bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic structure of black rat populations in a rural plague focus in Madagascar
Authors: Gilabert A. , Loiseau A. , Duplantier J.-M. , Rahelinirina S. , Rahalison L. , Chanteau S. , Brouat C.
Published: November 2007

The genetic structure of reservoir populations is a key characteristic in understanding the persistence of infectious diseases in natural systems. In the Highlands of Madagascar, where plague has persisted since 1920, the black rat, Rattus rattus (L., 1758), is the sole species acting as a reservoir of the disease. Ecological surveys have shown a clear correlation between the locations of the plague-persistence area in Madagascar (above 800 m elevation) and the distribution area of one endemic plague vector, the flea Synopsyllus fonquerniei , which is found exclusively on rats living outdoors. This clear habitat segregation has led to the suggestion that R. rattus populations in the central highlands are divided into indoor- and outdoor-dwelling populations. Using eight microsatellite markers, we analysed the genetic structure of R. rattus populations living within a human plague focus in relation to habitat and geographic distance. We found that habitat by itself was not a structuring factor, unlike geographic distance. Nevertheless, the significant genotypic differentiation of R. rattus populations that was found at a fine spatial scale might relate to differences in population dynamics between rats in indoor and outdoor habitats.
Terrestrial gastropod responses to an ecosystem-level calcium manipulation in a northern hardwood forest
Authors: Skeldon Monica A. , Vadeboncoeur Matthew A. , Hamburg Steven P. , Blum Joel D.
Published: November 2007

The effects of acid deposition on soil calcium (Ca), and in turn on land snail populations, have been of heightened concern for several decades. We compiled a 10 year record (1997–2006) of gastropod abundance on two small watersheds at the Hubbard Brook Experimental Forest, one of which was treated with a Ca addition in 1999. In years 3–7 post Ca addition, snail abundance in the treated watershed was 73% higher than in the reference area (p < 0.001); there was no significant difference in the 3 years prior to treatment, and no significant difference in slug abundance in any year. We analyzed relationships between snail density and microsite spatial variation in leaf-litter Ca concentration, litter-layer thickness, tree species composition, slope, dead wood, and forest-floor light level. We found that snail abundance was significantly correlated with litter Ca concentration (p < 0.001) and negatively correlated with the importance value of American beech (p = 0.05). Isotopic-tracer analysis indicated that, on average, 76% of Ca in snail shells 5 years post treatment was derived from the added Ca. However, interannual variation in snail numbers indicates that other factors beyond available Ca have a strong influence on snail abundance.
Socio-spatial organization of Eurasian badgers (Meles meles) in a low-density population of central Europe
Authors: Do Linh San Emmanuel , Ferrari Nicola , Weber Jean-Marc
Published: November 2007

We studied the socio-spatial organization of Eurasian badgers (or European badgers), Meles meles (L., 1758), in a low-density population (estimate 1.8 badgers/km2) inhabiting a semi-rural area of western Switzerland. For this purpose, 8 badgers (5 males and 3 females) were caught at 5 different main setts and were radio-tracked between May 1994 and November 1996. The size of individual home ranges varied from 0.27 to 3.74 km2 (1.69 ± 1.33 km2 (mean ± SD), n = 8, 100% MCP), seemingly according to local variations in habitat productivity. Individual home ranges were spatially stable, but their size decreased significantly during winter (0.26 ± 0.42 km2, n = 7, 100% MCP). Badger social units consisted of 1–5 adults and (or) subadults (2.2 ± 1.5 animals, n = 9) and their yearly offspring. Group-range size varied from 0.57 to 3.74 km2 (2.12 ± 1.30 km2, n = 4) and seemed to be influenced by the spatial distribution pattern of food resources. Indeed, each group range encompassed approximately the same surface of agricultural land (about 0.60 km2). Territories were not well marked, some group ranges partly overlapped. Latrines, which were not numerous and principally located inside rather than along borders of group ranges, were only used irregularly or sporadically. This prompts us to encourage the reconsideration of the role of territorial behaviour in promoting group formation in Eurasian badgers.
The effects of habitat fragmentation on animals: gaps in our knowledge and new approachesThis review is one of a series dealing with some aspects of the impact of habitat fragmentation on animals and plants. This series is one of several virtual symposia focussing on ecological topics that will be published in the Journal from time to time.
Authors: Stutchbury Bridget J.M.
Published: November 2007

Habitat fragmentation has a substantial impact on animals at many levels of ecology, including genetics, behaviour, demographics, and biodiversity. Despite a flood of research articles on habitat fragmentation in recent decades, there are still serious gaps in our knowledge that stem, in part, from inadequate experimental design and inconsistent methodology. The papers in this special series highlight the many challenges of designing robust studies to understand fragmentation impacts at the landscape scale and offer practical solutions.
The role of habitat area and edge in fragmented landscapes: definitively distinct or inevitably intertwined?This review is one of a series dealing with some aspects of the impact of habitat fragmentation on animals and plants. This series is one of several virtual symposia focussing on ecological topics that will be published in the Journal from time to time.
Authors: Fletcher, Jr. Robert J. , Ries Leslie , Battin James , Chalfoun Anna D.
Published: November 2007

Over the past few decades, much research has focussed on the effects of habitat area (i.e., patch size) and edges in fragmented landscapes. We review and synthesize the literature on area and edge effects to identify whether the ecological processes influenced by patch size and edge are distinct, to summarize evidence for the relative effect of each, and to discuss how estimating their independent effects may be accomplished in field studies. Area and edge directly influence ecological processes in distinct ways, yet indirect effects can be similar, making it difficult to isolate the effects of area and edge in nature. Many studies investigating both area and edge have been confounded in their design and (or) analysis (i.e., studies did not control for one potential effect while testing for the other). Nonconfounded studies have more frequently shown support for edge effects, and comparisons between nonconfounded and confounded studies suggest that some observed area effects could be explained by edge effects. We argue that by focussing on the fundamental processes directly influenced by area and edge, and by developing more rigorous study designs and analyses that isolate their relative influence, greater insight can be gained in future investigations on habitat loss and fragmentation.
HOW MAGNETIC IS THE NEUTRINO?
Authors: BELL N. F.
Published: November 2007

The existence of a neutrino magnetic moment implies contributions to the neutrino mass via radiative corrections. We derive model-independent "naturalness" upper bounds on the magnetic moments of Dirac and Majorana neutrinos, generated by physics above the electroweak scale. For Dirac neutrinos, the bound is several orders of magnitude more stringent than present experimental limits. However, for Majorana neutrinos the magnetic moment bounds are weaker than present experimental limits if μν is generated by new physics at ~ 1 TeV , and surpass current experimental sensitivity only for new physics scales > 10 – 100 TeV . The discovery of a neutrino magnetic moment near present limits would thus signify that neutrinos are Majorana particles.
PROPERTY VALUES
Authors: DELBOURGO R.
Published: November 2007

By ascribing a complex anticommuting variable ζ to each basic property of a field it is possible to describe all the fundamental particles as combinations of only five ζ and understand the occurrence of particle generations. An extension of space-time x to include property then specifies the 'where, when and what' of an event and allows for a generalized relativity where the gauge fields lie in the x - ζ sector and the Higgs fields in the ζ - ζ sector.
STERILE NEUTRINOS IN A 6 × 6 MATRIX APPROACH
Authors: GOLDMAN T.
Published: November 2007

Quark-lepton symmetry invites consideration of the existence of sterile neutrinos. Long ago, we showed that this approach predicts large neutrino mixing amplitudes. Using a Weyl spinor approach, we show, in an analytic example, how this, and pseudo-Dirac pairing, can develop within a reduced rank version of the conventional see-saw mechanism, from small intrinsic mixing strengths. We show by numerical examples that mixing of active and sterile neutrinos can affect the structure of oscillations relevant to extraction of neutrino mixing parameters from neutrino oscillation data.
CP VIOLATION
Authors: HE XIAO-GANG
Published: November 2007

In this contribution to the Festschrift in honor of Bruce McKellar and Girish Joshi, I discuss a model proposed recently1 in which the CP violating phase in the CKM matrix is identical to the phase in the Higgs potential resulting from spontaneous CP violation.
MSW IN REVERSE: WHAT SNO SAYS ABOUT PSEUDO-DIRAC NEUTRINOS
Authors: STEPHENSON G. J.
Published: November 2007

I discuss the implications of the SNO neutral current result for the allowed Δm2 values of pseudo-Dirac pairs. In particular, for certain parameter ranges, adiabatic MSW may occur in reverse as solar neutrinos traverse the earth's atmosphere.
SOME RECENT LATTICE QCD RESULTS FROM THE CSSM
Authors: BOINPOLLI S. , BOWMAN P. O. , HEDDITCH J. N. , HELLER U. M. , KAMLEH W. , LASSCOCK B. G. , LEINWEBER D. B. , WILLIAMS A. G. , ZANOTTI J. M. , ZHANG J. B.
Published: November 2007

Recent CSSM Lattice Collaboration studies of hadron electromagnetic structure and the exotic hadron spectrum are highlighted. The momentum dependence of quark and gluon propagators revealed in lattice simulations of full QCD are also illustrated.
PACKING A TRUCK — NOW WITH A TWIST!
Authors: EISENBRAND FRIEDRICH , FUNKE STEFAN , KARRENBAUER ANDREAS , REICHEL JOACHIM , SCHÖMER ELMAR
Published: November 2007

In an industry project with a German car manufacturer we are faced with the challenge of placing a maximum number of uniform rigid rectangular boxes in the interior of a car trunk. The problem is of practical importance due to a European industry norm which requires car manufacturers to state the trunk volume according to this measure.

No really satisfactory automated solution for this problem has been known in the past. In spite of its NP hardness, combinatorial optimization techniques, which consider only grid-aligned placements, produce solutions which are very close to the one achievable by a human expert in several hours of tedious work. The remaining gap is mostly due to the constraints imposed by the chosen grid.

In this paper we present a new approach which combines the grid-based combinatorial method with Simulated Annealing on a continuous model. This allows us to explore arbitrary orientations and placements of boxes, hence closing the gap even further, and – in some cases – even surpass the manual expert solution.

The implemented software system allows our industrial partner to incorporate the trunk volume in a very early stage of the car design process without relying on a repeated and cumbersome manual evaluation of the volume.
Electrochromic Properties of Mixed Metal Oxide Thin-Film and Its Application to Nitrate-Ion Sensor
Authors: Takeyasu Tomohiro , Takase Satoko , Shimizu Youichi
Published: November 2007

Electrochromic behavior of multicomponent metal oxide thin- film electrodes have been studied for the use of environmental ion sensing devices. Multicomponent metal oxide thin-film electrodes were prepared by a spin-coating method on ITO-glass substrates from solutions including various metal octylates at 500ºC. The transmittance variation of the SnO2:Mn(10mol%) thin- film electrode at cyclic voltammetry showed dependence on nitrate ion concentration at -0.75V vs SCE. The transmittance at 460 nm of SnO2:Mn(10mol%) thin-film electrode exhibited dependence on nitrate ion concentration at -0.75V vs SCE, and not depended on dihydrogen-phosphate ion and chloride ion.
Liquidus Temperature of Molten Cryolite-Based Aluminum Electrolyte
Authors: Kan Hong-Min , Wang Zhao-Wen , Shi Zhong-Ning , Ban Yun-Gang , Qiu Zhu-Xian
Published: November 2007

Liquidus temperature is one of important parameters for aluminum electrolysis. In this study, a new method is introduced; the liquidus temperature is measured with one Agilent 34401A meter connected to a computer. The whole process is controlled by computer software. Firstly, liquidus temperature of NaF and NaCl are measured for comparison. The result is proved to be convenient and accurate. The range of error is {plus minus}1~1.5{degree sign}C at 801{degree sign}C to 995{degree sign}C. Furthermore low temperature aluminum electrolyte composition is related. The liquidus temperature measurement of the system is NaF·AlF3(R=2.25)-Al2O3(3%)-CaF2(4%)-LiF(0~6%)-NaCl(0~6%). The result showed that the liquidus temperature is reduced greatly by adding NaCl and LiF. The mathematical model obtained is T({degree sign}C)=947.588-5.907×LiF(wt/%)-6.223×NaCl(wt/%). The authors expected these data are useful for industry production of aluminum electrolysis, since it can provide a scientific basis for choosing suitable low temperature aluminum electrolyte composition.
Electrochemical Performance and Microstructure of The LNF-SDC Composite Cathode for SOFC
Authors: Sornthummalee Potejanee , Sato Kazunori , Komatsu Takeshi , Orui Himeko , Chiba Reiichi , Arakawa Masayasu
Published: November 2007

Symmetric cells consisting of the LaNi0.6Fe0.4O3 (LNF)- Sm0.2Ce0.8O1.9 (SDC) composite cathodes and 8 mol%Y2O3- stabilized ZrO2 (YSZ) electrolyte have been investigated in order to evaluate the oxygen reduction performance of the composite cathode by AC impedance analysis. Cell performance and cathodic overvoltage were examined for cells consisting of the Ni-YSZ cermet anode, YSZ electrolyte, and composite cathode. The addition of 50 wt% SDC to LNF resulted in the lowest polarization resistance. A cell using the 50 wt% LNF + 50 wt% SDC composite cathode showed the maximum power density and the cathodic overvoltage for this cell showed as half as lower than that for a cell using the LNF cathode under the same condition. Enhancement of the electrochemical performance in the LNF-SDC composite cathode is most likely to be caused by the SDC particles connecting LNF particles with the electrolyte surface.
A Derivative Method for the Estimation of the Electrochemical Production Rate of Ozone in Sulfuric Acid
Authors: Limon-Petersen Juan G. , Gutiérrez-Murillo Hector , Ibanez Jorge G. , Flores-Saiffe Farias Bernardo
Published: November 2007

We report the use of a derivative method to estimate the rate of ozone, oxygen and hydrogen production at a Pt anode/graphite cathode laboratory system as a function of the gas volumes produced, using the ideal gas law with the corresponding pressure corrections. The rates were evaluated at different applied potentials and sulfuric acid concentrations.
Electrolysis of Methyl-t-Butyl Ether in Aqueous Solutions using Electro-generated Persulfate
Authors: Felix Rosa Maria , Inda Pablo , Diaz Artur , Lin Ho Shui Wai , Oropeza Mercedes
Published: November 2007

Aqueous sodium sulfate solutions containing dilute concentrations of methyl-t-butylmethylether (MTBE) were electrolyzed to destroy the MTBE. In this treatment, the sulfate / persulfate anion (S2O82-) redox couple servers as the mediator cycle to oxidize MTBE. The solution was circulated through the anode compartment of a two compartment cell, equipped with reticulated vitreous carbon electrodes with100 pores/inch and separated from the cathode compartment by a positively charged ion exchange membrane. The electrolysis successfully reduced the MTBE content of the solutions. The reaction proceeded best when the applied anode potentials were in the range 2 - 3 V vs SCE and the flow rates were 0.100 - 0.125 L/min. Graphite plate, gold screen and platinum screen anodes were briefly tested.
Development of Ionic Liquid Membranes for NOx Gas Detection and Storage Utilizing Calix[4]Arenes
Authors: Poplin Jane H. , Rudkevich Dmitry , Swatloski Richard , Rogers Robin D.
Published: November 2007

Models for NOx gas sensing or storage have been prepared by the dissolution of O-tetraalkylated calix[4]arene in the 1,3- alternate conformation (Calix1) in the hydrophobic ionic liquid (IL) 1-butyl-3-methylimidazolium bis (perfluoroethylsulfonyl)imide ([C4mim]-[BETI]). When dissolved in chloroform, this calixarene has previously been shown to undergo a rapid color change when it complexes the reactive nitrosonium ion. Here we demonstrate that these color changes also are observed when the calixarene is immobilized in a nonvolatile ionic liquid.
Ge on Si Photodiodes for Si CMOS Monolithic Optical Receivers
Authors: Huang Zhihong , Oh Jungwoo , Campbell Joe C.
Published: November 2007

We report a Ge growth technique on Si using thin SiGe buffer layers and also discuss photodiodes fabricated on the Ge for Si CMOS monolithic optical receiver applications. The effectiveness of thin SiGe buffer layers in terminating threading dislocations and reducing photodiode dark current for Ge epitaxially grown on Si (001) has been investigated for Ge photodiodes. The dark current of Ge on Si photodiodes can be reduced by over an order of magnitude by incorporating two different composition SiGe buffer layers. A backside- illuminated photodetector has been fabricated with the dark current as low as 3.6 mA/cm2 at 1 V reverse bias. To improve the speed of the photodiode, a device with thinner SiGe buffer layers was demonstrated and achieved 21.5 GHz bandwidth at 1.31 mm, resulting in a record high efficiency-bandwidth product of 12.9 GHz.
Wafer Bonding of Magneto-Optic Garnet and its Application to Waveguide Optical Devices
Authors: Mizumoto Tetsuya , Saito Hideki , Sakurai Kazumasa , Shoji Yuya
Published: November 2007

Bonding a magneto-optic garnet to III-V compound semiconductor and LiNbO3 is discussed focused on the application to waveguide optical isolators. Two types of waveguide isolators, an interferometric isolator and a semi-leaky isolator, are described. The interferometric isolator uses nonreciprocal phase shift. The isolator has the advantage of integratability with optical active devices, since we can use a GaInAsP guiding layer. The semi-leaky isolator, which is composed of a magneto-optic garnet guiding and a LiNbO3 upper cladding layer has the advantages of large fabrication tolerance and wide operating wavelength range. The performance of fabricated isolators is also described.
Demonstration of III-V Semiconductor/Benzocyclobutene Optical Nanowires and Nanotapers
Authors: Lauvernier Denis , Carette Michèle , Vilcot Jean-Pierre , Bernard Dororhee , Decoster Didier
Published: November 2007

High index contrast waveguides in the III-V material line are demonstrated here. Created thanks to a wafer bonding technology, they are made of a GaAs nanowire embedded in a benzocyclobutene (BCB) matrix. We also report some of those waveguides properties and an example of active device considered with this technology.
Effects of muscle metabolites on responses of muscle sympathetic nerve activity to mechanoreceptor(s) stimulation in healthy humans
Authors: Cui Jian , Mascarenhas Vernon , Moradkhan Raman , Blaha Cheryl , Sinoway Lawrence I.
Published: November 2007

Based on animal studies, it has been speculated that muscle metabolites sensitize muscle mechanoreceptors and increase mechanoreceptor-mediated muscle sympathetic nerve activity (MSNA). However, this hypothesis has not been directly tested in humans. In this study, we tested the hypothesis that in healthy individuals passive stretch of forearm muscles would evoke significant increases in mean MSNA when muscle metabolite concentrations were increased. In 12 young healthy subjects, MSNA, ECG, and blood pressure were recorded. Subjects performed static fatiguing isometric handgrip at 30% maximum voluntary contraction followed by 4 min of postexercise muscle ischemia (PEMI). After 2 min of PEMI, wrist extension (i.e., wrist dorsiflexion) was performed. The static stretch protocol was also performed during 1) a freely perfused condition, 2) ischemia alone, and 3) PEMI after nonfatiguing exercise. Finally, repetitive short bouts of wrist extension were also performed under freely perfused conditions. This last paradigm evoked transient increases in MSNA but had no significant effect on mean MSNA over the whole protocol. During the PEMI after fatiguing handgrip, static stretch induced significant increases in MSNA (552 ± 74 to 673 ± 90 U/min, P < 0.01) and mean blood pressure (102 ± 2 to 106 ± 2 mmHg, P < 0.001). Static stretch performed under the other three conditions had no significant effects on mean MSNA and blood pressure. The present data verified that in healthy humans mechanoreceptor(s) stimulation evokes significant increases in mean MSNA and blood pressure when muscle metabolite concentrations are increased above a certain threshold.
Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats
Authors: Marzetti Emanuele , Groban Leanne , Wohlgemuth Stephanie E. , Lees Hazel A. , Lin Marina , Jobe Harrison , Giovannini Silvia , Leeuwenburgh Christiaan , Carter Christy S.
Published: November 2007

Growth hormone (GH) supplementation at old age has been shown to improve body composition, although its effect on muscle performance is still debated. On the other hand, resistance training increases muscle mass and strength even when initiated at advanced age. In the present study, we investigated the effects of short-term GH supplementation and exercise training on physical performance and skeletal muscle apoptosis in aged rats. Old (28 mo) male Fischer 344 × Brown Norway rats were randomized to 4 wk of GH supplementation (300 μg subcutaneous, twice daily) or 4 wk of treadmill running or used as sedentary controls. Eight-month-old rats, sedentary or exercised, were used as young controls. Exercise training improved exercise capacity and muscle strength in old animals. In soleus muscle, age and exercise were not associated with significant changes in the extent of apoptosis. However, we detected an age-related increase of cleaved caspase-8 (+98%), cleaved caspase-3 (+136%), and apoptotic DNA fragmentation (+203%) in the extensor digitorum longus muscle of old sedentary rats, which was attenuated by exercise. GH administration neither ameliorated physical performance nor attenuated apoptosis in extensor digitorum longus and was associated with increased apoptosis in soleus muscle (+206% vs. old controls). Our findings indicate that a short-term program of exercise training started at advanced age reverses age-related skeletal muscle apoptosis and represents an effective strategy to improve physical performance. In contrast, short-term administration of GH late in life does not provide any protection against functional decline or muscle aging and may even accelerate apoptosis in slow-twitch muscles, such as the soleus.
Aplysia Bag Cells Function as a Distributed Neurosecretory Network
Authors: Hatcher Nathan G. , Sweedler Jonathan V.
Published: November 2007

The anatomical organization of many neuroendocrine systems implies multiple sites of hormone release in areas mediating multiple aspects of physiology and behavior, yet this neurosecretory complexity has not often been verified. Here we probe the well-characterized hormonal model, the reproductive bag cell neuroendocrine system of the sea slug Aplysia californica. The bag cell neurons of Aplysia mediate egg-laying behavior through the coordinated secretion of a suite of peptides derived from a single gene product, the egg-laying prohormone (proELH). Although the majority of bag cell neurons are located within two major abdominal bag cell clusters, smaller groups of egg-laying hormone-expressing cells have been observed in specific pleural and cerebral ganglia regions, some of which have been reported to be electrically connected to the abdominal bag cell clusters. Releasates are sampled from discrete locations within the Aplysia CNS before and during stimulation of afterdischarge activity and subsequently analyzed with matrix assisted laser desorption/ionization time-of-flight mass spectrometry. Site-specific release profiles are observed at bag cell cluster, pleural, and genital ganglion sites after site-specific electrophysiological activation of bag cell afterdischarges. These data demonstrate that the bag cell network has multiple neurohemal release sites, exhibits descending activation that travels from the cerebral and pleural ganglia down to the abdominal bag cell clusters, and releases spatially distinct profiles of proELH-derived peptides within the Aplysia nervous system. Such distributed neurosecretory organization may be a common feature of neuroendocrine systems across higher order organisms linking multiple behavioral aspects to a single neuronal network.
Random Noise Paradoxically Improves Light-Intensity Encoding in Hermissenda Photoreceptor Network
Authors: Butson Christopher R. , Clark Gregory A.
Published: November 2007

Neurons are notoriously noisy devices. Although the traditional view posits that noise degrades system performance, recent evidence suggests that noise may instead enhance neural information processing under certain conditions. Here we report that random channel and synaptic noise improve the ability of a biologically realistic computational model of the Hermissenda eye to encode light intensity. The model was created in GENESIS and is based on a previous model used to examine effects of changes in type B photoreceptor excitability, synaptic strength, and network architecture. The network consists of two type A and three type B multicompartmental photoreceptors. Each compartment contains a population of Hodgkin–Huxley-type ion channels and each cell is stimulated via artificial light currents. We found that the addition of random channel and synaptic noise yielded a significant improvement in the accuracy of the network's encoding of light intensity across eight light levels spanning 3.5 log units ( P < 0.001, modified Levene test). The benefits of noise remained after controlling for several consequences of randomness in the model. Additionally, improvements were not confined to perithreshold stimulus intensities. Finally, the effects of noise are not present in individual neurons, but rather are an emergent property of the synaptically connected network that is independent of stochastic resonance. These results suggest that noise plays a constructive role in neural information processing, a concept that could have important implications for understanding neural information processing or designing neural interface devices.
Disruption of the FA/BRCA pathway in bladder cancer
Authors: Neveling K. , Kalb R. , Florl A.R. , Herterich S. , Friedl R. , Hoehn H. , Hader C. , Hartmann F.H. , Nanda I. , Steinlein C. , Schmid M. , Tönnies H. , Hurst C.D. , Knowles M.A. , Hanenberg H. , Schulz W.A. , Schindler D.
Published: November 2007

Bladder carcinomas frequently show extensive deletions of chromosomes 9p and/or 9q, potentially including the loci of the Fanconi anemia (FA) genes FANCC and FANCG. FA is a rare recessive disease due to defects in anyone of 13 FANC genes manifesting with genetic instability and increased risk of neoplasia. FA cells are hypersensitive towards DNA crosslinking agents such as mitomycin C and cisplatin that are commonly employed in the chemotherapy of bladder cancers. These observations suggest the possibility of disruption of the FA/BRCA DNA repair pathway in bladder tumors. However, mutations in FANCC or FANCG could not be detected in any of 23 bladder carcinoma cell lines and ten surgical tumor specimens by LOH analysis or by FANCD2 immunoblotting assessing proficiency of the pathway. Only a single cell line, BFTC909, proved defective for FANCD2 monoubiquitination and was highly sensitive towards mitomycin C. This increased sensitivity was restored specifically by transfer of the FANCF gene. Sequencing of FANCF in BFTC909 failed to identify mutations, but methylation of cytosine residues in the FANCF promoter region was demonstrated by methylation-specific PCR, HpaII restriction and bisulfite DNA sequencing. Methylation-specific PCR uncovered only a single instance of FANCF promoter hypermethylation in surgical specimens of further 41 bladder carcinomas. These low proportions suggest that in contrast to other types of tumors silencing of FANCF is a rare event in bladder cancer and that an intact FA/BRCA pathway might be advantageous for tumor progression.
Influence of a nonfragile FHIT transgene on murine tumor susceptibility
Authors: McCorkell K.A. , Mancini R. , Siprashvili Z. , Barnoski B.L. , Iliopoulos D. , Siracusa L.D. , Zanesi N. , Croce C.M. , Fong L.Y.Y. , Druck T. , Huebner K.
Published: November 2007

FHIT, at a constitutively active chromosome fragile site, is often a target of chromosomal aberrations and deletion in a large fraction of human tumors. Inactivation of murine Fhit allelessignificantly increases susceptibility of mice to spontaneous and carcinogen-induced tumorigenesis. In this study, transgenic mice, carrying a human FHIT cDNA under control of the endogenous promoter, were produced to determine the effect of Fhit expression, from a nonfragile cDNA transgene outside the fragile region, on carcinogen-induced tumor susceptibility of wildtype and Fhit heterozygous mice. Mice received sufficient oral doses of N-nitrosomethybenzylamine (NMBA) to cause forestomach tumors in >80% of nontransgenic control mice. Although the level of expression of the FHIT transgene in the recombinant mouse strains was much lower than the level of endogenous Fhit expression, the tumor burden in NMBA-treated male transgenic mice was significantly reduced, while female transgenic mice were not protected. To determine if the difference in protection could be due to differences in epigenetic changes at the transgene loci in male versus female mice, we examined expression, hypermethylation and induced re-expression of FHIT transgenes in male and female mice or cells derived from them. The transgene was methylated in male and female mice and in cell lines established from male and female transgenic kidneys, the FHIT locus was both hypermethylated and deacetylated. It is likely that the FHIT transgene is more tightly silenced in female transgenic mice, leading to a lack of protection from tumor induction.
Exogenous mycoplasmal p37 protein alters gene expression, growth and morphology of prostate cancer cells
Authors: Goodison S. , Nakamura K. , Iczkowski K.A. , Anai S. , Boehlein S.K. , Rosser C.J.
Published: November 2007

We previously showed that the Mycoplasma hyorhinis-encoded protein p37 can promote invasion of cancer cells in a dose-dependent manner, an effect that was blocked by monoclonal antibodies specific for p37. In this study, we further elucidated changes in growth, morphology and gene expression in prostate cancer cell lines when treated with exogenous p37 protein. Incubation with recombinant p37 caused significant nuclear enlargement, denoting active, anaplastic cells and increased the migratory potential of both PC-3 and DU145 cells. Microarray analysis of p37-treated and untreated cells identified eight gene expression clusters that could be broadly classified into three basic patterns. These were an increase in both cell lines, a decrease in either cell line or a cell line-specific differential trend. The most represented functional gene categories included cell cycle, signal transduction and metabolic factors. Taken together, these observations suggest that p37 potentiates the aggressiveness of prostate cancer and thus molecular events triggered by p37 maybe target for therapy.
Familial cancer syndromes: catalog with comments
Authors: Hecht F.
Published: November 2007

A catalog of 50 family cancer syndromes is presented, representing all Mendelian modes of inheritance and influential genes on chromosomes 1–20, 22 and the X. Certain trends are emerging such as recurrent involvement of the RecQ family of DNA helicases and somatic overgrowth in the family cancer syndromes. A big question now is: can family cancer syndromes be reliably spotted by primary care clinicians?
The dynamics of cancer chromosomes and genomes
Authors: Ye C.J. , Liu G. , Bremer S.W. , Heng H.H.Q.
Published: November 2007

A key feature of cancer chromosomes and genomes is their high level of dynamics and the ability to constantly evolve. This unique characteristic forms the basis of genetic heterogeneity necessary for cancer formation, which presents major obstacles to current cancer diagnosis and treatment. It has been difficult to integrate such dynamics into traditional models of cancer progression. In this conceptual piece, we briefly discuss some of the recent exciting progress in the field of cancer genomics and genome research. In particular, a re-evaluation of the previously disregarded non-clonal chromosome aberrations (NCCAs) is reviewed, coupled with the progress of the detection of sub-chromosomal aberrations with array technologies. Clearly, the high level of genetic heterogeneity is directly caused by genome instability that is mediated by stochastic genomic changes, and genome variations defined by chromosome aberrations are the driving force of cancer progression. In addition to listing various types of non-recurrent chromosomal aberrations, we discuss the likely mechanism underlying cancer chromosome dynamics. Finally, we call for further examination of the features of dynamic genome diseases including cancer in the context of systems biology and the need to integrate this new knowledge into basic research and clinical applications. This genome centric concept will have a profound impact on the future of biological and medical research.
MicroRNAs in carcinogenesis
Authors: Hagan J.P. , Croce C.M.
Published: November 2007

MicroRNAs are an abundant class of noncoding RNAs, typically 20–23 nucleotides in length that are often evolutionarily conserved in metazoans and expressed in a cell and tissue specific manner. MicroRNAs exert their gene regulatory activity primarily by imperfectly base pairing to the 3′ UTR of their target mRNAs, leading to mRNA degradation or translational inhibition. In cancer, microRNAs are often dysregulated with their expression patterns being correlated with clinically relevant tumor characteristics. Recently, microRNAs were shown to be directly involved in cancer initiation and progression. This review focuses primarily on emerging developments in the microRNA field that impact our understanding of how these molecules contribute to carcinogenesis.
Non-random inactivation of large common fragile site genes in different cancers
Authors: McAvoy S. , Ganapathiraju S.C. , Ducharme-Smith A.L. , Pritchett J.R. , Kosari F. , Perez D.S. , Zhu Y. , James C.D. , Smith D.I.
Published: November 2007

The common fragile sites are regions of profound genomic instability found in all individuals. The full size of each region of instability ranges from under one megabase (Mb) to greater than 10 Mbs. At least half of the CFS regions have been found to span extremely large genes that spanned from 600 kb to greater than 2.0 Mbs. The large CFS genes are also very interesting from a cancer perspective as several of them, including FHIT and WWOX, have already demonstrated the capacity to function as tumor suppressor genes, both in vitro and in vivo. We estimate that there may be 40–50 large genes localized in CFS regions. The expression of a number of the large CFS genes has been previously shown to be lost in many different cancers and this is frequently associated with a worse clinical outcome for patients. To determine if there was selection for the inactivation of different large CFS genes in different cancers, we examined the expression of 13 of the 20 known large CFS genes: FHIT, WWOX, PARK2, GRID2, NBEA, DLG2, RORA isoforms 1 and 4, DAB1, CNTNAP2, DMD, IL1RAPL1, IMMP2L and LARGE in breast, ovarian, endometrial and brain cancers using real-time RT-PCR analysis. Each cancer had a distinct profile of different large CFS genes that were inactivated. Interestingly, in breast, ovarian and endometrial cancers there were some cancers that had inactivation of expression of none or only one of the tested genes, while in other specimens there was inactivation of multiple tested genes. Brain cancers had inactivation of many of the tested genes, a number of which function in normal neurological development. We find that there is no relationship between the frequency that any specific CFS is expressed and the frequency that the gene from that region is inactivated in different cancers. Instead, it appears that different cancers select for the inactivation of different large CFS genes.
DNA profiling by arrayCGH in acute myeloid leukemia and myelodysplastic syndromes
Authors: Suela J. , Alvarez S. , Cigudosa J.C.
Published: November 2007

Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent two distinct but related myeloid haematological neoplasms. At diagnosis, a substantial proportion of cases show cytogenetic and molecular genetic markers whose range of specificity is highly variable. Most specific reciprocal translocations, as t(8;21)(q21;q21) or t(15;17)(q22;q21), have been extensively studied and are currently introduced in clinical diagnosis. Two other major groups remain to be better characterized at the genetic and genomic level: cases with normal karyotype and cases with complex aberrations. Comparative genomic hybridization (CGH) performed on chromosomes was the first approach taken and nearly 300 cases studied by this technique have already been reported. Array based CGH has also been applied to a smaller number of cases. Both types of genomic studies have confirmed that recurrent genomic losses and gains can almost exclusively be found in cases with complex karyotype. In most cases with normal karyotype (as well as in others with single chromosome aberrations as trisomy 8), arrayCGH has been able to unveil small DNA copy number changes whose recurrence is very low. Recently, single- nucleotide-polymorphism based arrays have been used in AML showing that loss of heterozygosity (LOH) is a common feature in normal karyotype leukemia.
Cell migration patterns and ongoing somatic mutations in the progression of follicular lymphoma
Authors: Adam P. , Schoof J. , Hartmann M. , Schwarz S. , Puppe B. , Ott M. , Rosenwald A. , Ott G. , Müller-Hermelink H.K.
Published: November 2007

Follicular lymphoma (FL) constitutes the neoplastic equivalent of germinal center B-cells. Like its physiological counterpart, FL grows in (atypical) follicular structures, the formation of which is as yet poorly understood. Recent data indicate that in early tumour stages, neoplastic FL cells home to and colonise reactive germinal centers. Laser microdissection (LMD) and micromanipulation techniques now allow for the molecular genetic analysis of single cell mutation patterns in FL. The purpose of the present study was the analysis of the sequence and order of somatic mutations in FL, i.e. the influence of the germinal center microenvironment on the clonal evolution in different grades of FL. By generating phylogenetic trees as calculated from tumour cell sequences, the clonal evolution from a putative progenitor cell was elucidated and finally, the tumour cell migration pattern in disease progression was assessed by analyzing biopsies at different time points in relapsed tumours. Four patients suffering from FL were included in the study. A primary FL grade 1 showed clustering of genetically related subclones in distinct follicles. A moderate interfollicular exchange of tumour cells was detected. Three cases of FL grade 2 were found to show decreased subclonal clustering in follicles and an increase in the interfollicular migration. Accumulations of replacement mutations in antigen binding domains (CDR) and silent mutations in non-antigen binding domains (FR), respectively, indicating antigen influence on hypermutation were only found in the case of FL grade 1. Our conclusion is that the microenvironment in germinal centers exercises influence on clonal evolution and tumour cell distribution patterns in FL. With increasing histologic grade during disease progression, a reduced intraclonal diversity and selection of subclones also occurs outside the setting of transformation to high-grade lymphoma. Antigen-dependent hypermutations were only seen in FL grade 1, while in progressed FL, random mutation patterns and a decrease of clonal diversity were found.
Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression
Authors: Nanjangud G. , Rao P.H. , Teruya-Feldstein J. , Donnelly G. , Qin J. , Mehra S. , Jhanwar S.C. , Zelenetz A.D. , Chaganti R.S.K.
Published: November 2007

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11–q21, 6q11–q15 and 1p36 (15–77%). SKY detected nine additional sites (1p11–p13, 2p11–p13, 6q21, 8q24, 6q21, 9p13, 10q22–q24, 12q11–q13 and 17q11–q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2–3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13–p21, 2q11–q21, 2q31–q37, 12q12–q15, 17q21–q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11–q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11–p13, 1p36, 1q11–q21, 8q24, 9p13, and 17q11–q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).
The Gut in Systemic Inflammatory Response Syndrome and Sepsis
Authors: Suliburk J. , Helmer K. , Moore F. , Mercer D.
Published: November 2007

The prognosis and care of critically ill ICU patients has improved over recent years, but the development of multiple organ failure (MOF) continues to cause significant morbidity and mortality. Shock, with resultant organ ischemia, appears to play a critical role in the development of MOF. It is our global hypothesis that MOF is a gut-derived phenomenon and that novel interventions can improve outcome in shock-induced gut inflammation and dysfunction in critically ill patients. We have found that the anesthetic agent ketamine has a profound impact on the response to endotoxic shock. This review summarizes our findings on the mechanisms of action by which ketamine is able to modulate the nitric oxide, cyclo-oxygenase and heme-oxygenase enzyme systems to attenuate endotoxin-induced organ dysfunction.
Severe versus Local Odontogenic Bacterial Infections: Comparison of Microbial Isolates
Authors: Al-Nawas B. , Maeurer M.
Published: November 2007

Aim: It was the aim of this study to evaluate the clinical and microbiological differences between severe and local odontogenic abscesses. Methods: Thirty patients were prospectively enrolled. Sixteen of 30 patients suffered from a severe life-threatening abscess of the head and neck, whereas 14/30 patients presented with a localized submucous abscess. Anaerobic bacteria were identified and susceptibility testing was performed using E test strips for penicillin, amoxicillin + clavulanic acid, imipenem + cilastatin, clindamycin and metronidazole. Results: The mean duration until removal of all drains was 14.1 and 3.5 days, respectively. Anaerobic bacteria were found in all episodes of local abscesses, whereas 19% of the severe episodes were culture negative, and in 13%, only aerobes were identified. A total of 60 anaerobes were isolated from 27 patients (2.2 isolates/positive sample). The dominating species were Prevotella sp. (n = 17), Peptostreptococcus sp. (n = 15) and Propionibacterium sp. (n = 5). Eighty-seven percent of the isolates were susceptible to penicillin. Ninety-seven percent of the anaerobes were susceptible to amoxicillin + clavulanic acid, imipenem + cilastatin, and clindamycin. Eighty-three percent were susceptible to metronidazol. There was a tendency for a higher rate of episodes with penicillin-resistant bacteria in the patients with severe abscesses (14 vs. 31%). No difference in susceptibility regarding amoxicillin + clavulanic acid and clindamycin (7%) was observed.
A New Modification of Dismembered Pyeloplasty for Primary Ureteropelvic Junction Obstruction
Authors: Dayanc M. , Kibar Y. , Irkilata H.C. , Gok F. , Tahmaz L. , Ors O. , Akyol I.
Published: November 2007

Aim: To present the results of a new modification of dismembered pyeloplasty performed to prevent the occurrence of secondary obstruction. Methods: Modified dismembered pyeloplasty was performed in 35 children (age range 3 months to 16 years) who had unilateral ureteropelvic junction obstruction. In postoperative follow-up, presence of hydronephrosis on ultrasonography, differential renal function (DRF) and renal drainage half-time on technetium-99m diethylenetriaminepentaacetic acid (DTPA) renography were recorded and compared with preoperative data. Results: Mean anteroposterior renal pelvic diameter, mean preoperative DRF and radioisotope clearance half-time on DTPA renography of the affected kidneys were 61.4 mm, 38.6% and 34.3 min in children with prenatal hydronephrosis, and 67.5 mm, 37.6% and 39.4 min in children that presented with symptoms, respectively. After surgery, mean anteroposterior renal pelvic diameter, mean DRF and radioisotope clearance half-time on DTPA renography of the affected kidneys were 10.9 mm, 45.9% and 11.9 min in children with prenatal hydronephrosis, and 20 mm, 41.9% and 15.2 min in children that presented with symptoms, respectively. No failure was observed in any patient at an average follow-up of 26 months (range 1–5 years). Conclusions: Open dismembered pyeloplasty is the treatment of choice for intrinsic ureteropelvic junction obstruction. The modification of dismembered pyeloplasty that we performed is an alternative for the prevention of secondary obstruction.