bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate constants rather than biochemical mechanism determine behaviour of genetic clocks
Authors: Conrad Emery , Mayo Avraham E , Ninfa Alexander J , Forger Daniel B
Published: April 2008

Many biological systems contain both positive and negative feedbacks. These are often classified as resonators or integrators. Resonators respond preferentially to oscillating signals of a particular frequency. Integrators, on the other hand, accumulate a response to signals. Computational neuroscientists often refer to neurons showing integrator properties as type I neurons and those showing resonator properties as type II neurons. Guantes & Poyatos have shown that type I or type II behaviour can be seen in genetic clocks. They argue that when negative feedback occurs through transcription regulation and post-translationally, genetic clocks act as integrators and resonators, respectively. Here we show that either behaviour can be seen with either design and in a wide range of genetic clocks. This highlights the importance of parameters rather than biochemical mechanism in determining the system behaviour.
Novel preparation of graded porous structures for medical engineering
Authors: Muthutantri Anushini , Huang Jie , Edirisinghe Mohan
Published: April 2008

The gradation of porosity in a biomaterial can be very useful for a variety of medical engineering applications such as filtration, bone replacement and implant development. However, the preparation of such structures is not a technologically trivial task and replication methods do not offer an easy solution. In this work, we elucidate the preparation of structures having a graded porosity by electrohydrodynamic spraying, using zirconia (ZrO
2
), which is widely used in biomedical and other applications. The processes are generic and can be achieved using other bioactive ceramics with similar particle characteristics. The pores on the sprayed surface, the innermost surface and lengthwise cross sections have been analysed in addition to the change in depth of penetration as a function of spraying time. Control of porosity, pore size and depth of penetration has been obtained by varying parameters such as the spraying time, sintering temperature and the sacrificial template. It has been possible to obtain structures with interconnected pore networks of pore size greater than 100 μm as well as scattered pores smaller than 10 μm in size.
Mimetic butterflies support Wallace's model of sexual dimorphism
Authors: Kunte Krushnamegh
Published: April 2008

Theoretical and empirical observations generally support Darwin's view that sexual dimorphism evolves due to sexual selection on, and deviation in, exaggerated male traits. Wallace presented a radical alternative, which is largely untested, that sexual dimorphism results from naturally selected deviation in protective female coloration. This leads to the prediction that deviation in female rather than male phenotype causes sexual dimorphism. Here I test Wallace's model of sexual dimorphism by tracing the evolutionary history of Batesian mimicry—an example of naturally selected protective coloration—on a molecular phylogeny ofPapiliobutterflies. I show that sexual dimorphism inPapiliois significantly correlated with both female-limited Batesian mimicry, where females are mimetic and males are non-mimetic, and with the deviation of female wing colour patterns from the ancestral patterns conserved in males. Thus, Wallace's model largely explains sexual dimorphism inPapilio. This finding, along with indirect support from recent studies on birds and lizards, suggests that Wallace's model may be more widely useful in explaining sexual dimorphism. These results also highlight the contribution of naturally selected female traits in driving phenotypic divergence between species, instead of merely facilitating the divergence in male sexual traits as described by Darwin's model.
The costs of risky male behaviour: sex differences in seasonal survival in a small sexually monomorphic primate
Authors: Kraus Cornelia , Eberle Manfred , Kappeler Peter M
Published: April 2008

Male excess mortality is widespread among mammals and frequently interpreted as a cost of sexually selected traits that enhance male reproductive success. Sex differences in the propensity to engage in risky behaviours are often invoked to explain the sex gap in survival. Here, we aim to isolate and quantify the survival consequences of two potentially risky male behavioural strategies in a small sexually monomorphic primate, the grey mouse lemurMicrocebus murinus: (i) most females hibernate during a large part of the austral winter, whereas most males remain active and (ii) during the brief annual mating season males roam widely in search of receptive females. Using a 10-year capture–mark–recapture dataset from a population ofM. murinusin Kirindy Forest, western Madagascar, we statistically modelled sex-specific seasonal survival probabilities. Surprisingly, we did not find any evidence for direct survival benefits of hibernation—winter survival did not differ between males and females. By contrast, during the breeding season males survived less well than females (sex gap: 16%). Consistent with the ‘risky male behaviour’ hypothesis, the period for lowered male survival was restricted to the short mating season. Thus, sex differences in survival in a promiscuous mammal can be substantial even in the absence of sexual dimorphism.
Cone visual pigments in two marsupial species: the fat-tailed dunnart (Sminthopsis crassicaudata) and the honey possum (Tarsipes rostratus)
Authors: Cowing Jill A , Arrese Catherine A , Davies Wayne L , Beazley Lyn D , Hunt David M
Published: April 2008

Uniquely for non-primate mammals, three classes of cone photoreceptors have been previously identified by microspectrophotometry in two marsupial species: the polyprotodont fat-tailed dunnart (Sminthopsis crassicaudata) and the diprotodont honey possum (Tarsipes rostratus). This report focuses on the genetic basis for these three pigments. Two cone pigments were amplified from retinal cDNA of both species and identified by phylogenetics as members of the short wavelength-sensitive 1 (SWS1) and long wavelength-sensitive (LWS) opsin classes.In vitroexpression of the two sequences from the fat-tailed dunnart confirmed the peak absorbances at 363 nm in the UV for the SWS1 pigment and 533 nm for the LWS pigment. No additional expressed cone opsin sequences that could account for the middle wavelength cones could be amplified. However, amplification from the fat-tailed dunnart genomic DNA with RH1 (rod) opsin primer pairs identified two genes with identical coding regions but sequence differences in introns 2 and 3. Uniquely therefore for a mammal, the fat-tailed dunnart has two copies of an RH1 opsin gene. This raises the possibility that the middle wavelength cones express a rod rather than a cone pigment.
Genetic variation in threshold reaction norms for alternative reproductive tactics in male Atlantic salmon,Salmo salar
Authors: Piché Jacinthe , Hutchings Jeffrey A , Blanchard Wade
Published: April 2008

Alternative reproductive tactics may be a product of adaptive phenotypic plasticity, such that discontinuous variation in life history depends on both the genotype and the environment. Phenotypes that fall below a genetically determined threshold adopt one tactic, while those exceeding the threshold adopt the alternative tactic. We report evidence of genetic variability in maturation thresholds for male Atlantic salmon (Salmo salar) that mature either as large (more than 1 kg) anadromous males or as small (10–150 g) parr. Using a common-garden experimental protocol, we find that the growth rate at which the sneaker parr phenotype is expressed differs among pure- and mixed-population crosses. Maturation thresholds of hybrids were intermediate to those of pure crosses, consistent with the hypothesis that the life-history switch points are heritable. Our work provides evidence, for a vertebrate, that thresholds for alternative reproductive tactics differ genetically among populations and can be modelled as discontinuous reaction norms for age and size at maturity.
Extreme heterochiasmy and nascent sex chromosomes in European tree frogs
Authors: Berset-Brändli Laura , Jaquiéry Julie , Broquet Thomas , Ulrich Yuko , Perrin Nicolas
Published: April 2008

We investigated sex-specific recombination rates inHyla arborea, a species with nascent sex chromosomes and male heterogamety. Twenty microsatellites were clustered into six linkage groups, all showing suppressed or very low recombination in males. Seven markers were sex linked, none of them showing any sign of recombination in males (r=0.00 versus 0.43 on average in females). This opposes classical models of sex chromosome evolution, which envision an initially small differential segment that progressively expands as structural changes accumulate on the Y chromosome. For autosomes, maps were more than 14 times longer in females than in males, which seems the highest ratio documented so far in vertebrates. These results support the pleiotropic model of Haldane and Huxley, according to which recombination is reduced in the heterogametic sex by general modifiers that affect recombination on the whole genome.
A geometric flow-based approach for diffusion tensor image segmentation
Authors: Guo Weihong , Chen Yunmei , Zeng Qingguo
Published: April 2008

Diffusion tensor magnetic resonance imaging (DT-MRI, shortened as DTI) produces, from a set of diffusion-weighted magnetic resonance images, tensor-valued images where each voxel is assigned a 3×3 symmetric, positive-definite matrix. This tensor is simply the covariance matrix of a local Gaussian process with zero mean, modelling the average motion of water molecules. We propose a three-dimensional geometric flow-based model to segment the main core of cerebral white matter fibre tracts from DTI. The segmentation is carried out with a front propagation algorithm. The front is a three-dimensional surface that evolves along its normal direction with speed that is proportional to a linear combination of two measures: a similarity measure and a consistency measure. The similarity measure computes the similarity of the diffusion tensors at a voxel and its neighbouring voxels along the normal to the front; the consistency measure is able to speed up the propagation at locations where the evolving front is more consistent with the diffusion tensor field, to remove noise effect to some extent, and thus to improve results. We validate the proposed model and compare it with some other methods using synthetic and human brain DTI data; experimental results indicate that the proposed model improves the accuracy and efficiency in segmentation.
The neuroscience of primate intellectual evolution: natural selection and passive and intentional niche construction
Authors: Iriki Atsushi , Sakura Osamu
Published: April 2008

We trained Japanese macaque monkeys to use tools, an advanced cognitive function monkeys do not exhibit in the wild, and then examined their brains for signs of modification. Following tool-use training, we observed neurophysiological, molecular genetic and morphological changes within the monkey brain. Despite being ‘artificially’ induced, these novel behaviours and neural connectivity patterns reveal overlap with those of humans. Thus, they may provide us with a novel experimental platform for studying the mechanisms of human intelligence, for revealing the evolutionary path that created these mechanisms from the ‘raw material’ of the non-human primate brain, and for deepening our understanding of what cognitive abilities are and of those that are not uniquely human. On these bases, we propose a theory of ‘intentional niche construction’ as an extension of natural selection in order to reveal the evolutionary mechanisms that forged the uniquely intelligent human brain.
Comparative proteogenomics: Combining mass spectrometry and comparative genomics to analyze multiple genomes
Authors: Gupta Nitin , Benhamida Jamal , Bhargava Vipul , Goodman Daniel , Kain Elisabeth , Kerman Ian , Nguyen Ngan , Ollikainen Noah , Rodriguez Jesse , Wang Jian , Lipton Mary S. , Romine Margaret , Bafna Vineet , Smith Richard D. , Pevzner Pavel A.
Published: April 2008

Recent proliferation of low-cost DNA sequencing techniques will soon lead to an explosive growth in the number of sequenced genomes and will turn manual annotations into a luxury. Mass spectrometry recently emerged as a valuable technique for proteogenomic annotations that improves on the state-of-the-art in predicting genes and other features. However, previous proteogenomic approaches were limited to a single genome and did not take advantage of analyzing mass spectrometry data from multiple genomes at once. We show that such a comparative proteogenomics approach (like comparative genomics) allows one to address the problems that remained beyond the reach of the traditional “single proteome” approach in mass spectrometry. In particular, we show how comparative proteogenomics addresses the notoriously difficult problem of “one-hit-wonders” in proteomics, improves on the existing gene prediction tools in genomics, and allows identification of rare post-translational modifications. We therefore argue that complementing DNA sequencing projects by comparative proteogenomics projects can be a viable approach to improve both genomic and proteomic annotations.
Valproic acid resensitizes cisplatin‐resistant ovarian cancer cells
Authors: Lin Ching‐Tai , Lai Hung‐Cheng , Lee Hsin‐Yi , Lin Wei‐Hsin , Chang Cheng‐Chang , Chu Tang‐Yuan , Lin Ya‐Wen , Lee Kuan‐Der , Yu Mu‐Hsien
Published: April 2008

Although certain inhibitors of histone deacetylases have been shown to induce cytotoxicity alone or in combination with chemotherapeutic agents in cancer cells, the molecular mechanism is not clear. The goal of the present study was to determine whether the antiseizure drug valproic acid (2‐propylpentanoic acid; VPA), which is also able to inhibit histone deacetylase, exhibits synergistic cytotoxicity with cisplatin, and the possible pathways for this. Our results clearly show that VPA not only exhibits synergistic cytotoxicity with cisplatin in all of the ovarian carcinoma cells tested, but also can resensitize the cells that have acquired resistance to cisplatin. Consistent with the increased cytotoxicity, cotreatment with VPA was shown to upregulate the cisplatin‐mediated DNA damage revealed by phosphorylation of ataxia telangiectasia mutation and histone H2AX. Reactive oxygen species accumulation and tumor suppressor phosphatase and tensin homolog (PTEN) overexpression, which could contribute to the enhanced cytotoxicity, were also observed to be upregulated by VPA. Because PTEN knockdown by small interference RNA or antioxidant treatment can reduce cisplatin‐mediated cytotoxicity, it is suggested that upregulation of PTEN and reactive oxygen species by VPA contributes to the enhancement of cisplatin‐mediated cytotoxicity. These results with resensitization of cisplatin‐resistant cells particularly may provide benefits in the treatment of ovarian cancer patients. (Cancer Sci 2008; 99: 1218–1226)
Oncogenic role of miR‐17‐92 cluster in anaplastic thyroid cancer cells
Authors: Takakura Shu , Mitsutake Norisato , Nakashima Masahiro , Namba Hiroyuki , Saenko Vladimir A. , Rogounovitch Tatiana I. , Nakazawa Yuka , Hayashi Tomayoshi , Ohtsuru Akira , Yamashita Shunichi
Published: April 2008

Micro RNAs (miRNAs) are non‐coding small RNAs and constitute a novel class of negative gene regulators that are found in both plants and animals. Several miRNAs play crucial roles in cancer cell growth. To identify miRNAs specifically deregulated in anaplastic thyroid cancer (ATC) cells, we performed a comprehensive analysis of miRNA expressions in ARO cells and primary thyrocytes using miRNA microarrays. MiRNAs in a miR‐17‐92 cluster were overexpressed in ARO cells. We confirmed the overexpression of those miRNAs by Northern blot analysis in ARO and FRO cells. In 3 of 6 clinical ATC samples, miR‐17‐3p and miR‐17‐5p were robustly overexpressed in cancer lesions compared to adjacent normal tissue. To investigate the functional role of these miRNAs in ATC cells, ARO and FRO cells were transfected with miRNA inhibitors, antisense oligonucleotides containing locked nucleic acids. Suppression of miR‐17‐3p caused complete growth arrest, presumably due to caspase activation resulting in apoptosis. MiR‐17‐5p or miR‐19a inhibitor also induced strong growth reduction, but only miR‐17‐5p inhibitor led to cellular senescence. On the other hand, miR‐18a inhibitor only moderately attenuated the cell growth. Thus, we have clarified functional differences among the members of the cluster in ATC cells. In conclusion, these findings suggest that the miR‐17‐92 cluster plays an important role in certain types of ATCs and could be a novel target for ATC treatment. (Cancer Sci 2008; 99: 1147–1154)
Phase 1 trial of denosumab safety, pharmacokinetics, and pharmacodynamics in Japanese women with breast cancer–related bone metastases
Authors: Yonemori Kan , Fujiwara Yasuhiro , Minami Hironobu , Kitagawa Koichi , Fujii Hirofumi , Arai Tatsuhiro , Sohn Winnie , Ohkura Masayuki , Ohtsu Tomoko
Published: April 2008

Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor–kappa B ligand (RANKL), suppresses bone resorption. This open‐label, multicenter, phase 1 study evaluated the safety, pharmacodynamics, and pharmacokinetics of denosumab in Japanese women with breast cancer–related bone metastases. Patients (n = 18; median age, 57 years) received a single subcutaneous injection of denosumab 60 mg or 180 mg or three doses of denosumab 180 mg on days 1, 29, and 57 (every 4 weeks) and were followed for ≥ 141 days. No major safety concerns related to denosumab were noted in any cohort. All patients experienced at least 1 adverse event (AE); most were mild (grade ≤ 2). One patient reported grade 4 myositis and grade 3 anemia, malaise, and dysphagia that the investigator deemed treatment‐related; other treatment‐related AE were grade ≤ 2. No antidenosumab antibodies or clinically significant changes in laboratory findings, vital signs, or electrocardiograms were observed. Pharmacokinetics were approximately dose‐linear. Denosumab caused rapid, substantial, and sustained suppression of urinary N‐telopeptide corrected for creatinine (uNTx/Cr) across all doses; at day 85, the median change from baseline uNTx/Cr ranged from –61.9% to –90.8%. No dose‐limiting toxicity was observed at any dosage. Coupled with pharmacokinetic and pharmacodynamic data, these results were consistent with those observed in non‐Japanese populations. (Cancer Sci 2008; 99: 1237–1242)
Risk of metachronous squamous cell carcinoma in the upper aerodigestive tract of Japanese alcoholic men with esophageal squamous cell carcinoma: a long‐term endoscopic follow‐up study
Authors: Yokoyama Akira , Omori Tai , Yokoyama Tetsuji , Sato Yasuo , Kawakubo Hirofumi , Maruyama Katsuya
Published: April 2008

East Asian case–control studies have shown a strong relationship between alcohol consumption combined with inactive heterozygous aldehyde dehydrogenase‐2 (ALDH2*1/*2) and the development of squamous cell carcinoma (SCC), especially multiple SCC, of the upper aerodigestive tract (UADT). This study aimed to identify determinants of the development of metachronous SCC in the UADT in alcoholics with esophageal SCC. Follow‐up endoscopic examinations were carried out 4–160 months (median, 41 months) after initial diagnosis in 110 Japanese alcoholic men with esophageal SCC diagnosed by screening using endoscopy combined with oropharyngolaryngeal inspection and esophageal iodine staining. ALDH2*1/*2 was significantly associated with the presence of multiple primary intraesophageal SCC at the time of initial diagnosis. Metachronous primary SCC of the esophagus was diagnosed in 29 of the 81 patients whose initial esophageal SCC was treated by endoscopic mucosal resection alone, and metachronous primary SCC of the oropharyngolarynx was diagnosed in 23 of the 99 patients without synchronous primary SCC of the oropharyngolarynx at the time of initial diagnosis. The risks of metachronous esophageal SCC and oropharyngolaryngeal SCC were significantly higher in ALDH2*1/*2 heterozygotes than in ALDH2*1/*1 homozygotes (age‐adjusted and alcohol‐adjusted hazard ratio = 3.38 [95% confidence interval: 1.45–7.85] and 4.27 [1.42–12.89], respectively), and in patients with multiple intraesophageal SCC at the time of initial diagnosis than in patients with a solitary intraesophageal SCC (3.09 [1.41–6.78] and 3.25 [1.41–7.47], respectively). ALDH2*1/*2 and multiple synchronous intraesophageal SCC were found to be predictors of metachronous SCC in the UADT in this population. (Cancer Sci 2008; 99: 1164–1171)
Suicide gene/prodrug therapy using salmonella‐mediated delivery of Escherichia coli purine nucleoside phosphorylase gene and 6‐methoxypurine 2′‐deoxyriboside in murine mammary carcinoma 4T1 model
Authors: Fu Wei , Lan Hekui , Liang Shenghua , Gao Tong , Ren Daming
Published: April 2008

Attenuated salmonella have been reported to be capable of both selectively growing in tumors and expressing exogenous genes for tumor‐targeted therapy. As 6‐methoxypurine 2′‐deoxyriboside (MoPdR) is similar to 6‐methylpurine 2′‐deoxyriboside in structure, we aimed to evaluate the antitumoral effect of the Escherichia coli purine nucleoside phosphorylase (ePNP) gene, using an attenuated salmonella‐mediated delivery system, in combination with MoPdR. A novel mutant serovar Typhimurium (SC36) was used to carry the pEGFP‐C1‐ePNP vector that contains an enhanced green fluorescent protein and an ePNP gene under the control of the cytomegalovirus promoter. The function of the ePNP expression vector was confirmed in vitro using the enzymic conversion of MoPdR into methoxypurine. We also observed a high bystander effect induced by the ePNP/MoPdR system with a very low proportion (1%) of ePNP‐positive cells and 5 µg/mL MoPdR, although the growth of parental cells was affected appreciably by MoPdR. The killing effect and increased apoptosis induced by SC36 carrying the ePNP expression vector (SC/ePNP) were detected by cytotoxicity assay and propidium iodide staining flow cytometry analysis, in combination with MoPdR. SC/ePNP was given orally to mice bearing mammary carcinomas, and its antitumor effect was evaluated. SC/ePNP plus MoPdR significantly inhibited tumor growth by approximately 86.6–88.7% and prolonged the survival of tumor‐hosting mice. Our data support the view that MoPdR combined with the ePNP gene could be used in gene‐directed enzyme prodrug therapy. Attenuated salmonella could be a promising strategy to improve ePNP/MoPdR bystander killing due to its preferential accumulation and anticancer activity in tumors. (Cancer Sci 2008; 99: 1172–1179)
Resveratrol induces apoptosis in K562 (chronic myelogenous leukemia) cells by targeting a key survival protein, heat shock protein 70
Authors: Chakraborty Prabir K. , Mustafi Soumyajit Banerjee , Ganguly Sudipto , Chatterjee Mitali , Raha Sanghamitra
Published: April 2008

Chronic myelogenous leukemia (CML) is a myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia chromosome. This results in the expression of the Bcr‐Abl fusion protein, a constitutively active protein tyrosine kinase. Although there are a few treatment options with Bcr‐Abl kinase inhibitors, drug resistance is often encountered. One of the major obstacles in overcoming drug resistance in CML is the high endogenous levels of heat shock protein 70 (Hsp70). Resveratrol is a phytoalexin produced by several plants. We studied the chemotherapeutic effects and mode of action of resveratrol on K562 (CML) cells. Resveratrol induced apoptosis in K562 cells in a time‐dependent manner. This was established by increased annexin V binding, corroborated with an enhanced caspase‐3 activity and a rise in the sub‐G0/G1 population. Resveratrol treatment also caused suppression of Hsp70 both in mRNA and protein levels. The downregulation of Hsp70 by resveratrol exposure was correlated with a diminished presence of heat shock factor 1 (HSF1) in the nucleus, and the downregulation of transcriptional activity of HSF1. High endogenous levels of Hsp70 have been found to be a deterrent for sensitivity to chemotherapy. We show here that resveratrol could considerably enhance the apoptosis induction in K562 cells by 17‐allylamino‐17‐demethoxygeldanamycin, an anticancer agent that inhibits Hsp90 but augments Hsp70 levels. We conclude that resveratrol significantly downregulated Hsp70 levels through inhibition of HSF1 transcriptional activity and appreciably augmented the pro‐apoptotic effects of 17‐allylamino‐17‐demethoxygeldanamycin. (Cancer Sci 2008; 99: 1109–1116)
Activity of a novel Aurora kinase inhibitor against the T315I mutant form of BCR‐ABL: In vitro and in vivo studies
Authors: Akahane Daigo , Tauchi Tetsuzo , Okabe Seiichi , Nunoda Kousuke , Ohyashiki Kazuma
Published: April 2008

Despite promising results from clinical studies of ABL kinase inhibitors, a challenging problem that remains is the T315I mutation against which neither nilotinib nor dasatinib show significant activity. In the present study, we investigated the activity of a novel Aurora kinase inhibitor, VE‐465, against leukemia cells expressing wild‐type BCR‐ABL or the T315I mutant form of BCR‐ABL. We observed a dose‐dependent reduction in the level of BCR‐ABL autophosphorylation in VE‐465‐treated cells. Exposure to the combination of VE‐465 and imatinib exerted an enhanced apoptotic effect in K562 cells. Combined treatment with VE‐465 and imatinib caused more attenuation of the levels of phospho‐AKT and c‐Myc in K562 cells. Further, the isobologram indicated the synergistic effect of simultaneous exposure to VE‐465 and imatinib in K562 cells. To assess the in vivo efficacy of VE‐465, athymic nude mice were injected intravenously with BaF3 cells expressing wild‐type BCR‐ABL or the T315I mutant form. The vehicle‐treated mice died of a condition resembling acute leukemia by 28 days; however, nearly all mice treated with VE‐465 (75 mg/kg, twice daily; intraperitoneally for 14 days) survived for more than 56 days. Histopathological analysis of vehicle‐treated mice revealed infiltration of the spleen. In contrast, histopathological analysis of organs from VE‐465‐treated mice demonstrated normal tissue architecture. Taken together, the present study shows that VE‐465 exhibits a desirable therapeutic index that can reduce the in vivo growth of T315I mutant form and wild‐type BCR‐ABL‐expressing cells in an efficacious manner. (Cancer Sci 2008; 99: 1251–1257)
Soy consumption reduces the risk of non‐small‐cell lung cancers with epidermal growth factor receptor mutations among Japanese
Authors: Matsuo Keitaro , Hiraki Akio , Ito Hidemi , Kosaka Takayuki , Suzuki Takeshi , Hirose Kaoru , Wakai Kenji , Yatabe Yasushi , Mitsudomi Tetsuya , Tajima Kazuo
Published: April 2008

Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non‐small‐cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case‐control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild‐type) and 1765 age‐sex matched non‐cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild‐type NSCLCs, with multivariate‐adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50–1.27) and 0.56 (0.34–0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis. (Cancer Sci 2008; 99: 1202–1208)
Do ridge–ridge–fault triple junctions exist on Earth? Evidence from the Aden–Owen–Carlsberg junction in the NW Indian Ocean
Authors: Fournier M. , Petit C. , Chamot‐Rooke N. , Fabbri O. , Huchon P. , Maillot B. , Lepvrier C.
Published: April 2008

The triple junctions predicted to be ridge–ridge–fault (RRF) types on the basis of large‐scale plate motions are the Azores triple junction between the Gloria Fault and the Mid‐Atlantic Ridge, the Juan Fernandez triple junction between the Chile Transform and the East Pacific Rise and the Aden–Owen–Carlsberg (AOC) triple junction between the Owen fracture zone (OFZ) and the Carlsberg and Sheba ridges. In the first two cases, the expected RRF triple junction does not exist because the transform fault arm of the triple junction has evolved into a divergent boundary before connecting to the ridges. Here, we report the results of a marine geophysical survey of the AOC triple junction, which took place in 2006 aboard theR/V Beautemps‐Beaupré. We show that a rift basin currently forms at the southern end of the OFZ, indicating that a divergent plate boundary between Arabia and India is developing at the triple junction. The connection of this boundary with the Carlsberg and Sheba ridges is not clearly delineated and the triple junction presently corresponds to a widespread zone of distributed deformation. The AOC triple junction appears to be in a transient stage between a former triple junction of the ridge–fault–fault type and a future triple junction of the ridge–ridge–ridge (RRR) type. Consequently, the known three examples of potential RRF triple junctions are actually of the RRR type, and RRF triple junctions do not presently exist on Earth.
The association of adiponectin allele 45T/G and −11377C/G polymorphisms with Type 2 diabetes and rosiglitazone response in Chinese patients
Authors: Sun Hong , Gong Zhi‐Cheng , Yin Ji‐Ye , Liu Hai‐Ling , Liu Ying‐Zi , Guo Zhi‐Wei , Zhou Hong‐Hao , Wu Jing , Liu Zhao‐Qian
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients.

• The role of genetic factors that determine the marked interindividual variability in glucose‐lowering efficacy of rosiglitazone in Chinese patients is not known.

• The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and −11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D).

WHAT THIS STUDY ADDS

• The genetic polymorphisms of adiponectin alleles 45T/G and −11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment.

AIMS The aim of the present study was to evaluate the impact of adiponectin allele T45G and C‐11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).

METHODS Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and –11377C/G genotypes by polymerase chain reaction‐restriction fragment length polymorphism assay. Forty‐two T2D patients with different 45T/G or –11377C/G genotypes received orally rosiglitazone as a single‐dose therapy (4 mg day‐1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA‐IR), low‐density lipoprotein‐cholesterol, high‐density lipoprotein‐cholesterol (HDL‐c) and adiponectin concentration were determined before and after rosiglitazone treatment.

RESULTS We showed an attenuated rosiglitazone effect in patients with –11377CG+GG heterozygote genotype on FPG, PPG, HOMA‐IR compared with –11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with –11377CC homozygote genotype compared with –11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with –11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment.

CONCLUSIONS These data suggest that the adiponectin allele 45T/G and –11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple‐dose rosiglitazone in Chinese patients with T2D.
Use of erythropoiesis stimulating agents and intravenous iron for cancer and treatment‐related anaemia: the need for predictors and indicators of effectiveness has not abated
Authors: Katodritou Eirini , Zervas Konstantinos , Terpos Evangelos , Brugnara Carlo
Published: April 2008

Cancer and treatment‐related anaemia is a significant clinical problem. Erythropoiesis stimulating agents (ESA) improve anaemia and ultimately enhance patients’ quality of life. However, about one‐third of patients do not respond to ESA administration, mostly because of the impaired supply of iron to the erythroid marrow (functional iron deficiency). Concomitant administration of intravenous (IV) iron may improve responsiveness. The use of baseline predictors of response to ESA and of indicators of appropriateness of response and iron availability should allow targeted therapeutic interventions with both ESA and IV iron. Several biochemical and haematological indicators of response and of iron balance have been studied, but firm criteria for their use have not yet been rigorously established. The commonly used early predictive markers of response to ESA, such as baseline endogenous erythropoietin levels and an increase in haemoglobin, reticulocytes, and soluble transferrin receptor levels during ESA treatment, have not proved reliable due to their low sensitivity and specificity. Traditional markers of iron availability, such as serum ferritin and transferrin saturation display interpretation pitfalls. The need for predictors and indicators of responsiveness to ESA and IV iron is still current and clinically relevant.
Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation
Authors: Tichelli André , Bhatia Smita , Socié Gérard
Published: April 2008

Haematopoietic stem cell transplantation (HCT) is the treatment of choice for defined malignant and non‐malignant haematological disorders. The main drawbacks of HCT are early transplant‐related mortality and late complications, which interfere with patient outcome, health status and quality of life. In comparison with other post‐transplant complications, cardiac or cardiovascular consequences seem to occur at a much lower frequency. Early complications are usually associated with patient history before transplantation, primary diagnosis, age of the patient and associated comorbidities, and the type of transplantation and conditioning used. Late cardiac and cardiovascular events may occur years and even decades after HCT, and are related to cardiotoxic chemotherapy, mediastinal radiation therapy, gender, age at transplantation, cardiovascular risk factors and graft‐versus‐host disease in allogeneic HCT. As has been observed in long‐term survivors of Hodgkin lymphoma, where the incidence of cardiovascular complications emerged as a significant problem with increasing follow‐up, it is anticipated that the incidence of these complications after HCT will also increase significantly with increasing follow‐up of the survivors. This review presents the available data on early and late cardiac and cardiovascular consequences after HCT, and presents recommendations for cardiac assessment and management of these complications.
Response of native parasitoids to a range‐expanding host
Authors: CHRIS GRÖBLER B. , LEWIS OWEN T.
Published: April 2008

Abstract1. As species shift their geographic distributions, new feeding interactions with natural enemies such as parasitoids, and resources such as host plants, may be established, and existing interactions may be severed.

2. The leaf mining mothPhyllonorycter leucographella(Zeller, 1850) (Lep.: Gracillariidae) first colonised the southern United Kingdom in the mid 1980s associated with its ancestral host plantPyracantha coccineaM. Roem. (Rosaceae), which is widely cultivated in the U.K. The moth has since spread northwards to central Scotland and has been recorded feeding on a novel host plant,Crataegus monogynaL.

3. The combined effects of latitude and time since colonisation on parasitoid community responses to the arrival of this novel host were investigated across its U.K. range. The response of parasitoids to colonisation ofC. monogynawas also investigated.

4. Both the observed richness of parasitoid species associated withP. leucographella, and the proportion ofP. leucographellaparasitised declined with latitude and towards the current range margin. A combination of a latitudinal gradient in parasitoid and alternative host species richness is likely to lead to the trends in species richness and parasitism observed.

5. Experimental host patches exposed to parasitism beyond the current range margin ofP. leucographellaexperienced low levels of parasitism consistent with range‐margin populations, indicating an instantaneous response by native parasitoids to availability of the novel host. Parasitism levels and numbers of associated species in the U.K. were similar to those observed in the species’ native range in Turkey.

6. The host plant switch toC. monogynawas not associated with an altered parasitoid assemblage, but rates of parasitism were significantly higher on the novel host plant.

7. Alterations in the incidence and frequency of victim‐enemy interactions as species shift their geographic ranges may be key in determining rates of range expansion and the impact invading species have on ecological communities.
A plant surface mutation mediates predator interference among ladybird larvae
Authors: RUTLEDGE CLAIRE E. , EIGENBRODE SANFORD D. , DING HONGJIAN
Published: April 2008

Abstract 1. We investigated mechanisms causing predator–predator interference between fourth instar Hippodamia convergens larvae foraging for pea aphids on pea plants, Pisum sativum, with a wild‐type wax bloom, and the lack of such interference between larvae foraging on pea plants with a reduced‐wax bloom caused by the single gene mutation wel.

2. Observations showed that behavioural interactions between larvae were not affected by wax phenotype. Specifically, larvae did not encounter one another more frequently on normal‐wax peas as may have been predicted because reduced ability by coccinellids to attach to normal‐wax plant surfaces could restrict them to foraging on only some parts of these plants.

3. In a controlled bioassay on normal‐wax peas, H. convergens larvae avoided leaflets previously exposed to another larva. On reduced‐wax peas, this effect was not detected.

4. In microcosm experiments, inter‐predator interference in terms of prey consumption occurred on normal‐wax peas, but not on reduced‐wax peas. The interference on normal‐wax peas occurred whether two H. convergens larvae were placed on a pea aphid‐infested, normal‐wax plant simultaneously or sequentially.

5. We conclude that the observed inter‐predator interference is not as a result of direct physical contact, but rather arises because of (i) inhibition of foraging by chemical trails left by other larvae, (ii) the inability of larvae to access portions of the normal‐wax plants creating aphid refugia, or (iii) a combination of these factors.
Tendances nouvelles dans la protection des plantes
Authors: Biliotti E.
Published: April 2008

Sommaire

La situation d'après‐guerre, où la lutte chimique plutǒt préventive semblait pouvoir assurer une protection adéquate des cultures, s'est modifiée lorsque les effets secondaires des traitements ont porté préjudice à leur rentabilité et que s'est posé le problème des résidus. Une nouvelle tendance, qui se fonde sur une détermination préalable de la nécessité des interventions, fait appel aux notions de lutte intégrée, qui associent les diverses possibilités de lutte biologique (introduction de parasites ou prédateurs, élevage et lâchers d'auxiliaires, lutte génétique, emploi d'attractifs) à d'autres procédés (sélection des plantes en vue de leur résistance, mesures culturales). Une étroite coopération entre chercheurs actifs dans ces différents domaines est préconisée.
New Tendencies in Plant Protection
Authors: Biliotti E.
Published: April 2008

Concern about pesticide residues and the unprofitability of classical treatments through secondary complications has led to a new approach to plant protection problems. Applications must be based on the assessment of their necessity and full account must be taken of the advantages offered by various possibilities of biological control (introduction of parasites or predators, their mass‐breeding, genetical control, use of attractants) and other procedures (breeding for resistance, cultural measures). Close co‐operation between the various sectors of research involved is recommended.
The Present Status of Hormonal Insect Control
Authors: Wilde J. de
Published: April 2008

Since hormones are agents which can basically change insect development they offer excellent possibilities in the field of pest control (minor risks for human health and for the environment; no problems of insect resistance). However, they must be considered in conjunction with other methods. Three groups are concerned: the ecdysones, the juvenile hormone and its analogues, and the brain hormone. The characteristics, mode of action, selectivity, toxicity and economical aspects of these compounds are being described.
Situation actuelle de la lutte contre les insectes au moyen d'hormones
Authors: de Wilde J.
Published: April 2008

Sommaire

Les hormones susceptibles de dérégler le développement des insectes ouvrent des possibilités de lutte alléchantes (faibles risques pour la santé humaine et pour l'environnement, aucun problème de résistance) mais doivent être considérées conjointement avec d'autres méthodes. Il s'agit de trois groupes: les ecdysons, l'hormone juvénile et l'hormone cérébrale, dont les caractéristiques, le mode d'action, la sélectivité, la toxicité et les aspects économiques sont successivement examinés.
Plant Protection with and without Risks
Authors: Steiner H.
Published: April 2008

Conventional plant protection procedures and integrated control are being compared in the light of their profitability. Control measures must be based on the density of pest populations. The fluctuations concerned can be usefully reproduced by means of a mathematic pendulum oscillating over a logarithmical scale of the densities. The model shows that better crop yields can be obtained through a reduced application of chemicals. Moreover, the expenditure incurred in integrated control is less and risks of failure are also lower.
Protection des végétaux avec et sans risques
Authors: Steiner H.
Published: April 2008

Summaire

La protection des végétaux dans sa forme classique est comparée à la lutte intégrée sous l'angle de la rentabilité. La lutte doit être fondée sur la densité de population des ravageurs dont les fluctuations sont bien reflétées par un pendule mathématique qui oscille sur une échelle logarithmique. A l'aide de ce modèle il est démontré que l'emploi réduit de produits chimiques assure de meilleures récoltes. En outre, la lutte intégrée est d'un prix de revient moins élevé et elle compotte moins de risques d'échec.
The Actual Status of Crop Loss Assessment
Authors: Strickland A.H.
Published: April 2008

The history of loss assessment over the past 100 years is indicated, and the three principles: detection, measurement, and evaluation, are discussed. Economic and political pressures now demand objective justification for widely used methods of loss control, and the trend is towards a clear indication of the opportunities for gain which occur when harmful organisms are efficiently controlled. New emphasis is being given to predicting the need for controls. Accurate loss assessments are expensive in terms of money and trained staff, and the most important single factor in efficient investment is an unambiguous statement of aims so that full advantage can be taken of the economies offered by modern methods.
Ouverture
Authors: Maan W.J.
Published: April 2008

Summaire

Les traitements ULV présentent l'avantage de couvrir une plus grande surface par unité de temps, ce qui permet d'améliorer la rentabilité des applications aériennes. En dehors d'autres aspects avantageux, ils ont cependant l'inconvénient d'augmenter les risques de dérive des produits utilisés. C'est d'ailleurs pour cette raison que le diamètre des gouttelettes est de l'ordre de 100 microns et que les composés chimiques spécialement formulés sont appliqués de préférence à l'aube ou en début de soirée. Les risques de phytotoxicité sont à considérer avec soin et il faut s'attendre à une persistance accrue du produit et à une meilleure pénétration des cultures.
Opening Address
Authors: Maan W.J.
Published: April 2008

ULV treatments can cover bigger surfaces per time unit, thus providing an improved economic basis for aerial applications. Moreover, they have several secondary advantages. Their main operational restriction is in the increased risk of drift. Droplets of some 100 microns are therefore used and treatments are carried out at dawn or towards the evening. Special formulation of the chemicals is necessary. Risks of phytotoxicity must always be considered but the effect of ULV treatments can be more persistent and they can assure a better penetration of the crop.
Low Volume and Ultra‐low Volume Application of Pesticides in Yugoslavia
Authors: Topalovic G.
Published: April 2008

For the Agricultural Aviation Section of the Yugoslav Air Company JAT, economic considerations have been the main reason for introducing low volume and ultra‐low volume pesticide applications into practice. Their planes have been fitted with « micronair » and « turbair » rotary equipment. The ULV techniques have been developed recently and will be applied as of 1970 in agriculture (sugar beet noctuids, Bothynoderes [Cleonus] punctiventris Germ., aphids, Eurygaster, Lema), in forests (Lymantria, etc.) and in mosquito control. LV applications of fungicides mainly concern vineyards (downy mildew), sugar beets (Cercospora) and arboriculture.
Normal and Low Volume Spraying Methods in Italy
Authors: Picece P. , Pucci E.
Published: April 2008

In Italy, conventional spraying techniques are still commonly used in the South, the Centre as well as in several northern regions. Applications at semi‐low volume (1,800–2,000 1./ha.) mainly on fruit trees and tobacco represent 10 to 20% of the total. Ground equipment is seldom used with low and ultra‐low applications whereas the surface covered by aerial treatments is rapidly increasing reaching now 70,000 ha. per annum.
Pulvérisations classiques et pulvérisations à volume réduit en Italle
Authors: Picece P. , Pucci E.
Published: April 2008

Summaire

Les méthodes classiques de pulvérisation sont encore couramment employées dans le sud et le centre du pays ainsi que dans certaines régions septentrionales. Les traitements à semi‐bas volume (1.800 à 2.000 1/ha), surtout sur arbres fruitiers et tabac, représentent 10 à 20% du total. En ce qui concerne les applications à bas et ultra‐bas volume, les appareils terrestres sont rarement employés mais la superficie traitée par avion ou hélicoptère est en rapide augmentation et concerne maintenant 70.000 ha par an.