The cAMP-producing agonist beraprost inhibits human vascular smooth muscle cell migration via exchange protein directly activated by cAMP

This work was supported by the British Heart foundation (grant FS/11/23/28730). J.S.M. was funded by a British Heart Foundation PhD studentship. Funding to pay the Open Access publication charges for this article was provided by the Charities Open Access Fund (UK).Peer reviewedPublisher PD

Representational specializations of the hippocampus in phylogenetic perspective

In a major evolutionary transition that occurred more than 520 million years ago, the earliest vertebrates adapted to a life of mobile, predatory foraging guided by distance receptors concentrated on their heads. Vision and olfaction served as the principal sensory systems for guiding their search for nutrients and safe haven. Among their neural innovations, these animals had a telencephalon that included a homologue of the hippocampus. Experiments on goldfish, turtles, lizards, rodents, macaque monkeys and humans have provided insight into the initial adaptive advantages provided by the hippocampus homologue. These findings indicate that it housed specialized map-like representations of odors and sights encountered at various locations in an animal’s home range, including the order and timing in which they should be encountered during a journey. Once these representations emerged in early vertebrates, they also enabled a variety of behaviors beyond navigation. In modern rodents and primates, for example, the specialized representations of the hippocampus enable the learning and performance of tasks involving serial order, timing, recency, relations, sequences of events and behavioral contexts. During primate evolution, certain aspects of these representations gained particular prominence, in part due to the advent of foveal vision in haplorhines. As anthropoid primates—the ancestors of monkeys, apes and humans—changed from small animals that foraged locally into large ones with an extensive home range, they made foraging choices at a distance based on visual scenes. Experimental evidence shows that the hippocampus of monkeys specializes in memories that reflect the representation of such scenes, rather than spatial processing in a general sense. Furthermore, and contrary to the idea that the hippocampus functions in memory to the exclusion of perception, brain imaging studies and lesion effects in humans show that its specialized representations support both the perception and memory of scenes and sequences

Eddington's demon: Inferring galaxy mass functions and other distributions from uncertain data

We present a general modified maximum likelihood (MML) method for inferring generative distribution functions from uncertain and biased data. The MML estimator is identical to, but easier and many orders of magnitude faster to compute than the solution of the exact Bayesian hierarchical modelling of all measurement errors. As a key application, this method can accurately recover the mass function (MF) of galaxies, while simultaneously dealing with observational uncertainties (Eddington bias), complex selection functions and unknown cosmic large-scale structure. The MML method is free of binning and natively accounts for small number statistics and non-detections. Its fast implementation in the R-package dftools is equally applicable to other objects, such as haloes, groups, and clusters, as well as observables other than mass. The formalism readily extends to multidimensional distribution functions, e.g. a Choloniewski function for the galaxy mass-angular momentum distribution, also handled by dftools. The code provides uncertainties and covariances for the fitted model parameters and approximate Bayesian evidences. We use numerous mock surveys to illustrate and test the MML method, as well as to emphasize the necessity of accounting for observational uncertainties in MFs of modern galaxy surveys

Development of an Automated Digestion and Droplet Deposition Microfluidic Chip for MALDI-TOF MS

An automated proteolytic digestion bioreactor and droplet deposition system was constructed with a plastic microfluidic device for off-line interfacing to matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The microfluidic chips were fabricated in poly(methyl methacrylate) (PMMA), using a micromilling machine and incorporated a bioreactor, which was 100 μm wide, 100 μm deep, and possessed a 4 cm effective channel length (400 nL volume). The chip was operated by pressure-driven flow and mounted on a robotic fraction collector system. The PMMA bioreactor contained surface immobilized trypsin, which was covalently attached to the UV-modified PMMA surface using coupling reagents N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and hydroxysulfosuccinimide (sulfo-NHS). The digested peptides were mixed with a MALDI matrix on-chip and deposited as discrete spots on MALDI targets. The bioreactor provided efficient digestion of a test protein, cytochrome c, at a flow rate of 1 μL/min, producing a reaction time of ∼24 s to give adequate sequence coverage for protein identification. Other proteins were also evaluated using this solid-phase bioreactor. The efficiency of digestion was evaluated by monitoring the sequence coverage, which was 64%, 35%, 58%, and 47% for cytochrome c, bovine serum albumin (BSA), myoglobin, and phosphorylase b, respectively. © 2008 American Society for Mass Spectrometry

Residential Exposure to Traffic-Related Air Pollution and Survival after Heart Failure

Background: Although patients with heart failure (HF) have been identified as particularly susceptible to the acute effects of air pollution, the effects of long-term exposure to air pollution on patients with this increasingly prevalent disease are largely unknown. Objective: This study was designed to examine the mortality risk associated with residential exposure to traffic-related air pollution among HF patients. Methods: A total of 1,389 patients hospitalized with acute HF in greater Worcester, Massachusetts, during 2000 were followed for survival through December 2005. We used daily traffic within 100 and 300 m of residence as well as the distance from residence to major roadways and to bus routes as proxies for residential exposure to traffic-related air pollution. We assessed mortality risks for each exposure variable using Cox proportional hazards models adjusted for prognostic factors. Results: After the 5-year follow-up, only 334 (24%) subjects were still alive. An interquartile range increase in daily traffic within 100 m of home was associated with a mortality hazard ratio (HR) of 1.15 [95% confidence interval (CI), 1.05–1.25], whereas for traffic within 300 m this association was 1.09 (95% CI, 1.01–1.19). The mortality risk decreased with increasing distance to bus routes (HR = 0.88; 95% CI, 0.81–0.96) and was larger for those living within 100 m of a major roadway or 50 m of a bus route (HR = 1.30; 95% CI, 1.13–1.49). Adjustment for area-based income and educational level slightly attenuated these associations. Conclusions: Residential exposure to traffic-related air pollution increases the mortality risk after hospitalization with acute HF. Reducing exposure to traffic-related emissions may improve the long-term prognosis of HF patients

Chimera States for Coupled Oscillators

Arrays of identical oscillators can display a remarkable spatiotemporal pattern in which phase-locked oscillators coexist with drifting ones. Discovered two years ago, such "chimera states" are believed to be impossible for locally or globally coupled systems; they are peculiar to the intermediate case of nonlocal coupling. Here we present an exact solution for this state, for a ring of phase oscillators coupled by a cosine kernel. We show that the stable chimera state bifurcates from a spatially modulated drift state, and dies in a saddle-node bifurcation with an unstable chimera.Comment: 4 pages, 4 figure

Molecular Phylogenetics and Diagnosis of \u3ci\u3eAnisakis\u3c/i\u3e, \u3ci\u3ePseudoterranova\u3c/i\u3e, and \u3ci\u3eContracaecum\u3c/i\u3e from Northern Pacific Marine Mammals

Individual specimens of Anisakis, Pseudoterranova, and Contracaecum collected from marine mammals inhabiting northern Pacific waters were used for comparative diagnostic and molecular phylogenetic analyses. Forty-eight new sequences were obtained for this study of 14 Anisakis taxa, 8 Pseudoterranova taxa, 4 Contracaecum taxa, and 4 outgroup species. Partial 28S (LSU) and complete internal transcribed spacer (ITS-1, 5.8S, ITS-2) ribosomal DNA was amplified by the polymerase chain reaction and sequenced. Sequences of ITS indicated that Pseudoterranova specimens from Zalophus californianus (California sea lion), Mirounga angustirostris (northern elephant seal), Phoca vitulina (harbor seal), Enhydra lutris (sea otter), and Eumetopias jubatus (Steller’s sea lion) exactly matched P. decipiens s. str., extending the host and geographic range of this species. Anisakis from northern Pacific marine mammals were most closely related to members of the A. simplex species complex. Comparison of Anisakis ITS sequences diagnosed the presence of A. simplex C in 2 M. angustirostris hosts, which is a new host record. Anisakis specimens from Phocoena phocoena (harbor porpoise), Lissodelphis borealis (Pacific rightwhale porpoise), and E. jubatus included 3 ITS sequences that did not match any known species. Contracaecum adults obtained from Z. californianus were most closely related to C. ogmorhini s.l. and C. rudolphii, but ITS sequences of these Contracaecum specimens did not match C. ogmorhini s. str. or C. margolisi. These novel Anisakis and Contracaecum ITS sequences may represent previously uncharacterized species. Phylogenetic analysis of LSU sequences revealed strong support for the monophyly of Anisakinae, Contracaecum plus Phocascaris, Pseudoterranova, and Anisakis. Phylogenetic trees inferred from ITS sequences yielded robustly supported relationships for Pseudoterranova and Anisakis species that are primarily consistent with previously published phenograms based on multilocus electrophoretic data

Sensitivity of Prescribing High-Intensity, Interval Training Using the Critical Power Concept

International Journal of Exercise Science 8(3): 202-212, 2015. The critical power (CP) concept enables the calculation of time to exhaustion (tLIM) for a given power output above CP using the equation of tLIM = W’/(power – CP), where W’ is the curvature constant, and CP is the asymptote for the power-tLIM relationship. The CP concept offers great promise for prescribing high-intensity interval training (HIIT); however, knowledge on the concept’s sensitivity is lacking (i.e., how much of a difference in W’ expenditure is needed to evoke different metabolic responses). We tested if two different power-tLIM configurations expending identical proportions of W’ would evoke different end-exercise oxygen uptake (VO2) and heart rate (HR) values. Five men and five women completed a graded exercise test, 3-min all-out exercise tests, and intervals prescribed to deplete either 70 or 80% of W’ on separate visits. Consistency statistics of intraclass correlation (ICC a), standard error of measure (SEM), and coefficient of variation (CV) were calculated on end-exercise values. End-exercise VO2 were similar for the 3.5- and 5-min bouts, depleting 70% of W’ (ICC a = 0.91, SEM = 3.23 mL·kg-1·min-1, CV = 8.1%) and similar for the 4- and 5-min bouts, depleting 80% of W’ (ICC a = 0.95, SEM = 2.34 mL·kg-1·min-1, CV = 8.1%). No VO2 differences were observed between trials or conditions (p = 0.58). Similarly, HR values (~181 b·min-1) did not differ between trials or conditions (p = 0.45). Use of the CP concept for HIIT prescriptions of different power-tLIM configurations evokes similar end-exercise VO2 values on a given day. Our findings indicate that \u3e10% W’ depletion is necessary to evoke different metabolic responses to HIIT