bluuebunny/crossref_metadata_2025 huggingface dataset:
A genetic analysis of group movement in an isolated population of tree-roosting bats
Authors: Metheny Jackie D , Kalcounis-Rueppell Matina C , Bondo Kristin J , Brigham R. Mark
Published: June 2008

Group fission is an important dispersal mechanism for philopatric adults. In Cypress Hills Interprovincial Park, Saskatchewan, tree-roosting big brown bats (
Eptesicus fuscus
) exhibit fission–fusion roosting behaviour. During 2004–2007, the majority of females previously resident to roosting area 1 (RA1) moved to a new roosting area (RA4). We examined how genetic relationships, inferred from data for microsatellite loci and mitochondrial DNA, influenced new roost area (RA) selection during 2006 when colony members were split between the RAs. We found that females who moved to RA4 had higher average relatedness than those that remained in RA1. We found that nearly all females belonging to matrilines with high average relatedness moved to RA4 while females from matrilines with low average relatedness were split between the two RAs. These results suggest that closely related maternal kin preferentially move to new RAs. However, daily roosting preferences within a RA are not based on genetic relationships probably because daily roosting associations between kin and non-kin are used to ensure adequate roost group size. Studying the effects of kinship on the fission and movements of groups not only enhances our understanding of social behaviour and population genetics but also informs conservation decisions.
Genes and causation
Authors: Noble Denis
Published: June 2008

Relating genotypes to phenotypes is problematic not only owing to the extreme complexity of the interactions between genes, proteins and high-level physiological functions but also because the paradigms for genetic causality in biological systems are seriously confused. This paper examines some of the misconceptions, starting with the changing definitions of a gene, from the cause of phenotype characters to the stretches of DNA. I then assess whether the ‘digital’ nature of DNA sequences guarantees primacy in causation compared to non-DNA inheritance, whether it is meaningful or useful to refer to genetic programs, and the role of high-level (downward) causation. The metaphors that served us well during the molecular biological phase of recent decades have limited or even misleading impacts in the multilevel world of systems biology. New paradigms are needed if we are to succeed in unravelling multifactorial genetic causation at higher levels of physiological function and so to explain the phenomena that genetics was originally about. Because it can solve the ‘genetic differential effect problem’, modelling of biological function has an essential role to play in unravelling genetic causation.
Knowledge environments representing molecular entities for the virtual physiological human
Authors: Hofmann-Apitius Martin , Fluck Juliane , Furlong Laura , Fornes Oriol , Kolářik Corinna , Hanser Susanne , Boeker Martin , Schulz Stefan , Sanz Ferran , Klinger Roman , Mevissen Theo , Gattermayer Tobias , Oliva Baldo , Friedrich Christoph M
Published: June 2008

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH. Our strategy to generate knowledge environments representing molecular entities is based on the combination of information extraction from scientific text and the integration of information from biomolecular databases. We introduce @neuLink, a first prototype of an automatically generated, disease-specific knowledge environment combining biomolecular, chemical, genetic and medical information. Finally, we provide a perspective for the future implementation and use of knowledge environments representing molecular entities for the VPH.
Genomic analysis of the immune gene repertoire of amphioxus reveals extraordinary innate complexity and diversity
Authors: Huang Shengfeng , Yuan Shaochun , Guo Lei , Yu Yanhong , Li Jun , Wu Tao , Liu Tong , Yang Manyi , Wu Kui , Liu Huiling , Ge Jin , Yu Yingcai , Huang Huiqing , Dong Meiling , Yu Cuiling , Chen Shangwu , Xu Anlong
Published: June 2008

It has been speculated that before vertebrates evolved somatic diversity-based adaptive immunity, the germline-encoded diversity of innate immunity may have been more developed. Amphioxus occupies the basal position of the chordate phylum and hence is an important reference to the evolution of vertebrate immunity. Here we report the first comprehensive genomic survey of the immune gene repertoire of the amphioxus Branchiostoma floridae. It has been reported that the purple sea urchin has a vastly expanded innate receptor repertoire not previously seen in other species, which includes 222 toll-like receptors (TLRs), 203 NOD/NALP-like receptors (NLRs), and 218 scavenger receptors (SRs). We discovered that the amphioxus genome contains comparable expansion with 71 TLR gene models, 118 NLR models, and 270 SR models. Amphioxus also expands other receptor-like families, including 1215 C-type lectin models, 240 LRR and IGcam-containing models, 1363 other LRR-containing models, 75 C1q-like models, 98 ficolin-like models, and hundreds of models containing complement-related domains. The expansion is not restricted to receptors but is likely to extend to intermediate signal transducers because there are 58 TIR adapter-like models, 36 TRAF models, 44 initiator caspase models, and 541 death-fold domain-containing models in the genome. Amphioxus also has a sophisticated TNF system and a complicated complement system not previously seen in other invertebrates. Besides the increase of gene number, domain combinations of immune proteins are also increased. Altogether, this survey suggests that the amphioxus, a species without vertebrate-type adaptive immunity, holds extraordinary innate complexity and diversity.
The amphioxus genome illuminates vertebrate origins and cephalochordate biology
Authors: Holland Linda Z. , Albalat Ricard , Azumi Kaoru , Benito-Gutiérrez Èlia , Blow Matthew J. , Bronner-Fraser Marianne , Brunet Frederic , Butts Thomas , Candiani Simona , Dishaw Larry J. , Ferrier David E.K. , Garcia-Fernàndez Jordi , Gibson-Brown Jeremy J. , Gissi Carmela , Godzik Adam , Hallböök Finn , Hirose Dan , Hosomichi Kazuyoshi , Ikuta Tetsuro , Inoko Hidetoshi , Kasahara Masanori , Kasamatsu Jun , Kawashima Takeshi , Kimura Ayuko , Kobayashi Masaaki , Kozmik Zbynek , Kubokawa Kaoru , Laudet Vincent , Litman Gary W. , McHardy Alice C. , Meulemans Daniel , Nonaka Masaru , Olinski Robert P. , Pancer Zeev , Pennacchio Len A. , Pestarino Mario , Rast Jonathan P. , Rigoutsos Isidore , Robinson-Rechavi Marc , Roch Graeme , Saiga Hidetoshi , Sasakura Yasunori , Satake Masanobu , Satou Yutaka , Schubert Michael , Sherwood Nancy , Shiina Takashi , Takatori Naohito , Tello Javier , Vopalensky Pavel , Wada Shuichi , Xu Anlong , Ye Yuzhen , Yoshida Keita , Yoshizaki Fumiko , Yu Jr-Kai , Zhang Qing , Zmasek Christian M. , de Jong Pieter J. , Osoegawa Kazutoyo , Putnam Nicholas H. , Rokhsar Daniel S. , Satoh Noriyuki , Holland Peter W.H.
Published: June 2008

Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates—a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.
Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily
Authors: Ohnishi Satoshi , Tochio Naoya , Tomizawa Tadashi , Akasaka Ryogo , Harada Takushi , Seki Eiko , Sato Manami , Watanabe Satoru , Fujikura Yukiko , Koshiba Seizo , Terada Takaho , Shirouzu Mikako , Tanaka Akiko , Kigawa Takanori , Yokoyama Shigeyuki
Published: June 2008

The second WW domain in mammalian Salvador protein (SAV1 WW2) is quite atypical, as it forms a β‐clam‐like homodimer. The second WW domain in human MAGI1 (membrane associated guanylate kinase, WW and PDZ domain containing 1) (MAGI1 WW2) shares high sequence similarity with SAV1 WW2, suggesting comparable dimerization. However, an analytical ultracentrifugation study revealed that MAGI1 WW2 (Leu355–Pro390) chiefly exists as a monomer at low protein concentrations, with an association constant of 1.3 × 102 M−1. We determined its solution structure, and a structural comparison with the dimeric SAV1 WW2 suggested that an Asp residue is crucial for the inhibition of the dimerization. The substitution of this acidic residue with Ser resulted in the dimerization of MAGI1 WW2. The spin‐relaxation data suggested that the MAGI1 WW2 undergoes a dynamic process of transient dimerization that is limited by the charge repulsion. Additionally, we characterized a longer construct of this WW domain with a C‐terminal extension (Leu355–Glu401), as the formation of an extra α‐helix was predicted. An NMR structural determination confirmed the formation of an α‐helix in the extended C‐terminal region, which appears to be independent from the dimerization regulation. A thermal denaturation study revealed that the dimerized MAGI1 WW2 with the Asp‐to‐Ser mutation gained apparent stability in a protein concentration‐dependent manner. A structural comparison between the two constructs with different lengths suggested that the formation of the C‐terminal α‐helix stabilized the global fold by facilitating contacts between the N‐terminal linker region and the main body of the WW domain.
Habitat shifts of endangered species under altered climate conditions: importance of biotic interactions
Authors: PRESTON KRISTINE L. , ROTENBERRY JOHN T. , REDAK RICHARD A. , ALLEN MICHAEL F.
Published: June 2008

Predicting changes in potential habitat for endangered species as a result of global warming requires considering more than future climate conditions; it is also necessary to evaluate biotic associations. Most distribution models predicting species responses to climate change include climate variables and occasionally topographic and edaphic parameters, rarely are biotic interactions included. Here, we incorporate biotic interactions into niche models to predict suitable habitat for species under altered climates. We constructed and evaluated niche models for an endangered butterfly and a threatened bird species, both are habitat specialists restricted to semiarid shrublands of southern California. To incorporate their dependency on shrubs, we first developed climate‐based niche models for shrubland vegetation and individual shrub species. We also developed models for the butterfly's larval host plants. Outputs from these models were included in the environmental variable dataset used to create butterfly and bird niche models. For both animal species, abiotic–biotic models outperformed the climate‐only model, with climate‐only models over‐predicting suitable habitat under current climate conditions. We used the climate‐only and abiotic–biotic models to calculate amounts of suitable habitat under altered climates and to evaluate species' sensitivities to climate change. We varied temperature (+0.6, +1.7, and +2.8 °C) and precipitation (50%, 90%, 100%, 110%, and 150%) relative to current climate averages and within ranges predicted by global climate change models. Suitable habitat for each species was reduced at all levels of temperature increase. Both species were sensitive to precipitation changes, particularly increases. Under altered climates, including biotic variables reduced habitat by 68–100% relative to the climate‐only model. To design reserve systems conserving sensitive species under global warming, it is important to consider biotic interactions, particularly for habitat specialists and species with strong dependencies on other species.
Small round blue cell tumours: diagnostic and prognostic usefulness of the expression of B7‐H3 surface molecule
Authors: Gregorio A , Corrias M V , Castriconi R , Dondero A , Mosconi M , Gambini C , Moretta A , Moretta L , Bottino C
Published: June 2008

Aims:  To assess whether the expression of B7‐H3 surface molecule could improve differential diagnosis of small cell round tumours.

Methods and results:  One hundred and one well‐characterized paraffin‐embedded small round cell tumours, stored in the pathology archive of the Gaslini Institute, were immunohistochemically analysed with the 5B14 monoclonal antibody, which recognizes the surface molecule B7‐H3. All lymphoblastic lymphomas and the blastematous component of Wilms’ tumours were completely negative and a few Ewing’s sarcoma and Burkitt’s lymphoma specimens showed focal positivity, whereas 74% of neuroblastomas, 67% of rhabdomyosarcomas and 100% of medulloblastomas were positive. The pattern of immunoreactivity of 5B14 mAb observed in rhabdomyosarcoma, neuroblastoma and medulloblastoma specimens was limited to the cytoplasmic membrane, and in neuroblastomas areas of rosette formation or of ganglion differentiation were preferentially stained. Interestingly, in neuroblastoma patients high expression of the antigen recognized by the 5B14 mAb was associated with a worse event‐free survival.

Conclusions:  The 5B14 mAb represents an additional tool for the differential diagnosis of small round cell tumours and might be useful in identifying neuroblastoma patients at risk of relapse who may take advantage of more careful follow‐up.
The expression of P‐glycoprotein is increased in vessels with blood‐brain barrier impairment in a stroke‐prone hypertensive model
Authors: Ueno M. , Nakagawa T. , Huang C.‐l. , Ueki M. , Kusaka T. , Hosomi N. , Kanenishi K. , Onodera M. , Wu B. , Sakamoto H.
Published: June 2008

Aims: We previously reported that the blood‐brain barrier (BBB) function was impaired in vessels in the hippocampus in 3‐month‐old stroke‐prone spontaneously hypertensive rats (SHRSP). In this study, we examined gene and protein expressions of P‐glycoprotein, a representative efflux transporter of cerebral vessels, in the BBB‐damaged hippocampal vessels of SHRSP and in the vessels of Wistar Kyoto (WKY) rats as controls, to clarify roles of the efflux transporter in the BBB‐damaged vessels. Methods: The expression of P‐glycoprotein in hippocampal and cortical samples was examined by real‐time quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR), Western blotting and immunoelectron microscopic techniques. Results: Real‐time RT‐PCR and Western blotting analyses revealed that the gene and protein expressions of P‐glycoprotein were increased in the hippocampal samples of 3‐month‐old SHRSP compared with hippocampal samples of 3‐month‐old WKY rats or with cortical samples of SHRSP. The gene expression of P‐glycoprotein was also increased in the hippocampal samples of 4‐week‐old SHRSP. Immunoelectron microscopic examination revealed that immunosignals of P‐glycoprotein were seen in the luminal and ab‐luminal cytoplasmic membranes of endothelial cells and the basal lamina, that the labelling density of P‐glycoprotein in the vessel wall was higher in the hippocampus of 3‐month‐old SHRSP than in other groups and that the immunosignals of P‐glycoprotein were occasionally co‐located with those of albumin. Conclusions: These findings indicate that the expression of P‐glycoprotein is increased in BBB‐damaged hippocampal vessels in hypertensive SHRSP compared with those in WKY rats.
Elevated Levels of MMP‐9 and TIMP‐1 in the Cerebrospinal Fluid of Children with Echovirus Type 30 and Mumps Meningitis
Authors: Sulik A. , Wojtkowska M. , Oldak E.
Published: June 2008

Matrix metalloproteinases are involved in leucocyte invasion into the central nervous system (CNS) during meningitis. The aim of the study was to determine whether there are differences in the expression patterns of matrix metalloproteinase‐9 (MMP‐9) and the tissue inhibitor of metalloproteinase‐1 (TIMP‐1) in the cerebrospinal fluid (CSF) of patients with meningitis caused by one of two known distinct viral agents. Concentrations were measured by using an enzyme‐linked immunosorbent assay (ELISA) in 16 children with mumps meningitis, in 25 children with echovirus type 30 meningitis and in a control group of 23 children without any CNS infection. Increased levels of MMP‐9 were found in children with mumps (median 0.48 ng/ml; P < 0.001) and enteroviral meningitis (median 2.76 ng/ml; P < 0.001) compared with that in controls (median: 0.01 ng/ml). Concentrations of TIMP‐1 greatly exceeded concentrations of MMP‐9 and were elevated in children with mumps (median: 56 ng/ml) and echovirus type 30 meningitis (median: 55 ng/ml) compared to controls (median: 17 ng/ml). No significant differences in MMP‐9 or TIMP‐1 levels were detected between the two meningitis groups. The MMP‐9/TIMP‐1 ratio was greater in children with echovirus type 30 than in those with mumps meningitis. There was no correlation between MMP‐9 levels and total CSF cell count. MMP‐9 correlated with CSF absolute neutrophil count in children with echovirus type 30 meningitis (r = 0.431; P < 0.05). The concentration of MMP‐9 is higher in children with viral meningitis, possibly because of infiltrating polymorphonuclear cells present in the initial phase of the disease.
Seasonal rhythms of seed rain and seedling emergence in two tropical rain forests in southern Brazil
Authors: Marques M. C. M. , Oliveira P. E. A. M.
Published: June 2008

Seasonal tropical forests show rhythms in reproductive activities due to water stress during dry seasons. If both seed dispersal and seed germination occur in the best environmental conditions, mortality will be minimised and forest regeneration will occur. To evaluate whether non‐seasonal forests also show rhythms, for 2 years we studied the seed rain and seedling emergence in two sandy coastal forests (flooded and unflooded) in southern Brazil. In each forest, one 100 × 30‐m grid was marked and inside it 30 stations comprising two seed traps (0.5 × 0.5 m each) and one plot (2 × 2 m) were established for monthly monitoring of seed rain and a seedling emergence study, respectively. Despite differences in soil moisture and incident light on the understorey, flooded and unflooded forests had similar dispersal and germination patterns. Seed rain was seasonal and bimodal (peaks at the end of the wetter season and in the less wet season) and seedling emergence was seasonal and unimodal (peaking in the wetter season). Approximately 57% of the total species number had seedling emergence 4 or more months after dispersal. Therefore, both seed dormancy and the timing of seed dispersal drive the rhythm of seedling emergence in these forests. The peak in germination occurs in the wetter season, when soil fertility is higher and other phenological events also occur. The strong seasonality in these plant communities, even in this weakly seasonal climate, suggests that factors such as daylength, plant sensitivity to small changes in the environment (e.g. water and nutrient availability) or phylogenetic constraints cause seasonal rhythms in the plants.
EXACERBATION BY NICOTINE OF THE CYCLOSPORINE A‐INDUCED IMPAIRMENT OF β‐ADRENOCEPTOR‐MEDIATED RENAL VASODILATION IN RATS
Authors: El‐Gowilly Sahar M , Ghazal Abdel‐Rheem M , Gohar Eman Y , El‐Mas Mahmoud M
Published: June 2008

Nicotine is implicated in smoking‐related renovascular impairment and worsening of existing nephropathies. In the present study, we investigated whether nicotine aggravates the deleterious effect of the immunosuppressant drug cyclosporine A (CsA) on renal vasodilation induced by the β‐adrenoceptor agonist isoprenaline.

Bolus isoprenaline (0.03–8.0 µmol) elicited dose‐dependent vasodilation of phenylephrine‐preconstricted perfused kidneys that was attenuated by infusion at 5 mL/min of nicotine (5 × 10−4 mol/L) or CsA (2 µmol/L). Further, chronic administration of nicotine (0.4 mg/kg per day) or CsA (20 mg/kg per day) for 3 weeks reduced isoprenaline‐induced vasodilation and elevated plasma urea and creatinine concentrations, effects that were magnified when both nicotine and CsA were administered concurrently.

The role of endothelial and smooth muscle signalling in the acute nicotine/CsA renovascular interaction was investigated. Vasodilation caused by 0.25 µmol isoprenaline was attenuated by 6 µmol/L propranolol and 10 mmol/L tetraethylammonium (TEA), potentiated by 100 µmol/L hexamethonium and 7 µmol/L diclophenac, and virtually abolished in 80 mmol/L KCl‐preconstricted tissues.NG‐Nitro‐l‐arginine (l‐NNA; 200 µmol/L), methylene blue (10 µmol/L), 3‐[(3‐cholamidopropyl)‐dimethyl‐ammonio]‐1‐propane‐sulphonate (CHAPS; 0.2% for 30 s), nifedipine (750 nmol/L), atropine (1 µmol/L) and SQ22536 (an adenylyl cyclase inhibitor; 3 × 10−5 mol/L) had no effect on isoprenaline responses.

Nicotine (5 × 10−4 mol/L) reduced isoprenaline‐induced vasodilation and this effect was potentiated by concurrent CsA (2 µmol/L) infusion. Nicotine‐induced impairment of the vasodilator response to isoprenaline was reduced by hexamethonium and potentiated byl‐NNA, methylene blue, CHAPS and nifedipine. Alternatively, CsA exacerbation of the nicotine–isoprenaline interaction was abolished by propranolol,l‐NNA, methylene blue, CHAPS,l‐arginine, TEA and nifedipine.

In summary, nicotine and CsA produce additive impairment of kidney function and β‐adrenoceptor‐mediated renovascular control, nitric oxide (NO)–cGMP signalling tonically restrains nicotine‐induced impairment of isoprenaline vasodilation and the endothelial NO–K+pathway modulates the aggravating effect of CsA on nicotine–isoprenaline interactions.
MORPHINE DEPENDENCE PROTECTS RAT KIDNEY AGAINST ISCHAEMIA–REPERFUSION INJURY
Authors: Habibey Rouhollah , Pazoki‐Toroudi Hamidreza
Published: June 2008

Ischaemic preconditioning (IPC) protects the heart and kidneys against ischaemia–reperfusion (I/R) injury. It has been shown that opioid receptor activation can mimic cardiac IPC. In a kidney model of I/R, a single dose of morphine failed to mimic IPC. The aim of the present study was to determine the role of chronic morphine (dependence) in protection against renal I/R injury.

Male Wistar rats were treated with increasing doses of morphine (20–30 mg/kg per day, s.c., for 5 days) to develop morphine dependence (MD). Three weeks before the I/R procedure, the right kidney was removed. Ischaemia–reperfusion injury was induced by clamping the left renal artery for 45 min, followed by 24 h reperfusion. Some MD rats were pretreated with naloxone (5 mg/kg, s.c.). Twenty‐four hours later, creatinine and sodium concentrations were measured in serum and urine, then creatinine clearance (CCr) and the fractional excretion of sodium (FENa) were calculated. Blood urea nitrogen (BUN) was measured only in serum samples. Kidneys were also assessed histologically for evidence of tissue injury.

In the present study, MD decreased tissue injury (histological score), serum creatinine and BUN levels, increased CCr and decreased FENa after I/R. Pretreatment with naloxone attenuated the protective effects of MD. Morphine dependence did not have any significant effect on urine volume.

In conclusion, it seems that morphine dependence protects the kidney against I/R injury via opioid receptor‐dependent pathways. Further studies are required to clearly determine the mechanisms involved.
MODULATORY EFFECT OF NARINGENIN ONN‐METHYL‐N′‐NITRO‐N‐NITROSOGUANIDINE‐ AND SATURATED SODIUM CHLORIDE‐INDUCED GASTRIC CARCINOGENESIS IN MALE WISTAR RATS
Authors: Ganapathy Ekambaram , Peramaiyan Rajendran , Rajasekaran Devaraja , Venkataraman Magesh , Dhanapal Sakthisekaran
Published: June 2008

Naringenin is a flavanone that is believed to have many biological actions, including as an anti‐oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced byN‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) and saturated sodium chloride (S‐NaCl) in rats.

Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S‐NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks.

In Group II rats in which gastric cancer was inducted with MNNG and S‐NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6‐phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochromeb5and NADPH cytochromecreductase, with concomitant decreases in the activity of the phase II enzymes glutathione S‐transferase and UDP‐glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels.

These results indicate that naringenin has a chemopreventive action against MNNG‐induced gastric carcinoma in experimental rats.
EFFECT OF THIGH CUFFS ON HAEMODYNAMIC CHANGES OF THE MIDDLE CEREBRAL ARTERY AND ON ORTHOSTATIC INTOLERANCE INDUCED BY 10 DAYS HEAD‐DOWN BED REST
Authors: Yao Yong‐Jie , Jiang Shi‐Zhong , Jiang Chang‐Lin , Sun Xi‐Qing , Cao Xin‐Sheng , Yang Chang‐Bin
Published: June 2008

Thigh cuffs are used by cosmonauts to limit fluid shift during space flight, but the appropriate level of cuff pressure and the duration of application to optimize their beneficial effects require further detailed investigations.

In the present study, 10 days head‐down tilt (HDT) bed rest was performed to assess the effects of thigh cuffs (40 mmHg, 10 h/day) on haemodynamic changes of the middle cerebral artery (MCA) and on orthostatic tolerance in six healthy male volunteers. Another six healthy male volunteers without thigh cuffs served as the control group. Haemodynamic parameters of the MCA were measured using transcranial Doppler. Orthostatic tolerance was assessed before and after HDT.

After HDT, the mean upright time in the control and thigh cuff groups was 14.0 ± 4.1 and 19.2 ± 0.7 min, respectively. Compared with values before HDT, the percentage increase in heart rate from baseline in the upright position after HDT was significantly higher in the control group and the percentage change from baseline of mean diastolic arterial blood decreased more after HDT in this group. In the control group, systolic blood velocity (Vs) and mean blood velocity (Vm) of the right MCA decreased significantly during HDT. In the thigh cuffs group, the Vs of the right MCA decreased significantly on Days 3 and 7 of HDT and the Vm of the right MCA decreased significantly on Day 7 of HDT.

The results indicate that daily use of thigh cuffs during 10 days of HDT does not completely prevent the decrease in haemodynamics of the right MCA, but is effective in preventing orthostatic intolerance.
Intravascular haemolysis in a patient on ceftriaxone with demonstration of anticeftriaxone antibodies
Authors: Dinesh D. , Dugan N. , Carter J.
Published: June 2008

Drug‐induced haemolytic anaemia can be life threatening. We report a case of ceftriaxone‐induced severe haemolytic anaemia in a previously healthy 68‐year‐old woman. The patient had a positive direct antiglobulin test (anti‐C3d positive, anti‐immunoglobulin G negative). Serological tests showed ceftriaxone‐specific antibodies. The patient recovered after cessation of the drug. This complication may cause milder anaemia and thus be poorly recognized.
Cardiovascular testing in Fabry disease: exercise capacity reduction, chronotropic incompetence and improved anaerobic threshold after enzyme replacement
Authors: Lobo T. , Morgan J. , Bjorksten A. , Nicholls K. , Grigg L. , Centra E. , Becker G.
Published: June 2008

Aim:  The aim of this study was to document exercise capacity and serial electrocardiogram and echocardiograph findings in a cohort of Australian patients with Fabry disease, in relation to their history of enzyme replacement therapy (ERT).

Background:  Fabry disease has multifactorial effects on the cardiovascular system. Most previous studies have focused on electrocardiographic and echocardiographic parameters. Exercise capacity can be used as an integrated measure of cardiovascular function and allows the effects of treatment to be monitored.

Methods:  A total of 38 patients (30 men and 8 women) with Fabry disease were monitored by 12‐lead electrocardiograms every 6–12 months, and by annual standardized‐protocol echocardiograms. Bicycle stress tests with VO2 max measurement and once‐only 6 minutes’ walk tests were also carried out in subsets of patients whose general health status allowed testing.

Results:  Seventy per cent of patients met electrocardiogram criteria for left ventricular hypertrophy. Left ventricular hypertrophy on echocardiograph was present in 64% of patients (80% of men). Exercise capacity was reduced in patients with Fabry disease compared with that predicted from normative population data. Mild improvement in anaerobic threshold was seen in the first year of ERT (14.1 ± 3.0 to 15.8 ± 3.0, P = 0.02), but no consistent further increase was seen beyond the first year. Most patients had resting bradycardia, with impaired ability to increase heart rate during exercise. Serial testing on ERT showed an improvement in anaerobic threshold but no significant change in VO2 max.

Conclusions:  Male patients with Fabry disease were unable to attain predicted maximal heart rate on exercise or to achieve normal exercise levels. ERT was associated with a small improvement in anaerobic threshold over the first year.
Thulium laser resection via a flexible cystoscope for recurrent non‐muscle‐invasive bladder cancer: initial clinical experience
Authors: Gao Xu , Ren Shancheng , Xu Chuanliang , Sun Yinghao
Published: June 2008

OBJECTIVE

To present our initial experience of thulium laser resection via a flexible cystoscope for recurrent non‐muscle‐invasive bladder cancer (ThuRBT), as transurethral resection for bladder tumour (TURBT) is regarded as the reference standard for treating this disease, but alternative laser resection or ablation is suitable especially for recurrent tumours.

PATIENTS AND METHODS

From January 2005 to October 2005, 32 patients with early recurrent bladder tumour (recurrent within a year after TURBT) were treated with ThuRBT via a flexible cystoscope. The follow‐up included urine analysis, ultrasonography and cystoscopy every 3 months.

RESULTS

All patients were treated successfully with ThuRBT in one session, with no bladder haemorrhage, obturator nerve reflex or vesicle perforation. Randomized biopsies taken after surgery on and adjacent to the resection surface revealed no residual tumours. The mean (range) tumour diameter was 1.5 (0.5–3) cm and the mean operative duration was 25 (15–35) min. During the first year of follow‐up, local and heterotopic recurrences were found in three and six patients, respectively. The accumulated recurrence rates at 3, 6 and 12 months were 9%, 22% and 28%, respectively.

CONCLUSIONS

ThuRBT is a reliable therapy with minimal morbidity and invasiveness for selected patients with bladder cancer.
Genistein combined polysaccharide enhances activity of docetaxel, bicalutamide and Src kinase inhibition in androgen‐dependent and independent prostate cancer cell lines
Authors: Burich Rebekah A. , Holland William S. , Vinall Ruth L. , Tepper Clifford , DeVere White Ralph W. , Mack Philip C.
Published: June 2008

OBJECTIVE

To determine the benefit of genistein combined polysaccharide (GCP) in combination with the androgen receptor antagonist bicalutamide, the antimicrotubule taxane docetaxel, and the Src kinase inhibitor pp2 as part of a treatment regimen for advanced prostate cancer (CaP).

MATERIALS AND METHODS

The growth inhibitory and apoptotic effects of GCP in combination with bicalutamide, docetaxel and pp2 were evaluated in both the androgen‐dependent LNCaP line, and three androgen‐independent lines: CWR22Rv1, PC‐3, and LNCaP‐R273H. The LNCaP‐R273H model is an LNCaP variant expressing a p53GOF allele; like CWR22Rv1 and PC‐3, it is able to grow in a minimal androgen environment. The effects of GCP treatment in combination with the aforementioned drugs were measured using an MTT assay, Western blotting, flow cytometric analysis, and caspase activation assay. Altered schedules of drug administration were explored using combinations of GCP and docetaxel.

RESULTS

GCP potentiated the activity of docetaxel in all four cell lines, resulting in growth inhibition and increased apoptosis. The combination of GCP and bicalutamide had enhanced activity in both the LNCaP and LNCaP‐R273H lines, which may better represent patient tumour cells after progression to androgen independence. Administration of docetaxel followed by GCP resulted in a synergistic interaction in LNCaP cells, with increased apoptosis. By contrast, GCP administered first showed subadditivity, probably resulting from GCP‐mediated induction of G1 arrest interfering with docetaxel activity.

CONCLUSION

These data suggest that GCP, an isoflavone‐enriched compound with minimal side‐effects and far superior intestinal absorption rate of genistein, has significant clinical potential in combination with docetaxel, bicalutamide or targeted agents for the treatment of advanced CaP.
Concomitant pathology in the prostate in cystoprostatectomy specimens: a prospective study and review
Authors: Saad Mohamed , Abdel‐Rahim Mona , Abol‐Enein Hassan , Ghoneim Mohammed A.
Published: June 2008

OBJECTIVES

To investigate possible associated pathology in the prostate removed from patients with invasive bladder cancer and determine if there is a justification for prostate‐sparing cystectomy.

PATIENTS AND METHODS

Between March 2005 and July 2007, 425 men (mean age 59 years, sd 8.23) had a cystoprostatectomy at our institute. The prostate was step sectioned at 2–3 mm intervals and any associated pathology determined; patient and tumour characteristics were correlated with prostatic pathology. The results were compared with those published previously, and the potential functional advantages of prostate sparing are reviewed and discussed.

RESULTS

Prostatic adenocarcinoma was detected in 90 of the 425 (21.2%) patients. There was no significant correlation between preoperative prostate‐specific antigen level and the presence of adenocarcinoma, Gleason score or prostatic tumour stage. There was prostatic involvement as a result of direct invasion by the primary bladder tumour (contiguous) in 39 cases (9.2%). Concomitant (non‐contiguous) transitional cell carcinoma of the prostatic urethra and/or ducts was detected in 27 specimens (6.4%). Additional findings were high‐grade prostatic intraepithelial neoplasia in 43 patients (10.1%) and benign prostatic hyperplasia in 175 (41.2%).

CONCLUSION

We think that the potential oncological risks of prostate‐sparing cystectomy outweigh any small and possible functional benefits; accordingly, the prostate should not be retained.
Lingua francaorlingua frankensteinia? English in European integration and globalisation1
Authors: PHILLIPSON ROBERT
Published: June 2008

ABSTRACT: The paper explores how we think of English and ‘English Studies’ in present‐day Europe. It questions the apparent neutrality of the termlingua francaby suggesting a more differentiated set of terms. It relates the current consolidation and expansion of English to processes of global Americanisation and Europeanisation. The European Union (EU) member states are increasingly integrating their economies and cultures in a US‐dominated world. The history and many divergent uses of the termlingua francaare explored, and related to discourses and policies that tend to reinforce English linguistic hegemony uncritically. The paper explores the policies of the EU for maintaining multilingualism, and contemporary constraints and pressures in European academia. It analyses the promotion of ‘global’ English in terms of the project, the product, and the processes, and considers criteria for assessing whether its advance is as alingua francaor rather as alingua frankensteinia.
Effect of levetiracetam on the postmastectomy pain syndrome
Authors: Vilholm O. J. , Cold S. , Rasmussen L. , Sindrup S. H.
Published: June 2008

Background and purpose:  The aim of this randomized, double‐blind, placebo‐controlled, cross‐over study was to test whether levetiracetam relieves the postmastectomy pain syndrome (PMPS).

Methods:  Postmastectomy pain syndrome was defined as pain of neuropathic character located in the area of the surgery and/or the ipsilateral arm. The inclusion criteria were: age more than 18 years, characteristic symptoms corresponding to PMPS more than 6 months after surgery for breast cancer, pain duration more than 3 months, peripheral nerve lesions confirmed by abnormal neurological and quantitative sensory tests, intensity of pain more than 4 on a numeric rating scale from 0 to 10 and pain present at least 4 days a week.

Results:  Forty‐nine patients were screened for participation and 27 patients were included in the study. Twenty‐five patients completed two treatment phases of 4 weeks duration with levetiracetam (3000 mg/day) and placebo. There was no difference in the rating of pain relief between treatment with levetiracetam (P = 0.83) and placebo nor when adjusted for possible period effect (P = 0.60). Analysis defining response as pain relief more than 4 on an eleven‐point numeric rating scale showed no significant difference between treatment with levetiracetam and placebo (P = 1.00).

Conclusions:  Levetiracetam apparently does not relieve peripheral neuropathic pain in PMPS.
After Bananas: The IMF and the Politics of Stabilisation and Diversification in Dominica
Authors: PAYNE ANTHONY
Published: June 2008

Dominica was the quintessential banana island but now faces a major turning point in its history caused by the changing position of this crop within the global political economy. As the decline of its banana industry generated a major economic crisis, it was forced in 2002 to make a desperate turn towards the International Monetary Fund (IMF). It has remained under IMF supervision ever since, but has at last begun to chart the bases of a post‐banana development strategy under the leadership of Roosevelt Skerrit, projected into the leadership of his country at an early age by the death of his predecessor but since re‐elected to office in May 2005.
Afro‐Cuban Religion, Ethnobotany and Healthcare in the Context of Global Political and Economic Change
Authors: MORET ERICA
Published: June 2008

‘Globalisation’, driven by neoliberal‐based policies, can be seen to have significant impacts on ethnobotanical practices, particularly through the commercialisation of traditional knowledge and rise in identity‐based social movements. Despite its relative political and economic isolation in comparison to more ‘neoliberalised’ areas of Latin America, local‐level shifts occurring in post‐Soviet Cuba are similar to those occurring elsewhere in the region. Afro‐Cuban ritual activities have proliferated, particularly in Havana, leading to an increased dependence on the rich magico‐medicinal pharmacopoeias employed in hybridised religions such as santería and palo monte – suggesting that ‘globalisation’ may have profound, albeit indirect, implications for even the most economically marginalised countries such as Cuba.
Synapse‐specific changes in serotonin signalling contribute to age‐related changes in the feeding behaviour of the pond snail, Lymnaea
Authors: Yeoman Mark S. , Patel Bhavik A. , Arundell Martin , Parker Kim , O’Hare Danny
Published: June 2008

This study utilised the pond snail, Lymnaea to examine the contribution that alterations in serotonergic signalling make to age‐related changes in feeding. Age‐related decreases in 5‐HIAA levels in feeding ganglia were positively correlated with a decrease in the number of sucrose‐evoked bites and negatively correlated with an increase in inter‐bite interval, implicating alterations in serotonergic signalling in the aged phenotype. Analysis of the serotonergic cerebral giant cell (CGC) input to the protraction motor neurone (B1) demonstrated that fluoxetine (10–100 nM) increased the amplitude/duration of the evoked EPSP in both young and middle aged but not in old neurones, suggesting an age‐related attenuation of the serotonin transporter. 5‐HT evoked a concentration‐dependent increase in the amplitude/duration of B1 EPSP, which was greater in old neurones compared to both young and middle aged. Conversely, the 5‐HT‐evoked depolarisation and conditional bursting of the swallow motor neurone (B4) were attenuated in old neurones, functions critical for a full feeding rhythm. The CGCs’ ability to excite B1 was blocked by cinanserin but not by methysergide. Conversely, the CGC to B4 connection was completely blocked by methysergide and only partially by cinanserin suggesting that age‐related changes may be receptor‐specific. In summary, synapse‐specific attenuation of the CGC‐B4 connection and enhancement of the CGC‐B1 connection would slow the swallow phase and maintain protraction, consistent with behavioural observations.
Sympathetic histamine exerts different pre‐ and post‐synaptic functions according to the frequencies of nerve stimulation in guinea pig vas deferens
Authors: He Gonghao , Hu Jing , Ma Xue , Li Mingkai , Wang Hui , Meng Jingru , Jia Min , Luo Xiaoxing
Published: June 2008

Histamine (HA) was found to be present in the sympathetic nerve terminals of guinea pig hearts and vasa deferentia in our previous study; however, little is known about the functions of this neurogenic HA. In this study, we used guinea pig vasa deferentia to investigate the pre‐ and post‐synaptic functions of HA evoked by different frequencies of sympathetic nerve stimulation. We found that sympathetic nerve stimulation could evoke HA release, which was independent to mast cell degranulator compound 48/80 and mast cell stabilizer cromolyn, but was highly sensitive to Na+channel blocker tetrodotoxin and chemical sympathectomy with 6‐hydroxydopamine. The neurogenically released HA evoked by 12.5 Hz of nerve stimulation activated only pre‐synaptic H3receptors and mediated pre‐synaptic inhibitory effects, while under 25 or 50 Hz stimulation condition, HA simultaneously activated both pre‐synaptic H3receptors and post‐synaptic H1receptors. However, the direct contractile responses evoked by sympathetic HA via H1receptors were observed at 50 Hz. HA release and HA‐mediated contractile responses upon sympathetic nerve stimulation were significantly inhibited by pre‐treatment of histidine decarboxylase inhibitor α‐fluoromethylhistidine. Furthermore, application of exogenous HA could mimic these pre‐ and post‐synaptic effects. Our findings indicate that HA in sympathetic neurons acts as a neurotransmitter and its functions vary from pre‐synaptic inhibition, to post‐synaptic facilitation, to direct post‐synaptic contractile responses according to sympathetic nerve stimulation frequencies.
Ultrahigh‐pressure garnet peridotites from the devolatilization of sea‐floor hydrated ultramafic rocks
Authors: YANG J‐J. , POWELL R.
Published: June 2008

Garnet peridotites occur in quartzofeldspathic gneisses in the Northern Qaidam Mountains, western China. They are rich in Mg and Cr, with mineral compositions similar to those in mantle peridotites found in other orogenic belts and as xenoliths in kimberlite. Garnet‐bearing lherzolites interlayered with dunite display oriented ilmenite and chromite lamellae in olivine and pyroxene lamellae in garnet that have been interpreted to indicate pressures in excess of 6 GPa. However, some garnet porphyroblasts include hornblende, chlorite and spinel + orthopyroxene symplectite after garnet; some clinopyroxene porphyroblasts include abundant actinolite/edenite, calcite and lizardite in the lherzolite; some olivine porphyroblasts (Fo92) include an earlier generation Mg‐rich olivine (Fo95–99), F‐rich clinohumite, pyroxene, chromite, anthophyllite/cummingtonite, Cl‐rich lizardite, carbonates and a new type of brittle mica, here termed ‘Ca‐phlogopite’, in the associated dunite. The pyrope content of garnet increases from core to rim, reaching the pyrope content (72 mol.%) of garnet typically found in the xenoliths in kimberlite. The simplest interpretation of these observations is that the rock association was formerly mantle peridotite emplaced into the oceanic crust that was subjected to serpentinization by seawater‐derived fluids near the sea floor. Dehydration during subduction to 3.0–3.5 GPa and 700 °C transformed these serpentinites into garnet lherzolite and dunite, depending on their Al and Ca contents. Pseudosection modelling usingthermocalcshows that dehydration of the serpentinites is progressive, and involved three stages for Al‐rich and two stages for Al‐poor serpentinites, corresponding to the breakdown of the key hydrous minerals. Static burial and exhumation make olivine a pressure vessel for the pre‐subduction mineral inclusions during ultrahigh‐pressure (UHP) metamorphism. The time span of the UHP event is constrained by the clear interface between the two generations of olivine to be very short, implying rapid subduction and exhumation.
Marginal Hazards Regression for Retrospective Studies within Cohort with Possibly Correlated Failure Time Data
Authors: Kang Sangwook , Cai Jianwen
Published: June 2008

Summary A retrospective dental study was conducted to evaluate the degree to which pulpal involvement affects tooth survival. Due to the clustering of teeth, the survival times within each subject could be correlated and thus the conventional method for the case–control studies cannot be directly applied. In this article, we propose a marginal model approach for this type of correlated case–control within cohort data. Weighted estimating equations are proposed for the estimation of the regression parameters. Different types of weights are also considered for improving the efficiency. Asymptotic properties of the proposed estimators are investigated and their finite sample properties are assessed via simulations studies. The proposed method is applied to the aforementioned dental study.