Chemosensory-Mediated Deposit Feeding in the Spionid Polychaete Dipolydora Quadrilobata.

Deposit feeding organisms live and feed in marine soft-sediment habitats. This sediment makes up a majority of the material ingested by deposit feeders and contains a variety of edible material that may constitute their principal nutrient source. However, the specific components that are assimilated by these organisms, and the strategies they employ to efficiently collect those components, remain unclear. Sensory interactions between an organism and its surrounding environment typically play an important role in helping the organism detect and locate potential food. Accordingly, chemical sensing by deposit feeders is most likely involved in feeding, yet few specifics about this role and its ecological implications are known. This study, a multi-disciplined investigation of chemoreception, focuses on putative chemosensory structures located on the palps of the deposit-feeding spionid polychaete Diplydora quadrilobata. Using behavioral studies, neurophysiological methods, and molecular biological techniques, this study examines the sensory capabilities of this deposit feeder and their potential role as a mediator of selective feeding. A series of behavioral assays tested for feeding responses to a selected number of potential cues that might be used to indicate food availability or quality. Two sets of glass beads, one with and one without covalently bound compounds such as single amino acids, mixtures of amino acids, and single simple sugars, were separately presented to an organism. The differences in observed responses were used to identify these compounds as stimulatory, inhibitory, or inactive. Stirnulatory cues identified in the behavioral studies were then used to label, in an activity-dependent manner, putative receptor neurons in the palps. Stimulatory cues were perfused over the palp in the presence of the cationic molecule agmatine. Agmatine can enter into stimulated receptor neurons via activated non-selective cation channels. Those cells containing agmatine are then stained using an anti-agmatine antibody followed by silver intensification. Four putative sensory cell types located in the palps were identified by comparing cell labeling in response to the perfusion of a mixture of amino acids in the presence of agmatine to controls of agmatine in the absence of stimuli. Two of these cells types appear to be mechanosensory in function, and two appear to be chemosensory in function. Finally, molecular biological techniques were employed in attempts at isolating gene sequences that code for chemoreceptor proteins. Using RNA isolated fiom two tissues, D. quadrilobata palps and tails, single-stranded complementary DNA was constructed and amplified via the polymerase chain reaction. Gene expression patterns in the two tissues were compared (i.e. differential display) in order to isolate genes differentially expressed in the palps with the goal of finding receptor gene sequences. These studies indicate that chemoreception is an important influence in particle selection by this organism, and similarly suggest that this influence is at least partially mediated via chemoreceptor structures of the palp

Asymptotic Expansions for the Conditional Sojourn Time Distribution in the M/M/1M/M/1-PS Queue

We consider the $M/M/1$ queue with processor sharing. We study the conditional sojourn time distribution, conditioned on the customer's service requirement, in various asymptotic limits. These include large time and/or large service request, and heavy traffic, where the arrival rate is only slightly less than the service rate. The asymptotic formulas relate to, and extend, some results of Morrison \cite{MO} and Flatto \cite{FL}.Comment: 30 pages, 3 figures and 1 tabl

Ariel - Volume 5 Number 6

Editors J.D. Kanofsky Mark Dembert Entertainment Robert Breckenridge Joe Conti Gary Kaskey Photographer Scot Kastner Overseas Editor Mike Sinason Circulation Jay Amsterdam Humorist Jim McCann Staff Ken Jaffe Bob Sklaroff Janet Welsh Dave Jacoby Phil Nimoityn Frank Chervane

Book Reviews

Reviews of the following books: Was Baseball Really Invented in Maine? by Will Anderson; Acadian Hard Times: The Farm Security Administration in Maine\u27s St. John Valley, 1940-1943 by C. Stewart Doty; The Latchstring Was Always Out: A History of Lodging Hospitality and Tourism in Bartlett, New Hampshire by Aileen M. Carroll; A Fair Field and No Favor: A Concise History of the Maine State Grange by Stanley Russell Howe; Dell Turner: The Stories of His Life by John T. Meader; Hail Britannia: Maine Pewter and Silverplate: An Exhibition of Maine Britannia Ware and Silverplate, 1829-1941, in the Collections of the Maine State Museum, May 15, 1992-May 15, 1993 by Edwin A. Churchil

Powers of Hamilton cycles in pseudorandom graphs

We study the appearance of powers of Hamilton cycles in pseudorandom graphs, using the following comparatively weak pseudorandomness notion. A graph $G$ is $(\varepsilon,p,k,\ell)$-pseudorandom if for all disjoint $X$ and $Y\subset V(G)$ with $|X|\ge\varepsilon p^kn$ and $|Y|\ge\varepsilon p^\ell n$ we have $e(X,Y)=(1\pm\varepsilon)p|X||Y|$. We prove that for all $\beta>0$ there is an $\varepsilon>0$ such that an $(\varepsilon,p,1,2)$-pseudorandom graph on $n$ vertices with minimum degree at least $\beta pn$ contains the square of a Hamilton cycle. In particular, this implies that $(n,d,\lambda)$-graphs with $\lambda\ll d^{5/2 }n^{-3/2}$ contain the square of a Hamilton cycle, and thus a triangle factor if $n$ is a multiple of $3$. This improves on a result of Krivelevich, Sudakov and Szab\'o [Triangle factors in sparse pseudo-random graphs, Combinatorica 24 (2004), no. 3, 403--426]. We also extend our result to higher powers of Hamilton cycles and establish corresponding counting versions.Comment: 30 pages, 1 figur

Anti-angiogenic effect of high doses of ascorbic acid

Pharmaceutical doses of ascorbic acid (AA, vitamin C, or its salts) have been reported to exert anticancer activity in vitro and in vivo. One proposed mechanism involves direct cytotoxicity mediated by accumulation of ascorbic acid radicals and hydrogen peroxide in the extracellular environment of tumor cells. However, therapeutic effects have been reported at concentrations insufficient to induce direct tumor cell death. We hypothesized that AA may exert anti-angiogenic effects. To test this, we expanded endothelial progenitor cells (EPCs) from peripheral blood and assessed, whether or not high dose AA would inhibit EPC ability to migrate, change energy metabolism, and tube formation ability. We also evaluated the effects of high dose AA on angiogenic activities of HUVECs (human umbilical vein endothelial cells) and HUAECs (human umbilical arterial endothelial cells). According to our data, concentrations of AA higher than 100 mg/dl suppressed capillary-like tube formation on Matrigel for all cells tested and the effect was more pronounced for progenitor cells in comparison with mature cells. Co-culture of differentiated endothelial cells with progenitor cells showed that there was incorporation of EPCs in vessels formed by HUVECs and HUAECs. Cell migration was assessed using an in vitro wound healing model. The results of these experiments showed an inverse correlation between AA concentrations relative to both cell migration and gap filling capacity. Suppression of NO (nitric oxide) generation appeared to be one of the mechanisms by which AA mediated angiostatic effects. This study supports further investigation into non-cytotoxic antitumor activities of AA

Diminished Self-Chaperoning Activity of the ΔF508 Mutant of CFTR Results in Protein Misfolding

The absence of a functional ATP Binding Cassette (ABC) protein called the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) from apical membranes of epithelial cells is responsible for cystic fibrosis (CF). Over 90% of CF patients carry at least one mutant allele with deletion of phenylalanine at position 508 located in the N-terminal nucleotide binding domain (NBD1). Biochemical and cell biological studies show that the ΔF508 mutant exhibits inefficient biosynthetic maturation and susceptibility to degradation probably due to misfolding of NBD1 and the resultant misassembly of other domains. However, little is known about the direct effect of the Phe508 deletion on the NBD1 folding, which is essential for rational design strategies of cystic fibrosis treatment. Here we show that the deletion of Phe508 alters the folding dynamics and kinetics of NBD1, thus possibly affecting the assembly of the complete CFTR. Using molecular dynamics simulations, we find that meta-stable intermediate states appearing on wild type and mutant folding pathways are populated differently and that their kinetic accessibilities are distinct. The structural basis of the increased misfolding propensity of the ΔF508 NBD1 mutant is the perturbation of interactions in residue pairs Q493/P574 and F575/F578 found in loop S7-H6. As a proof-of-principle that the S7-H6 loop conformation can modulate the folding kinetics of NBD1, we virtually design rescue mutations in the identified critical interactions to force the S7-H6 loop into the wild type conformation. Two redesigned NBD1-ΔF508 variants exhibited significantly higher folding probabilities than the original NBD1-ΔF508, thereby partially rescuing folding ability of the NBD1-ΔF508 mutant. We propose that these observed defects in folding kinetics of mutant NBD1 may also be modulated by structures separate from the 508 site. The identified structural determinants of increased misfolding propensity of NBD1-ΔF508 are essential information in correcting this pathogenic mutant

Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis

The cystic fibrosis gene was recently cloned, and a three-base deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes. We used the polymerase chain reaction and hybridization with allele-specific oligonucleotides to analyze the presence or absence of this mutation on 439 cystic fibrosis chromosomes and 433 normal chromosomes from non-Ashkenazic white families. This mutation was present on 75.8 percent of the cystic fibrosis chromosomes. Using the DNA markers XV-2c and KM-19, we found that 96 percent of cystic fibrosis chromosomes with the mutation had a single DNA haplotype that occurs frequently with cystic fibrosis chromosomes. This haplotype was also found on 54 percent of the cystic fibrosis chromosomes without the three-base deletion. The three-base deletion was found on only 30.3 percent of cystic fibrosis chromosomes from Ashkenazic families, although the common cystic fibrosis haplotype was present on 97 percent of cystic fibrosis chromosomes from Ashkenazic families. The ability to detect the common mutation causing cystic fibrosis represents a major improvement in prenatal diagnosis and heterozygote detection, particularly in families in which no DNA sample is available from the affected child, and provides an improved method of testing for spouses of carriers of cystic fibrosis. Mutation analysis introduces the possibility of population-based screening programs for carriers, which on the basis of the sample in this study, would currently identify about 57 percent of the non-Ashkenazic white couples at risk.published_or_final_versio

Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)

Bovine TB is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5%, while the accuracy of the test employed to detect infected cattle explained less than 3% of the variance in the number of infected cattle

Taking stock of gene therapy for cystic fibrosis

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy