Na-H exchange inhibition with Cariporide limits functional impairment caused by repetitive ischemia

Journal ArticleIntracellular calcium ([Ca]i) overload on reperfusion may be one of the mechanisms responsible for ischemia-induced regional myocardial dysfunction. Because inhibiting the Na-H exchanger (NHE) limits intracellular sodium ([Na]i) and subsequent [Ca]i accumulation, we hypothesized that NHE inhibition would attenuate regional dysfunction in response to 25 cycles of ischemia (I, 2-min) and reperfusion (R, 8-min) of the left circumflex coronary artery (LCx) in conscious swine. Six animals were instrumented to measure arterial pressure, regional myocardial blood flow (colored microspheres), systolic wall thickening (WTh) in the normally perfused (left anterior descending, LAD) and LCx regions (sonomicrometry), LCx blood flow velocity (Doppler), and to reversibly occlude the LCx (hydraulic occluder)

Rho family GTPases regulate mammary epithelium cell growth and metastasis through distinguishable pathways.

BACKGROUND: Relatively few genes have been shown to directly affect the metastatic phenotype of breast cancer epithelial cells in vivo. The Rho family of proteins, incluing the Rho, Rac and Cdc42 subfamilies, are related to the small GTP binding protein Ras and regulated diverse biological processes including gene transcription, cytoskeletal organization, cell proliferation and transformation. The effects of Cdc42, Rac and Rho on the actin cytoskeleton suggested a possible role for Rho proteins in cellular motility and metastasis; however, a formal analysis of the role of Rho proteins in breast cancer cellular growth and metastasis in vivo had not previously been performed. MATERIALS AND METHODS: We generated a panel of MTLn3 rat mammary adenocarcinoma cells that expressed similar levels of dominant inhibitory mutants of Cdc42-, Rac- and Rho-dependent signaling, to examine the contribution of these GTPases to cell spreading, guided chemotaxis, and metastasis in vivo. The ability of Rho proteins to regulate intravasation into the peripheral blood was determined by implanting MTLn3 cell stable dominant negative lines in nude mice and measuring the formation of breast cancer cell colonies grown from the peripheral blood. Serial sectioning of the lungs was performed to determine the presence of metastasis in mice in which mammary tumors expressing the dominant negative Rho family proteins had grown to a similar size. RESULTS: Cell spreading of MTLn3 cells was selectively abrogated by N17Rac1. N19RhoA and N17Cdc42 reduced the number of focal contacts (FCs) and disrupted the co-localization of vinculin with phosphotyrosine at FCs. While N17Rac1 and N17Cdc42 preferentially inhibited colony formation in soft agar, all three GTPases affected cell growth in vivo. To distinguish effects on tumorigenicity from intravasation into the bloodstream, implanted tumors were grown to the same size in nude mice. Each dominant inhibitory Rho protein reduced intravasation into the peripheral blood. Lung metastasis of MTLn3 cells was also abrogated by the dominant inhibitory Rho proteins, despite the presence of residual CFU. CONCLUSIONS: These studies demonstrate for the first time a critical role for the Rho GTPases involving independent signaling pathways to limit mammary tumor cellular growth and metastasis in vivo

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3

Pion, kaon, proton and anti-proton transverse momentum distributions from p+p and d+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

Identified mid-rapidity particle spectra of $\pi^{\pm}$, $K^{\pm}$, and $p(\bar{p})$ from 200 GeV p+p and d+Au collisions are reported. A time-of-flight detector based on multi-gap resistive plate chamber technology is used for particle identification. The particle-species dependence of the Cronin effect is observed to be significantly smaller than that at lower energies. The ratio of the nuclear modification factor ($R_{dAu}$) between protons $(p+\bar{p})$ and charged hadrons ($h$) in the transverse momentum range $1.2<{p_{T}}<3.0$ GeV/c is measured to be $1.19\pm0.05$(stat)$\pm0.03$(syst) in minimum-bias collisions and shows little centrality dependence. The yield ratio of $(p+\bar{p})/h$ in minimum-bias d+Au collisions is found to be a factor of 2 lower than that in Au+Au collisions, indicating that the Cronin effect alone is not enough to account for the relative baryon enhancement observed in heavy ion collisions at RHIC.Comment: 6 pages, 4 figures, 1 table. We extended the pion spectra from transverse momentum 1.8 GeV/c to 3. GeV/

Precis of Vaulting Ambition: Sociobiology and the Quest for Human Nature

The debate about the credentials of sociobiology has persisted because scholars have failed to distinguish the varieties of sociobiology and because too little attention has been paid to the details of the arguments that are supposed to support the provocative claims about human social behavior. I seek to remedy both dcfieieneies. After analysis of the relationships among different kinds of sociobiology and contemporary evolutionary theory, I attempt to show how some of the studies of the behavior of nonhuman animals meet the methodological standards appropriate to evolutionary research. I contend that the efforts of E. O. Wilson, Richard Alexander, Charles Lumsden, and others to generate conclusions about human nature are flawed, both because they apply evolutionary ideas in an unrigorous fashion and because they use dubious assumptions to connect their evolutionary analyses with their conclusions. This contention rests on analyses of many of the major sociobiological proposals about human social behavior, including: differences in sex roles, racial hostility, homosexuality, conflict between parents and adolescent offspring, incest avoidance, the avunculate, alliances in combat, female infanticide, and gene-culture coevolution. Vaulting Ambition thus seeks to identify what is good in sociobiology, to expose the errors of premature speculations about human nature, and to prepare the way for serious study of the evolution of human social behavior

The self-reference effect in dementia: Differential involvement of cortical midline structures in Alzheimer’s disease and behavioural-variant frontotemporal dementia

Encoding information in reference to the self enhances subsequent memory for the source of this information. In healthy adults, self-referential processing has been proposed to be mediated by the cortical midline structures (CMS), with functional differentiation between anterior-ventral, anterior-dorsal and posterior regions. While both Alzheimer’s disease (AD) and behavioural-variant frontotemporal dementia (bvFTD) patients show source memory impairment, it remains unclear whether they show a typical memory advantage for self-referenced materials. We also sought to identify the neural correlates of this so-called ‘self-reference effect’ (SRE) in these patient groups. The SRE paradigm was tested in AD (n=16) and bvFTD (n=22) patients and age-matched healthy controls (n=17). In this task, participants studied pictures of common objects paired with one of two background scenes (sources) under self-reference or other-reference encoding instructions, followed by an item and source recognition memory test. Voxel-based morphometry was used to investigate correlations between SRE measures and regions of grey matter atrophy in the CMS. The behavioural results indicated that self-referential encoding did not ameliorate the significant source memory impairments in AD and bvFTD patients. Furthermore, the reduced benefit of self-referential relative to other-referential encoding was not related to general episodic memory deficits. Our imaging findings revealed that reductions in the SRE were associated with atrophy in the anterior-dorsal CMS across both patient groups, with additional involvement of the posterior CMS in AD and anterior-ventral CMS in bvFTD. These findings suggest that although the SRE is comparably reduced in AD and bvFTD, this arises due to impairments in different subcomponents of self-referential processing

Congruence and diversity of butterfly-host plant associations at higher taxonomic levels

We aggregated data on butterfly-host plant associations from existing sources in order to address the following questions: (1) is there a general correlation between host diversity and butterfly species richness?, (2) has the evolution of host plant use followed consistent patterns across butterfly lineages?, (3) what is the common ancestral host plant for all butterfly lineages? The compilation included 44,148 records from 5,152 butterfly species (28.6% of worldwide species of Papilionoidea) and 1,193 genera (66.3%). The overwhelming majority of butterflies use angiosperms as host plants. Fabales is used by most species (1,007 spp.) from all seven butterfly families and most subfamilies, Poales is the second most frequently used order, but is mostly restricted to two species-rich subfamilies: Hesperiinae (56.5% of all Hesperiidae), and Satyrinae (42.6% of all Nymphalidae). We found a significant and strong correlation between host plant diversity and butterfly species richness. A global test for congruence (Parafit test) was sensitive to uncertainty in the butterfly cladogram, and suggests a mixed system with congruent associations between Papilionidae and magnoliids, Hesperiidae and monocots, and the remaining subfamilies with the eudicots (fabids and malvids), but also numerous random associations. The congruent associations are also recovered as the most probable ancestral states in each node using maximum likelihood methods. The shift from basal groups to eudicots appears to be more likely than the other way around, with the only exception being a Satyrine-clade within the Nymphalidae that feed on monocots. Our analysis contributes to the visualization of the complex pattern of interactions at superfamily level and provides a context to discuss the timing of changes in host plant utilization that might have promoted diversification in some butterfly lineages

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

2015 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp