bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual selection and its effect on the fixation of an asexual clone
Authors: Salathé Marcel
Published: September 2006

Sexual selection is a powerful and ubiquitous force in sexual populations. It has recently been argued that sexual selection can eliminate the twofold cost of sex even with low genomic mutation rates. By means of differential male mating success, deleterious mutations in males become more deleterious than in females, and it has been shown that sexual selection can drastically reduce the mutational load in a sexual population, with or without any form of epistasis. However, any mechanism that claims to maintain sexual reproduction must be able to prevent the fixation of an asexual mutant clone with a twofold fitness advantage. Here, I show that despite very strong sexual selection, the fixation of an asexual mutant cannot be prevented under reasonable genomic mutation rates. Sexual selection can have a strong effect on the average mutational load in a sexual population, but as it cannot prevent the fixation of an asexual mutant, it is unlikely to play a key role on the maintenance of sexual reproduction.
Selectivity of harvesting differs between local and foreign roe deer hunters: trophy stalkers have the first shot at the right place
Authors: Mysterud Atle , Tryjanowski Piotr , Panek Marek
Published: September 2006

Harvesting represents a major source of mortality in many deer populations. The extent to which harvesting is selective for specific traits is important in order to understand contemporary evolutionary processes. In addition, since such data are frequently used in life-history studies, it is important to know the pattern of selectivity as a source of bias. Recently, it was demonstrated that different hunting methods were selected for different weights in red deer (
Cervus elaphus
), but little insight was offered into why this occurs. In this study, we show that foreign trophy stalkers select for larger antlers when hunting roe deer (
Capreolus capreolus
) than local hunters, but that close to half of the difference in selectivity was due to foreigners hunting earlier in the season and in locations with larger males. The relationship between antler size and age was nevertheless fairly similar based on whether deer was shot by foreign or local hunters.
Modelling the checkpoint response to telomere uncapping in budding yeast
Authors: Proctor C.J , Lydall D.A , Boys R.J , Gillespie C.S , Shanley D.P , Wilkinson D.J , Kirkwood T.B.L
Published: September 2006

One of the DNA damage-response mechanisms in budding yeast is temporary cell-cycle arrest while DNA repair takes place. The DNA damage response requires the coordinated interaction between DNA repair and checkpoint pathways. Telomeres of budding yeast are capped by the Cdc13 complex. In the temperature-sensitive
cdc13-1
strain, telomeres are unprotected over a specific temperature range leading to activation of the DNA damage response and subsequently cell-cycle arrest. Inactivation of
cdc13-1
results in the generation of long regions of single-stranded DNA (ssDNA) and is affected by the activity of various checkpoint proteins and nucleases.

This paper describes a mathematical model of how uncapped telomeres in budding yeast initiate the checkpoint pathway leading to cell-cycle arrest. The model was encoded in the Systems Biology Markup Language (SBML) and simulated using the stochastic simulation system Biology of Ageing e-Science Integration and Simulation (BASIS). Each simulation follows the time course of one mother cell keeping track of the number of cell divisions, the level of activity of each of the checkpoint proteins, the activity of nucleases and the amount of ssDNA generated. The model can be used to carry out a variety of
in silico
experiments in which different genes are knocked out and the results of simulation are compared to experimental data. Possible extensions to the model are also discussed.
On the motion of two particles translating with equal velocities through a colloidal dispersion
Authors: Khair Aditya S , Brady John F
Published: September 2006

We study the motion of two colloidal (‘probe’) particles translating along their line of centres with fixed, equal velocities in an otherwise quiescent colloidal dispersion. The moving probes drive the microstructure of the dispersion out of equilibrium; resisting this is the Brownian diffusion of the dispersion ‘bath’ particles. As a result of the microstructural deformation, the dispersion exerts an entropic, or thermal, force on the probes. The non-equilibrium microstructure and entropic forces are computed to first order in the volume fraction of bath particles, as a function of the probe separation (

d

) and the Péclet number (
Pe
), neglecting hydrodynamic interactions. Here,
Pe
is the dimensionless velocity of the probes, which sets the degree of microstructural distortion. For
Pe
≪1—the linear-response regime—the microstructural deformation is proportional to
Pe
. In this limit, for sufficiently large

d

, the deformation is nearly fore-aft symmetric about each probe; consequently, the entropic forces on them (which are opposite the direction of motion) are almost equal. However, for sufficiently small

d

, the symmetry is broken and, rather unexpectedly, the entropic force on the trailing probe is now in the direction of motion, whereas the force on the leading probe remains opposite to the direction of motion. Away from equilibrium,
Pe
>1 (and for all

d

), the leading probe acts as a ‘bulldozer’, accumulating bath particles in a thin boundary layer on its upstream side, while leaving a wake of bath-particle free suspending fluid downstream, in which the trailing probe travels. In this (nonlinear) regime, the entropic forces are once more both opposite the direction of motion; however, the force on the leading probe is greater (in magnitude) than that on the trailing probe. Finally, far from equilibrium (
Pe
≫1), the entropic force on the trailing probe vanishes, whereas the force on the leading probe approaches a limiting value, equal to that for a single probe moving through the dispersion.
Periodical cicadas use light for oviposition site selection
Authors: Yang Louie H
Published: September 2006

Organisms use incomplete information from local experience to assess the suitability of potential habitat sites over a wide range of spatial and temporal scales. Although ecologists have long recognized the importance of spatial scales in habitat selection, few studies have investigated the temporal scales of habitat selection. In particular, cues in the immediate environment may commonly provide indirect information about future habitat quality. In periodical cicadas (
Magicicada
spp.), oviposition site selection represents a very long-term habitat choice. Adult female cicadas insert eggs into tree branches during a few weeks in the summer of emergence, but their oviposition choices determine the underground habitats of root-feeding nymphs over the following 13 or 17 years. Here, field experiments are used to show that female cicadas use the local light environment of host trees during the summer of emergence to select long-term host trees. Light environments may also influence oviposition microsite selection within hosts, suggesting a potential behavioural mechanism for associating solar cues with host trees. In contrast, experimental nutrient enrichment of host trees did not influence cicada oviposition densities. These findings suggest that the light environments around host trees may provide a robust predictor of host tree quality in the near future. This habitat selection may influence the spatial distribution of several cicada-mediated ecological processes in eastern North American forests.
Are liquid crystalline properties of nucleosomes involved in chromosome structure and dynamics?
Authors: Livolant Françoise , Mangenot Stéphanie , Leforestier Amélie , Bertin Aurélie , Frutos Marta de , Raspaud Eric , Durand Dominique
Published: September 2006

Nucleosome core particles correspond to the structural units of eukaryotic chromatin. They are charged colloids, 101 Å in diameter and 55 Å in length, formed by the coiling of a 146/147 bp DNA fragment (50 nm) around the histone protein octamer. Solutions of these particles can be concentrated, under osmotic pressure, up to the concentrations found in the nuclei of living cells. In the presence of monovalent cations (Na
+
), nucleosomes self-assemble into crystalline or liquid crystalline phases. A lamello-columnar phase is observed at ‘low salt’ concentrations, while a two-dimensional hexagonal phase and a three-dimensional quasi-hexagonal phase form at ‘high salt’ concentrations. We followed the formation of these phases from the dilute isotropic solutions to the ordered phases by combining cryoelectron microscopy and X-ray diffraction analyses. The phase diagram is presented as a function of the monovalent salt concentration and applied osmotic pressure. An alternative method to condense nucleosomes is to induce their aggregation upon addition of divalent or multivalent cations (Mg
2+
, spermidine
3+
and spermine
4+
). Ordered phases are also found in the aggregates. We also discuss whether these condensed phases of nucleosomes may be relevant from a biological point of view.
Kinetics of blood flow during healing of excisional full‐thickness skin wounds in pigs as monitored by laser speckle perfusion imaging
Authors: Stewart C. J. , Gallant‐Behm C. L. , Forrester K. , Tulip J. , Hart D. A. , Bray R. C.
Published: October 2006

Background/purpose: The laser speckle perfusion imaging (LSPI) system is a new, non‐invasive technique for rapidly and reproducibly measuring tissue perfusion. The high resolution and frame rate of the LSPI overcome many of the limitations of traditional laser Doppler imaging techniques. Therefore, LSPI is a useful means for evaluating blood flow in a variety of situations. The present study investigates the ability of the LSPI system to detect temporal changes in blood flow during the healing of cutaneous wounds in a well‐characterized animal model.

Methods: Full‐thickness excisional skin wounds (2 × 2 cm) were created on the backs of juvenile female red Duroc pigs. Every week post‐injury, the wounds were measured and photographed, and normalized blood flow values were determined using the LSPI system.

Results: Tissue perfusion values were available after complete re‐epithelialization and removal of the eschar, at day 21. At this point, wound blood flow was significantly elevated as compared with the surrounding, uninvolved skin. Wound blood flow declined steadily during healing, and approached normal values by day 35 post‐injury.

Conclusion: The kinetics of blood flow during excisional wound healing in the red Duroc model are comparable with that previously observed in laser Doppler imaging of healing human skin wounds and hypertrophic scars. These results therefore confirm that the red Duroc is a good model of human wound healing, and further indicates that the LSPI is an excellent technique for evaluating angiogenesis and neovascularization during healing in this and other models.
Acyclovir concentrations in the skin of humans after a single oral dose assessed by in vivo cutaneous microdialysis
Authors: Farfal Sylwia , Klimowicz Adam , Bielecka‐Grzela Stanislawa
Published: October 2006

Background/purpose: Acyclovir is a synthetic deoxyguanosine analogue used in the treatment of certain viral diseases. This drug is effective primarily against Herpes simplex virus, Varicella zoster virus and to a lesser extent against Epstein–Barr virus and cytomegalovirus. The aim of the study was to determine the acyclovir concentrations in plasma and skin (cutaneous microdialysate) and to compare its penetration into real (skin) and theoretical peripheral compartment after administration of a single 0.4 g oral dose.

Methods: To evaluate the skin concentrations of the examined agent in 10 healthy male volunteers linear microdialysis probes with 2 kDa molecular‐weight cut‐off were inserted intradermally and were perfused with Ringer solution up to 6 h after drug ingestion.

Results: The mean maximum acyclovir concentrations in the plasma, skin and theoretical peripheral compartment were 3.16±0.86, 0.94±0.34 and 1.85±0.69 μmol/L, respectively, and were achieved after 1.6±0.4, 2.4±0.3 and 3.7±0.7 h. The degree of penetration into the real (skin) and theoretical peripheral compartment was 0.36±0.15 and 0.74±0.12, respectively, and the differences were statistically significant. Similarly, also, the maximum concentration, time to maximum concentration and area under the concentration–time curve differed significantly between the plasma and skin as well as between the skin and the theoretical peripheral compartment.

Conclusions: In selected cases skin concentrations should be determined rather than those in blood plasma when studying the distribution of orally administered drugs. Evaluation of acyclovir concentrations in the skin cannot be replaced by the calculation of the theoretical peripheral compartment.
Vibrio vulnificus infection and metalloprotease
Authors: MIYOSHI Shin‐ichi
Published: September 2006

Vibrio vulnificus is ubiquitous in aquatic environments; however, it occasionally causes serious and often fatal infections in humans. These include invasive septicemia contracted through consumption of raw seafood, as well as wound infections acquired through contact with brackish or marine waters. In most cases of septicemia, the patients have underlying disease(s), such as liver dysfunction or alcoholic cirrhosis, and the secondary skin lesions including cellulitis, edema and hemorrhagic bulla appear on the limbs. Although V. Vul produces various virulent factors including polysaccharide capsule, type IV pili, hemolysin and proteolytic enzymes, the 45‐kDa metalloprotease may be a causative factor of the skin lesions, because the purified protease enhances vascular permeability through generation of chemical mediators and also induces serious hemorrhagic damage through digestion of the vascular basement membrane. As well as other bacteria, V. Vul can regulate the protease production through the quorum‐sensing system depending on bacterial cell density. However, this system operates efficiently at 25°C, but not at 37°C. Therefore, V. vulnificus may produce sufficient amounts of the protease only in the interstitial tissue of the limbs, in which temperature is lower than the internal temperature of the human body.
Frequency of sister chromatid exchanges in the lymphocytes of patients with atopic dermatitis
Authors: KARAMAN Ali , ALIAĞAOĞLU Cihangir
Published: September 2006

The combination of genetic susceptibility and environmental factors can induce allergic sensitization and subsequent local inflammation, resulting in atopic dermatitis (AD). Sister chromatid exchange (SCE) is a sensitive method that may reflect an instability in DNA or a deficiency in DNA repair. The aim of the present study was to investigate whether patients with AD have defects in DNA repair and whether SCE frequency can be used as a genetic marker in the pathogenesis of AD. Between September 2004 and July 2005, SCE was analyzed in the peripheral blood lymphocyte chromosomes of 32 patients with AD and 28 control subjects at the Dermatology Unit of Erzurum State Hospital. This study found that the SCE frequency was significantly increased in patients with AD (P < 0.00001). The prevalence of SCE was not correlated with patient age, sex, disease duration or AD disease severity. Our results indicate that increased chromosome instability may play an important role in the etiology of AD.
Newborn infant with hemophagocytic lymphohistiocytosis and generalized skin eruptions
Authors: BAY Ali , CALKA Omer , AKDENIZ Necmettin , ÖNER Ahmet Faik , KIRIMI Ercan
Published: September 2006

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease resulting from abnormal proliferation of histiocytes in tissues and organs. The incidence of HLH is 1:50 000–300 000. Cutaneous eruptions have been reported in 6–65% of the cases. It's important to differentiate the eruptions from other systemic diseases. We present an infant with prominent skin manifestations of HLH. On the 11th day of life, she was admitted to our hospital with complaint of a generalized rash that had started the previous day. The eruptions consisted of irregularly shaped maculopapular erythematous rash and purpura. Bone marrow aspiration on the 25th day of life revealed hemophagocytosis with increased macrophages and histiocytes, consistent with HLH. Treatment was started with dexamethasone followed by induction chemotherapy with etoposide. All skin manifestations resolved in a few days. Although the clinical features are nonspecific, HLH should be kept in mind as an accompanying disease in neonates presenting with skin eruptions.
Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma with atypical presentation
Authors: KIM Sung Kwon , KIM You Chan , KANG Hee Young
Published: September 2006

Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma is characterized by a proliferation of epidermotropic CD8+ cytotoxic T cells and an aggressive clinical behavior. Patients present with localized or disseminated eruptive papules, nodules and tumors. We report a case of primary cutaneous aggressive epidermotropic CD8+ cytotoxic T‐cell lymphoma with unusual clinical manifestation. The lesion occurred as multiple brownish macules and flat‐topped papules on the hands, feet and face in a 25‐year‐old woman.
Familial pigmented purpuric dermatoses
Authors: SETHURAMAN Gomathy , SUGANDHAN Selvendran , BANSAL Arika , DAS Anup Kumar , SHARMA Vinod K
Published: September 2006

Pigmented purpuric dermatoses (PPD) are chronic, asymptomatic dermatoses characterized by petechiae, pigmentation and rarely telangiectasias. Familial occurrence of PPD is very rare. We report four individuals in a family over three generations. The inheritance is suggestive of an autosomal dominant pattern.
Multiple tumor suppressor genes are increasingly methylated with age in non‐neoplastic gastric epithelia
Authors: So Kanji , Tamura Gen , Honda Teiichiro , Homma Naoyuki , Waki Takayoshi , Togawa Naoyuki , Nishizuka Satoshi , Motoyama Teiichi
Published: September 2006

A number of tumor suppressor and tumor‐related genes are silenced by promoter hypermethylation in gastric cancer. Hypermethylation is not restricted to cancer cells, but is also present in non‐neoplastic cells during aging. Such age‐related methylation in non‐neoplastic gastric epithelia is postulated to constitute a field defect that increases the risk for development of gastric cancer. To quantitatively evaluate age‐related methylation in non‐neoplastic gastric epithelia, we used a fiber‐type DNA microarray on which methylated and unmethylated sequence probes were mounted. After bisulfite modification, a part of the promoter CpG island of four tumor suppressor genes, lysyl oxidase (LOX), p16, RUNX3 and tazarotene‐induced gene 1 (TIG1), were amplified by PCR using Cy5 end labeled primers. Methylation rates (MRs) were calculated as the ratio of the fluorescence intensity of a methylated sequence probe to the total fluorescence intensity of methylated and unmethylated probes. Non‐neoplastic gastric mucosa was obtained from 24 non‐cancer‐bearing stomachs at autopsy. MRs ranged from 0.0% to 77.2% (mean, 15.8%) for LOX, 0.0% to 45.8% (mean, 10.0%) for p16, 0.0% to 83.8% (mean, 9.0%) for RUNX3, and 0.0% to 46.1% (mean, 6.6%) for TIG1, and significantly correlated with aging (P < 0.01). The regression curves were: y = 0.013x2 − 0.6184x + 4.0512, R2 = 0.5728 (P < 0.001) for LOX; y = 0.0107x2 − 0.6055x + 5.2943, R2 = 0.7891 (P < 0.00001) for p16; y = 0.0182x2 − 1.2234x + 11.566, R2 = 0.5595 (P < 0.001) for RUNX3; and y = 0.0068x2 − 0.3586x + 2.4306, R2 = 0.4670 (P < 0.01) for TIG1. Thus, our present results are consistent with the notion that age‐related methylation is associated with cancer susceptibility in the elderly. Quantitative analysis of DNA methylation using DNA microarrays is a promising method for risk assessment in the development of gastric cancer. (Cancer Sci 2006; 97: 1155–1158)
Expression profile of LIT1/KCNQ1OT1 and epigenetic status at the KvDMR1 in colorectal cancers
Authors: Nakano Seiji , Murakami Kazuhiro , Meguro Makiko , Soejima Hidenobu , Higashimoto Ken , Urano Takeshi , Kugoh Hiroyuki , Mukai Tsunehiro , Ikeguchi Masahide , Oshimura Mitsuo
Published: September 2006

The human chromosome region 11p15.5 contains a number of maternally and paternally imprinted genes, and the LIT1/KCNQ1OT1 locus acts as an imprinting center in the proximal domain of 11p15.5. Loss of imprinting (LOI) of LIT1 and its correlation with methylation status at a differentially methylated region, the KvDMR1, were investigated in 69 colorectal cancer tissue specimens. LIT1 expression profiles were also examined by RNA‐fluorescence in situ hybridization in 13 colorectal cancer cell lines. In 69 colorectal cancer tissue specimens, LOI of LIT1 was observed in nine of the 17 (53%) informative cases. Moreover, LOI of LIT1 was only observed in tumor samples. In the cell lines, methylation status at the KvDMR1 correlated well with LIT1 expression profiles. Loss of expression of LIT1 also correlated with enrichment of H3 lysine 9 (H3‐K9) dimethylation and reduction of H3 lysine 4 (H3‐K4) dimethylation. Thus, LIT1 expression appears to be controlled by epigenetic modifications at the KvDMR1, although CDKN1C expression, which is considered to be controlled by LIT1, was not associated with epigenetic status at the KvDMR1 in some colorectal cancer cell lines. Therefore, these findings suggest that LOI of LIT1 via epigenetic disruption plays an important role in colorectal carcinogenesis, but it is not necessarily associated with CDKN1C expression. (Cancer Sci 2006; 97: 1147–1154)
Interleukin‐12‐responding asialoGM1+CD8+ central memory‐type T cells as precursor cells for interferon‐γ‐producing killer T cells
Authors: Kosaka Akemi , Lee Ushaku , Wakita Daiko , Matsubara Naoki , Togashi Yuji , Nishimura Shin‐Ichiro , Kitamura Hidemitsu , Nishimura Takashi
Published: September 2006

While investigating CD8+ memory T cells in unimmunized C57BL/6 mice, we found that there were unique memory‐type CD8+ T cells expressing asialoGM1 (ASGM1), CD62L and CCR7 cell surface molecules, which occupied approximately 10% of CD8+ T cells and 35% of CD44+ memory CD8+ T cells. Culture of freshly isolated ASGM1+CD8+ T cells with interleukin (IL)‐12 plus IL‐2 caused the proliferation and generation of killer T cells. Moreover, ASGM1+CD8+ T cells, but not ASGM1−CD8+ T cells, produced high levels of interferon (IFN)‐γ in response to IL‐12 plus IL‐2. Although ASGM1+CD8+ T cells showed no significant responses to IL‐12 alone or IL‐2 alone, pulse incubation of ASGM1+CD8+ T cells with IL‐12 at an earlier time (0–12 h), and subsequently with IL‐2 at a later time (12–24 h), caused the same levels of proliferation, killer cell generation and IFN‐γ production as when they were incubated simultaneously with IL‐12 plus IL‐2 for 24 h. Thus, ASGM1+CD8+ T cells appeared to respond to IL‐12 directly to acquire IL‐2 responsiveness and differentiate into IFN‐γ‐producing killer T cells. Indeed, freshly isolated ASGM1+CD8+ T cells, but not ASGM1−CD8+ T cells, expressed higher levels of IL‐12R β2 mRNA. The fact that IL‐12 administration in vivo caused the generation of ASGM1+CD8+ killer T cells in an IFN‐γ‐dependent manner further indicated a physiological significance of ASGM1+CD8+ central memory‐type T cells in IL‐12‐induced immunoregulation for the therapy of tumors and infectious diseases. (Cancer Sci 2006; 97: 1236–1241)
CCR4 as a novel molecular target for immunotherapy of cancer
Authors: Ishida Takashi , Ueda Ryuzo
Published: September 2006

Leukocyte trafficking, which is critically regulated by chemokines and their receptors, shares many of the characteristics of tumor cell infiltration and metastasis. Expression of CC chemokine receptor 4 (CCR4) by tumor cells is associated with skin involvement, but CCR4 also has an important role in normal and tumor immunity. In a subset of patients with CCR4+ T‐cell leukemia/lymphoma, the tumor cells themselves function as regulatory T (Treg) cells, contributing to tumor survival in the face of host antitumor immune responses. In other types of cancers, the chemokines TARC/CCL17 and MDC/CCL22, specific ligands for CCR4 that are produced by tumor cells and the tumor microenvironment, attract CCR4+ Treg cells to the tumor, where they create a favorable environment for tumor escape from host immune responses. A novel humanized anti‐CCR4 monoclonal antibody (mAb) has been developed, the Fc region of which is defucosylated to enhance antibody‐dependent cellular cytotoxicity by increasing its binding affinity to Fc receptor on effector cells. We are now conducting a phase I clinical trial of this anti‐CCR4 mAb in patients with CCR4+ T‐cell leukemia/lymphoma in Japan (clinical trials gov. identifier: NCT00355472). Anti‐CCR4 mAb could be an ideal treatment modality for many different cancers, not only to directly kill the CCR4+ tumor cells, but also to overcome the suppressive effect of CCR4+ Treg cells on the host immune response to tumor cells. (Cancer Sci 2006; 97: 1139–1146)
Upregulation of fibroblast growth factor receptor 3 and epidermal growth factor receptors, in association with Raf‐1, in urothelial dysplasia and carcinoma in situ after the Chernobyl accident
Authors: Romanenko Alina M. , Morimura Keiichirou , Kinoshita Anna , Wanibuchi Hideki , Takahashi Satoru , Zaparin Wadim K. , Vinnichenko Wladimir I. , Vozianov Alexander F. , Fukushima Shoji
Published: September 2006

The present study was carried out in order to examine the molecular status of selected growth factor receptors (GFR) in urinary bladder lesions, recently described by our group as representing ‘Chernobyl cystitis’. Fibroblast growth factor receptor 3 (FGFR3), epidermal growth factor receptor 1 (EGFR1), EGFR2neu (a member of the same family), p53 and Raf‐1 serine/threonine kinase expression were evaluated immunohistochemically in urinary bladder biopsies from 22 men with benign prostate hyperplasia (group 1). For comparison, 16 men with benign prostate hyperplasia and five women with chronic cystitis living in non‐radio‐contaminated areas of the country were also investigated as controls (group 2). Additionally, 14 patients with dysplasia, carcinoma in situ (CIS) and primary urothelial carcinoma (UC) operated before the Chernobyl accident as well as 23 patients with UC living in the radio‐contaminated areas were included as pre‐ and post‐Chernobyl UC groups 1 and 2, respectively. Chronic proliferative atypical cystitis (‘Chernobyl cystitis’) was observed in group 1 patients. Foci of dysplasia and CIS were found in 22 (100%) and 19 (86%) of the 22 cases, respectively; moreover, two small UC were also detected. Elevated levels of FGFR3, EGFR2/neu, p53 and to a lesser extent EGFR1 and Raf‐1 expression in the urothelial dysplasia and CIS were evident for patients of group 1. Statistically significant differences in immunohistochemical scores for FGFR3, EGFR1, p53 and Raf‐1 were observed between groups 1 and 2 and between group 1 and the post‐Chernobyl UC group 2, where a change in expression of EGFR2/neu was also noted. A significant decrease in FGFR3 expression in additional pre‐Chernobyl UC group 1 with dysplasia, CIS and UC compared with group 1 Chernobyl cystitis cases was detected. Our findings suggest that FGFR and EGFR signaling pathways, associated with p53 and Raf‐1 activation, may contribute to multistage urothelial carcinogenesis caused by irradiation, through autocrine or paracrine growth stimulation. (Cancer Sci 2006; 97: 1168–1174)
Meat, milk, saturated fatty acids, the Pro12Ala and C161T polymorphisms of the PPARγ gene and colorectal cancer risk in Japanese
Authors: Kuriki Kiyonori , Hirose Kaoru , Matsuo Keitaro , Wakai Kenji , Ito Hidemi , Kanemitsu Yukihide , Hirai Takashi , Kato Tomoyuki , Hamajima Nobuyuki , Takezaki Toshiro , Suzuki Takeshi , Saito Toshiko , Tanaka Rie , Tajima Kazuo
Published: September 2006

The peroxisome proliferator‐activated receptor gamma (PPARγ) gene plays important roles in energy homeostasis. To examine interactions between consumption of foods and fatty acids and the Pro12Ala and C161T (His447His) polymorphisms for colorectal cancer, we performed two case‐control studies in Japanese. In study 1, there were 128 colorectal cancer cases and 238 non‐cancer controls, and in study 2 there were 257 cases and 771 (age‐ and sex‐matched) non‐cancer controls. Assessment of food and nutrients consumption in study 1 was via a nine‐item questionnaire, while in study 2 assessment of consumption was according to a more detailed semiquantitative food frequency questionnaire. Consumption of foods and fatty acids was divided into low, moderate and high groups. The overall frequency of the Ala allele was <4%, and the frequencies of the Pro/Pro + C/C and Pro/Pro + (C/T + T/T) genotypes were 70–73% and 20–26%, respectively. Compared with subjects with low meat intake and the Pro/Pro + C/C genotype, those with high meat consumption and the same genotype had a stronger increased risk in study 1 [OR, 2.88; 95% CI, 1.14–7.30; P for trend = 0.02], but a positive association with processed meat consumption was greatest in those with the Pro/Pro + (C/T + T/T) genotype (P for trend = 0.05) in study 2. Likewise, high consumption of saturated fatty acids and milk appeared to confer marginal increased risk and stronger decreased risk, respectively, in those with the Pro/Pro and Pro/Pro + C/C genotypes (OR, 1.35 and 0.65; 95% CI, 0.93–1.96 and 0.43–1.00; P for trend = 0.10 and 0.06). Further large‐scale studies are needed to determine colorectal cancer risk according to relationships between the PPARγ gene polymorphisms and dietary intakes of meat, processed meat, milk and saturated fatty acids in Japanese with very low frequency of the Ala allele. (Cancer Sci 2006; 97: 1226–1235)
Human homolog of Drosophila tumor suppressor Scribble negatively regulates cell‐cycle progression from G1 to S phase by localizing at the basolateral membrane in epithelial cells
Authors: Nagasaka Kazunori , Nakagawa Shunsuke , Yano Tetsu , Takizawa Shin , Matsumoto Yoko , Tsuruga Tetsushi , Nakagawa Keiichi , Minaguchi Takeo , Oda Katsutoshi , Hiraike‐Wada Osamu , Ooishi Hajime , Yasugi Toshiharu , Taketani Yuji
Published: September 2006

Drosophila tumor suppressor Scribble has been identified as an apical‐basolateral polarity determinant in epithelia. A human homolog of Drosophila Scribble, human Scribble (hScrib), has been identified as a protein targeted by human papillomavirus E6 for the ubiquitin‐mediated degradation dependent on E6AP, a cellular ubiquitin‐protein ligase. Human Scribble is classified as a LAP protein, having leucine‐rich repeats (LRRs) and PDZ domains. We investigated whether hScrib, which is thought to have a role in polarity determination based on the data of its Drosophila homolog, is involved in cell‐cycle regulation and proliferation control of epithelia. Transfection of hScrib inhibits cell‐cycle progression from G1 to S phase, and it up‐ and down‐regulates expression of adenomatous polyposis coli and cyclins A and D1, respectively. Knockdown of hScrib expression by siRNA leads to cell‐cycle progression from G1 to S phase. We explored functional domain mapping to reveal which domains of hScrib are critical for its cellular proliferation control and localization at the basolateral membrane. We found that LRRs and PDZ domain 1 are indispensable for hScrib to inhibit cell growth by blocking cell‐cycle progression and to keep its proper localization. These data indicate that basolateral membrane localization of hScrib is closely related to its proliferation control. Our findings suggest the possibility that hScrib is involved in signal transduction to negatively regulate cell proliferation by localizing at the basolateral membrane of epithelial cells through LRRs and PDZ domains. (Cancer Sci 2006; 97: 1217–1225)
Lower ability to oxidize lipids in adult patients with growth hormone (GH) deficiency: reversal under GH treatment
Authors: Brandou F. , Aloulou I. , Razimbaud A. , Fédou C. , Mercier J. , Brun J. F.
Published: September 2006

Background  The aim of the study was to characterize lipid oxidation at exercise in adults with growth hormone deficiency (GHD) and to evaluate the effect of 6 and 12 months of GH replacement therapy on substrate carbohydrate (CHO) and lipid utilization at exercise.

Patients and measurements  Twenty‐five patients with GHD and 40 matched controls participated in the study. Ten of the 25 GH‐deficient patients were treated with recombinant GH for 12 months. Anthropometric measurements and exercise calorimetry were performed before and after treatment. Maximal fat oxidation and the crossover point [that is the percentage of the theoretical maximal power (Wmax th) where CHO become the predominant fuel used for oxidation] were determined.

Results and conclusion  The GH‐deficient patients exhibited a highly significant shift in the balance of substrate oxidation during exercise, towards a decrease in fat oxidation, and a shift towards lower intensities of the crossover (52 ± 5·5%vs. 72·6 ± 6·6% of Wmax th, P < 0·03) and maximal fat oxidation (131·04 ± 14 vs. 234·4 ± 30·1 mg/min, P < 0·03) in the GHD and control groups, respectively. However, GH treatment at 6 and 12 months partially reversed this defect, resulting in an increase (+83%, P < 0·001) in the maximal ability to oxidize fat during exercise. These findings are consistent with the hypothesis that a lack of GH reduces the ability to oxidize lipids during exercise and that GH treatment restores this muscular metabolic property.
Effect of recombinant hGH (rhGH) replacement on gonadal function in male patients with organic adult‐onset GH deficiency
Authors: Giavoli Claudia , Ferrante Emanuele , Ermetici Federica , Bergamaschi Silvia , Ronchi Cristina L. , Lania Andrea G. , Ambrosi Bruno , Spada Anna , Beck‐Peccoz Paolo
Published: September 2006

Objective  Previous evidence indicated that, in adults with organic hypopituitarism, GH deficiency (GHD) may mask the presence of other pituitary deficits, in particular central hypothyroidism and hypoadrenalism. Little and conflicting information is available about the relationship between GHD, rhGH therapy and gonadal function in males. The aim of the present study was to investigate the hypothalamic–pituitary–gonadal axis (HPG) in male adults with organic GHD and normal HPG axis.

Patients  Twelve male adults (mean age 48 ± 7 years) with organic GHD and normal HPG axis.

Measurements  Serum levels of testosterone, LH and FSH (basal and after GnRH stimulation test), SHBG and IGF‐I and percentage body fat (BF%) were evaluated before and during rhGH (mean dose 0·24 ± 0·02 mg/day for 13 ± 1 months) treatment.

Results  Serum IGF‐I levels normalized during rhGH treatment and BF% significantly decreased. Serum testosterone levels significantly decreased (from 18·1 ± 1·7 to 14·2 ± 1·6 nmol/l, P = 0·01), with a parallel and significant decrease of serum SHBG (from 31·1 ± 3·6 to 24·3 ± 2·3 nmol/l, P < 0·05). Thus, calculated free testosterone (cFT) did not change (from 0·39 ± 0·17 to 0·33 ± 0·14 nmol/l, P = ns). Finally, no difference was found in basal and GnRH stimulated gonadotrophins levels.

Conclusions  In conclusion, the condition of GHD does not seem to mask central hypogonadism, in contrast to what is observed for central hypothyroidism and hypoadrenalism. However, the significant decrease in serum testosterone levels, strictly related to SHBG decrease, suggests that evaluation of the HPG axis during rhGH treatment cannot be based on the measurement of total testosterone levels, but should mainly rely on calculation of cFT and a careful clinical evaluation, in order to avoid unnecessary replacement therapy.
Determinants of quality in a long‐lived colonial species
Authors: LEWIS SUE , WANLESS SARAH , ELSTON DAVID A. , SCHULTZ MEG DUHR , MACKLEY ELIZABETH , DU TOIT MICHELLE , UNDERHILL JENNY G. , HARRIS MIKE P.
Published: September 2006

In many animal populations a small proportion of individuals produce the majority of surviving offspring, but the underlying mechanisms are unclear. Behaviour may be an important determinant of variation in fitness: ‘high‐quality’ individuals may have enhanced abilities in foraging or predator and parasite avoidance.

The role of behaviour in determining variation in quality was examined using the common guillemotUria aalge, a monogamous seabird with biparental care. Using a novel mixed model approach, we analysed binary data on breeding success of each pair attempting to breed in each year with variables critical to breeding success (timing of breeding; inferred age; breeding experience and success; number of nest sites and partners) as fixed effects. Random effects for year, male, female and each distinct pairing of a male and a female were included in the model, allowing a quality estimate to be derived for each individual and pair. A range of behaviours associated with breeding were examined in relation to these quality estimates.

Breeding success declined with timing of breeding, and increased initially with age before declining in old age. It increased with previous successful experience, not breeding experienceper se, until senescence effects became apparent. For males, breeding success declined with increasing numbers of mates.

The most important behavioural determinants of quality operated at the level of the pair, with the time mates spent together at the site and chick feeding rates both positively related to quality. At the individual level, trip durations and feeding rates were associated with female but not male quality, suggesting that pair quality was operating principally through the female. However, removal of laying date, the most important component in the binomial model, confirmed that the pair effect was much larger than the female effect.

This study demonstrates the potential of mixed modelling to determine quality estimates based on long‐term breeding histories. The probability of a successful reproductive attempt was explained by the timing of breeding, age, successful breeding experience and number of mates. Behaviour was an important proximate mechanism underlying quality, in particular the foraging abilities of the pair, and the female's contribution to offspring provisioning. In species with biparental care, behavioural correlates of quality operate most strongly at the scale of the breeding pair, because contributions from both individuals are required for a successful outcome.
Are ectoparasite communities structured? Species co‐occurrence, temporal variation and null models
Authors: KRASNOV BORIS R. , STANKO MICHAL , MORAND SERGE
Published: September 2006

We studied temporal variation in the structure of flea communities on small mammalian hosts from eastern Slovakia using null models. We asked (a) whether flea co‐occurrences in infracommunities (in the individual hosts) in different hosts as well as in the component communities (in the host species) demonstrate a non‐random pattern; (b) whether this pattern is indicative of either positive or negative flea species interactions; (c) whether this pattern varies temporally; and (d) whether the expression of this pattern is related to population size of either fleas or hosts or both.

We constructed a presence/absence matrix of flea species for each temporal sample of a host species and calculated four metrics of co‐occurrence, namely the C‐score, the number of checkerboard species pairs, the number of species combinations and the variance ratio (V‐ratio). Then we compared these metrics with the respective indices calculated for 5000 null matrices that were assembled randomly using two algorithms, namely fixed‐fixed (FF) and fixed‐equiprobable (FE).

Most co‐occurrence metrics calculated for real data did not differ significantly from the metrics calculated for simulated matrices using the FF algorithm. However, the indices observed for 42 of 75 presence/absence matrices differed significantly from the null expectations for the FE models. Non‐randomness was detected mainly by the C‐score and V‐ratio metrics. In all cases, the direction of non‐randomness was the same, namely the aggregation, not competition, of flea species in host individuals and host species.

The inclusion or exclusion of the uninfested hosts in the FE models did not affect the results for individual host species. However, exclusion of the uninfested host species led to the acceptance of the null hypothesis for only six of 13 temporal samples of the component flea communities for which non‐randomness was detected when the uninfested hosts were included in the analysis.

In most host species, the absolute values of the standardized size effect of both the C‐score and V‐ratio increased with an increase in host density and a concomitant decrease in flea abundance and prevalence.

Results of this study demonstrated that (a) flea assemblages on small mammalian hosts were structured at some times, whereas they appeared to be randomly assembled at other times; (b) whenever non‐randomness of flea co‐occurrences was detected, it suggested aggregation but never segregation of flea species in host individuals or populations; and (c) the expression of structure in flea assemblages depended on the level of density of both fleas and hosts.
Images of self and others as computer users: the role of gender and experience
Authors: Mercier E. M. , Barron B. , O'Connor K. M.
Published: September 2006

Abstract
Gender differences in the pursuit of technology careers are a current issue of concern. We report on two studies that use surveys, drawings and interviews to examine sixth‐ and eighth‐grade students' perceptions of knowledgeable computer users and their self‐perception as a computer‐type person. In Study 1, participants were asked to generate representations of computer users in pictures or words. The results indicate that the majority of representations were of male users and they frequently wore glasses. Students of both genders were more likely to draw males. Eighth‐grade students' representations included more stereotypical features than those of sixth‐grade students. In Study 2, students were asked whether they believed that there was such a thing as a computer‐type person and whether they perceived themselves to be one. Eighty per cent of students rejected this characterization. They differed from students who accepted it in their levels of past experience, their confidence, and the probability that they shared their knowledge with others. The results of both studies suggest that while there is a male image of computer science in general, it is not overly negative and students' self‐perception is not governed by their own gender as much as by other variables.
Interactions with talking books: phonological awareness affects boys' use of talking books
Authors: Littleton K. , Wood C. , Chera P.
Published: September 2006

Abstract
Framed by current concerns about boys' attainment in literacy, this paper investigates the potential of talking books software to support the literacy development of male beginning readers. The study primarily considered whether typically developing boys who showed lower levels of attainment in phonological awareness would show a greater degree of improvement in phonological awareness or a change in reading strategy, following a talking books intervention, than boys who were demonstrating higher levels of phonological awareness. It also examined whether the boys' phonological awareness attainment would affect how they used the software to support their attempts at reading, both in terms of their interactions with the computer and the types of speech feedback that they selected. The analysis also considered whether there was any association between the nature of the boys' teaching and learning interactions with the computer and any changes in their reading strategies from pre‐ to post‐test. The findings suggest that the use of the talking books software was particularly beneficial for boys who initially showed lower phonological proficiency, and that the boys in this study utilised the talking books software adaptively depending on their phonological proficiency. Moreover, there was evidence that contact with the talking books affected the reading strategies of the boys who had higher phonological awareness. There was also evidence of an association between the way in which the boys interacted with the software and changes in their reading strategy between pre‐ and post‐test.
The digital divide: the special case of gender
Authors: Cooper J.
Published: September 2006

Abstract
This paper examines the evidence for the digital divide based on gender. An overview of research published in the last 20 years draws to the conclusion that females are at a disadvantage relative to men when learning about computers or learning other material with the aid of computer‐assisted software. The evidence shows that the digital divide affects people of all ages and across international boundaries. We suggest that the digital divide is fundamentally a problem of computer anxiety whose roots are deep in socialization patterns of boys and girls and that interact with the stereotype of computers as toys for boys. A model of the digital divide is presented that examines gender stereotypes, attribution patterns, and stereotype threat as antecedents of computer anxiety. Computer anxiety in turn leads to differences in computer attitudes and computer performance. A number of suggestions are offered to reduce the impact of the digital divide.
Parenting stress of mothers and fathers of young children with cognitive delays in Vietnam
Authors: Shin J. , Nhan N. V. , Crittenden K. S. , Hong H. T. D. , Flory M. , Ladinsky J.
Published: September 2006

Background  This research examined the effects of child and family variables on stress experienced by mothers and fathers of young children with cognitive delays in Vietnam.

Methods  The mothers (n = 106) and fathers (n = 93) whose children (age range = 3–6 years) were identified as having cognitive delays participated in the interview survey. The survey consisted of a set of the standardized questionnaires that were translated into Vietnamese and assessed for the content validity in the Vietnamese context.

Results  Mothers experienced more stress than fathers. Path analyses were conducted for mothers and fathers separately. Mothers with female children, those with children of lower intellectual functioning, and those whose husbands had health conditions experienced more stress than the other mothers. Fathers with lower economic status and a smaller social support network were more stressed than the other fathers. Both mothers and fathers were more stressed when they experienced stronger stigma, although the effects were not significant when other variables were considered together in path analyses.

Conclusions  The findings revealed traditional gender roles. Mothers were more affected by the child’s characteristics and the spouse’s functioning; they anticipated future problems related to the child’s functioning more than fathers did. Fathers were more affected by concerns about the family’s connection to the wider world such as economic issues and the social support network. Longitudinal studies of how social support and stigma affect families would be valuable.