bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of picornavirus RNA replication within infected cells
Authors: Belsham Graham J. , Normann Preben
Published: January 2008

Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks the initiation of negative-strand synthesis. We have now examined the dynamics of RNA replication, measured by quantitative RT-PCR, within cells infected with either swine vesicular disease virus (an enterovirus) or foot-and-mouth disease virus as regulated by the presence or absence of guanidine. Following the removal of guanidine from the infected cells, RNA replication occurs after a significant lag phase. This restoration of RNA synthesis requires de novo protein synthesis. Viral RNA can be maintained for at least 72 h within cells in the absence of apparent replication but guanidine-resistant virus can become predominant. Amino acid substitutions within the 2C protein that confer guanidine resistance to swine vesicular disease virus and foot-and-mouth disease virus have been identified. Even when RNA synthesis is well established, the addition of guanidine has a major impact on the level of RNA replication. Thus, the guanidine-sensitive step in RNA synthesis is important throughout the virus life cycle in cells.
Human endogenous retrovirus HERV-K113 is capable of producing intact viral particles
Authors: Boller Klaus , Schönfeld Kurt , Lischer Stefanie , Fischer Nicole , Hoffmann Andreas , Kurth Reinhard , Tönjes Ralf R.
Published: January 2008

Of all human endogenous retroviruses known today, HERV-K is the only one that has been shown to produce viral particles. While the first of the approximately 30 HERV-K sequences integrated into the human genome more than 40 million years ago, evidence is accumulating that HERV-K was active more recently, provirus HERV-K113 being the youngest sequence found. However, it is unclear which HERV-K sequences code for the viral particles that are produced by human germ-cell tumours or melanomas. Here, we show that the provirus HERV-K113, cloned into a baculovirus expression vector, is capable of producing intact particles of retroviral morphology, exhibiting the typical structure of those particles that were characterized in cell lines derived from human germ-cell tumours. Thus, the HERV-K113 sequence is a candidate for particle production in vivo and for an active human endogenous retrovirus of today.
Pre‐eclampsia is associated with airway hyperresponsiveness
Authors: Siddiqui S , Goodman N , McKenna S , Goldie M , Waugh J , Brightling CE
Published: January 2008

Several large retrospective cohort studies demonstrate that pre‐eclampsia is common in asthmatics. Whether airway hyperresponsiveness (AHR), a hallmark of asthma, is associated with pre‐eclampsia is unknown. We measured AHR, using a methacholine challenge, and atopy in 19 women 3–60 months postpartum following pre‐eclamptic or normotensive pregnancies. The geometric mean (95% CI) concentration of methacholine required to produce a >20% fall in the forced expiratory volume in 1 second (PC20 FEV1) was 8.9 (2.2–36) mg/ml in pre‐eclamptics versus 72 (32–131) mg/ml in controls (P = 0.01) and 9 (1.9–40) mg/ml in atopic pre‐eclamptics without asthma versus 54 (17–174) mg/ml (P = 0.038) in matched controls. Therefore, AHR was increased in women who have had pre‐eclampsia. This association and its possible mechanisms warrant further investigation.
Severe surfing-related ocular injuries: the Stanford Northern Californian experience
Authors: Zoumalan C I , Blumenkranz M S , McCulley T J , Moshfeghi D M
Published: January 2008

There is a growing body of literature describing severe surfing-related ocular injuries that result in permanent vision loss. We describe three severe surfing-related ocular injuries that occurred on beaches in northern California. One particular case stresses the need to tailor treatment to the patient and injury because of the possibility of good outcomes despite severe injury. Attention should also be directed towards commercially available safety gear and providing additional safety measures to prevent other orbital and ocular injuries.
Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood
Authors: Chatzi L , Torrent M , Romieu I , Garcia-Esteban R , Ferrer C , Vioque J , Kogevinas M , Sunyer J
Published: January 2008

Introduction:

Dietary intake of specific nutrients or food groups during pregnancy could play a role in the risk of asthma and atopy in offspring, but specific dietary patterns have not been implicated. The authors evaluated the impact of maternal (during pregnancy) and child adherence to a Mediterranean diet on asthma and atopy in childhood.

Methods:

Women presenting for antenatal care at all general practices in Menorca, a Mediterranean island in Spain, over a 12 month period starting in mid-1997 were recruited. 460 children were included in the analysis after 6.5 years of follow-up. Maternal dietary intake during pregnancy and children’s dietary intake at age 6.5 years were assessed by food frequency questionnaires, and adherence to a Mediterranean diet was evaluated by a priori defined scores. During follow-up, parents completed questionnaires on the child’s respiratory and allergic symptoms. Children underwent skin prick tests with six common aeroallergens.

Results:

The prevalence rates of persistent wheeze, atopic wheeze and atopy at age 6.5 years were 13.2%, 5.8% and 17.0%, respectively. One-third (36.1%) of mothers had a low quality Mediterranean diet during pregnancy according to the Mediterranean Diet Score, while the rest had a high score. A high Mediterranean Diet Score during pregnancy (at two levels, using “low” score as the reference) was found to be protective for persistent wheeze (OR 0.22; 95% CI 0.08 to 0.58), atopic wheeze (OR 0.30; 95% CI 0.10 to 0.90) and atopy (OR 0.55; 95% CI 0.31 to 0.97) at age 6.5 years after adjusting for potential confounders. Childhood adherence to a Mediterranean diet was negatively associated with persistent wheeze and atopy although the associations did not reach statistical significance.

Conclusion:

These results support a protective effect of a high level of adherence to a Mediterranean diet during pregnancy against asthma-like symptoms and atopy in childhood.
Cryptosporiopsisspecies isolated from the roots of aspen in central Alberta: identification, morphology, and interactions with the host, in vitroThis article is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Wang Wei , Tsuneda Akihiko , Gibas Connie Fe , Currah Randolph S.
Published: January 2008

Cryptosporiopsis Bubák & Kabát isolates were obtained for the first time from roots of apparently healthy aspen seedlings in Alberta. These isolates were similar in all the major morphological features previously used to separate Cryptosporiopsis species, but sequencing data of the ITS1-5.8S-ITS2 region indicated that they were separated into two groups, one belonging to Cryptosporiopsis ericae Sigler and the other to Cryptosporiopsis radicicola Kowalski & Bartnik. Scanning electron microscopy of ex-type cultures and selected isolates from aspen roots revealed that C. ericae and C. radicicola differed in morphogenesis and structure of conidiomata: those of C. ericae were either synnematous or sporodochial, whereas those of C. radicicola possessed a peridium-like mycelial envelope bearing amorphous adhesive material. Phialides in the hymenium of C. radicicola were also embedded in amorphous matrix material but such material was absent in C. ericae. Microscopic examination of artificially inoculated aspen roots indicated that both species are endophytes of the host. Hyphal penetration by C. ericae was only occasional and confined to the host epidermis, whereas C. radicicola was more aggressive and its hyphal ingress extended to the cortical region.
Poplar research in Canada — a historical perspective with a view to the futureThis minireview is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Richardson J. , Cooke J. E.K. , Isebrands J. G. , Thomas B. R. , Van Rees K. C.J.
Published: January 2008

This paper provides a brief history of the development of poplar research in Canada within the broader North American context, as background to the present collection of papers on current Canadian poplar research. After the earliest times and European settlement, a few individual scientists played a pioneering role in early selection and breeding of poplars. The development of farm shelterbelts in the prairies over the last 100 years, including the widespread distribution of adapted poplars, has had a significant impact on the landscape. In the last 30 years, industrial strategies for the development and use of poplars have been the most important driver for poplar research. All of these components have in some way foreshadowed the present dramatic leading-edge research in poplar genomics. With the increasing diversity and sophistication of poplar research, particularly in recent years, a need is seen for identification of research priorities and coordination of research activities by disparate parties.
Natural dynamics-based silviculture for maintaining plant biodiversity in Populus tremuloides-dominated boreal forests of eastern CanadaThis article is one of a selection of papers published in the Special Issue on Poplar Research in Canada.
Authors: Haeussler Sybille , Bergeron Yves , Brais Suzanne , Harvey Brian D.
Published: January 2008

Southern boreal forests dominated by trembling aspen ( Populus tremuloides Michx.) are notable for the biological richness of their plant communities. We used 12 plant community and plant functional group indicators to test the hypothesis that natural dynamics-based silvicultural systems better maintain biodiversity in aspen plant communities than conventional clear-cutting. Using CA ordination, box-and-whisker diagrams, and ANOVA, we compared the range of variability of our 12 bioindicators among five experimental stand types of the sylviculture et aménagement forestier écosystémiques (SAFE) project: mature (78 years) uncut; mature 1/3 partial-cut; mature 2/3 partial-cut; young (3 years) unburned clear-cut; young burned clear-cut; and three closely matched aspen stand types of northwest Quebec and northeast Ontario: old (105 years) uncut; young unburned clear-cut; young wildfire. Burned clearcuts partially emulated wildfires by reducing tall shrub abundance and regenerating post-fire specialists, but snags were lacking. The dual disturbance also retarded aspen regrowth and caused a 7-fold increase in non-native plants. Partial-cuts retained most attributes of mature uncut stands, but after 3 years showed little evidence of accelerating development of old stand characteristics. We concluded that SAFE natural dynamics-based silviculture better recreated the range of variability of naturally disturbed aspen plant communities than conventional clear-cutting. Improvements, including alternative burn prescriptions and snag or green tree retention in clearcuts, are nontheless warranted.
Effects of pesticide adjuvants on membrane lipid composition and fluidity in Lemna minor
Authors: Caux P.-Y. , Weinberger P. , Szabo A.
Published: January 2008

Lemna minor L. plants were exposed to 40 μM of the pesticide adjuvants Triton® X-15, X-35, X-100, and X-114 for a period of 2 weeks under laboratory conditions. Investigation on the individual principal phospholipids in Lemna membranes (phosphatidyl-choline, -ethanolamine, -glycerol, and -inositol) showed an increase in phosphatidyl-choline and -ethanolamine and a decrease in phosphatidyl-glycerol and -inositol. An analysis of the percentages of fatty acids of the phospholipids indicated a differential Triton® effect on phosphatidyl-ethanolamine; the hydrophobic adjuvants (Triton® X-15 and X-35) induced a greater unsaturation than the hydrophilic adjuvants (Triton® X-114 and X-100). Membrane lipid order was also perturbed as the membrane lipid fluidity of chloroplast membranes as determined by fluorescence polarization increased following adjuvant treatment. Radiolabeled investigations with two Triton® isotopes (14C ring labelled X-35 and X-100) showed membrane lipid to adjuvant ratios in chloroplasts at 100:4 for X-35 and 100:2 for X-100. This investigation further substantiates the fact that some adjuvants in pesticide formulations are not inert and can be phytotoxic. Key words: adjuvants, Lemna minor, membranes, lipids, fluidity.
Sensitivity of Populus tremuloides to toxic metabolites of Hypoxylon mammatum and susceptibility to H. mammatum infection
Authors: Kruger Brian M. , Manion Paul D.
Published: January 2008

The response of 17 aspen tissue culture clones to bioassays with metabolites of Hypoxylon mammatum and in vitro inoculation with H. mammatum ascospores was determined. Although statistically significant variation among aspen clones was observed in response to both bioassays, response of the clones to the assays was not related (r = 0.361). This suggests that H. mammatum metabolites are not essential for the infection of tissue cultured aspen. Forty plantation-grown aspen differing in response to natural H. mammatum infection were also tested for sensitivity to metabolites of H. mammatum. Large differences in the sensitivity of the clones to the metabolites were observed, but these differences were not related to the disease condition of the clones. The toxic metabolites isolated from H. mammatum had no effect on the growth of fungi isolated from healthy aspen stems. Overall, these results suggest that the sensitivity of aspen to H. mammatum toxic metabolites is only one of the several factors influencing susceptibility. Key words: Populus tremuloides, Hypoxylon mammatum, phytotoxin.
Growth and toxicity in Prymnesium patelliferum (Prymnesiophyceae) isolated from Norwegian waters
Authors: Larsen Aud , Eikrem Wenche , Paasche Eystein
Published: January 2008

Blooms of Prymnesium causing mortality in farmed fish have been registered in fjords belonging to the Sandsfjord system, southwestern Norway, annually since 1989. These blooms consist of two closely related species, P. patelliferum and P. parvum. Cultures of the former species were established from field samples, and their identity was confirmed by transmission electron microscopy. Growth rates of this P. patelliferum strain were compared with those of an Australian strain of the same species and with a Danish strain of P. parvum. In a 3-month growth experiment at 20 °C, both P. patelliferum strains grew significantly faster than P. parvum. The Australian P. patelliferum strain grew faster than the Norwegian strain at 20 °C, and this difference was accentuated at 28 °C. The optimum salinity range for growth was 8–25‰ for all three strains. All showed toxicity to Anemia nauplii, though the Norwegian P. patelliferum appeared significantly less toxic than the others. In all strains, increased toxicity was seen in phosphorus-deficient cells. Key words: Prymnesium, scale fine structure, growth rate, salinity, toxicity, phosphorus.
Effects of soil and seed characteristics on seed germination and their possible roles in determining field emergence patterns of four Agulhas Plain (South Africa) Proteaceae
Authors: Mustart P. J. , Cowling R. M.
Published: January 2008

Seedling emergence patterns of Protea susannae, Leucadendron coniferum, Protea obtusifolia, and Leucadendron meridianum were investigated in the field. Possible factors contributing to these patterns were investigated in laboratory experiments. In the field all species had less complete, more intermittent emergence in colluvial sands (poorer water-retention properties) than in the adjacent limestone (greater water retention) soil type. Protea susannae had the highest emergence percentage in both soils. In the colluvial sands both Protea spp. showed less scattered emergence than the Leucadendron spp. In the laboratory, imbibed seeds of all species lost less water after a drying treatment when planted in limestone soil than in colluvial sands, indicating that the former soil acts as a better buffer. Protea susannae showed superior ability to imbibe, and to retain water after drying, in both soils. These results corroborated the field emergence patterns. Imbibed seeds of each of the Protea spp. (higher pericarp to embryo ratios) retained more water than the Leucadendron spp. (lower ratios) after subsequent drying in air, suggesting that the thicker pericarps help minimise water loss. Germination success following wetting–drying cycles (on filter paper in Petri dishes) led to higher percent germination of P. susannae than L. coniferum seeds, further helping explain the field emergence patterns. Key words: field seedling emergence, germination ecology, seed morphology, seed wetting–drying, soil moisture properties, South African fynbos Proteaceae.
Neutron diffraction and proton nuclear magnetic resonance: complementary probes of in situ cellulose dimensions and primary plant cell wall structure
Authors: Martel P. , Taylor Iain E. P.
Published: January 2008

Neutron diffraction was used to monitor the microscopic structure of cell walls from etiolated bean (Phaseolus vulgaris L.) hypocotyls after successive chemical fractionations with ammonium oxalate – oxalic acid and potassium hydroxide. Wide angle neutron scattering measurements showed that there was no highly ordered long range structure and confirm results from proton nuclear magnetic resonance techniques that there is alteration of the cell wall cellulose by chemical fractionations. Small angle scattering measurements showed that the residual cellulose microfibrils increased in diameter from 75.0 ± 2.3 to 110.0 ± 4.2 Å (1 Å = 0.1 nm) after successive treatments with ammonium oxalate – oxalic acid and potassium hydroxide. The technique has potential applications to study cellulose dimensions in situ. Key words: plant cell wall, cellulose dimensions, neutron diffraction, proton NMR.
Nectar secretion pattern and removal effects in three species of Solanaceae
Authors: Galetto Leonardo , Bernardello Luis
Published: January 2008

Nectar secretion pattern and effects of nectar removal were compared in three Argentinean Solanaceae: Nicotiana glauca, which is hummingbird pollinated, and Nicotiana longiflora and Petunia axillaris, which are sphinx moth pollinated. Nectar volume, concentration, and sugar production were measured at different time intervals according to the species' flower life span. Nectar volume and total sugar production increased as a function of flower age in both species of Nicotiana analyzed; however, these parameters were quite stable in P. axillaris. This species produced less nectar and nectar sugar than the other two. When all sets with nectar removal were compared with the controls, significant differences were found in nectar volume and quantity of nectar sugar in N. longiflora, and in sugar concentration in P. axillaris. In the latter, the observed difference did not affect the total amount of sugar secreted. Nicotiana glauca did not show any significant difference in the parameters analyzed. Total nectar production was inhibited by periodic removal in N. longiflora, while in N. glauca and P. axillaris it was unaffected. Key words: nectar secretion pattern, nectar removal, Nicotiana, Petunia, Solanaceae.
Use of a tree volume equation based on two lower-stem diameters to estimate forest volume from sample tree counts
Authors: Lynch Thomas B.
Published: January 2008

A recently developed method of individual-tree volume prediction uses measurements of two lower-stem diameters, rather than the more traditional DBH and height measurements, to estimate stemwood. One form of the equation is linear with respect to volume between the two diameter measurements, as computed by Smalian's formula, and can be algebraically rearranged into the sum of two equations, one linear with respect to the square of the topmost lower-stem diameter, the other linear with respect to the square of the bottom lower-stem diameter. These two equations have the same form as local volume equations that are linear functions of the square of diameter. Because of this, a variation of horizontal point sampling can be used to select trees with probability exactly proportional to each of the equations. Forest volumes can be estimated from counts of trees obtained by comparing the point sampling gauge angle with individual tree diameters at the lower-stem diameter measurement points used by the individual-tree volume equation. To account for the negative intercept term in the linear equations, trees within a small fixed-radius plot are not included in the counts.
Effets d'un gradient de lumière sur la croissance en hauteur et la morphologie de la cime du sapin baumier régénéré naturellement
Authors: Parent Sylvain , Messier Christian
Published: January 2008

This study characterized the height growth and crown form of 14-year-old balsam fir regenerated naturally under a light gradient varying from 3 to 83% of photosynthetic photon flux density (PPFD). After 14 years, total height growth was correlated with percent PPFD (R2 = 0.766; p < 0.001). From 3 to 25% of PPFD, balsam firs went from a suppressed stage with an umbrella type crown shape to a full grown stage with a cone type crown shape. This morphological change was caused by a greater increase in leader length compared to the mean nodal branches length. The number of nodal and internodal branches increased with PPFD. Balsam fir crown morphology showed a strong plasticity with a light gradient going from 3 to 83% of PPFD.
The spatial distribution of Armillaria root disease in an uneven-aged, spatially clumped Douglas-fir stand
Authors: Van Der Kamp Bart J.
Published: January 2008

The location, species, and infection status of all trees and stumps in nine 40 by 40 m plots located in a single large Armillaria root disease (caused by Armillariaostoyae (Romagnesi) Herink) infested area in the Interior Douglas-fir Zone in British Columbia were recorded. The area was logged to a diameter limit in 1963 and then left undisturbed. Spatial analysis using variance over mean ratios of number of trees per grid square for a series of grid sizes showed that stumps were randomly distributed, trees were strongly clumped, and infected trees occurred in small clumps that were themselves randomly distributed. Analysis of intertree distances showed that clumps of infected trees ranged from 1 to 29 trees (average 3.2 trees). Incidence of infection did not decline with distance from old stumps. Infection incidence in spatial domains surrounding each stump ranged from 0 to 100%. Nevertheless, variation in incidence among stump domains could not be attributed to variation in inoculum potential at the time of logging. It is concluded that in the experimental area, 30 years after the last major disturbance by partial cutting, Armillaria occurs in small domains, largely on the root systems of trees regenerated since logging. In these circumstances, bridge tree removal spacing, which removes all trees from a band around each infected tree, may isolate most of the viable Armillaria inoculum colonies from the remainder of the stand.
STRING SCALE GAUGE COUPLING UNIFICATION WITH VECTOR-LIKE EXOTICS AND NONCANONICAL U(1)Y NORMALIZATION
Authors: BARGER V. , JIANG JING , LANGACKER PAUL , LI TIANJUN
Published: January 2008

We use a new approach to study string scale gauge coupling unification systematically, allowing both the possibility of noncanonical U (1)Y normalization and the existence of vector-like particles whose quantum numbers are the same as those of the Standard Model (SM) fermions and their Hermitian conjugates and the SM adjoint particles. We first give all the independent sets (Yi) of particles that can be employed to achieve SU (3)C and SU (2)L string scale gauge coupling unification and calculate their masses. Second, for a noncanonical U (1)Y normalization, we obtain string scale SU (3)C × SU (2)L × U (1)Y gauge coupling unification by choosing suitable U (1)Y normalizations for each of the Yi sets. Alternatively, for the canonical U (1)Y normalization, we achieve string scale gauge coupling unification by considering suitable combinations of the Yi sets or by introducing additional independent sets (Zi), that do not affect the SU (3)C × SU (2)L unification at tree level, and then choosing suitable combinations, one from the Yi sets and one from the Zi sets. We also briefly discuss string scale gauge coupling unification in models with higher Kac–Moody levels for SU (2)L or SU (3)C.
THE RELATIVISTIC OSCILLATOR ALGEBRA REVISITED IN THE QUANTUM GROUPS FORMALISM
Authors: SCARFONE A. M. , NARAYANA SWAMY P.
Published: January 2008

We revisit the harmonic oscillator algebra in an indefinite metric by reinterpreting consistently the time-like components in a way compatible with a positive-definite metric. We show that, despite its unusual features, the relativistic oscillator algebra can be derived starting from the Euclidean q-oscillator algebra. The consistency of this isomorphism is examined at different levels including the possible implication on the dynamics of the two formalisms by means of their respective Hamiltonians.
Z0 →2γ AND THE TWISTED COPRODUCT OF THE POINCARÉ GROUP
Authors: BALACHANDRAN A. P. , JO S. G.
Published: January 2008

Yang's theorem forbids the process Z0 →2γ in any Poincaré invariant theory if photons are bosons and their two-particle states transform under the Poincaré group in the standard way (under the standard coproduct of the Poincaré group). This is an important result as it does not depend on the assumptions of quantum field theory. Recent work on noncommutative geometry requires deforming the above coproduct by the Drinfel'd twist. We prove that Z0 →2γ is forbidden for the twisted coproduct as well. This result is also independent of the assumptions of quantum field theory. As an illustration of the use of our general formulae, we further show that Z0 →ν+ ν is forbidden for the standard or twisted coproduct of the Poincaré group if the neutrino is massless, even if lepton number is violated. This is a special case of our general result that a massive particle of spin j cannot decay into two identical massless particles of the same helicity if j is odd, regardless of the coproduct used.
SEMICLASSICAL AND QUANTUM BLACK HOLES AND THEIR EVAPORATION, DE SITTER AND ANTI-DE SITTER REGIMES, GRAVITATIONAL AND STRING PHASE TRANSITIONS
Authors: RAMÓN MEDRANO M. , SÁNCHEZ N. G.
Published: January 2008

An effective string theory in physically relevant cosmological and black hole space–times is reviewed. Explicit computations of the quantum string entropy, partition function and quantum string emission by black holes (Schwarzschild, rotating, charged, asymptotically flat, de Sitter dS and anti-de Sitter AdS space–times) in the framework of effective string theory in curved backgrounds provide an amount of new quantum gravity results as: (i) gravitational phase transitions appear with a distinctive universal feature: a square-root branch point singularity in any space–time dimensions. This is of the type of the de Vega–Sánchez transition for the thermal self-gravitating gas of point particles. (ii) There are no phase transitions in AdS alone. (iii) For dS background, upper bounds of the Hubble constant H are found, dictated by the quantum string phase transition. (iv) The Hawking temperature and the Hagedorn temperature are the same concept but in different (semiclassical and quantum) gravity regimes respectively. (v) The last stage of black hole evaporation is a microscopic string state with a finite string critical temperature which decays as usual quantum strings do in nonthermal pure quantum radiation (no information loss). (vi) New lower string bounds are given for the Kerr–Newman black hole angular momentum and charge, which are entirely different from the upper classical bounds. (vii) Semiclassical gravity states undergo a phase transition into quantum string states of the same system, these states are duals of each other in the precise sense of the usual classical–quantum (wave–particle) duality, which is universal irrespective of any symmetry or isommetry of the space–time and of the number or the kind of space–time dimensions.
EXTENDED CHAMSEDDINE–FRÖHLICH APPROACH TO NONCOMMUTATIVE GEOMETRY AND THE TWO-DOUBLETS HIGGS MODEL
Authors: MEBARKI N. , HARRAT M. , BOUSSAHEL M.
Published: January 2008

The Chamseddine–Fröhlich approach to noncommutative geometry is extended by the introduction of the strong interaction sector in the mathematical formalism, and generalization of the Dirac operator and scalar product. This new approach is applied to the reformulation of the two-doublets Higgs model where the fuzzy mass, coupling and unitarity relations as well as mixing angles are derived. These tree level relations are no more preserved under the renormalization group flow in the context of the standard quantization method.
TEMPERATURE EFFECT ON IMPURITY-BOUND POLARONIC ENERGY LEVELS IN A PARABOLIC QUANTUM DOT IN MAGNETIC FIELDS
Authors: CHEN SHI-HUA , XIAO JING-LIN
Published: January 2008

Energy levels of an impurity atom and its binding energy in a quantum dot with electron–phonon interactions are obtained by the second-order Rayleigh–Schrodinger perturbation theory. The energy correction is expressed as a function of the temperature, the applied magnetic field, and the effective confinement length of the quantum dot. We apply our calculations to GaAs .
Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone
Authors: Herman Melissa A. , Niedringhaus Mark , Alayan Alisa , Verbalis Joseph G. , Sahibzada Niaz , Gillis Richard A.
Published: January 2008

Quantitative analysis of innervation to dorsal motor nucleus of the vagus (DMV) fundus-projecting neurons indicates that ∼17% of input neurons are noradrenergic. To determine whether this small percentage of neurons innervating DMV output to the stomach is physiologically relevant, we evaluated the role of norepinephrine at the DMV in mediating a vagovagal reflex controlling the fundus. A strain gauge was sutured onto the fundus of isoflurane-anesthetized rats to monitor changes in tone evoked by esophageal distension (ED). ED produced a decrease in fundus tone of 0.31 ± 0.02 g ( P < 0.05), which could be reproduced after a 30-min interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous NG-nitro-l-arginine methyl ester had no effect. Bilateral microinjection of α2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of α2-adrenoreceptor antagonists, ED decreased fundus tone by 0.33 ± 0.05 g ( P < 0.05). After antagonist microinjection, ED decreased fundus tone by only 0.05 ± 0.06 g ( P > 0.05). Bilateral microinjection of prazosin into the DMV had no effect on the response. Microinjection of norepinephrine into the DMV mimicked the effect of ED and was also prevented by prior microinjection of an α2-adrenoreceptor antagonist. Our results indicate that noradrenergic innervation of DMV fundus-projecting neurons is physiologically important and suggest that norepinephrine released at the DMV acts on α2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.
Congenic strains reveal the effect of the renin gene on skeletal muscle angiogenesis induced by electrical stimulation
Authors: de Resende Micheline M. , Amaral Sandra L. , Moreno Carol , Greene Andrew S.
Published: January 2008

Previous studies have indicated the importance of angiotensin II (ANG II) in skeletal muscle angiogenesis. The present study explored the effect of regulation of the renin gene on angiogenesis induced by electrical stimulation with the use of physiological, pharmacological, and genetic manipulations of the renin-angiotensin system (RAS). Transfer of the entire chromosome 13, containing the physiologically regulated renin gene, from the normotensive inbred Brown Norway (BN) rat into the background of an inbred substrain of the Dahl salt-sensitive (SS/Mcwi) rat restored renin levels and the angiogenic response after electrical stimulation. This restored response was significantly attenuated when SS-13BN/Mcwi consomic rats were treated with lisinopril or high-salt diet. The role of ANG II on this effect was confirmed by the complete restoration of skeletal muscle angiogenesis in SS/Mcwi rats infused with subpressor doses of ANG II. Congenic strains derived from the SS-13BN/Mcwi consomic were used to further verify the role of the renin gene in this response. Microvessel density was markedly increased after stimulation in congenic strains that contained the renin gene from the BN rat (congenic lines A and D). This angiogenic response was suppressed in control strains that carried regions of the BN genome just above (congenic line C) or just below (congenic line B) the renin gene. The present study emphasizes the importance of maintaining normal renin regulation as well as ANG II levels during the angiogenesis process with a combination of physiological, genetic, and pharmacological manipulation of the RAS.
Cyclooxygenase-2 Expression during Immortalization and Breast Cancer Progression
Authors: Zhao Xiangshan , Goswami Monica , Pokhriyal Nidhi , Ma Hui , Du Hongyan , Yao Jun , Victor Thomas A. , Polyak Kornelia , Sturgis Charles D. , Band Hamid , Band Vimla
Published: January 2008

Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells. [Cancer Res 2008;68(2):467–75]
p19Arf Inhibits the Invasion of Hepatocellular Carcinoma Cells by Binding to C-terminal Binding Protein
Authors: Chen Ya-Wen , Paliwal Seema , Draheim Kyle , Grossman Steven R. , Lewis Brian C.
Published: January 2008

The INK4A/ARF tumor suppressor locus is frequently inactivated in hepatocellular carcinoma (HCC), yet the consequences of this remain unknown. We recently described a HCC mouse model in which loss of the Ink4a/Arf locus accelerates the development of metastasis and enhances tumor cell migration and invasion in cell culture assays. We show here that knockdown of p19Arf in an HCC cell line increases invasion in cell culture assays. Furthermore, reintroduction of p19Arf into HCC cell lines lacking Ink4a/Arf inhibits tumor cell invasion, without affecting cell proliferation, or cell transformation as measured by soft agar colony formation. Inhibition of cell invasion by p19Arf was dependent on its C-terminal binding protein (CtBP) interaction domain but independent of Mdm2 binding and nucleolar localization. Indeed, RNA interference–mediated knockdown of CtBP1 or CtBP2 decreased cell invasion, and ectopic expression of CtBP2 enhanced tumor cell migration and invasion. Thus, our data indicate a novel role for the Arf tumor suppressor protein in regulating phenotypes associated with tumor progression and metastasis in HCC cells. [Cancer Res 2008;68(2):476–82]
The Adenocarcinoma-Associated Antigen, AGR2, Promotes Tumor Growth, Cell Migration, and Cellular Transformation
Authors: Wang Zheng , Hao Ying , Lowe Anson W.
Published: January 2008

The AGR2 gene encodes a secretory protein that is highly expressed in adenocarcinomas of the esophagus, pancreas, breast, and prostate. This study explores the effect of AGR2 expression with well-established in vitro and in vivo assays that screen for cellular transformation and tumor growth. AGR2 expression in SEG-1 esophageal adenocarcinoma cells was reduced with RNA interference. Cellular transformation was examined using NIH3T3 cells that express AGR2 after stable transfection. The cell lines were studied in vitro with assays for density-dependent and anchorage-independent growth, and in vivo as tumor xenografts in nude mice. SEG-1 cells with reduced AGR2 expression showed an 82% decrease in anchorage-independent colony growth and a 60% reduction in tumor xenograft size. In vitro assays of AGR2-expressing NIH3T3 cells displayed enhanced foci formation and anchorage-independent growth. In vivo, AGR2-expressing NIH3T3 cells established tumors in nude mice. Thus, AGR2 expression promotes tumor growth in esophageal adenocarcinoma cells and is able to transform NIH3T3 cells. Immunohistochemistry of the normal mouse intestine detected AGR2 expression in proliferating and differentiated intestinal cells of secretory lineage. AGR2 may be important for the growth and development of the intestine as well as esophageal adenocarcinomas. [Cancer Res 2008;68(2):492–7]
Critical Role of the Stress Chaperone GRP78/BiP in Tumor Proliferation, Survival, and Tumor Angiogenesis in Transgene-Induced Mammary Tumor Development
Authors: Dong Dezheng , Ni Min , Li Jianze , Xiong Shigang , Ye Wei , Virrey Jenilyn J. , Mao Changhui , Ye Risheng , Wang Miao , Pen Ligaya , Dubeau Louis , Groshen Susan , Hofman Florence M. , Lee Amy S.
Published: January 2008

The unfolded protein response (UPR) is an evolutionarily conserved mechanism that activates both proapoptotic and survival pathways to allow eukaryotic cells to adapt to endoplasmic reticulum (ER) stress. Although the UPR has been implicated in tumorigenesis, its precise role in endogenous cancer remains unclear. A major UPR protective response is the induction of the ER chaperone GRP78/BiP, which is expressed at high levels in a variety of tumors and confers drug resistance in both proliferating and dormant cancer cells. To determine the physiologic role of GRP78 in in situ–generated tumor and the consequence of its suppression on normal organs, we used a genetic model of breast cancer in the Grp78 heterozygous mice where GRP78 expression level was reduced by about half, mimicking anti-GRP78 agents that achieve partial suppression of GRP78 expression. Here, we report that Grp78 heterozygosity has no effect on organ development or antibody production but prolongs the latency period and significantly impedes tumor growth. Our results reveal three major mechanisms mediated by GRP78 for cancer progression: enhancement of tumor cell proliferation, protection against apoptosis, and promotion of tumor angiogenesis. Importantly, although partial reduction of GRP78 in the Grp78 heterozygous mice substantially reduces the tumor microvessel density, it has no effect on vasculature of normal organs. Our findings establish that a key UPR target GRP78 is preferably required for pathophysiologic conditions, such as tumor proliferation, survival, and angiogenesis, underscoring its potential value as a novel therapeutic target for dual antitumor and antiangiogenesis activity. [Cancer Res 2008;68(2):498–505]
Development of a New Tracking Tool for the Human Monomeric Laminin-γ2 Chain In vitro and In vivo
Authors: Koshikawa Naohiko , Minegishi Tomoko , Nabeshima Kazuki , Seiki Motoharu
Published: January 2008

Laminin-5 (Ln-5), a heterotrimer composed of three different laminin chains [laminin-α3 (Ln-α3), laminin-β3 (Ln-β3), and laminin-γ2 (Ln-γ2)], is a major component of the basement membrane in most adult tissues. One of the chains, Ln-γ2, is a specific marker of invasive tumors because it is frequently expressed as a monomer in malignant tumors. However, there is no simple and direct method to detect the monomeric form of Ln-γ2 selectively in the presence of Ln-5 because all available antibodies recognize both monomeric and heterotrimeric forms of Ln-γ2. In this study, we developed a new monoclonal antibody (mAb) termed 1H3 that reacts specifically with human Ln-γ2 monomers during immunoprecipitation, ELISA, Western blotting, and immunostaining. Ln-5 was not recognized by mAb 1H3 after denaturation with detergents under nonreducing conditions, but reactivity was recovered when denaturation was done under reducing conditions. The epitope of the antibody was mapped to region on the coiled-coil structure formed between Ln-γ2 and its partner chains Ln-α3 and Ln-β3 in Ln-5, whose structure is further stabilized by disulfide bonds. In normal tissue samples, the basement membrane was stained with conventional antibody against Ln-γ2 but not by mAb 1H3. In contrast, tumor cells in tissue sections could be stained with mAb 1H3 as efficiently as with conventional antibody. Thus, mAb 1H3 holds promise as a powerful tracking tool for the specific detection of monomeric Ln-γ2 in vivo and in vitro and is potentially useful as a diagnostic tool for detecting tumors and as a vehicle for drug delivery to cancer tissues. [Cancer Res 2008;68(2):530–6]
Chronic Hypoxia Decreases Synthesis of Homologous Recombination Proteins to Offset Chemoresistance and Radioresistance
Authors: Chan Norman , Koritzinsky Marianne , Zhao Helen , Bindra Ranjit , Glazer Peter M. , Powell Simon , Belmaaza Abdellah , Wouters Brad , Bristow Robert G.
Published: January 2008

Hypoxic and/or anoxic tumor cells can have increased rates of mutagenesis and altered DNA repair protein expression. Yet very little is known regarding the functional consequences of any hypoxia-induced changes in the expression of proteins involved in DNA double-strand break repair. We have developed a unique hypoxic model system using H1299 cells expressing an integrated direct repeat green fluorescent protein (DR-GFP) homologous recombination (HR) reporter system to study HR under prolonged chronic hypoxia (up to 72 h under 0.2% O2) without bias from altered proliferation, cell cycle checkpoint activation, or severe cell toxicity. We observed decreased expression of HR proteins due to a novel mechanism involving decreased HR protein synthesis. Error-free HR was suppressed 3-fold under 0.2% O2 as measured by the DR-GFP reporter system. This decrease in functional HR resulted in increased sensitivity to the DNA cross-linking agents mitomycin C and cisplatin but not to the microtubule-interfering agent, paclitaxel. Chronically hypoxic H1299 cells that had decreased functional HR were relatively radiosensitive [oxygen enhancement ratio (OER), 1.37] when compared with acutely hypoxic or anoxic cells (OER, 1.96–2.61). Using CAPAN1 cells isogenic for BRCA2 and siRNA to RAD51, we confirmed that the hypoxia-induced radiosensitivity was due to decreased HR capacity. Persistent down-regulation of HR function by the tumor microenvironment could result in low-fidelity DNA repair and have significant implications for response to therapy and genetic instability in human cancers. [Cancer Res 2008;68(2):605–14]
A Rapid Outcomes Ascertainment System Improves the Quality of Prognostic and Pharmacogenetic Outcomes from Observational Studies
Authors: Bradbury Penelope A. , Heist Rebecca Suk , Kulke Matthew H. , Zhou Wei , Marshall Ariela L. , Miller David P. , Su Li , Park Sohee , Temel Jennifer , Fidias Panos , Sequist Lecia , Lynch Thomas J. , Wain John C. , Shepherd Frances A. , Christiani David C. , Liu Geoffrey
Published: January 2008

Purpose: Case-control and observational studies are popular choices for evaluating molecular prognostic/pharmacogenetic outcomes, but data quality is rarely tested. Using clinical trial and epidemiologic methods, we assessed the quality of prognostic and outcomes data obtainable from a large case-control study of lung cancer.

Methods: We developed an explicit algorithm (set of standard operating procedures forming a rapid outcomes ascertainment system) that encompassed multiple tests of quality assurance, and quality of data for a range of prognostic and outcomes variables, in several cancers, across several centers and two countries were assessed. Based on these assessments, the algorithm was revised and physicians' clinical practice changed. We reevaluated the quality of outcomes after these revisions.

Results: Development of an algorithm with internal quality controls showed specific patterns of data collection errors, which were fixable. Although the major discrepancy rate in retrospective data collection was low (0.6%) when compared with external validated sources, complete data were found in <50% of patients for treatment response rate, toxicity, and documentation of patient palliative symptoms. Prospective data collection and changes to clinical practice led to significantly improved data quality. Complete data on response rate increased from 45% to 76% (P = 0.01, Fisher's exact test), for toxicity data, from 26% to 56% (P = 0.02), and for palliative symptoms, from 25% to 70% (P < 0.05), in one large lung cancer case-control study.

Conclusions: Observational studies can be a useful source for studying molecular prognostic and pharmacogenetic outcomes. A rapid outcomes ascertainment system with strict ongoing quality control measures is an excellent means of monitoring key variables. (Cancer Epidemiol Biomarkers Prev 2008;17(1):204–11)
Regular Adult Aspirin Use Decreases the Risk of Non-Small Cell Lung Cancer among Women
Authors: Van Dyke Alison L. , Cote Michele L. , Prysak Geoffrey , Claeys Gina B. , Wenzlaff Angie S. , Schwartz Ann G.
Published: January 2008

Background: Prior studies indicate that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of non-small cell lung cancer (NSCLC); however, results have been contradictory in part because of variation in study design. Few studies have examined the use of aspirin or other NSAIDs on risk of NSCLC in women.

Methods: Through a case-control study of African American and Caucasian women with and without NSCLC, we examined the relationship between use of aspirin, NSAIDs, and acetaminophen and risk of NSCLC. Risk was estimated by calculating odds ratios and 95% confidence intervals for ever/never use, duration of use, and duration of use category (never, 1-5 years, >5 years) after adjusting for major risk factors for lung cancer. Risk estimates were stratified by race, age, smoking history, and body mass index.

Results: Ever use of adult-strength aspirin was associated with a significant reduction in risk of NSCLC (odds ratio, 0.66; 95% confidence interval, 0.46-0.94). Additionally, there was a significant trend toward a reduced risk of NSCLC in adult-strength aspirin users with increasing duration of use (Ptrend = 0.02). In stratified analyses, aspirin use was associated with a significantly reduced risk of lung cancer among Caucasians and 55- to 64-year-olds. Baby aspirin and NSAID use was associated with a significant reduction in risk of NSCLC only among 65- to 74-year-olds.

Conclusion: Our results suggest that long-term use of adult-strength aspirin may reduce the risk of NSCLC in women. (Cancer Epidemiol Biomarkers Prev 2008;17(1):148–57)