bluuebunny/crossref_metadata_2025 huggingface dataset:
Ceratomyxa shasta Noble, 1950 (Myxozoa: Myxosporea) present in the Fraser River system of British Columbia
Authors: McDonald T. E.
Published: January 2010

An examination of 220 chinook salmon (Oncorhynchus tshawytscha), 84 coho salmon (O. kisutch), 145 steelhead trout (Salmo gairdneri), and 21 cutthroat trout (S. clarki) for Ceratomyxa shasta (Myxozoa: Myxosporea) from 16 localities in the Fraser River drainage, British Columbia, showed that at all sites examined these salmonid species were infected, with a prevalence ranging between 11 and 100%. The study concludes that C. shasta, the causative agent of the salmonid disease ceratomyxosis, is widely distributed in the Fraser drainage basin and discusses these results in relation to proposed fish culture in the region.
Development and infectivity of the procercoid of Triaenophorus crassus Forel and mortality of the first intermediate host
Authors: Rosen R. , Dick T. A.
Published: January 2010

Mortality of Cyclops bicuspidatus thomasi infected with the procercoid of Triaenophorus crassus was assessed and factors influencing the infectivity of the procercoid to the second intermediate host were evaluated. Over 80% of C. b. thomasi infected with T. crassus died after 28 days, and there was a bimodal pattern to cyclopid mortality. A decrease in the mean intensity over time indicated that this mortality was related to parasite numbers. The frequency of T. crassus in C. b. thomasi after 28 days fitted the negative binomial distribution. A higher proportion of lightly infected cyclopids at this time resulted from mortality of heavily infected hosts. Female cyclopids had larger procercoids than males, but the ratio of differentiated to undifferentiated procercoids did not vary between sexes. Procercoid size was smaller and the proportion of differentiated procercoids decreased with increasing intensities of infection. Exposure of laboratory-reared whitefish, Coregonus clupeaformis, and cisco, Coregonus artedii, to procercoids from crowded infections resulted in a low percent recovery of plerocercoids, while less crowded infections of procercoids produced a high percent recovery of plerocercoids in fish. The number of procercoids to which fish were exposed affected the percent recovery of plerocercoids.
Seasonal population dynamics of five species of intestinal helminths of the brook stickleback, Culaea inconstans
Authors: Font William F.
Published: January 2010

Seasonal changes in populations of five species of enteric helminths that parasitize the brook stickleback (Culaea inconstans) were studied during a 14-month period in Wisconsin. The trematodes Bunodera eucaliae, B. luciopercae, and immature Halipegus sp., the acanthocephalan Neoechinorhynchus pungitius, and the larval cestode Proteocephalus sp. each displayed pronounced seasonal patterns of prevalence in Sioux Creek sticklebacks. Bunodera eucaliae, the most abundant species, infected sticklebacks in early summer. By late summer, most B. eucaliae had completed egg production and were expelled from their hosts. Some B. eucaliae overwintered in sticklebacks and completed development in late spring. In contrast, B. luciopercae displayed low prevalence in sticklebacks and produced eggs at the coldest period of the year. The relative density of N. pungitius increased throughout fall and winter. These acanthocephalans were most numerous and attained maximum development in late spring. Unencysted metacercariae of Halipegus sp. parasitized sticklebacks in midsummer but thereafter declined in relative density. Sticklebacks possibly acted as paratenic hosts for H. eccentricus which occur commonly in Rana pipiens and R. clamitans in Sioux Creek. A few sticklebacks harbored Proteocephalus sp. plerocercoids in midsummer but this parasite was virtually absent throughout the remainder of the year.
Effets histopathologiques de l'ingestion de plantes de milieux ouverts sur le foie de la souris de laboratoire
Authors: Bergeron Jean-Marie , Jodoin Louise
Published: January 2010

In previous studies, Bergeron and Goulet and Bergeron and Jodoin examined the effects of plant secondary products on the body weight and on the weight of different organs in laboratory mice; we made a histopathological study of the liver of the same animals. Within experimental groups kept on commercial feed and on shredded plants for 6 days, mice fed on ground ivy (Glecoma hederacea), strigose fleabane (Erigeron strigosus), lesser starwort (Stellaria graminea), hop-clover (Trifolium agrarium), and common rush (Juncus effusus) suffered centro- and peri-lobular necrosis. Apart from these extreme cases, other ailments were identified: hemorrhages, pycnosis, mononucleated cell infiltrations, congestion, and vacuole formation.[Translated by the Journal]
Mineral lick use by moose in Alaska
Authors: Tankersley Nancy G. , Gasaway William C.
Published: January 2010

Chemical analyses and observations of lick use indicated that natural licks are an important source of sodium for moose (Alces alces) in Alaska during early summer (June). Most lick use occurred in late evening, unlike the diel activity patterns of moose not at licks. Bulls used licks earlier in the summer than cows and there was a disproportionately high rate of lick use by bulls. Calves used licks less than dams and started using licks later in the season. Sex and age differences in lick use would bias population counts from lick observations. Natural licks appeared to influence movements and distribution of moose during spring and summer.
Effets inhibiteurs de la présence d'un congénère sur la maturation des ovocytes chez Acanthoscelides obtectus Say (Coléoptère: Bruchidae)
Authors: Biémont Jean-Claude , Jarry Marc
Published: January 2010

The bean weevil Acanthoscelides obtectus, which is found over a large geographical area, can live in habitats where its host plant is not continuously available throughout the year. In such cases, the females must wait for favorable egg-laying conditions during part of the year. Individuals of this species may concentrate in temporary shelters such as dry leaves for example. The effect of the grouping of two individuals (female and male; female and female) on the reproductive physiology of females from a Cuban strain led to an inhibition or a decrease in oogenesis. This phenomenon was also observed when a female cohabited with a male whose aedeagus had been removed. However, oocyte maturation was stimulated when 4-day-old females were placed in the presence of a male for 4 h. The variability observed between two generations is discussed along with the often neglected role of relationships among individuals. The adaptive role of the inhibition of oocyte maturation induced by the grouping of two individuals is discussed.
Density estimation as a function of live-trapping grid and home range size
Authors: Bondrup-Nielsen Søren
Published: January 2010

Edge effect is an inherent problem when using live-trapping grids to census animals in populations. The relationship between grid size and home range size, shape, and dispersion pattern was investigated by a mathematical model and computer simulation. A simple relationship between overestimate of population density and grid size to home range size was found. To minimize the effect of home range size, shape, and dispersion pattern on census results, grid sizes at least 16 times larger than the average home range size should be used.
Colonial nesting of the Hudson Bay eider duck
Authors: Schmutz Josef K. , Robertson Raleigh J. , Cooke Fred
Published: January 2010

This study was designed to evaluate the factors influencing colonial nesting of the Hudson Bay eider duck (Somateria mollissima sedentaria). Colonial nesting reflected both selection of appropriate nesting habitat by female common eiders and advantages gained through social cooperation in predator defense. Female common eiders preferred to nest on small islands or on promontories near the shore and under shrubs of medium height. Nesting densities were greatest where a relatively large expanse of open water facilitated landing and taking flight. Nesting females gave alarm calls and formed dense flocks in response to a fox model. Egg predation was less in artificial nests which were close to an incubating female than in those situated further away. There was no correlation between degree of nesting synchrony and density of females on an island. Certain groups, however, exhibited greater nesting synchrony than expected by chance and the variance in egg shape among these females suggested that they were genetically related.
A new species of Prosimulium (Diptera: Simuliidae): an interchange as a primary reproductive isolating mechanism?
Authors: Rothfels Klaus , Freeman D. Margaret
Published: January 2010

A previously undescribed species of the IIIL-1 group of Prosimulium differs from Prosimulium mixtum, its nearest relative, principally by a whole-arm interchange. It shares the sex chromosomes of P. mixtum, as well as an X chromosome and autosomal polymorphism. It is apparently a very local species (Centre County, Pennsylvania) that differs from P. mixtum in larval habitat preference and other aspects of its biology. It is argued that the interchange provided a chromosomal basis for reproductive isolation between P. mixtum and the new species, which progressively diverged in biology and mating system.
Prevalence of renal coccidia in wild waterfowl in Saskatchewan
Authors: Gajadhar A. A. , Cawthorn R. J. , Wobeser Gary A. , Stockdale P. H. G.
Published: January 2010

Using a modified flotation technique, 627 waterfowl were examined for the presence of oocysts of renal coccidia. From kidneys collected during 1980 to 1982 oocysts of Eimeria spp. were detected in 151 of 336 individuals of 11 species of ducks, 130 of 287 birds of two species of geese, and two of four whistling swans (Cygnus columbianus). Renal coccidia are reported for the first time from the common goldeneye (Bucephala clangula) and the whistling swan.
Changes in plasma concentrations of gonadotropin, 17β-estradiol, testosterone, and 17α-hydroxy-20β-dihydroprogesterone during spontaneous and brain lesion induced ovulation in goldfish
Authors: Stacey N. E. , Peter R. E. , Cook A. F. , Truscott B. , Walsh J. M. , Idler D. R.
Published: January 2010

Female goldfish (Carassius auratus) were held at 20–21 °C and ovulation was triggered by radiofrequency lesion of the anterior portion of the nucleus preopticus periventricularis (NPP) as in previous studies. NPP lesions induced a rapid and dramatic increase in blood gonadotropin (GtH) which reached peak levels between 9 and 15 h postlesioning and persisted for at least 48 h postlesioning. Unlike spontaneous ovulation, which is synchronized with photoperiod, NPP lesion-induced ovulation at 20–21 °C occurs 10–14 h postlesioning regardless of the time of day the operation is performed. 17α-hydroxy-20β-dihydroprogesterone, a potent inducer of oocyte final maturation in goldfish, could be detected in plasma of lesioned fish only at 5 h after the operation, Plasma testosterone levels peaked 2.5 h postlesioning (about 10 h prior to ovulation) and tended to decrease at subsequent sampling times. In contrast, peak levels of estradiol were not seen until 15 h postlesioning (several hours after ovulation). Pre- and post-ovulatory samples from spontaneously ovulating fish demonstrated a similar pattern of decreasing testosterone and increasing estradiol.
Ovulatory and steroidal responses in the lamprey following administration of salmon gonadotropin and agonistic and antagonistic analogues of gonadotropin-releasing hormone
Authors: Sower Stacia A. , Dickhoff Walton W. , Gorbman Aubrey , Rivier Jean E. , Vale Wylie W.
Published: January 2010

Hormone injection experiments were conducted for 2 years during the spring when adult Petromyzon marinus returned to a freshwater stream to spawn. Successive injections of salmon gonadotropin and synthetic analogue of hypothalamic GnRH (gonadotropin-releasing hormone) advanced ovulation by 2 to 3 weeks in the tests of the 1 st year. Such treatment in the doses used also elevated plasma estradiol levels almost threefold above those of untreated females prior to ovulation. A more extensive 2nd year experiment had essentially similar results, though the experiment was complicated by the delaying effects of an extended period of low ambient water temperatures. At temperatures which permitted eventual ovulation, either salmon gonadotropin or active GnRH in a dose-related manner advanced ovulation by at least several weeks. However, even in the extended period preceding ovulation, at low temperatures either salmon gonadotropin or GnRH injections elevated plasma estradiol levels in a dose-related and time-related manner. Injections of another analogue of GnRH, which in mammalian tests is a competitive inhibitor of GnRH, had little or no effect either on plasma estradiol levels or on incidence of ovulation. These results indicate that there may be hypothalamic control over pituitary and gonadal function in lampreys.
A preliminary survey of known and potentially Canadian millipedes (Diplopoda)
Authors: Kevan D. Keith McE.
Published: January 2010

This paper complements a similar one in this issue for the Centipedes (Chilopoda) and Symphyla. The diplopod fauna of Canada, as currently known, is briefly discussed and the relevant literature is summarized. The main body of the paper comprises a classified checklist of species, with their recorded distribution, known to occur in Canada and the adjacent United States of America, together with a few others from a little farther south that might conceivably be anticipated. Over 60 species are listed for Canada and Alaska, together with about the same number of additional species hitherto known only as far north as those states immediately south of the international boundary. The European Archiboreoiulus pallidus (Brade-Birks) is recorded for the first time from North America.
MAXIMIZING THE AREA OF OVERLAP OF TWO UNIONS OF DISKS UNDER RIGID MOTION
Authors: CABELLO SERGIO , DE BERG MARK , GIANNOPOULOS PANOS , KNAUER CHRISTIAN , VAN OOSTRUM RENÉ , VELTKAMP REMCO C.
Published: January 2010

Let A and B be two sets of n resp. m disjoint unit disks in the plane, with m ≥ n. We consider the problem of finding a translation or rigid motion of A that maximizes the total area of overlap with B. The function describing the area of overlap is quite complex, even for combinatorially equivalent translations and, hence, we turn our attention to approximation algorithms. We give deterministic (1 - ∊)-approximation algorithms for translations and for rigid motions, which run in O((nm/∊2) log (m/∊)) and O((n2m2/∊3) log m)) time, respectively. For rigid motions, we can also compute a (1 - ∊)-approximation in O((m2n4/3Δ1/3/∊3) log n log m) time, where Δ is the diameter of set A. Under the condition that the maximum area of overlap is at least a constant fraction of the area of A, we give a probabilistic (1 - ∊)-approximation algorithm for rigid motions that runs in O((m2/∊4) log 2(m/∊) log m) time and succeeds with high probability. Our results generalize to the case where A and B consist of possibly intersecting disks of different radii, provided that (i) the ratio of the radii of any two disks in A ∪ B is bounded, and (ii) within each set, the maximum number of disks with a non-empty intersection is bounded.
Dynamics of uncertainty in geological interpretation
Authors: Polson Debbie , Curtis Andrew
Published: January 2010

Interpretation of geological data is based on both personal judgement and previous experience of related scenarios. In combining such information geologists employ heuristics (rules of thumb), and are therefore subject to biases that are well known in cognitive psychology and are common to all expert judgements. Here we analyse dynamic uncertainty in an evolving geological interpretation. Through a well-designed elicitation process we show how the inclusion of multiple experts influences interpretational bias. In particular, group convergence of opinion is observed, and we show how this can be differentiated from ‘herding' behaviour similar to that observed in economic bubbles by forcing a consensus to be reached. Thus we can identify when and why the judgement of a single geological expert should be treated with caution. This process can be applied to any geological interpretational scenario.
Cratonic basins and the long-term subsidence history of continental interiors
Authors: Armitage John J. , Allen Philip A.
Published: January 2010

Cratonic basins form within stable regions of the continental interior and initiate during periods of break-up and dispersal of supercontinental assemblies, when the continental lithosphere may experience tensional stress. We investigate the subsidence of cratonic basins using a 1D forward model of protracted stretching at low strain rates of thick continental lithosphere. At low strain rates, subsidence history departs from the uniform instantaneous model, as supported by calculations of the thermal Péclet number. Cooling as a result of upward advection is matched by thermal diffusion, producing a subsidence trajectory with a near-constant slope and a slight elbow when stretching ceases. The model is used to evaluate the subsidence history of boreholes in cratonic basin-fills. Marked accelerations and decelerations of subsidence, attributed to secondary mechanisms such as the dynamic response to mantle convection, are removed from the backstripped, water-loaded subsidence curves to obtain the ‘reduced' subsidence. Fits to the reduced curves indicate strain rates ofc. 10−16s−1, stretching durations of 50 Ma, and stretch factors of as little as 1.1–1.3, despite the extreme longevity of subsidence. Cratonic basins are therefore part of the rift–drift suite, occupying a portion of the existence field at low stretch factors and low extensional strain rate.
Fluid Dynamics of Urban Atmospheres in Complex Terrain
Authors: Fernando H.J.S.
Published: January 2010

A majority of the world's urban centers are located in complex terrain, in which local airflow patterns are driven by pressure gradients and thermal forcing, while being strongly influenced by topographic effects and human (anthropogenic) activities. A paradigm in this context is a city located in a valley surrounded by mountains, slopes, and escarpments, in which the airflow is determined by terrain-induced perturbations to synoptic (background) flow, mesoscale thermal circulation (valley/slope flows) generated by local heating or cooling, and by their interaction with factitious (e.g., buildings and roads) and natural (e.g., vegetation and terrain) elements. The dynamics of airflows intrinsic to urban areas in complex terrain is reviewed here by employing idealized flow configurations to illustrate fundamental processes. Urban flows span a wide range of space and time scales and the emphasis here is on mesoscales (1–100 km). Basic fluid dynamics plays a central role in explaining observations of urban flow and in developing subgrid parameterizations for predictive models.
Singular Perturbation Theory: A Viscous Flow out of Göttingen
Authors: O'Malley Robert E.
Published: January 2010

This review describes how singular perturbation theory grew out of Prandtl's fluid dynamical boundary-layer theory of 1904. Developments were centered at Göttingen until 1933, when research spread worldwide. After that, singular perturbations developed more rapidly as the subject became centered within applied mathematics.
The cellular force-frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus
Authors: Warren Daniel E. , Galli Gina L. J. , Patrick Simon M. , Shiels Holly A.
Published: January 2010

To investigate the cellular mechanisms underlying the negative force-frequency relationship (FFR) in the ventricle of the varanid lizard, Varanus exanthematicus , we measured sarcomere and cell shortening, intracellular Ca2+([Ca2+]i), action potentials (APs), and K+currents in isolated ventricular myocytes. Experiments were conducted between 0.2 and 1.0 Hz, which spans the physiological range of in vivo heart rates at 20–22°C for this species. As stimulation frequency increased, diastolic length, percent change in sarcomere length, and relaxation time all decreased significantly. Shortening velocity was unaffected. These changes corresponded to a faster rate of rise of [Ca2+]i, a decrease in [Ca2+]itransient amplitude, and a seven-fold increase in diastolic [Ca2+]i. The time constant for the decay of the Ca2+transient (τ) decreased at higher frequencies, indicating a frequency-dependent acceleration of relaxation (FDAR) but then reached a plateau at moderate frequencies and did not change above 0.5 Hz. The rate of rise of the AP was unaffected, but the AP duration (APD) decreased with increasing frequency. Peak depolarization tended to decrease, but it was only significant at 1.0 Hz. The decrease in APD was not due to frequency-dependent changes in the delayed inward rectifier ( IKr) or the transient outward ( Ito) current, as neither appeared to be present in varanid ventricular myocytes. Our results suggest that a negative FFR relationship in varanid lizard ventricle is caused by decreased amplitude of the Ca2+transient coupled with an increase in diastolic Ca2+, which leads to incomplete relaxation between beats at high frequencies. This coincides with shortened APD at higher frequencies.
cAMP stimulates apical V-ATPase accumulation, microvillar elongation, and proton extrusion in kidney collecting duct A-intercalated cells
Authors: Păunescu Teodor G. , Ljubojevic Marija , Russo Leileata M. , Winter Christian , McLaughlin Margaret M. , Wagner Carsten A. , Breton Sylvie , Brown Dennis
Published: January 2010

Kidney proton-secreting A-intercalated cells (A-IC) respond to systemic acidosis by accumulating the vacuolar ATPase (V-ATPase) in their apical membrane and by increasing the length and number of apical microvilli. We show here that the cell-permeant cAMP analog CPT-cAMP, infused in vivo, results in an almost twofold increase in apical V-ATPase accumulation in AE1-positive A-IC within 15 min and that these cells develop an extensive array of apical microvilli compared with controls. In contrast, no significant change in V-ATPase distribution could be detected by immunocytochemistry in B-intercalated cells at the acute time point examined. To show a direct effect of cAMP on A-IC, we prepared cell suspensions from the medulla of transgenic mice expressing EGFP in IC (driven by the B1-subunit promoter of the V-ATPase) and exposed them to cAMP analogs in vitro. Three-dimensional reconstructions of confocal images revealed that cAMP induced a time-dependent growth of apical microvilli, starting within minutes after addition. This effect was blocked by the PKA inhibitor myristoylated PKI. These morphological changes were paralleled by increased cAMP-mediated proton extrusion (pHirecovery) by A-IC in outer medullary collecting ducts measured using the ratiometric probe BCECF. These results, and our prior data showing that the bicarbonate-stimulated soluble adenylyl cyclase (sAC) is highly expressed in kidney intercalated cells, support the idea that cAMP generated either by sAC, or by activation of other signaling pathways, is part of the signal transduction mechanism involved in acid-base sensing and V-ATPase membrane trafficking in kidney intercalated cells.
CREBtrans-activation of disruptor of telomeric silencing-1 mediates forskolin inhibition of CTGF transcription in mesangial cells
Authors: Yu Zhiyuan , Kong Qun , Kone Bruce C.
Published: January 2010

Connective tissue growth factor (CTGF) participates in diverse fibrotic processes including glomerulosclerosis. The adenylyl cyclase agonist forskolin inhibits CTGF expression in mesangial cells by unclear mechanisms. We recently reported that the histone H3K79 methyltransferase disruptor of telomeric silencing-1 (Dot1) suppresses CTGF gene expression in collecting duct cells ( J Clin Invest 117: 773–783, 2007) and HEK 293 cells ( J Biol Chem In press). In the present study, we characterized the involvement of Dot1 in mediating the inhibitory effect of forskolin on CTGF transcription in mouse mesangial cells. Overexpression of Dot1 or treatment with forskolin dramatically suppressed basal CTGF mRNA levels and CTGF promoter-luciferase activity, while hypermethylating H3K79 in chromatin associated with the CTGF promoter. siRNA knockdown of Dot1 abrogated the inhibitory effect of forskolin on CTGF mRNA expression. Analysis of the Dot1 promoter sequence identified a CREB response element (CRE) at −384/−380. Overexpression of CREB enhanced forskolin-stimulated Dot1 promoter activity. A constitutively active CREB mutant (CREB-VP16) strongly induced Dot1 promoter-luciferase activity, whereas overexpression of CREBdLZ-VP16, which lacks the CREB DNA-binding domain, abolished this activation. Mutation of the −384/−380 CRE resulted in 70% lower levels of Dot1 promoter activity. ChIP assays confirmed CREB binding to the Dot1 promoter in chromatin. We conclude that forskolin stimulates CREB-mediated trans-activation of the Dot1 gene, which leads to hypermethylation of histone H3K79 at the CTGF promoter, and inhibition of CTGF transcription. These data are the first to describe regulation of the Dot1 gene, and disclose a complex network of genetic and epigenetic controls on CTGF transcription.
Vitamins B2 and B6 and Genetic Polymorphisms Related to One-Carbon Metabolism as Risk Factors for Gastric Adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition
Authors: Eussen Simone J.P.M. , Vollset Stein Emil , Hustad Steinar , Midttun Øivind , Meyer Klaus , Fredriksen Åse , Ueland Per Magne , Jenab Mazda , Slimani Nadia , Ferrari Pietro , Agudo Antonio , Sala Núria , Capellá Gabriel , Del Giudice Giuseppe , Palli Domenico , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , Büchner Frederike L. , Carneiro Fátima , Berrino Franco , Vineis Paolo , Tumino Rosario , Panico Salvatore , Berglund Göran , Manjer Jonas , Stenling Roger , Hallmans Göran , Martínez Carmen , Arrizola Larraitz , Barricarte Aurelio , Navarro Carmen , Rodriguez Laudina , Bingham Sheila , Linseisen Jakob , Kaaks Rudolf , Overvad Kim , Tjønneland Anne , Peeters Petra H.M. , Numans Mattijs E. , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Morois Sophie , Trichopoulou Antonia , Lund Eiliv , Plebani Mario , Riboli Elio , González Carlos A.
Published: January 2010

B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5′-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, Ptrend) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk. Cancer Epidemiol Biomarkers Prev; 19(1); 28–38
Comparison of Liquid Chromatography-Tandem Mass Spectrometry, RIA, and ELISA Methods for Measurement of Urinary Estrogens
Authors: Faupel-Badger Jessica M. , Fuhrman Barbara J. , Xu Xia , Falk Roni T. , Keefer Larry K. , Veenstra Timothy D. , Hoover Robert N. , Ziegler Regina G.
Published: January 2010

Absolute and relative concentrations of estrogens and estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used for measuring estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of estrone, estradiol, and estriol measured by indirect RIA and of 2-hydroxyestrone and 16α-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15 estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P < 0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (rs) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (rs = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16α-hydroxyestrone ratio, a putative biomarker of breast cancer risk, were moderately correlated in premenopausal women (rs = 0.6-0.7) but only weakly correlated in postmenopausal women (rs = 0.2). LC-MS/MS had higher intraclass correlation coefficients (≥99.6%) and lower coefficients of variation (≤9.4%) than ELISA (≥97.2% and ≤14.2%) and RIA (≥95.2% and ≤17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA estrogen metabolite measures may be problematic, especially at low estrogen metabolite levels characteristic of postmenopausal women. Cancer Epidemiol Biomarkers Prev; 19(1); 292–300
Familial Melanoma: A Meta-analysis and Estimates of Attributable Fraction
Authors: Olsen Catherine M. , Carroll Heidi J. , Whiteman David C.
Published: January 2010

Melanoma commonly clusters in families, and the recent identification of numerous genotypes predicting higher risks of melanoma has led to the widespread perception that this cancer is predominantly a genetic disease. We conducted a systematic review of the literature and meta-analysis to quantify the contribution of familial factors to melanoma, estimated by the population attributable fraction (PAF). Eligible studies were those that permitted quantitative assessment of the association between histologically confirmed melanoma and family history of the disease; we identified 22 such studies using citation databases, followed by manual review of retrieved references. We calculated summary RRs using weighted averages of the log RR, taking into account random effects, and used these to estimate the PAF. Overall, family history was associated with a significant 2-fold increased risk of melanoma (odds ratio, 2.06; 95% confidence interval, 1.72-2.45); however, there was significant heterogeneity (P = 0.01). The pooled estimate for population-based studies (n = 11) was 2.03 (1.70-2.43), and 2.51 (1.55-4.07) for clinic/hospital-based studies (n = 11), both with significant heterogeneity (P = 0.049 and P = 0.013, respectively). Two studies used record linkage to verify family history in relatives; the pooled risk estimate from these two studies was 2.52 (2.11-3.00) with no evidence of heterogeneity (P = 0.258). Estimates of PAF associated with a positive family history ranged from 0.007 for Northern Europe to 0.064 for Australia (0.040 for all regions combined). Our findings suggest that only a small percentage of melanoma cases (always <7%) are attributable to familial risk; the majority of melanomas are presumably attributable to other factors. Cancer Epidemiol Biomarkers Prev; 19(1); 65–73
Multifactorial Regulation of E-Cadherin Expression: An Integrative Study
Authors: Reinhold William C. , Reimers Mark A. , Lorenzi Philip , Ho Jennifer , Shankavaram Uma T. , Ziegler Micah S. , Bussey Kimberly J. , Nishizuka Satoshi , Ikediobi Ogechi , Pommier Yves G. , Weinstein John N.
Published: January 2010

E-cadherin (E-cad) is an adhesion molecule associated with tumor invasion and metastasis. Its down-regulation is associated with poor prognosis for many epithelial tumor types. We have profiled E-cad in the NCI-60 cancer cell lines at the DNA, RNA, and protein levels using six different microarray platforms plus bisulfite sequencing. Here we consider the effects on E-cad expression of eight potential regulatory factors: E-cad promoter DNA methylation, the transcript levels of six transcriptional repressors (SNAI1, SNAI2, TCF3, TCF8, TWIST1, and ZFHX1B), and E-cad DNA copy number. Combined bioinformatic and pharmacological analyses indicate the following ranking of influence on E-cad expression: (1) E-cad promoter methylation appears predominant, is strongly correlated with E-cad expression, and shows a 20% to 30% threshold above which E-cad expression is silenced; (2) TCF8 expression levels correlate with (−0.62) and predict (P < 0.00001) E-cad expression; (3) SNAI2 and ZFHX1B expression levels correlate positively with each other (+0.83) and also correlate with (−0.32 and −0.30, respectively) and predict (P = 0.03 and 0.01, respectively) E-cad expression; (4) TWIST1 correlates with (−0.34) but does not predict E-cad expression; and (5) SNAI1 expression, TCF3 expression, and E-cad DNA copy number do not correlate with or predict E-cad expression. Predictions of E-cad regulation based on the above factors were tested and verified by demethylation studies using 5-aza-2′-deoxycytidine treatment; siRNA knock-down of TCF8, SNAI2, or ZFHX1B expression; and combined treatment with 5-aza-2′-deoxycytidine and TCF8 siRNA. Finally, levels of cellular E-cad expression are associated with levels of cell-cell adhesion and response to drug treatment. Mol Cancer Ther; 9(1); 1–16
Inhibition of Tumor Angiogenesis by the Matrix Metalloproteinase–Activated Anthrax Lethal Toxin in an Orthotopic Model of Anaplastic Thyroid Carcinoma
Authors: Alfano Randall W. , Leppla Stephen H. , Liu Shihui , Bugge Thomas H. , Ortiz Janelle M. , Lairmore Terry C. , Duesbery Nicholas S. , Mitchell Ian C. , Nwariaku Fiemu , Frankel Arthur E.
Published: January 2010

Patients with anaplastic thyroid carcinoma (ATC) typically succumb to their disease months after diagnosis despite aggressive therapy. A large percentage of ATCs have been shown to harbor the V600E B-Raf point mutation, leading to the constitutive activation of the mitogen-activated protein kinase pathway. ATC invasion, metastasis, and angiogenesis are in part dependent on the gelatinase class of matrix metalloproteinases (MMP). The explicit targeting of these two tumor markers may provide a novel therapeutic strategy for the treatment of ATC. The MMP-activated anthrax lethal toxin (LeTx), a novel recombinant protein toxin combination, shows potent mitogen-activated protein kinase pathway inhibition in gelatinase-expressing V600E B-Raf tumor cells in vitro. However, preliminary in vivo studies showed that the MMP-activated LeTx also exhibited dramatic antitumor activity against xenografts that did not show significant antiproliferative responses to the LeTx in vitro. Here, we show that the MMP-activated LeTx inhibits orthotopic ATC xenograft progression in both toxin-sensitive and toxin-resistant ATC cells via reduced endothelial cell recruitment and subsequent tumor vascularization. This in turn translates to an improved long-term survival that is comparable with that produced by the multikinase inhibitor sorafenib. Our results also indicate that therapy with the MMP-activated LeTx is extremely effective against advanced tumors with well-established vascular networks. Taken together, these results suggest that the MMP-activated LeTx-mediated endothelial cell targeting is the primary in vivo antitumor mechanism of this novel toxin. Therefore, the MMP-activated LeTx could be used not only in the clinical management of V600E B-Raf ATC but potentially in any solid tumor. Mol Cancer Ther; 9(1); 190–201
Astrocyte Elevated Gene-1: A Novel Target for Human Glioma Therapy
Authors: Emdad Luni , Sarkar Devanand , Lee Seok-Geun , Su Zhao Zhong , Yoo Byoung Kwon , Dash Rupesh , Yacoub Adly , Fuller Christine E. , Shah Khalid , Dent Paul , Bruce Jeffrey N. , Fisher Paul B.
Published: January 2010

Malignant gliomas including glioblastoma multiforme (GBM) and anaplastic astrocytomas are the most common primary brain tumors. Despite multimodal treatment including surgery, chemotherapy, and radiation, median survival for patients with GBMs is only 12 to 15 months. Identifying molecules critical for glioma progression is crucial for devising effective targeted therapy. In the present study, we investigated the potential contribution of astrocyte elevated gene-1 (AEG-1) in gliomagenesis and explored the possibility of AEG-1 as a therapeutic target for malignant glioma. We analyzed the expression levels of AEG-1 in 9 normal brain tissues and 98 brain tumor patient samples by Western blot analysis and immunohistochemistry. AEG-1 expression was significantly elevated in >90% of diverse human brain tumor samples including GBMs and astrocytic tumors, and also in human glioma cell lines compared with normal brain tissues and normal astrocytes. Knockdown of AEG-1 by small interfering RNA inhibited cell viability, cloning efficiency, and invasive ability of U87 human glioma cells and 9L rat gliosarcoma cells. We also found that matrix metalloproteases (MMP-2 and MMP-9) are involved in AEG-1–mediated invasion of glioma cells. In an orthotopic nude mouse brain tumor model using primary human GBM12 tumor cells, AEG-1 small interfering RNA significantly suppressed glioma cell growth in vivo. Taken together, these provocative results indicate that AEG-1 may play a crucial role in the pathogenesis of glioma and that AEG-1 could represent a viable potential target for malignant glioma therapy. Mol Cancer Ther; 9(1); 79–88
DOC45, a Novel DNA Damage–Regulated Nucleocytoplasmic ATPase That Is Overexpressed in Multiple Human Malignancies
Authors: Sun Hong , Luo Xiuquan , Montalbano JoAnne , Jin Weixin , Shi Jingxue , Sheikh M. Saeed , Huang Ying
Published: January 2010

In this article, we report the characterization of a novel DNA damage–regulated gene, named DNA damage–regulated overexpressed in cancer 45 (DOC45). Our results indicate that DNA damage–inducing agents, including doxorubicin (adriamycin), etoposide, and ionizing and UV radiation, strongly downregulate DOC45 expression, whereas endoplasmic reticulum stress–inducing agents do not. Our results also indicate that DOC45 is overexpressed in several human malignancies, including cancers of the colon, rectum, ovary, lung, stomach, and uterus. DOC45 harbors conserved nucleotide triphosphate–binding motifs and is capable of ATP hydrolysis, findings that highlight its function as a novel ATPase. Although predominantly cytoplasmic, DOC45 exhibits a characteristic nucleocytoplasmic distribution and, on inhibition of nuclear export, predominantly accumulates in the nucleoli. These results suggest that DOC45 may shuttle between nucleus and cytoplasm to carry out its function. Our results also indicate that DOC45 expression is enhanced during oncogenic Ras-mediated transformation and that its expression is linked to phosphoinositide 3-kinase signaling pathway. Furthermore, short hairpin RNA–mediated knockdown of DOC45 in human colon cancer cells inhibits their proliferation and enhances cellular sensitivity to doxorubicin-induced cell death, suggesting that DOC45 plays an important role in cell proliferation and survival. Collectively, our results indicate that DOC45 is a novel ATPase that is linked to cellular stress response and tumorigenesis, and may also serve as a valuable tumor marker. Mol Cancer Res; 8(1); 57–66
Ccdc33, a Predominantly Testis-Expressed Gene, Encodes a Putative Peroxisomal Protein
Authors: Kaczmarek K. , Niedzialkowska E. , Studencka M. , Schulz Y. , Grzmil P.
Published: January 2010

Many genes crucial for male fertility are often predominantly or exclusively expressed in male germ cells. The analysis of mouse models has demonstrated the functional importance of peroxisomes in spermatogenesis. The CCDC33 protein has been reported to be a cancer/testis (CT) antigen. We found that mouse Ccdc33 is predominantly expressed in the testis and undergoes alternative splicing to produce at least 4 different transcripts. The protein encoded by Ccdc33 contains 3 coiled-coil domains, a C2-domain, 2 ER membrane retention signal-like motifs and 2 putative peroxisomal targeting signals type 2 (PTS2). We could demonstrate that the second PTS2 sequence is functional and responsible for the targeting of CCDC33 to peroxisomes. Moreover, in HeLa cells CCDC33-dsRED fusion protein co-localized with a known peroxisomal protein, namely PXT1, and showed punctuate intracellular distribution. Taken together, the mouse Ccdc33 encodes a putative peroxisomal protein and is predominantly expressed in male germ cells. The expression starts at the primary spermatocyte stage, suggesting an important role of this protein during spermatogenesis.
Hepatitis A: Clinical Manifestations and Management
Authors: Jeong Sook-Hyang , Lee Hyo-Suk
Published: January 2010

Due to improved living conditions and subsequent changes in hepatitis A epidemiology, the disease burden of hepatitis A is increasing in many regions. Recently, Korea has faced a large, community-wide outbreak of hepatitis A, which has prompted a vaccination program. The clinical spectrum of hepatitis A virus infection ranges from asymptomatic infection to fulminant hepatitis. Clinical manifestations depend on the age of the host: less than 30% of infected young children are symptomatic, while about 80% of infected adults manifest severe hepatitis with remarkably elevated serum aminotransferases. Fulminant hepatitis is rare, with a reported incidence from 0.015 to 0.5%. Atypical manifestations include relapsing hepatitis and prolonged cholestasis, and complicated cases with acute kidney injury have been reported. Extrahepatic manifestations, such as autoimmune hemolytic anemia, aplastic anemia, pure red cell aplasia, pleural or pericardial effusion, acute reactive arthritis, acute pancreatitis, acalculous cholecystitis, mononeuritis, and Guillain-Barré syndrome, have been rarely reported. Management of hepatitis A includes general supportive care, and critical decisions regarding liver transplantation await further studies on prognostic predictors. Fundamental management of hepatitis A is active vaccination. However, a vaccination program should be adapted to the regional situation, according to differing epidemiology and disease burden.
Double-Filtration Plasmapheresis plus IFN for HCV-1b Patients with Non-Sustained Virological Response to Previous Combination Therapy: Early Viral Dynamics
Authors: Kim Soo Ryang , Imoto Susumu , Kudo Masatoshi , Mita Keiji , Taniguchi Miyuki , Kim Ke Ih , Sasase Noriko , Shoji Ikuo , Nagano-Fujii Motoko , El-Shamy Ahmed , Hotta Hak , Nagai Tomoyuki , Nagata Yoshiaki , Hayashi Yoshitake
Published: January 2010

Double-filtration plasmapheresis (DFPP) was approved in Japan in April 2008 for the retreatment of chronic hepatitis C patients with genotype 1b and high viral loads, whose hepatitis C virus was not eradicated by earlier IFN therapy or by pegylated IFN plus ribavirin (PEG-IFN/RBV) combination therapy. In this study, we assessed the early viral dynamics of 9 patients with non-sustained virological response to the combination therapy. The overall viral dynamics of DFPP plus IFN treatment with or without RBV for 4 weeks showed a reduction of ≧1 log in the viral load in 22% (2 of 9 patients), 55.6% (5/9), 77.8% (7/9) and 77.8% (7/9) at 24 h, 1, 2 and 4 weeks after the start of treatment. By contrast, DFPP plus consecutive intravenous IFN-β for 4 weeks reduced the viral load by ≧1 log in 33% (2/6), 50% (3/6), 83.3% (5/6) and 83.3% (5/6) at 24 h, 1, 2 and 4 weeks. The viral load declined by ≧2 log in 50% (3/6) at 4 weeks after the start of treatment. DFPP plus consecutive intravenous IFN-β for 4 weeks is a promising treatment for non-sustained virolgical response patients.
Examination of the Antiglycemic Properties of Vinegar in Healthy Adults
Authors: Johnston Carol S. , Steplewska Iwona , Long Cindy A. , Harris Lafe N. , Ryals Romina H.
Published: January 2010

Background: Vinegar reduces postprandial glycemia (PPG) in healthy adults. This study investigated the vinegar dosage (10 vs. 20 g), timing (during mealtime vs. 5 h before meal) and application (acetic acid as vinegar vs. neutralized salt) for reducing PPG. Methods: Four randomized crossover trials were conducted in adults (n = 9–10/trial) with type 2 diabetes (1 trial) or without diabetes (3 trials). All trials followed the same protocol: a standardized meal the evening prior to testing, an overnight fast (>10 h) and 2-hour glucose testing following consumption of a bagel and juice test meal (3 trials) or dextrose solution (1 trial). For each trial, PPG was compared between treatments using area-under-the-curve calculations 120 min after the meal. Results: Two teaspoons of vinegar (∼10 g) effectively reduced PPG, and this effect was most pronounced when vinegar was ingested during mealtime as compared to 5 h before the meal. Vinegar did not alter PPG when ingested with monosaccharides, suggesting that the antiglycemic action of vinegar is related to the digestion of carbohydrates. Finally, sodium acetate did not alter PPG, indicating that acetate salts lack antiglycemic properties. Conclusions: The antiglycemic properties of vinegar are evident when small amounts of vinegar are ingested with meals composed of complex carbohydrates. In these situations, vinegar attenuated PPG by ∼20% compared to placebo.
Henry Charlton Bastian (1837–1915): Neglected Neurologist and Scientist
Authors: Pearce J.M.S.
Published: January 2010

Henry Charlton Bastian was born in Truro, Cornwall. He graduated in 1861 at the University College, London, where he worked most of his life. He was one of the first neurologists appointed to the National Hospital, Queen Square. There, he conducted original investigations and pursued wide interests both in medical and biological sciences. He was elected a Fellow of the Royal Society in 1868. In addition to his reputation as a neurological diagnostician and intellectual, he became an advocate of the vexed doctrine of abiogenesis.