Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals

PURPOSE: Dietary sodium intake guidelines is ≤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 ± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium) and the other week placebo-capsule supplemented (LS: 2,300 mg/day of sodium). At the end of each week, peripheral hemodynamic measurements [blood flow (BF), shear rate (SR), and flow mediated dilation (FMD)/SR)] of the brachial and superficial femoral artery were taken during handgrip (HG) and plantar flexion (PF) exercise, respectively. Each exercise workload was 3 minutes and progressed by 8 kilograms until exhaustion. RESULTS: There were no differences between LS and HS in blood pressure (82 ± 4 v 80 ± 5 mmHg; p = 0.3) or heart rate (56 ± 6 v 59 ± 10 bpm; p = 0.4). HG and PF exercise increased BF, SR, and FMD/SR across workload (p \u3c 0.03 for all), but no difference between diets (p \u3e 0.05 for all). CONCLUSION: Despite previous reports that HS impairs resting vascular function, this study revealed that peripheral vascular function and blood flow regulation during exercise is not impacted by a HS diet.https://scholarscompass.vcu.edu/gradposters/1082/thumbnail.jp

T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions.

T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process

Crystal structures of Burkholderia cenocepacia dihydropteroate synthase in the apo-form and complexed with the product 7,8-dihydropteroate

<p>Abstract</p> <p>Background</p> <p>The enzyme dihydropteroate synthase (DHPS) participates in the <it>de novo </it>synthesis of folate cofactors by catalyzing the formation of 7,8-dihydropteroate from condensation of <it>p</it>-aminobenzoic acid with 6-hydroxymethyl-7,8-dihydropteroate pyrophosphate. DHPS is absent from humans, who acquire folates from diet, and has been validated as an antimicrobial therapeutic target by chemical and genetic means. The bacterium <it>Burkholderia cenocepacia </it>is an opportunistic pathogen and an infective agent of cystic fibrosis patients. The organism is highly resistant to antibiotics and there is a recognized need for the identification of new drugs against <it>Burkholderia </it>and related Gram-negative pathogens. Our characterization of the DHPS active site and interactions with the enzyme product are designed to underpin early stage drug discovery.</p> <p>Results</p> <p>An efficient recombinant protein expression system for DHPS from <it>B. cenocepacia </it>(<it>Bc</it>DHPS) was prepared, the dimeric enzyme purified in high yield and crystallized. The structure of the apo-enzyme and the complex with the product 7,8-dihydropteroate have been determined to 2.35 Å and 1.95 Å resolution respectively in distinct orthorhombic crystal forms. The latter represents the first crystal structure of the DHPS-pterin product complex, reveals key interactions involved in ligand binding, and reinforces data generated by other structural studies. Comparisons with orthologues identify plasticity near the substrate-binding pocket and in particular a range of loop conformations that contribute to the architecture of the DHPS active site. These structural data provide a foundation for hit discovery. An intriguing observation, an artifact of the analysis, that of a potential sulfenamide bond within the ligand complex structure is mentioned.</p> <p>Conclusion</p> <p>Structural similarities between <it>Bc</it>DHPS and orthologues from other Gram-negative species are evident as expected on the basis of a high level of sequence identity. The presence of 7,8-dihydropteroate in the binding site provides details about ligand recognition by the enzyme and the different states of the enzyme allow us to visualize distinct conformational states of loops adjacent to the active site. Improved drugs to combat infections by <it>Burkholderia sp. </it>and related Gram-negative bacteria are sought and our study now provides templates to assist that process and allow us to discuss new ways of inhibiting DHPS.</p

Analysing star cluster populations with stochastic models: the HST/WFC3 sample of clusters in M83

The majority of clusters in the Universe have masses well below 10^5 Msun. Hence their integrated fluxes and colors can be affected by the random presence of a few bright stars introduced by stochastic sampling of the stellar mass function. Specific methods are being developed to extend the analysis of cluster SEDs into the low-mass regime. In this paper, we apply such a method to observations of star clusters, in the nearby spiral galaxy M83. We reassess ages and masses of a sample of 1242 objects for which UBVIHalpha fluxes were obtained with the HST/WFC3 images. Synthetic clusters with known properties are used to characterize the limitations of the method. The ensemble of color predictions of the discrete cluster models are in good agreement with the distribution of observed colors. We emphasize the important role of the Halpha data in the assessment of the fraction of young objects, particularly in breaking the age-extinction degeneracy that hampers an analysis based on UBVI only. We find the mass distribution of the cluster sample to follow a power-law of index -2.1 +/-0.2, and the distribution of ages a power-law of index -1.0 +/-0.2 for M > 10^3.5 Msun and ages between 10^7 and 10^9 yr. An extension of our main method, that makes full use of the probability distributions of age and mass of the individual clusters, is explored. It produces similar power-law slopes and will deserve further investigation. Although the properties derived for individual clusters significantly differ from those obtained with traditional, non-stochastic models in ~30% of the objects, the first order aspect of the age and mass distributions are similar to those obtained previously for this M83 sample in the range of overlap of the studies. We extend the power-law description to lower masses with better mass and age resolution and without most of the artifacts produced by the classical method.Comment: accepted for publication in ApJ, 29 pages, 20 figure

Protocol for "Seal or Varnish?" (SoV) trial: a randomised controlled trial to measure the relative cost and effectiveness of pit and fissure sealants and fluoride varnish in preventing dental decay.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Dental caries remains a significant public health problem, prevalence being linked to social and economic deprivation. Occlusal surfaces of first permanent molars are the most susceptible site in the developing permanent dentition. Cochrane reviews have shown pit and fissure sealants (PFS) and fluoride varnish (FV) to be effective over no intervention in preventing caries. However, the comparative cost and effectiveness of these treatments is uncertain. The primary aim of the trial described in this protocol is to compare the clinical effectiveness of PFS and FV in preventing dental caries in first permanent molars in 6-7 year-olds. Secondary aims include: establishing the costs and the relative cost-effectiveness of PFS and FV delivered in a community/school setting; examining the impact of PFS and FV on children and their parents/carers in terms of quality of life/treatment acceptability measures; and examining the implementation of treatment in a community setting. METHODS/DESIGN: The trial design comprises a randomised, assessor-blinded, two-arm, parallel group trial in 6-7 year old schoolchildren. Clinical procedures and assessments will be performed at 66 primary schools, in deprived areas in South Wales. Treatments will be delivered via a mobile dental clinic. In total, 920 children will be recruited (460 per trial arm). At baseline and annually for 36 months dental caries will be recorded using the International Caries Detection and Assessment System (ICDAS) by trained and calibrated dentists. PFS and FV will be applied by trained dental hygienists. The FV will be applied at baseline, 6, 12, 18, 24 and 30 months. The PFS will be applied at baseline and re-examined at 6, 12, 18, 24, and 30 months, and will be re-applied if the existing sealant has become detached/is insufficient. The economic analysis will estimate the costs of providing the PFS versus FV. The process evaluation will assess implementation and acceptability through acceptability scales, a schools questionnaire and interviews with children, parents, dentists, dental nurses and school staff. The primary outcome measure will be the proportion of children developing new caries on any one of up to four treated first permanent molars. DISCUSSION: The objectives of this study have been identified by the National Institute for Health Research as one of importance to the National Health Service in the UK. The results of this trial will provide guidance on which of these technologies should be adopted for the prevention of dental decay in the most susceptible tooth-surface in the most at risk children. TRIAL REGISTRATIONS: ISRCTN ref: ISRCTN17029222 EudraCT: 2010-023476-23 UKCRN ref: 9273.This trial is funded by the National Institute for Health Research (NIHR) – Health Technology Assessment Programme (project number 08/104/04 http://www.hta.ac.uk/2202)

Miniature biplanar coils for alkali-metal-vapor magnetometry

Atomic spin sensors offer precision measurements using compact, microfabricated packages, placing them in a competitive position for both market and research applications. Performance of these sensors such as dynamic range may be enhanced through magnetic field control. In this work, we discuss the design of miniature coils for three-dimensional, localized field control by direct placement around the sensor, as a flexible and compact alternative to global approaches used previously. Coils are designed on biplanar surfaces using a stream-function approach and then fabricated using standard printed-circuit techniques. Application to a laboratory-scale optically pumped magnetometer of sensitivity $\sim$20 fT/Hz$^{1/2}$ is shown. We also demonstrate the performance of a coil set measuring $7 \times 17 \times 17$ mm$^3$ that is optimized specifically for magnetoencephalography, where multiple sensors are operated in proximity to one another. Characterization of the field profile using $^{87}$Rb free-induction spectroscopy and other techniques show $>$96% field homogeneity over the target volume of a MEMS vapor cell and a compact stray field contour of $\sim$1% at 20 mm from the center of the cell

The rotation curve and mass-distribution in highly flattened galaxies

A new method is developed which permits the reconstruction of the surface-density distribution in the galactic disk of finite radius from an arbitrary smooth distribution of the angular velocity via two simple quadratures. The existence of upper limits for disk's mass and radius during the analytic continuation of rotation curves into the hidden (non-radiating) part of the disk is demonstrated.Comment: 13 pages, 2 figure

Targeting HOX-PBX interactions causes death in oral potentially malignant and squamous carcinoma cells but not normal oral keratinocytes

YesBackground: High HOX gene expression has been described in many cancers, including oral squamous cell carcinoma and the functional roles of these genes are gradually being understood. The pattern of overexpression suggests that inhibition may be useful therapeutically. Inhibition of HOX protein binding to PBX cofactors by the use of synthetic peptides, such as HXR9, results in apoptosis in multiple cancers. Methods: Activity of the HOX-PBX inhibiting peptide HXR9 was tested in immortalised normal oral (NOK), potentially-malignant (PMOL) and squamous cell carcinoma (OSCC) cells, compared to the inactive peptide CXR9. Cytotoxicity was assessed by LDH assay. Expression of PBX1/2 and c-Fos was assessed by qPCR and western blotting. Apoptosis was assessed by Annexin-V assay. Results: PMOL and OSCC cells expressed PBX1/2. HOX-PBX inhibition by HXR9 caused death of PMOL and OSCC cells, but not NOKs. HXR9 treatment resulted in apoptosis and increased expression of c-Fos in some cells, whereas CXR9 did not. A correlation was observed between HOX expression and resistance to HXR9. Conclusion: Inhibition of HOX-PBX interactions causes selective apoptosis of OSCC/PMOL, indicating selective toxicity that may be useful clinically.Intercalated Degree Scholarship from the Harry Bottom Trust; scholarship by Becas Chile, Comisión Nacional de Investigación Científica y Tecnológica de Chile (CONICYT), Grant 7216004

The ACS Nearby Galaxy Survey Treasury. X. Quantifying the Star Cluster Formation Efficiency of Nearby Dwarf Galaxies

We study the relationship between the field star formation and cluster formation properties in a large sample of nearby dwarf galaxies. We use optical data from the Hubble Space Telescope and from ground-based telescopes to derive the ages and masses of the young (t_age < 100Myr) cluster sample. Our data provides the first constraints on two proposed relationships between the star formation rate of galaxies and the properties of their cluster systems in the low star formation rate regime. The data show broad agreement with these relationships, but significant galaxy-to-galaxy scatter exists. In part, this scatter can be accounted for by simulating the small number of clusters detected from stochastically sampling the cluster mass function. However, this stochasticity does not fully account for the observed scatter in our data suggesting there may be true variations in the fraction of stars formed in clusters in dwarf galaxies. Comparison of the cluster formation and the brightest cluster in our sample galaxies also provide constraints on cluster destruction models.Comment: 16 pages, 9 figures, Accepted to Ap