181 research outputs found

    Dynamics of precipitation pattern formation at geothermal hot springs

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    We formulate and model the dynamics of spatial patterns arising during the precipitation of calcium carbonate from a supersaturated shallow water flow. The model describes the formation of travertine deposits at geothermal hot springs and rimstone dams of calcite in caves. We find explicit solutions for travertine domes at low flow rates, identify the linear instabilities which generate dam and pond formation on sloped substrates, and present simulations of statistical landscape evolution

    Oral health-related quality of life of paediatric patients with AIDS

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    <p>Abstract</p> <p>Background</p> <p>Children with Acquired Immune Deficiency Syndrome (AIDS) exhibit impaired dental status, which can affect their quality of life. This study assessed the oral health-related quality of life of these patients and associated factors.</p> <p>Methods</p> <p>The "Child Perceptions Questionnaire 11-14", rating overall and domain-specific (oral symptoms, functional limitations, emotional well being, and social well being) oral health-related quality of life (OHR-QoL) was completed by 88 children with AIDS assisted in the Child Institute, Sao Paulo, Brazil. Parents or guardians provided behavioural and socio-demographic information. The clinical status was provided by hospital records. OHR-QoL covariates were assessed by Poisson regression analysis.</p> <p>Results</p> <p>The most affected OHR-QoL subscale concerned oral symptoms, whose rate was 23.9%. The direct answer for oral health and well being made up a rate of 47.7%. Brushing the teeth less than two times a day and viral load exceeding 10,000 HIV-RNA copies per millilitre of plasma were directly associated (p < 0.05) with a poorer oral health-related quality of life.</p> <p>Conclusions</p> <p>Children with more severe AIDS manifestations complained of poorer status of oral symptoms, functional limitations, emotional and social well being related to their oral health. Recognizing the factors that are associated with poorer OHR-QoL in children with AIDS may contribute to the planning of dental services for this population.</p

    Numerical investigation of nanostructured silica PCFs for sensing applications.

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    Photonic crystal fibers (PCFs) developed using nanostructured composite materials provide special optical properties. PCF light propagation and modal characteristics can be tailored by modifying their structural and material parameters. Structuring and infusion of liquid crystal materials enhances the capabilities of all silica PCFs, facilitating their operation in different spectral regimes. The wavelength tunability feature of nanostructured PCFs can be utilized for many advanced sensing applications. This paper discusses a new approach to modify the optical properties of PCFs by periodic nanostructuring and composite material (liquid crystal-silica) infiltration. PCF characteristics like confinement wavelength, confinement loss, mode field diameter (MFD) and bandwidth are investigated by varying the structural parameters and material infiltrations. Theoretical study revealed that composite material infusion resulted in a spectral band shift accompanied by an improvement in PCF bandwidth. Moreover, nanostructured PCFs also achieved reduced confinement losses and improved MFD which is very important in long-distance remote sensing applications

    Hsp70 chaperones: Cellular functions and molecular mechanism

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    Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100

    Vernonia cinerea Less. supplementation and strenuous exercise reduce smoking rate: relation to oxidative stress status and beta-endorphin release in active smokers

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    <p>Abstract</p> <p>Purpose</p> <p>The aim of this study was to evaluate the effects of <it>Vernonia cinerea </it>Less. (VC) supplementation and exercise on oxidative stress biomarkers, beta-endorphin release, and the rate of cigarette smoking.</p> <p>Methods</p> <p>Volunteer smokers were randomly divided into four groups: group 1: VC supplement; group 2: exercise with VC supplement; group 3: exercise; and group 4: control. VC was prepared by wash and dry techniques and taken orally before smoking, matching the frequency of strenuous exercise (three times weekly). Before and after a two month period, exhaled carbon monoxide (CO), blood oxidative stress (malondialdehyde [MDA], nitric oxide [NOx], protein hydroperoxide [PrOOH] and total antioxidant capacity [TAC]), beta-endorphin and smoking rate were measured, and statistically analyzed.</p> <p>Results</p> <p>In Group 1, MDA, PrOOH, and NOx significantly decreased, whereas TAC increased (p < 0.05). In Group 2, MDA and PrOOH decreased (p < 0.05), with no other changes noted (p > 0.05). In Group 3, MDA, PrOOH, NOx, TAC, and beta-endorphin levels increased significantly (p < 0.05). Group 4 showed no change in oxidative stress variables or beta-endorphine levels (p > 0.05). All groups had lower levels of CO after the intervention. The smoking rate for light cigarette decreased in group 2(62.7%), 1(59.52%), 3 (53.57%) and 4(14.04%), whereas in self-rolled cigarettes it decreased in group 1 (54.47%), 3 (42.30%), 2 (40%) and 4 (9.2%).</p> <p>Conclusion</p> <p>Supplementation with <it>Vernonia cinerea </it>Less and exercise provided benefit related to reduced smoking rate, which may be related to oxidaive stress and beta-endorphine levels.</p

    High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

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    BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing &gt;160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

    Resolving the homology-function relationship through comparative genomics of membrane-trafficking machinery and parasite cell biology

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    With advances in DNA sequencing technology, it is increasingly common and tractable to informatically look for genes of interest in the genomic databases of parasitic organisms and infer cellular states. Assignment of a putative gene function based on homology to functionally characterized genes in other organisms, though powerful, relies on the implicit assumption of functional homology, i.e. that orthology indicates conserved function. Eukaryotes reveal a dazzling array of cellular features and structural organization, suggesting a concomitant diversity in their underlying molecular machinery. Significantly, examples of novel functions for pre-existing or new paralogues are not uncommon. Do these examples undermine the basic assumption of functional homology, especially in parasitic protists, which are often highly derived? Here we examine the extent to which functional homology exists between organisms spanning the eukaryotic lineage. By comparing membrane trafficking proteins between parasitic protists and traditional model organisms, where direct functional evidence is available, we find that function is indeed largely conserved between orthologues, albeit with significant adaptation arising from the unique biological features within each lineage

    Discovery of a NAPE-PLD inhibitor that modulates emotional behavior in mice

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    N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids. Using a high-throughput screen, chemical proteomics and targeted lipidomics, we report here the discovery and characterization of LEI-401 as a CNS-active N-acylphosphatidylethanolamine phospholipase D (NAPE-PLD) inhibitor. LEI-401 reduced NAE levels in neuroblastoma cells and in the brain of freely moving mice, but not in NAPE-PLD KO cells and mice, respectively. LEI-401 activated the hypothalamus–pituitary–adrenal axis and impaired fear extinction, thereby emulating the effect of a cannabinoid CB1 receptor antagonist, which could be reversed by a fatty acid amide hydrolase inhibitor. Our findings highlight the distinctive role of NAPE-PLD in NAE biosynthesis in the brain and suggest the presence of an endogenous NAE tone controlling emotional behavior.NWOMicrobial Biotechnolog
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