient low-amplitude depolarization of most sensory spinal neurons (dorsal sensory cells), this changing smoothly to long-term hyperpolarization by 2–7 mV. The input resistance of the cell membranes in these cases showed no significant change (n = 8). Data were obtained which provided a better understanding of the mechanism by which 5-HT modulates the activity of spinal neurons. Thus, 5-HT facilitates chemoreceptive currents induced by application of NMDA to motoneurons and interneurons, while the NMDA responses of dorsal sensory cells were decreased by 5-HT. 5-HT affected the post-spike afterresponses of neurons. 5-HT significantly decreased the amplitude of afterhyperpolarization arising at the end of the descending phase of action potentials in motoneurons and interneurons and increased the amplitude of afterdepolarization in these types of cells. In sensory spinal neurons, 5-HT had no great effect on post-spike afterresponses. The results obtained here support the suggestion that 5-HT significantly modulates the activity of spinal neurons of different functional types. 5-HT facilitates excitation induced by subthreshold depolarization in motoneurons and some interneurons, facilitating the generation of rhythmic discharges by decreasing afterhyperpolarization. In sensory cells, 5-HT enhances inhibition due to hyperpolarization, suppressing NMDA currents. The differences in the effects of 5-HT on functionally diverse neurons are presumed to be associated with the combination of different types of 5-HT receptors on the membranes of these types of spinal neurons

Nevirapine- and efavirenz-associated hepatotoxicity under programmatic conditions in Kenya and Mozambique.

To describe the frequency, risk factors, and clinical signs and symptoms associated with hepatotoxicity (HT) in patients on nevirapine- or efavirenz-based antiretroviral therapy (ART), we conducted a retrospective cohort analysis of patients attending the ART clinic in Kibera, Kenya, from April 2003 to December 2006 and in Mavalane, Mozambique, from December 2002 to March 2007. Data were collected on 5832 HIV-positive individuals who had initiated nevirapine- or efavirenz-based ART. Median baseline CD4+ count was 125 cells/μL (interquartile range [IQR] 55-196). Over a median follow-up time of 426 (IQR 147-693) days, 124 (2.4%) patients developed HT. Forty-one (54.7%) of 75 patients with grade 3 HT compared with 21 (80.8%) of 26 with grade 4 had associated clinical signs or symptoms (P = 0.018). Four (5.7%) of 124 patients with HT died in the first six months compared with 271 (5.3%) of 5159 patients who did not develop HT (P = 0.315). The proportion of patients developing HT was low and HT was not associated with increased mortality. Clinical signs and symptoms identified 50% of grade 3 HT and most cases of grade 4 HT. This suggests that in settings where alanine aminotransferase measurement is not feasible, nevirapine- and efavirenz-based ART may be given safely without laboratory monitoring

How Complex Is a Fractal? Head/tail Breaks and Fractional Hierarchy

A fractal bears a complex structure that is reflected in a scaling hierarchy, indicating that there are far more small things than large ones. This scaling hierarchy can be effectively derived using head/tail breaks - a clustering and visualization tool for data with a heavy-tailed distribution - and quantified by an ht-index, indicating the number of clusters or hierarchical levels, a head/tail breaks-induced integer. However, this integral ht-index has been found to be less precise for many fractals at their different phrases of development. This paper refines the ht-index as a fraction to measure the scaling hierarchy of a fractal more precisely within a coherent whole, and further assigns a fractional ht-index - the fht-index - to an individual data value of a data series that represents the fractal. We developed two case studies to demonstrate the advantages of the fht-index, in comparison with the ht-index. We found that the fractional ht-index or fractional hierarchy in general can help characterize a fractal set or pattern in a much more precise manner. The index may help create intermediate map scales between two consecutive map scales. Keywords: Ht-index, fractal, scaling, complexity, fht-indexComment: 7 pages, 2 figure

G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans.

G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive grk-2 or by the selective expression of grk-2 in hermaphrodite-specific neurons. The addition of 5-HT or inhibition of 5-HT metabolism also rescued the egg laying defect. Furthermore, we demonstrate that AMX-2 is the primary monoamine oxidase that metabolizes 5-HT in C. elegans, and we also found that grk-2 loss-of-function strains have abnormally high levels of AMX-2 compared with wild-type nematodes. Interestingly, GRK-2 was also found to interact with and promote the phosphorylation of AMX-2. Additional studies reveal that 5-HIAA functions to inhibit egg laying in a manner dependent on the 5-HT receptor SER-1 and the G protein GOA-1. These results demonstrate that GRK-2 modulates 5-HT metabolism by regulating AMX-2 function and that 5-HIAA may function in the SER-1 signaling pathway

A role for antizyme inhibitor 2 in the biosynthesis and content of serotonin and histamine in mouse mast cells

Polyamines (putrescine, spermidine and spermine; PAs) are essential for the majority of living cells. Antizymes and antizyme inhibitors are key regulatory proteins of PA levels by affecting ornithine decarboxylase and PA uptake. In addition to PAs, mast cells (MC) synthesize and store in their granules histamine (Hia) and serotonin (5-HT), which are critical for their function. Our previous studies have indicated a metabolic interplay among PAs, Hia and 5-HT in this cell type. For instance, we showed that PAs affect Hia synthesis during early stages of IL-3-induced bone marrow cell differentiation into bone marrow derived MCs (BMMCs) and demonstrated that PAs are present in MC secretory granules and are important for granule homeostasis, including Hia storage and 5-HT levels. A few years ago, a novel antizyme inhibitor (AZIN2) was described whose expression is restricted to a few tissues and cell types including brain, testis and MCs. In MCs, it was recently proposed that AZIN2 could act as a local regulator of PA biosynthesis in association with 5-HT-containing granules and with 5-HT release following MC activation. To gain insight into the role of AZIN2 in the biosynthesis and storage of 5-HT and also Hia, we have generated BMMCs from both wild-type and transgenic mice with severe Azin2 hypomorphism, and have analyzed the content of PAs, 5-HT and Hia, and some elements of their metabolisms. Spermine and 5-HT levels were reduced in Azin2 hypomorphic BMMCs compared with wild-type controls, whereas the amount of Hia was increased. Accordingly, the level of tryptophan hydroxylase 1 (the key enzyme for 5-HT biosynthesis) was reduced and the amount of enzymatic activity of histidine decarboxylase (the enzyme responsible for Hia biosynthesis) was increased in Azin2 hypomorphic BMMCs. Taken together, our results show evidence that AZIN2 has an important role in the regulation of 5-HT and Hia biosynthesis and storage in MCsUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work was supported by SAF2011-26518 (MINECO, Spain) and P10-CVI-6585 and Bio-267 (Junta de Andalucia, Spain). CIBERER is an iniciative of Instituto de Salud Carlos III (Spain)

The association between muscle strength and activity limitations in patients with the hypermobility type of Ehlers–Danlos syndrome : the impact of proprioception

Purpose: The patients diagnosed with Ehlers-Danlos Syndrome Hypermobility Type (EDS-HT) are characterized by pain, proprioceptive inacuity, muscle weakness, potentially leading to activity limitations. In EDS-HT, a direct relationship between muscle strength, proprioception and activity limitations has never been studied. The objective of the study was to establish the association between muscle strength and activity limitations and the impact of proprioception on this association in EDS-HT patients. Methods: Twenty-four EDS-HT patients were compared with 24 controls. Activity limitations were quantified by Health Assessment Questionnaire (HAQ), Six-Minute Walk test (6MWT) and 30-s chair-rise test (30CRT). Muscle strength was quantified by handheld dynamometry. Proprioception was quantified by movement detection paradigm. In analyses, the association between muscle strength and activity limitations was controlled for proprioception and confounders. Results: Muscle strength was associated with 30CRT (r = 0.67, p = <0.001), 6MWT (r = 0.58, p = <0.001) and HAQ (r = 0.63, p = <0.001). Proprioception was associated with 30CRT (r = 0.55, p <0.001), 6MWT (r = 0.40, p = <0.05) and HAQ (r = 0.46, p < 0.05). Muscle strength was found to be associated with activity limitations, however, proprioceptive inacuity confounded this association. Conclusions: Muscle strength is associated with activity limitations in EDS-HT patients. Joint proprioception is of influence on this association and should be considered in the development of new treatment strategies for patients with EDS-HT. Implications for rehabilitation : Reducing activity limitations by enhancing muscle strength is frequently applied in the treatment of EDS-HT patients. Although evidence regarding treatment efficacy is scarce, the current paper confirms the rationality that muscle strength is an important factor in the occurrence of activity limitations in EDS-HT patients. Although muscle strength is the most dominant factor that is associated with activity limitations, this association is confounded by proprioception. In contrast to common belief proprioception was not directly associated with activity limitations but confounded this association. Controlling muscle strength on the bases of proprioceptive input may be more important for reducing activity limitations than just enhancing sheer muscle strength