bluuebunny/crossref_metadata_2025 huggingface dataset:
Event-Related Potentials, Reaction Time, and Response Selection of Skilled and Less-Skilled Cricket Batsmen
Authors: Taliep M Sharhidd , Gibson A St Clair , Gray J , van der Merwe L , Vaughan C L , Noakes T D , Kellaway L A , John L R
Published: February 2008

The differences in P300 latency, P300 amplitude, response selection, and reaction time between skilled and less-skilled cricket batsmen have been investigated. Eight skilled and ten less-skilled right-handed batsmen each viewed 100 in-swing, 100 out-swing, and 40 slower deliveries displayed in random sequence from projected video footage whilst their responses and electro-encephalograms were recorded. Logistic regression was used to derive a discriminative function for the P300 data. This was done to determine whether the skilled batsmen differed from the less-skilled batsmen on the basis of pooled P300 amplitude and latency data. All the batsmen were correctly characterised as being skilled or less-skilled. Logistic regression equations with reaction time and correctness of response data indicated that behavioural data do not correctly classify skilled performance. It is suggested that skilled cricket batsmen have a superior perceptual decision-making ability compared with less-skilled cricket batsmen, as measured by P300 latency and amplitude. This appears to be the first study showing a link between skill and cerebral cortical activity during a perceptual cricket batting task and it could pave the way for future studies on mental processing in cricket batsmen.
Structure and mechanism of IFN-γ antagonism by an orthopoxvirus IFN-γ-binding protein
Authors: Nuara Anthony A. , Walter Leigh J. , Logsdon Naomi J. , Yoon Sung Il , Jones Brandi C. , Schriewer Jill M. , Buller R. Mark , Walter Mark R.
Published: February 2008

Ectromelia virus (ECTV) encodes an IFN-γ-binding protein (IFN-γBP
ECTV
) that disrupts IFN-γ signaling and its ability to induce an antiviral state within cells. IFN-γBP
ECTV
is an important virulence factor that is highly conserved (>90%) in all orthopoxviruses, including variola virus, the causative agent of smallpox. The 2.2-Å crystal structure of the IFN-γBP
ECTV
/IFN-γ complex reveals IFN-γBP
ECTV
consists of an IFN-γR1 ligand-binding domain and a 57-aa helix-turn-helix (HTH) motif that is structurally related to the transcription factor TFIIA. The HTH motif forms a tetramerization domain that results in an IFN-γBP
ECTV
/IFN-γ complex containing four IFN-γBP
ECTV
chains and two IFN-γ dimers. The structure, combined with biochemical and cell-based assays, demonstrates that IFN-γBP
ECTV
tetramers are required for efficient IFN-γ antagonism.
Symbiotic gut microbes modulate human metabolic phenotypes
Authors: Li Min , Wang Baohong , Zhang Menghui , Rantalainen Mattias , Wang Shengyue , Zhou Haokui , Zhang Yan , Shen Jian , Pang Xiaoyan , Zhang Meiling , Wei Hua , Chen Yu , Lu Haifeng , Zuo Jian , Su Mingming , Qiu Yunping , Jia Wei , Xiao Chaoni , Smith Leon M. , Yang Shengli , Holmes Elaine , Tang Huiru , Zhao Guoping , Nicholson Jeremy K. , Li Lanjuan , Zhao Liping
Published: February 2008

Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe–host interactions and the roles of individual bacterial species are obscure. We now demonstrate a“transgenomic” approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial–host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as “the characterization of key functional members of the microbiome that most influence host metabolism and hence health.” For example,
Faecalibacterium prausnitzii
population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.
Pre‐acclimation to exercise in normobaric hypoxia
Authors: Pedlar Charles R. , Whyte Gregory P. , Godfrey Richard J.
Published: February 2008

Training in normobaric hypoxia prior to ascent to high altitude has been shown to induce acclimation to altitude in mountaineers. It is therefore likely that a similar training paradigm will be useful for athletes travelling to moderate altitude for training or competition. To test this contention, the acute effects of normobaric hypoxia upon selected physiological and performance parameters during treadmill exercise were examined. The parameters chosen were heart rate, blood lactate concentration, ventilation, oxyhaemoglobin saturation, and 5‐km treadmill time‐trial performance. The participants were 12 endurance‐trained athletes (mean age 29.4 years, s=5.3; stature 1.80 m, s=0.8; body mass 78.3 kg, s=9.6). Tests were conducted once in sham conditions (FIO2=0.209, PIO2=159 mmHg, sea level; ST trial) and once in normobaric hypoxic conditions (FIO2=0.149, PIO2=85 mmHg, ∼2500 m; HT1 trial) using a normobaric hypoxic chamber system. Subsequently, the participants were assigned to two groups to train (75 min·day−1, 8 days, at a running speed corresponding to ≤2 mmol·l−1) in normobaric hypoxia (FIO2=0.149; n=6, hypoxia group) or sham conditions (FIO2=0.209; n=6, sham group). Acutely (ST vs. HT1), 5‐km time‐trial performance time was significantly extended in HT1 (13.6%, range 6.3–22.5%; P<0.01). Following training (HT2), performance improved by 0.8% and 2.3% for the sham and hypoxia training group respectively, but the improvement was not significant for either group (P>0.05). The individual data showed wide heterogeneity. In conclusion, aerobic training in normobaric hypoxia for 75 min·day−1 for 8 days does not enhance performance in hypoxia. However, due to the heterogeneity of response, it is evident that it may be effective at improving performance in hypoxia in some individuals.
Implicit Learning of Second-, Third-, and Fourth-Order Adjacent and Nonadjacent Sequential Dependencies
Authors: Remillard Gilbert
Published: February 2008

Serial reaction time (SRT) task studies have established that people can implicitly learn first- and second-order adjacent dependencies. Sequential confounds have made it impossible to draw conclusions regarding learning of nonadjacent dependencies and learning of third- and fourth-order adjacent dependencies. Addressing the confounds, the present study shows that people can implicitly learn second-, third-, and fourth-order adjacent and nonadjacent dependencies embedded in probabilistic sequences of target locations.
Competition During the Processing of Quantifier Scope Ambiguities: Evidence from Eye Movements during Reading
Authors: Paterson Kevin B. , Filik Ruth , Liversedge Simon P.
Published: February 2008

We investigated the processing of sentences containing a quantifier scope ambiguity, such as Kelly showed a photo to each critic, which is ambiguous between the indefinite phrase ( a photo) having one or many referents. Ambiguity resolution requires the computation of relative quantifier scope, with either a photo or each critic taking wide scope, thereby determining the number of referents. Using eye tracking, we established that multiple factors, including the grammatical function and surface linear order of quantified phrases, along with their lexical characteristics, interact during the processing of relative quantifier scope, with conflict between factors incurring a processing cost. We discuss the results in terms of theoretical accounts attributing sentence-processing difficulty to either reanalysis (e.g., Fodor, 1982) or competition between rival analyses (e.g., Kurtzman & MacDonald, 1993).
Deficits in Verbal Long-Term Memory and Learning in Children with Poor Phonological Short-Term Memory Skills
Authors: Gathercole Susan E. , Briscoe Josie , Thorn Annabel , Tiffany Claire ,   ALSPAC Study Team
Published: February 2008

Possible links between phonological short-term memory and both longer term memory and learning in 8-year-old children were investigated in this study. Performance on a range of tests of long-term memory and learning was compared for a group of 16 children with poor phonological short-term memory skills and a comparison group of children of the same age with matched nonverbal reasoning abilities but memory scores in the average range. The low-phonological-memory group were impaired on longer term memory and learning tasks that taxed memory for arbitrary verbal material such as names and nonwords. However, the two groups performed at comparable levels on tasks requiring the retention of visuo-spatial information and of meaningful material and at carrying out prospective memory tasks in which the children were asked to carry out actions at a future point in time. The results are consistent with the view that poor short-term memory function impairs the longer term retention and ease of learning of novel verbal material.
Short Article: Lexical and Sublexical Processes in the Perception of Transposed-Letter Anagrams
Authors: Frankish Clive , Barnes Lisa
Published: February 2008

Evidence from priming and lexical decision tasks suggests that nonwords created by transposing adjacent letter pairs (TL nonwords) are very effective in activating lexical representations of their base words, because the process of orthographic matching tolerates minor changes in letter position. However, this account disregards the possible role of sublexical processing in reading. TL nonwords are perceptually ambiguous, with lexical and sublexical processing giving rise to conflicting interpretations. The consequences of this ambiguity were investigated in a lexical decision experiment with primes that were either high or low bigram frequency TL versions of target words. Priming effects were much larger for low BF primes (e.g., pucnh–PUNCH) than for high BF primes (e.g., panit– PAINT). This finding is interpreted as evidence that lexical activation can be inhibited by competing output resulting from sublexical processing of TL letter string. We conclude that phonological processing is an important determinant of responses to TL stimuli, and we consider how this interpretation might be accommodated within the dual-route cascaded (DRC) model of word recognition.
Prediction of recursive convex hull class assignments for protein residues
Authors: Stout Michael , Bacardit Jaume , Hirst Jonathan D. , Krasnogor Natalio
Published: February 2008

Motivation: We introduce a new method for designating the location of residues in folded protein structures based on the recursive convex hull (RCH) of a point set of atomic coordinates. The RCH can be calculated with an efficient and parameterless algorithm.

Results: We show that residue RCH class contains information complementary to widely studied measures such as solvent accessibility (SA), residue depth (RD) and to the distance of residues from the centroid of the chain, the residues’ exposure (Exp). RCH is more conserved for related structures across folds and correlates better with changes in thermal stability of mutants than the other measures. Further, we assess the predictability of these measures using three types of machine-learning technique: decision trees (C4.5), Naive Bayes and Learning Classifier Systems (LCS) showing that RCH is more easily predicted than the other measures. As an exemplar application of predicted RCH class (in combination with other measures), we show that RCH is potentially helpful in improving prediction of residue contact numbers (CN).

Contact:  nxk@cs.nott.ac.uk

Supplementary Information: For Supplementary data please refer to Datasets: www.infobiotic.net/datasets, RCH Prediction Servers: www.infobiotic.net
History and Progress of Japanese Acupuncture
Authors: Kobayashi Akiko , Uefuji Miwa , Yasumo Washiro
Published: February 2008

After Chiso brought acupuncture to Japan from Wu (China) in the sixth century, it has progressed in unique ways within the various historical milieus of the past 1500 years. Ishitsu‐rei, the first medical law of Japan established in 701, explains the medical system of acupuncture in detail showing that acupuncture was being administered under the authorization of the national government. For the next 1200 years, acupuncture continued to be an important facet of public health in Japan. From the Azuchimomoyama through the Edo period, the knowledge exchange with China became active and people who studied in China developed new styles and techniques of acupuncture treatment and organized their own private schools or ryu-ha in Japan. In 1635, when the Edo government decided to close the country, Japan cut‐off exchange with foreign countries for over 200 years. The national isolation caused some development that was unique to Japan. During that time, acupuncture filtered into people′s everyday lives. Moxibustion, in particular, became popular as a treatment that ordinary people could practice by themselves. Also in this period of isolation, Western medicine was imported from Holland, the only country allowed to maintain trade with Japan. This novel modern medicine had a strong impact on Japanese medicine, which has its foundation of Chinese traditional medicine. At the same time, Japanese acupuncture was introduced into Europe via Holland. When Japan opened its borders in 1865 period, the new government was eager to accept Western culture to the extent of prohibiting the progress of Japanese acupuncture for a period of time. Even so, Japanese acupuncture has survived and flourished up to the present day due to the strong demand and the great efforts of the practitioners. Scientific studies are now in the process of establishing a firm evidence base for over a millennium of clinical use, respecting the classic ideas of the traditional treatment.
Hurry-up and hatch: selective filial cannibalism of slower developing eggs
Authors: Klug Hope , Lindström Kai
Published: February 2008

Filial cannibalism (the consumption of one's own offspring) is thought to represent an adaptive strategy in many animals. However, little is known about the details of which offspring are consumed when a parent cannibalizes. Here, we examined patterns of within-brood filial cannibalism in the sand goby (
Pomatoschistus minutus
). Males spawned sequentially with two females, and we asked whether males cannibalized selectively with regard to egg size or the order in which eggs were received. Males preferentially consumed the larger eggs of the second female they spawned with. Because larger eggs took longer to hatch, and because female 2's eggs were up to 1 day behind those of female 1, such preferential cannibalism might allow males to decrease the time spent caring for the current brood and re-enter the mating pool sooner. More work is needed to understand the fitness consequences of such selective cannibalism.
Winter feeding of birds increases productivity in the subsequent breeding season
Authors: Robb Gillian N , McDonald Robbie A , Chamberlain Dan E , Reynolds S. James , Harrison Timothy J.E , Bearhop Stuart
Published: February 2008

Supplementary food given to birds can have contemporary effects by reducing the risk of starvation, increasing survival and altering movements and reproductive performance. There is, however, a widely held perception that birds benefit from extra food over winter, but that it is better that they ‘look after themselves’ during breeding. Here we describe a landscape-scale experiment showing for the first time that the effects of increasing food availability only during the winter can be carried over to the subsequent breeding season. Even though food supplementation stopped six weeks prior to breeding, birds living on sites provisioned over winter had advanced laying dates and increased fledging success compared with birds living on unprovisioned sites. Thus, supplemental feeding of wild birds during winter, in a manner mimicking householders provisioning in gardens and backyards, has the potential to alter bird population dynamics by altering future reproductive performance. With levels of bird feeding by the public continuing to increase, the impacts of this additional food supply on wild bird populations may be considerable.
Brainless but not clueless: earthworms boost their ejaculates when they detect fecund non-virgin partners
Authors: Velando Alberto , Eiroa Julio , Domínguez Jorge
Published: February 2008

In many animals in which females store sperm, males may detect female mating status and, in order to outcompete rival sperm, increase ejaculate size when copulating with non-virgin females. Although most studies have been restricted to organisms with separate sexes, theoretical models suggest that sperm competition should also be an important selective agent shaping life-history traits in simultaneous hermaphrodites. Nevertheless, the empirical support for ejaculate adjustment in a mating opportunity is scarce in hermaphrodites. In the present study, we performed a double-mating experiment to determine whether earthworms (Eisenia andrei) detect the mating status of their partners and whether they respond by adjusting their ejaculate. We found that earthworms triplicated the donated sperm when mating with a non-virgin mate. Moreover, such increases were greater when the worms were mated with larger (more fecund) partners, indicating that earthworms perform a fine-tune control of ejaculate volume. The results of the present study suggest that, under high intensity of sperm competition, partner evaluation is subject to intense selection in hermaphrodite animals, and donors are selective about to whom they donate how much sperm.
Alternative stress indicators in sea bass Dicentrarchus labrax, L.
Authors: Simontacchi C. , Poltronieri C. , Carraro C. , Bertotto D. , Xiccato G. , Trocino A. , Radaelli G.
Published: February 2008

Stress indicators (plasma cortisol, glucose and lactate) were evaluated in sea bass Dicentrarchus labrax submitted to different pre‐slaughter conditions, and cortisol levels in plasma were found to correlate with those detected in mucus, gut contents and muscle. The results demonstrate new possibilities for monitoring stress status in fishes in which blood sampling is difficult or impossible.
Lack of metabolic thermal compensation during the early life stages of ocean pout Zoarces americanus (Bloch & Schneider) : a benthic, cold‐water marine species
Authors: Killen S. S. , Brown J. A. , Gamperl A. K.
Published: February 2008

The present study investigated the metabolic response of young ocean pout Zoarces americanus to temperature acclimation (3 v. 11° C), and to acute changes in water temperature from 3 to 17° C. The Q10 value for standard metabolic rate between acclimation temperatures was 5·3, warm‐acclimated fish displayed higher rates of oxygen uptake at all temperatures during the acute thermal challenge, and changes in whole‐body citrate synthase activity were qualitatively similar to those seen for metabolism. These results indicate that, in contrast to temperate species, young ocean pout from Newfoundland do not show thermal compensation in response to long‐term temperature changes.
Sex steroid receptors expression and hormone‐induced cell proliferation in human osteosarcoma
Authors: Dohi Osamu , Hatori Masahito , Suzuki Takashi , Ono Katsuhiko , Hosaka Masami , Akahira Jun‐ichi , Miki Yasuhiro , Nagasaki Shuji , Itoi Eiji , Sasano Hironobu
Published: February 2008

Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG‐63 human osteosarcoma cell line, which expressed all of these receptors. ER‐β and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER‐α and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER‐β and Ki‐67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG‐63 cells was significantly stimulated by estradiol, progesterone, and 5α‐dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions. (Cancer Sci 2008; 99: 518–523)
Membrane‐anchored growth factors, the epidermal growth factor family: Beyond receptor ligands
Authors: Higashiyama Shigeki , Iwabuki Hidehiko , Morimoto Chie , Hieda Miki , Inoue Hirofumi , Matsushita Natsuki
Published: February 2008

The epidermal growth factor (EGF) family and the EGF receptor (EGFR, ErbB) tyrosine kinase family have been spearheading the studies of signal transduction events that determine cell fate and behavior in vitro and in vivo. The EGFR family and their signaling pathways are giving us tremendous advantages in developing fascinating molecular target strategies for cancer therapy. Currently, two important types of EGFR inhibitors are in clinical use: neutralizing antibodies of EGFR or ErbB2, and synthetic small compounds of tyrosine kinase inhibitors designed for receptors. On the other hand, basic research of the EGF family ligands presents new challenges as membrane‐anchored growth factors. All members of the EGF family have important roles in development and diseases and are shed from the plasma membrane by metalloproteases. The ectodomain shedding of the ligands has emerged as a critical component in the functional transactivation of EGFRs in interreceptor cross‐talk in response to various shedding stimulants such as G‐protein coupled receptor agonists, growth factors, cytokines, and various physicochemical stresses. Among the EGFR‐ligands, heparin‐binding EGF‐like growth factor (HB‐EGF) is a prominent ligand in our understanding of the pathophysiological roles of ectodomain shedding in cancer, wound healing, cardiac diseases, etc. Here we focus on ectodomain shedding of the EGF family ligands, especially HB‐EGF by disintegrin and metalloproteases, which are not only key events of receptor cross talk, but also novel intercellular signaling by their carboxy‐terminal fragments to regulate gene expression directly. (Cancer Sci 2008; 99: 214–220)
Expression of glucose transporters and hexokinase II in cholangiocellular carcinoma compared using [18F]‐2‐fluro‐2‐deoxy‐d‐glucose positron emission tomography
Authors: Paudyal Bishnuhari , Oriuchi Noboru , Paudyal Pramila , Higuchi Tetsuya , Nakajima Takashi , Endo Keigo
Published: February 2008

Cholangiocellular carcinoma (CCC) has been reported to have a high glucose uptake; however, the mechanism of glucose entry into these cells is still unclear. We investigated the relationship between [18F]‐2‐fluro‐2‐deoxy‐d‐glucose (18F‐FDG) uptake and the expression of facilitative glucose transporters (Glut) and hexokinase (HK) II, as well as the association between the expression of different histological types of CCC. The expression of Glut (1–5) and HK II was studied using immunohistochemistry of 26 patients with CCC who underwent whole‐body 18F‐FDG positron emission tomography before surgery or biopsy. CCC expressed immunohistochemically detectable Glut 1 in 81%, Glut 2 in 54%, Glut 3 in 19%, and HK II in 77% of the total cases. Glut 1, Glut 2, Glut 3, and HK II were more often detected in moderately differentiated and poorly differentiated than in well‐differentiated CCC. A significant correlation was observed between 18F‐FDG uptake and the staining scores of Glut 1 and HK II (P = 0.02, ρ = 0.45 and P = 0.001, ρ = 0.59). The staining scores of Glut 1 and HK II were also significantly correlated (P = 0.002, ρ = 0.3). Multivariate regression analysis revealed that lymph‐node metastasis was independently associated with 18F‐FDG uptake. Our study showed a significant association between the expression of Glut 1 and HK II with 18F‐FDG uptake, indicating that Glut 1 is a major glucose transporter expressed in CCC and that HK II contributes to the increased metabolism of glucose, especially in moderately and poorly differentiated CCC. (Cancer Sci 2008; 99: 260–266)
Induction of a novel histone deacetylase 1/c‐Myc/Mnt/Max complex formation is implicated in parity‐induced refractoriness to mammary carcinogenesis
Authors: Matsuoka Yoichiro , Fukamachi Katsumi , Uehara Norihisa , Tsuda Hiroyuki , Tsubura Airo
Published: February 2008

Refractoriness to carcinogen‐induced increases in epithelial cell proliferation is a very important characteristic of parous mammary glands. We found that N‐methyl‐N‐nitrosourea (MNU)‐induced proliferative burst in the mammary ductal epithelium was blocked in parous glands but not in age‐matched virgin (AMV) glands. The inhibition of the proliferative burst in MNU‐treated parous mammary glands coincided with the upregulation of Mnt, a Myc‐suppressor, and the formation of histone deacetylase 1/Mnt/Max complexes that unexpectedly contained c‐Myc. These complexes formed on the promoters of Myc targets, such as ornithine decarboxylase, cyclin D2, and transforming growth factor β1 genes, in quiescent fibroblasts, and were disassembled in serum‐stimulated cells. These results suggest that the complexes also function as transcription repressors of the growth‐related Myc targets in MNU‐treated parous mammary glands. Using the chemical mammary carcinogenesis model of human c‐Ha‐ras transgenic (Tg) rats, we confirmed that parity protected the mammary glands at the postinitiation phase of tumorigenesis. Although the incidence of 7,12‐dimethylbenz[α]anthracene‐induced palpable tumors was reduced from 61.5% in the AMV Tg rats to 28.5% in the parous animals, the incidence of early neoplastic lesions in the parous rats was the same as that in the AMV rats. Restriction fragment length polymorphism analysis detected mutations in the human c‐Ha‐ras gene in most of the normal‐appearing parous Tg glands, as well as in the virgin glands. We propose that accelerated formation of HDAC1/c‐Myc/Mnt/Max complexes in response to carcinogen exposure results in down‐regulation of growth‐related genes, leading to the refractoriness of parous mammary glands at the postinitiation phase of carcinogenesis. (Cancer Sci 2008; 99: 309–315)
Whole‐genome profiling of chromosomal aberrations in hepatoblastoma using high‐density single‐nucleotide polymorphism genotyping microarrays
Authors: Suzuki Makoto , Kato Motohiro , Yuyan Chen , Takita Junko , Sanada Masashi , Nannya Yasuhito , Yamamoto Go , Takahashi Atsushi , Ikeda Hitoshi , Kuwano Hiroyuki , Ogawa Seishi , Hayashi Yasuhide
Published: February 2008

To identify the genomic profile and elucidate the pathogenesis of hepatoblastoma (HBL), the most common pediatric hepatic tumor, we performed high‐density genome‐wide single‐nucleotide polymorphism (SNP) microarray analyses of 17 HBL samples. The copy number analyzer for GeneChip® (CNAG) and allele‐specific copy number analysis using anonymous references (AsCNAR) algorithms enabled simple but sensitive inference of allelic composition without using paired normal DNA. Chromosomal aberrations were observed in 15 cases (88%). Gains in chromosomes 1q, 2 (or 2q), 8, 17q, and 20 and losses in chromosomes 4q and 11q were frequently identified. High‐grade amplifications were detected at 7q34, 14q11.2, and 11q22.2. Several types of deletions, except homozygous deletion, were identified. Most importantly, copy‐neutral loss of heterozygosity (uniparental disomy [UPD]) at 11p15 was detected in four of the 17 HBL samples. Insulin‐like growth factor II (IGF2) and H19 genes were located within this region. The methylated status of this region indicated the paternal origin of the UPD. The expression patterns of IGF2 and H19 were opposite between genes with and without the UPD. This difference in the expression patterns might influence the clinical features of HBL. (Cancer Sci 2008; 99: 564–570)
Cisplatin up‐regulates ICAM‐1 expression in endothelial cell via a NF‐κB dependent pathway
Authors: Yu Minghua , Han Jianqun , Cui Peilin , Dai Min , Li Hongwei , Zhang Jian , Xiu Ruijuan
Published: February 2008

The anticancer drug cis‐diammindichloroplatin (cisplatin) can cause severe side‐effects, but to date, the mechanisms of action of these dangerous side‐effects have not been completely elucidated. Since cellular adhesion molecules (CAMs), by mediating the recruitment of circulating leukocytes to the blood vessel wall and their subsequent migration into the subendothelial spaces, play a crucial role in several pathophysiologic processes, we sought potential proof for CAMs in the pathophysiology of cisplatin‐induced vascular damage. In vitro, human umbilical vein endothelial cells (HUVECs) were subjected to various concentrations of cisplatin, considerable up‐regulation of intercellular adhesion molecule‐1 (ICAM‐1) but not P‐selectin, E‐selectin, and vascular cell adhesion molecule 1 at both messenger mRNA and protein expression levels were observed. Electrophoretic mobility shift assays and Western blotting analysis revealed that cisplatin up‐regulates ICAM‐1 expression in HUVECs via an NF‐kappaB‐dependent pathway. Further intravital microscopy study demonstrated that significantly higher (P < 0.01) numbers of rolling and sticking leukocytes on the wall of postcapillary venules in male Golden Syrian hamster's cheek pouch bearing a human cervical carcinoma were observed, while inhibition of ICAM‐1 by using specific anti‐ICAM‐1 antibody can attenuate cisplatin‐stimulated leukocyte/endothelium interactions. These data suggest that ICAM‐1 involves in the pathophsiologic process of cisplatin‐induced vascular toxicity and may be exploited for therapeutic advantage. (Cancer Sci 2008; 99: 391–397)
Explaining the convergence of male and female smoking prevalence in Australia
Authors: Morley Katherine I. , Hall Wayne D.
Published: February 2008

Objective  To examine changes in age of tobacco experimentation and progression to daily smoking in men and women between birth cohorts that differ in exposure to public health programmes that aim to discourage smoking.

Design  Analysis of national cross‐sectional household surveys of smoking patterns, conducted in Australia in 2001 and 2004.

Setting and participants  Australian adults aged 22 years and over in 2001 and 2004 who responded to the National Drug Strategy Household Survey.

Main outcome measures  Prevalence of tobacco experimentation and progression to daily smoking by age 21, estimated by sex and birth cohort. Odds of tobacco experimentation and progression to daily smoking by age 21 estimated by sex for each birth cohort, with corrections for the effects of ‘forward telescoping’ in recalling age of use.

Results  Sex differences in smoking prevalence are smaller in younger birth cohorts. Tobacco experimentation has increased among women, while progression to daily smoking has decreased among men.

Conclusions  Sex differences in smoking experimentation and progression to daily smoking have decreased in younger birth cohorts. However, a significant proportion of younger males and females continue to experiment with tobacco and become daily smokers despite strong public health efforts to discourage smoking. More research is needed to determine why sex differences in smoking behaviour are not evident in younger birth cohorts.
Intranasal naloxone for the treatment of suspected heroin overdose
Authors: Kerr Debra , Dietze Paul , Kelly Anne‐Maree
Published: February 2008

Aims  This paper reviews available literature regarding the effectiveness, safety and utility of intranasal (i.n.) naloxone for the treatment of heroin overdose.

Methods  Scientific literature in the form of published articles during the period January 1984 to August 2007 were identified by searching several databases including Medline, Cinahl and Embase for the following terms: naloxone, narcan, intranasal, nose. The data extracted included study design, patient selection, numbers, outcomes and adverse events.

Results  Reports of the pharmacological investigation and administration of i.n. naloxone for heroin overdose are included in this review. Treatment of heroin overdose by administration of i.n. naloxone has been introduced as first‐line treatment in some jurisdictions in North America, and is currently under investigation in Australia.

Conclusion  Currently there is not enough evidence to support i.n. naloxone as first‐line intervention by paramedics for treatment of heroin overdose in the pre‐hospital setting. Further research is required to confirm its clinical effectiveness, safety and utility. If proved effective, the i.n. route may be useful for drug administration in community settings (including peer‐based administration), as it reduces risk of needlestick injury in a population at higher risk of blood‐borne viruses. Problematically, naloxone is not manufactured currently in an ideal form for i.n. administration.
Modern management of chronic granulomatous disease
Authors: Seger Reinhard A.
Published: February 2008

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim‐sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene‐replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life‐threatening infections.
The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma
Authors: Evans Robert P. , Naber Claudia , Steffler Tara , Checkland Tamara , Maxwell Christopher A. , Keats Jonathan J. , Belch Andrew R. , Pilarski Linda M. , Lai Raymond , Reiman Tony
Published: February 2008

Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti‐myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AZD1152‐induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti‐myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138+ BM plasma cells from myeloma patients but also, as expected, was toxic to CD138− marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152‐inhibited tumour growth at well‐tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.
PI3K/AKT pathway activation in acute myeloid leukaemias is not associated with AKT1 pleckstrin homology domain mutation
Authors: Tibes Raoul , Kornblau Steven M. , Qiu Yihua , Mousses Spyro M. , Robbins Christiane , Moses Tracy , Carpten John D.
Published: February 2008

Despite its’ central role, the precise mechanisms of the phosphoinositide 3‐kinase/Akt (PI3K)/Akt pathway activation in acute myeloid leukaemia (AML) have not been elucidated. Recently, a recurrent novel AKT1 pleckstrin homology domain (PHD) mutation leading to membrane translocation, constitutive AKT activation and leukaemia development in mice was described. To assess AKT1 PHD mutations in AML, we sequenced 57 specimens from 49 AML patients, all of whom showed PI3K/AKT pathway activation by analysis of total and phospho‐protein expression for AKT, mTor, p70S6Kinase, S6ribosomal protein and PTEN. No mutations in AKT1 PHD were identified, making this mutation an unlikely cause of PI3K/AKT pathway activation in AML.
Thalidomide has limited single‐agent activity in relapsed or refractory indolent non‐Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B
Authors: Smith Sonali M. , Grinblatt David , Johnson Jeffrey L. , Niedzwiecki Donna , Rizzieri David , Bartlett Nancy L. , Cheson Bruce D. ,   for the Cancer and Leukemia Group B
Published: February 2008

Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1–2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1–4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12·5% (95% confidence interval: 2·6–32·4%). Eleven patients progressed during therapy. Grade 3–4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.
A rapid two‐step procedure for the purification of human peripheral blood basophils to near homogeneity
Authors: Gibbs B. F. , Papenfuss K. , Falcone F. H.
Published: February 2008

Background
Basophils are increasingly utilized as indicators of allergic inflammation and as primary allergic effector cells to study signalling pathways. However, until the present, their enrichment has been time consuming, costly and limited to relatively few specialized laboratories.

Objective
We have therefore devised a reproducible and rapid method for the purification of human basophils from small quantities of peripheral blood within 1.5 h, which does not require the use of specialized equipment such as elutriators.

Methods
Human basophils were obtained from healthy volunteers undergoing venipuncture. Heparinized or K3‐ethylenediaminetetraacetic acid blood samples were first subjected to centrifugation in Hetasep, directly followed by negative selection using immunomagnetic beads. Basophil morphology and purity were assessed by May–Grünwald staining of cytospins. IgE‐mediated histamine release was analysed spectrofluorometrically and IL‐4 and IL‐13 production by quantitative RT‐PCR. CD203c and CD63 surface expression was measured using flow cytometry before and after activation with anti‐IgE.

Results
Using this protocol, basophils were enriched close to homogeneity in most cases with a mean purity of 99.34±0.88% (range 97–100%, n=18) and a mean recovery of 75.6 (range 39–100%, n=8). Basophil viability following purification was 99.6±0.89% using Trypan blue exclusion. The purification procedure gave rise to basophils with normal functional responses to anti‐IgE regarding histamine release as well as IL‐4 and IL‐13 mRNA expression. Moreover, constitutive cell‐surface CD203c/CD63 expressions were not elevated before anti‐IgE stimulation.

Conclusion
The rapidity, simplicity and reproducibility of this method will facilitate the employment of basophils in high‐output ex vivo studies.
Weak founder effect signal in a recent introduction of CaribbeanAnolis
Authors: EALES J. , THORPE R. S. , MALHOTRA A.
Published: February 2008

Species introductions provide a rare opportunity to study rapid evolutionary and genetic processes in natural systems, often under novel environmental pressures. Few empirical studies have been able to characterize genetic founder effects associated with demographic bottlenecks at the earliest stages of species introductions. This study utilizes prior mitochondrial DNA information which identifies the putative source population for a recently established (c. 7 years between import and sampling) species introduction. We investigated the evidence for a founder effect in a highly successful introduction of a Puerto RicanAnolisspecies that has established itself on Dominica to the localized exclusion of the native, endemic anole. Five highly polymorphic microsatellite loci were used to explore the partitioning of genetic diversity within and between native source, native nonsource, and introduced populations ofAnolis cristatellus. Group comparisons reveal significantly lower allelic richness and expected heterozygosity in introduced populations compared to native populations; however, tests for heterozygosity excess relative to allelic richness failed to provide consistent evidence for a founder effect within introduced populations. Significant levels of within‐population genetic variation were present in both native and introduced populations. We suggest that aspects of the reproductive ecology ofAnolis(high fecundity, sperm storage and multiple paternity) offer an important mechanism by which genetic variation may be maintained following demographic bottlenecks and founder events in some squamate taxa.
Transcriptome profiling of grapefruit flavedo following exposure to low temperature and conditioning treatments uncovers principal molecular components involved in chilling tolerance and susceptibility
Authors: MAUL PILAR , McCOLLUM GREGORY T. , POPP MICK , GUY CHARLES L. , PORAT RON
Published: February 2008

A pre‐storage conditioning (CD) treatment of 16 °C for 7 d enhanced chilling tolerance of grapefruit and reduced the development of chilling injuries during storage at 5 °C. To gain a better understanding of the molecular mechanisms involved in the responses of citrus fruit to low temperatures, we performed genome‐wide transcriptional profiling analysis of RNA isolated from grapefruit flavedo using the newly developed Affymetrix Citrus GeneChip microarray. Utilizing very restrictive cut‐off criteria, including pair‐wise anova comparisons significantly different at P ≤ 0.05 and induction or repression of transcript levels by at least fourfold, we found that out of 30 171 probe sets on the microarray, 1345 probe sets were significantly affected by chilling in both control and CD‐treated fruits, 509 probe sets were affected by chilling specifically in the CD‐treated fruits, and 417 probe sets were specifically expressed in chilling‐sensitive control fruits. Overall, exposure to chilling led to expression arrest of general cellular metabolic activity, including concretive down‐regulation of cell wall, pathogen defence, photosynthesis, respiration, and protein, nucleic acid and secondary metabolism. On the other hand, chilling enhanced adaptation processes that involve changes in the expression of transcripts related to membranes, lipid, sterol and carbohydrate metabolism, stress stimuli, hormone biosynthesis, and modifications in DNA binding and transcription factors.
Evolution of C4 phosphoenolpyruvate carboxylase in Flaveria: determinants for high tolerance towards the inhibitor L‐malate
Authors: JACOBS BIANCA , ENGELMANN SASCHA , WESTHOFF PETER , GOWIK UDO
Published: February 2008

During the evolution of angiosperms, C4 phosphoenolpyruvate carboxylases have evolved several times independently from ancestral non‐photosynthetic isoforms. They show distinct kinetic and regulatory properties when compared with the C3 isozymes. To identify the evolutionary alterations which are responsible for C4‐specific properties, particularly the increased tolerance towards the allosteric inhibitor L‐malate, the photosynthetic phosphoenolpyruvate carboxylase of Flaveria trinervia Mohr (C4) and its ortholog from the closely related C3 plant Flaveria pringlei Gand. were examined using reciprocal enzyme chimeras. The main determinants for a high tolerance towards L‐malate were located in the C‐terminal region of the C4 enzyme. The effect of interchanging the region between amino acids 296 and 437 was strongly dependent upon the activation of the enzyme by glucose‐6‐phosphate. This confirms earlier observations that this region is important for the regulation of the enzyme by glucose‐6‐phosphate and that it harbours determinants for the different response of the C3 and the C4 enzyme towards this allosteric activator. In addition, it was possible to demonstrate that the only C4‐specific amino acid, a serine in the C‐terminal part of the enzyme, is not involved in conferring an increased L‐malate tolerance to the C4 enzyme.