‘Priming’ exercise and O2 uptake kinetics during treadmill running

We tested the hypothesis that priming exercise would speed kinetics during treadmill running. Eight subjects completed a square-wave protocol, involving two bouts of treadmill running at 70% of the difference between the running speeds at lactate threshold (LT) and max, separated by 6-min of walking at 4 km h−1, on two occasions. Oxygen uptake was measured breath-by-breath and subsequently modelled using non-linear regression techniques. Heart rate and blood lactate concentration were significantly elevated prior to the second exercise bout compared to the first. However, kinetics was not significantly different between the first and second exercise bouts (mean ± S.D., phase II time constant, Bout 1: 16 ± 3 s vs. Bout 2: 16 ± 4 s; slow component amplitude, Bout 1: 0.24 ± 0.10 L min−1vs. Bout 2: 0.20 ± 0.12 L min−1; mean response time, Bout 1: 34 ± 4 s vs. Bout 2: 34 ± 6 s; P > 0.05 for all comparisons). These results indicate that, contrary to previous findings with other exercise modalities, priming exercise does not alter kinetics during high-intensity treadmill running, at least in physically active young subjects. We speculate that the relatively fast kinetics and the relatively small slow component in the control (‘un-primed’) condition negated any enhancement of kinetics by priming exercise in this exercise modality

Consumer behaviour in tourism: Concepts, influences and opportunities

Although consumer behaviour (CB) is one of the most researched areas in the field of tourism, few extensive reviews of the body of knowledge in this area exist. This review article examines what we argue are the key concepts, external influences and opportune research contexts in contemporary tourism CB research. Using a narrative review, we examine the CB literature published in three major tourism journals from 2000 to 2012. Of 519 articles identified and reviewed, 191 are included in this article. We examine the development of and scope for future research on nine key concepts, including decision-making, values, motivations, self-concept and personality, expectations, attitudes, perceptions, satisfaction, trust and loyalty. We then examine three important external influences on tourism behaviour, technology, Generation Y and the rise in concern over ethical consumption. Finally, we identify and discuss five research contexts that represent major areas for future scholarship: group and joint decision-making, under-researched segments, cross-cultural issues in emerging markets, emotions and consumer misbehaviour. Our examination of key research gaps is concluded by arguing that the hedonic and affective aspects of CB research in tourism must be brought to bear on the wider CB and marketing literature

Functionalized boron nitride membranes with ultrafast solvent transport performance for molecular separation

Pressure-driven, superfast organic solvent filtration membranes have significant practical applications. An excellent filtration membrane should exhibit high selectivity and permeation in aqueous and organic solvents to meet increasing industrial demand. Here, we report an amino functionalized boron nitride (FBN) based filtration membrane with a nanochannel network for molecular separation and permeation. This membrane is highly stable in water and in several organic solvents and shows high transport performance for solvents depending on the membranes' thickness. In addition, the FBN membrane is applicable for solute screening in water as well as in organic solvents. More importantly, the FBN membranes are very stable in acidic, alkaline and oxidative media for up to one month. The fast-flow rate and good separation performance of the FBN membranes can be attributed to their stable networks of nanochannels and thin laminar structure, which provide the membranes with beneficial properties for practical separation and purification processes

Cell cycle-dependent phosphorylation of pRb-like protein in root meristem cells of Vicia faba

The retinoblastoma tumor suppressor protein (pRb) regulates cell cycle progression by controlling the G1-to-S phase transition. As evidenced in mammals, pRb has three functionally distinct binding domains and interacts with a number of proteins including the E2F family of transcription factors, proteins with a conserved LxCxE motif (D-type cyclin), and c-Abl tyrosine kinase. CDK-mediated phosphorylation of pRb inhibits its ability to bind target proteins, thus enabling further progression of the cell cycle. As yet, the roles of pRb and pRb-binding factors have not been well characterized in plants. By using antibody which specifically recognizes phosphorylated serines (S807/811) in the c-Abl tyrosine kinase binding C-domain of human pRb, we provide evidence for the cell cycle-dependent changes in pRb-like proteins in root meristems cells of Vicia faba. An increased phosphorylation of this protein has been found correlated with the G1-to-S phase transition

Activation of transcription factors by extracellular nucleotides in immune and related cell types

Extracellular nucleotides, acting through P2 receptors, can regulate gene expression via intracellular signaling pathways that control the activity of transcription factors. Relatively little is known about the activation of transcription factors by nucleotides in immune cells. The NF-κB family of transcription factors is critical for many immune and inflammatory responses. Nucleotides released from damaged or stressed cells can act alone through certain P2 receptors to alter NF-κB activity or they can enhance responses induced by pathogen-associated molecules such as LPS. Nucleotides have also been shown to regulate the activity of other transcription factors (AP-1, NFAT, CREB and STAT) in immune and related cell types. Here, we provide an overview of transcription factors shown to be activated by nucleotides in immune cells, and describe what is known about their mechanisms of activation and potential functions. Furthermore, we propose areas for future work in this new and expanding field

Highly Water-Stable Zirconium Metal-Organic Framework UiO-66 Membranes Supported on Alumina Hollow Fibers for Desalination

In this study, continuous zirconium(IV)-based metal-organic framework (Zr-MOF) membranes were prepared. The pure-phase Zr-MOF (i.e., UiO-66) polycrystalline membranes were fabricated on alumina hollow fibers using an in situ solvothermal synthesis method. Single-gas permeation and ion rejection tests were carried out to confirm membrane integrity and functionality. The membrane exhibited excellent multivalent ion rejection (e.g., 86.3% for Ca2+, 98.0% for Mg2+, and 99.3% for Al3+) on the basis of size exclusion with moderate permeance (0.14 L m-2 h-1 bar-1) and good permeability (0.28 L m-2 h-1 bar-1 μm). Benefiting from the exceptional chemical stability of the UiO-66 material, no degradation of membrane performance was observed for various tests up to 170 h toward a wide range of saline solutions. The high separation performance combined with its outstanding water stability suggests the developed UiO-66 membrane as a promising candidate for water desalination

Kinetics and Ligand-Binding Preferences of Mycobacterium tuberculosis Thymidylate Synthases, ThyA and ThyX

Mycobacterium tuberculosis kills approximately 2 million people each year and presents an urgent need to identify new targets and new antitubercular drugs. Thymidylate synthase (TS) enzymes from other species offer good targets for drug development and the M. tuberculosis genome contains two putative TS enzymes, a conventional ThyA and a flavin-based ThyX. In M. tuberculosis, both TS enzymes have been implicated as essential for growth, either based on drug-resistance studies or genome-wide mutagenesis screens. To facilitate future small molecule inhibitors against these proteins, a detailed enzymatic characterization was necessary.After cloning, overexpression, and purification, the thymidylate-synthesizing ability of ThyA and ThyX gene products were directly confirmed by HPLC analysis of reaction products and substrate saturation kinetics were established. 5-Fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) was a potent inhibitor of both ThyA and ThyX, offering important clues to double-targeting strategies. In contrast, the folate-based 1843U89 was a potent inhibitor of ThyA but not ThyX suggesting that it should be possible to find ThyX-specific antifolates. A turnover-dependent kinetic assay, combined with the active-site titration approach of Ackermann and Potter, revealed that both M. tuberculosis enzymes had very low k(cat) values. One possible explanation for the low catalytic activity of M. tuberculosis ThyX is that its true biological substrates remain to be identified. Alternatively, this slow-growing pathogen, with low demands for TMP, may have evolved to down-regulate TS activities by altering the turnover rate of individual enzyme molecules, perhaps to preserve total protein quantities for other purposes. In many organisms, TS is often used as a part of larger complexes of macromolecules that control replication and DNA repair.Thus, the present enzymatic characterization of ThyA and ThyX from M. tuberculosis provides a framework for future development of cell-active inhibitors and the biological roles of these TS enzymes in M. tuberculosis

A BCR-ABL Mutant Lacking Direct Binding Sites for the GRB2, CBL and CRKL Adapter Proteins Fails to Induce Leukemia in Mice

The BCR-ABL tyrosine kinase is the defining feature of chronic myeloid leukemia (CML) and its kinase activity is required for induction of this disease. Current thinking holds that BCR-ABL forms a multi-protein complex that incorporates several substrates and adaptor proteins and is stabilized by multiple direct and indirect interactions. Signaling output from this highly redundant network leads to cellular transformation. Proteins known to be associated with BCR-ABL in this complex include: GRB2, c-CBL, p62DOK, and CRKL. These proteins in turn, link BCR-ABL to various signaling pathways indicated in cellular transformation. In this study we show that a triple mutant of BCR-ABL with mutations of the direct binding sites for GRB2, CBL, p62DOK and CRKL, is defective for transformation of primary hematopoietic cells in vitro and in a murine CML model, while it retains the capacity to induce IL-3 independence in 32D cells. Compared to BCR-ABL, the triple mutant's ability to activate the MAP kinase and PI3-kinase pathways is severely compromised, while STAT5 phosphorylation is maintained, suggesting that the former are crucial for the transformation of primary cells, but dispensable for transformation of factor dependent cell lines. Our data suggest that inhibition of BCR-ABL-induced leukemia by disrupting protein interactions could be possible, but would require blocking of multiple sites

Pars plana vitrectomy for diabetic macular edema. Internal limiting membrane delamination vs posterior hyaloid removal. A prospective randomized trial

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field.BACKGROUND: Diabetes mellitus, as well as subsequent ocular complications such as cystoid macular edema (CME), are of fundametal socio-economic relevance. Therefore, we evaluated the influence of internal limiting membrane (ILM) removal on longterm morphological and functional outcome in patients with diabetes mellitus (DM) type 2 and chronic CME without evident vitreomacular traction. METHOD: Forty eyes with attached posterior hyaloid were included in this prospective trial and randomized intraoperatively. Prior focal (n = 31) or panretinal (n = 25) laser coagulation was permitted. Group I (n = 19 patients) underwent surgical induction of posterior vitreous detachment (PVD), group II (n = 20 patients) PVD and removal of the ILM. Eleven patients with detached posterior hyaloid (group III) were not randomized, and ILM removal was performed. One eye had to be excluded from further analysis. Examinations included ETDRS best-corrected visual acuity (BCVA), fluorescein angiography (FLA) and OCT at baseline, 3 and 6 months postoperatively. Main outcome measure was BCVA at 6 months, secondary was foveal thickness. RESULTS: Mean BCVA over 6 months remained unchanged in 85% of patients of group II, and decreased in 53% of patients of group I. Results were not statistically significant different [group I: mean decrease log MAR 95% CI (0.06; 0.32), group II: (-0.02; 0.11)]. OCT revealed a significantly greater reduction of foveal thickness following PVD with ILM removal [group I: mean change: 95% CI (-208.95 μm; -78.05 μm), group II: (-80.90 μm: +59.17 μm)]. CONCLUSION: Vitrectomy, PVD with or without ILM removal does not improve vision in patients with DM type 2 and cystoid diabetic macular edema without evident vitreoretinal traction. ILM delamination shows improved morphological results, and appears to be beneficial in eyes with preexisting PVD