bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of perA sequences and their correlation with autoaggregation in typical enteropathogenic Escherichia coli isolates collected in Japan and Thailand
Authors: Iida Mariko , Okamura Noboru , Yamazaki Mitsugu , Yatsuyanagi Jun , Kurazono Takayuki , Suzuki Rieko , Hiruta Noriaki , Isobe Junko , Seto Kazuko , Kawano Kimiko , Narimatsu Hiroshi , Ratchtrachenchai Orn‐Anong , Okabe Nobuhiko , Ito Kenitiro
Published: February 2010

Enteropathogenic Escherichia coli (EPEC) strains produce a bundle‐forming pilus (BFP) that mediates localized adherence (LA) to intestinal epithelial cells. The major structural subunit of the BFP is bundlin, which is encoded by the bfpA gene located on a large EAF plasmid. The perA gene has been shown to activate genes within the bfp operon. We analyzed perA gene polymorphism among typical (eae‐ and bfpA‐ positive) EPEC strains isolated from healthy and diarrheal persons in Japan (n= 27) and Thailand (n= 26) during the period 1995 to 2007 and compared this with virulence and phenotypic characteristics. Eight genotypes of perA were identified by heteroduplex mobility assay (HMA). The strains isolated in Thailand showed strong autoaggregation and had an intact perA, while most of those isolated in Japan showed weak or no autoaggregation, and had a truncated perA due to frameshift mutation. The degree of autoaggregation was well correlated with adherence to HEp‐2 cells, contact hemolysis and BFP expression. Our results showed that functional deficiency due to frameshift mutation and subsequent nonsense mutation in perA reduced BFP expression in typical EPEC strains isolated in Japan.
Low‐dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin‐3 in gynecologic cancers
Authors: Ohgami Tatsuhiro , Kato Kiyoko , Kobayashi Hiroaki , Sonoda Kenzo , Inoue Takafumi , Yamaguchi Shin‐ichiro , Yoneda Tomoko , Wake Norio
Published: February 2010

MDM2 is a direct negative regulator of p53. The p53‐independent mdm2‐P1 and p53‐dependent mdm2‐P2 promoters have been recently shown to harbor Sp1 binding sites. Mithramycin, an inhibitor of Sp1 DNA binding, has been used clinically to treat hypercalcemia and some types of neoplastic disorders. In this study, we investigated the mechanisms behind the anticancer effect of mithramycin. In gynecologic cancer cells expressing wild‐type p53, mithramycin stabilized p53 and increased the expression of the p53 downstream target genes PUMA and p21, arrested the cell cycle, and induced apoptosis. This activation of the p53 signaling pathway was a specific effect of MTH at concentrations <50 nm. Mithramycin temporally decreased transcription of both the mdm2‐P1 and ‐P2 promoters. This was followed by a subsequent increase of mdm2‐P2 promoter activity by activated p53. Up‐regulated MDM2 was in its active form, and consequently attenuated p53 activity. Although mithramycin activated p53 and suppressed the growth of human gynecologic cancer cell xenografts in mice, this was accompanied with a secondary up‐regulation of MDM2. Combined treatment with mithramycin and nutlin‐3, a drug that inhibits MDM2–p53 interaction, overcame a secondary up‐regulation of MDM2 and synergistically inhibited cancer cell growth by inducing apoptosis through activation of the p53 signaling pathway. These observations provide a better understanding of the mechanisms of mithramycin activity, and suggest a potential role for combining mithramycin and nutlin‐3 as a chemotherapeutic treatment for gynecologic cancers. (Cancer Sci 2010; 101: 1387–1395)
Histamine induces Th2 activation through the histamine receptor 1 in house dust mite rhinitic but not asthmatic patients
Authors: Botturi K. , Lacoeuille Y. , Vervloet D. , Magnan A.
Published: February 2010

Background
Effects of mast cell‐released histamine on smooth muscle and endothelial cells are considered as responsible of immediate symptoms of anaphylaxis. However, little is known about histamine effects on Th2 lymphocytes, which orchestrate the allergic reaction upstream of mast cells.

Objective
We addressed this question in house dust mite (HDM) allergics, according to the presence of rhinitis or asthma and allergen stimulation.

Methods
Peripheral blood mononuclear cell from 15 rhinitic and 14 asthmatic HDM‐allergic subjects and 16 controls were cultured with Der p 1 or histamine. The effect of Der p 1 on histamine receptor (H1R and H2R) expression was studied. T‐cell cytokine production was studied upon Der p 1 or histamine stimulation. The role of H1R in histamine effects was assessed with levocetirizine.

Results
H1R and H2R are overexpressed on T cells from asthmatic but not from rhinitic subjects. Der p 1 increases H1R expression on CD4+ cells from both allergic groups, and decreases it in controls, on CD4+ and CD8+ subsets. Der p 1 decreases T‐cell H2R expression in asthmatics. Allergen increases IL‐4 and IL‐13 in both allergic groups. Histamine increases Th2 cytokines in rhinitics only, and levocetirizine abolishes this effect. In asthmatics and controls, histamine decreases T‐cell cytokines through a non‐H1R dependent pathway.

Conclusion
In rhinitis but not in asthma, histamine is able to increase allergic inflammation by increasing Th2 cytokine production in a positive feedback dependent on H1R. This result could explain in part why H1R antagonists, are very efficient in rhinitis, but not in asthma.

Cite this as: K. Botturi, Y. Lacoeuille, D. Vervloet and A. Magnan, Clinical & Experimental Allergy, 2010 (40) 755–762.
The proximal half of the Drosophila E‐cadherin extracellular region is dispensable for many cadherin‐dependent events but required for ventral furrow formation
Authors: Haruta Tomohiro , Warrior Rahul , Yonemura Shigenobu , Oda Hiroki
Published: February 2010

The formation of the ventral furrow during Drosophila gastrulation is driven by coordinated apical constriction. Cell–cell adhesion is thought to regulate apical constriction, but the mechanisms are poorly understood. DE‐cadherin, an epithelial classic cadherin, has in its membrane‐proximal extracellular region a suite of domains absent from vertebrate/urochordate classic cadherins. We constructed DEΔP, a DE‐cadherin derivative that lacks the membrane‐proximal half of the extracellular region but retains the entire cytoplasmic domain and still exhibits strong cell–cell binding ability. The extracellular region of DEΔP consists of only cadherin repeats, mimicking vertebrate/urochordate classic cadherins. In animals lacking DE‐cadherin, DEΔP organized adherens junction assembly and functioned fully in many cadherin‐dependent processes, including oogenesis. Embryos in which DE‐cadherin was entirely replaced by DEΔP established the blastoderm epithelium but failed to form a ventral furrow. Apical constrictions were initiated relatively normally but subsequently decelerated. These were then followed by catastrophic disruption of the junctional network. Our results suggest that although the membrane‐proximal half of the DE‐cadherin extracellular region is dispensable for many developmental events, it is essential for efficient and robust apical constriction during ventral furrow formation.
Ternary complex formation of EphA4, FGFR and FRS2α plays an important role in the proliferation of embryonic neural stem/progenitor cells
Authors: Sawada Takahiro , Jing Xuefeng , Zhang Yueqiang , Shimada Emi , Yokote Hideyuki , Miyajima Masayasu , Sakaguchi Kazushige
Published: February 2010

EphA4 belongs to a superfamily of receptor tyrosine kinases and interacts with several molecules including fibroblast growth factor receptors (FGFRs) as we reported earlier. Several receptor tyrosine kinases, FGFRs, Trks, Alk and Ret, are currently known to transduce a signal through a docking protein, fibroblast growth factor receptor substrate 2α (FRS2α). However, nothing has been reported about the interaction of FRS2α with EphA4. Using the yeast two‐hybrid system and the in vitro binding and kinase assays, we found that the mid‐kinase region of EphA4 directly interacts with the FRS2α PTB domain upon tyrosine phosphorylation of the EphA4 juxtamembrane (JM) domain and EphA4 directly phosphorylates FRS2α. We also found that the FRS2α PTB domain and the amino‐terminal region of EphA4 bind to the amino‐ and carboxy‐terminal regions of the FGFR JM domain, respectively, suggesting that FRS2α and EphA4 interact with FGFR simultaneously. Furthermore, a kinase‐dead EphA4 mutant that constitutively binds to FGFR functions as a dominant‐negative molecule for signaling through both EphA4 and FGFR, and so does the truncated FRS2α lacking multiple tyrosine phosphorylation sites. These dominant‐negative mutants similarly inhibit the ligand‐dependent proliferation of the mouse embryonic neural stem/progenitor cells. These results suggest the formation of a ternary complex comprising EphA4, FGFR and FRS2α. The signaling complex appears to integrate the input from FGFR and EphA4, and release the output signal through FRS2α.
Parent age, lifespan and offspring survival: structured variation in life history in a wild population
Authors: Reid Jane M. , Bignal Eric M. , Bignal Sue , McCracken Davy I. , Bogdanova Maria I. , Monaghan Pat
Published: February 2010

1. Understanding the degree to which reproductive success varies with an individual’s age and lifespan, and the degree to which population‐level variation mirrors individual‐level variation, is central to understanding life‐history evolution and the dynamics of age‐structured populations. We quantified variation in the survival probability of offspring, one key component of reproductive success and fitness, in relation to parent age and lifespan in a wild population of red‐billed choughs (Pyrrhocorax pyrrhocorax).

2. On average across the study population, the first‐year survival probability of offspring decreased with increasing parent age and lifespan; offspring of old parents were less likely to survive than offspring of young parents, and offspring of long‐lived parents were less likely to survive than offspring of short‐lived parents.

3. However, survival did not vary with parent age across offspring produced by groups of parents that ultimately had similar lifespans.

4. Rather, across offspring produced by young parents, offspring survival decreased with increasing parent lifespan; parents that ultimately had long lifespans produced offspring that survived poorly, even when these parents were breeding at young ages.

5. The average decrease in offspring survival with increasing parent age observed across the population therefore reflected the gradual disappearance of short‐lived parents that produced offspring that survived well, not age‐specific variation in offspring survival within individual parents.

6. The negative correlation between offspring survival and maternal lifespan was strongest when environmental conditions meant that offspring survival was low across the population.

7. These data suggest an environment‐dependent trade‐off between parent and offspring survival, show consistent individual variation in the resolution of this trade‐off that is set early in a parent’s life, and demonstrate that such structured life‐history variation can generate spurious evidence of senescence in key fitness components when measured across a population.
When Thailand was an island – the phylogeny and biogeography of mite harvestmen (Opiliones, Cyphophthalmi, Stylocellidae) in Southeast Asia
Authors: Clouse Ronald M. , Giribet Gonzalo
Published: February 2010

Aim To develop a comprehensive explanation for the biological diversity of Southeast Asia, especially in the Wallacea and Sundaland regions. This study focuses on a group of arachnids, mite harvestmen, which are thought to be an extremely old group of endemic animals that have been present in the region since most of its land supposedly formed part of the northern rim of the supercontinent Gondwana.

Location Eastern Himalayas, Thai‐Malay Peninsula, Sumatra, Borneo, Java, Sulawesi, and New Guinea.

Methods Approximately 5.6 kb of sequence data were obtained from 110 South‐east Asian Cyphophthalmi specimens. Phylogenetic analyses were conducted under a variety of methods and analytical parameters, and the optimal tree was dated using calibration points derived from fossil data. Event based and paralogy‐free subtree biogeographical analyses were conducted.

Results The Southeast Asian family Stylocellidae was recovered as monophyletic, arising on what is now the Thai‐Malay Peninsula and diversifying into three main clades. One clade (Meghalaya, here formally placed in Stylocellidae) expanded north as far as the eastern Himalayas, a second clade entered Borneo and later expanded back across the Sundaland Peninsula to Sumatra, and a third clade expanded out of Borneo into the entire lower part of Sundaland. Molecular dating suggested that Stylocellidae separated from other Cyphophthalmi 295 Ma and began diversifying 258 Ma, and the lineage that inhabits mostly Borneo today began diversifying between 175 and 150 Ma.

Main conclusions The topology and molecular dating of our phylogenetic hypothesis suggest that Stylocellidae originated on Gondwana, arrived in Southeast Asia via the Cimmerian palaeocontinent, and subsequently diversified north, then south. Their present distribution in the Indo‐Malay Archipelago is explained largely by a diversification over the Sundaland Peninsula before western Sulawesi departed and the peninsula was extensively inundated.
The differential affinity of the usher for chaperone–subunit complexes is required for assembly of complete pili
Authors: Li Qinyuan , Ng Tony W. , Dodson Karen W. , So Stephane Shu Kin , Bayle Ken‐Michael , Pinkner Jerome S. , Scarlata Suzanne , Hultgren Scott J. , Thanassi David G.
Published: February 2010

Attachment to host cells via adhesive surface structures is a prerequisite for the pathogenesis of many bacteria. Uropathogenic Escherichia coli assemble P and type 1 pili for attachment to the host urothelium. Assembly of these pili requires the conserved chaperone/usher pathway, in which a periplasmic chaperone controls the folding of pilus subunits and an outer membrane usher provides a platform for pilus assembly and secretion. The usher has differential affinity for pilus subunits, with highest affinity for the tip‐localized adhesin. Here, we identify residues F21 and R652 of the P pilus usher PapC as functioning in the differential affinity of the usher. R652 is important for high‐affinity binding to the adhesin whereas F21 is important for limiting affinity for the PapA major rod subunit. PapC mutants in these residues are specifically defective for pilus assembly in the presence of PapA, demonstrating that differential affinity of the usher is required for assembly of complete pili. Analysis of PapG deletion mutants demonstrated that the adhesin is not required to initiate P pilus biogenesis. Thus, the differential affinity of the usher may be critical to ensure assembly of functional pilus fibres.
HtrA2/Omi‐immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and Cu/Zn superoxide dismutase (SOD1) mutant amyotrophic lateral sclerosis
Authors: Kawamoto Y. , Ito H. , Kobayashi Y. , Suzuki Y. , Akiguchi I. , Fujimura H. , Sakoda S. , Kusaka H. , Hirano A. , Takahashi R.
Published: February 2010

Y. Kawamoto, H. Ito, Y. Kobayashi, Y. Suzuki, I. Akiguchi, H. Fujimura, S. Sakoda, H. Kusaka, A. Hirano and R. Takahashi (2010) Neuropathology and Applied Neurobiology36, 331–344 HtrA2/Omi‐immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and Cu/Zn superoxide dismutase (SOD1) mutant amyotrophic lateral sclerosis

Aims: HtrA2/Omi is a mitochondrial serine protease that promotes the apoptotic processes, but the relationship between HtrA2/Omi and amyotrophic lateral sclerosis (ALS) is still unknown. The purpose of the present study was to determine whether abnormal expression of HtrA2/Omi occurs in patients with ALS. Methods: We prepared autopsied spinal cord tissues from 7 control subjects, 11 patients with sporadic ALS (SALS) and 4 patients with Cu/Zn superoxide dismutase (SOD1)‐related familial ALS (FALS). We then performed immunohistochemical studies on HtrA2/Omi using formalin‐fixed, paraffin‐embedded sections from all of the cases. Results: In the control subjects, the anterior horn cells were mildly to moderately immunostained with HtrA2/Omi. In the patients with SALS, strong HtrA2/Omi immunoreactivity was found in some skein‐like inclusions and round hyaline inclusions as well as many spheroids, but Bunina bodies were immunonegative for HtrA2/Omi. In the patients with SOD1‐related FALS, Lewy body‐like hyaline inclusions were observed in three cases and conglomerate inclusions were observed in the remaining case, and both types of inclusions were intensely immunopositive for HtrA2/Omi. Conclusions: These results suggest that abnormal accumulations of HtrA2/Omi may occur in several types of motor neuronal inclusions in the anterior horn from SALS and SOD1‐linked FALS cases, and that HtrA2/Omi may be associated with the pathogenesis of both types of ALS.
Growth, development and chemical characteristics of tobacco lines carrying black root rot resistance derived from Nicotiana glauca (Grah.)
Authors: Trojak‐Goluch A. , Berbeć A.
Published: February 2010

With 1 figure and 4 tables

Fertile sesquidiploid BC1 of interspecific hybrids between N. tabacum cv. ‘Wiślica’ and N. glauca were previously produced to transfer N. glauca‐type resistance into tobacco. Tobacco breeding lines (‘WGL’) BC2F5–BC2F7 carrying black root rot resistance were obtained after one generation of backcrossing to cv. ‘Wiślica’ followed by five to seven generations of selfpollination. A 3‐year study was conducted to compare the agronomic value of ‘WGL’ lines with that of the parental cultivar ‘Wiślica’. Plant height and number of leaves per plant in all ‘WGL’ lines were similar to that of ‘Wiślica’. There were some significant variations for leaf characteristics. The most distinct effect was extended duration of the vegetative stage. All the ‘WGL’ lines showed delayed flowering compared to ‘Wiślica’. The ‘WGL’ lines were inferior to the parental cultivar with regard to weight of 10 dm2 of leaf blade. There were no major differences for nitrogen, sugars and nicotine contents. These results indicate that incorporation of the N. glauca‐type resistance into tobacco genome did not produce negative effects on morphological and chemical traits.
Basal and residual lower esophageal pressures increase in old age in classic achalasia, but not vigorous achalasia
Authors: Jung Kee Wook , Jung Hwoon‐Yong , Yoon In Ja , Kim Do Hoon , Park Hye‐Won , Chung Jun‐Won , Choi Kwi‐Sook , Kim Kyung Jo , Choi Kee Don , Song Ho June , Lee Gin Hyug , Kim Jin‐Ho
Published: February 2010

Background and Aim:  The relationship between age and esophageal motility parameters (i.e. basal and residual pressure of the lower esophageal sphincter [LES]) remains to be established in achalasia patients, possibly because most previous studies did not distinguish between classic and vigorous achalasia patients. We investigated the relationship between age and esophageal motility parameters in both classic and vigorous achalasia patients.

Methods:  A retrospective review of esophageal manometry data in a single center was undertaken. Basal and residual pressure for LES was analyzed. A total of 103 achalasia patients were enrolled, comprising 84 classic and 19 vigorous types. They were subdivided into three different age groups as follows: 21–40 years old (group A), 41–60 years old (group B), and over 60 years old (group C).

Results:  In classic achalasia patients (M : F = 27:57, mean age = 44 ± 15 years old) the older age group showed a significantly higher basal LES pressure (49.62 ± 19.63 mmHg) than the younger age group (P < 0.0001). Moreover, the older age group also showed significantly high residual LES pressure (20.46 ± 8.61 mmHg) than the younger age group (P = 0.0006). In contrast, in vigorous achalasia patients (M : F = 12:7, mean age: 47 ± 15 years old) there were no difference between age and motility indices (all P > 0.05).

Conclusion:  In classic achalasia patients there appears to be a correlation between age and esophageal motility indices, especially basal and residual LES pressure. Such correlations do not appear to exist for vigorous achalasia patients.
Lower prevalence of hypercholesterolemia and hyperglyceridemia found in subjects with seropositivity for both Hepatitis B and C strains independently
Authors: Chen Jing‐Yi , Wang Jing‐Houng , Lin Chih‐Yun , Chen Pao‐Fei , Tseng Po‐Lin , Chen Chien‐Hung , Chang Kuo‐Chin , Tsai Lin‐San , Chen Shu‐Chuan , Lu Sheng‐Nan
Published: February 2010

Background and Aim:  To evaluate the association of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with hypercholesterolemia and hypertriglyceridemia.

Methods:  We analyzed the computerized health datasets of 56 336 residents from a community‐based comprehensive screening in Tainan County in southern Taiwan. The overall prevalence rates of HBV surface antigen (HBsAg) and anti‐HCV were 10.9% and 10.2%, respectively. Anti‐HCV, HBsAg, platelet counts, albumin/globulin ratio (A/G ratio), fasting glucose, triglyceride, cholesterol levels, and body mass index (BMI) were abstracted for analyses. Multivariate logistic analysis was used for identification of the independent factors of hypercholesterolemia and hypertriglyceridemia.

Results:  The prevalence of hypercholesterolemia and hypertriglyceridemia were 48.9% and 28.0%, respectively. Hypercholesterolemia and hypertriglyceridemia were associated with each other. Older age, negativity for HBsAg and anti‐HCV, normal platelet counts, A/G ratio ≥ 1, higher BMI, and being diagnosed as diabetic were common independently associated factors of both hypercholesterolemia and hypertriglyceridemia. Men had higher risk for hypertriglyceridemia, while women had higher risk for hypercholesterolemia.

Conclusions:  This large scale community‐based study demonstrated that subjects with seropositivity for Hepatitis C not only had lower prevalence of hypercholesterolemia and hypertriglyceridemia but subjects with seropositivity for Hepatitis B had the same trend.
Adverse clinical phenotype in inflammatory bowel disease: A cross sectional study identifying factors potentially amenable to change
Authors: Van Langenberg Daniel R , Lange Kylie , Hetzel David J , Holtmann Gerald J , Andrews Jane M
Published: February 2010

Background and Aim:  A significant proportion with inflammatory bowel disease (IBD) exhibit an adverse clinical phenotype reflected in endpoints like surgery and hospitalizations. We sought to identify clinico‐demographic factors associated with these adverse consequences that may be amenable to change.

Methods:  Over 6 months IBD patients visiting a metropolitan center were prospectively identified and given a comprehensive survey addressing patient knowledge, mental health and satisfaction with medical care along with other clinical data. Logistic regression analyses assessed for associations between clinico‐demographic variables and adverse clinical endpoints (previous surgery [ever] and/or recent inpatient admission over a 16 month observation period).

Results:  Of 256 IBD patients, 162 responded (response rate 63%); 95 (59%) had Crohn's disease (CD), 63 (40%) ulcerative colitis (UC), four indeterminate colitis; 53% were female. Factors associated with a greater likelihood of hospitalization included moderate/severe disease activity, psychological co‐morbidity, numbers of medications and outpatient visits (odds ratio [OR] 7.09 [2.83–17.76], 4.13 [1.25–13.61], 1.26 [1.03–1.54], 1.17 [1.00–1.37] respectively; all P < 0.05). Post‐surgical patients were more likely to have CD, more currently active disease and longer disease duration (OR 8.55 [2.43–29.4], 3.52 [1.26, 9.87], 1.14 [1.08, 1.21] respectively; all P < 0.02), yet were less likely to have previously seen a gastroenterologist, OR 0.25 [0.08–0.76] (P = 0.01).

Conclusions:  ‘At risk’ patients (those previously operated, with ongoing disease activity, dissatisfaction and/or psychological comorbidities) may benefit from early identification and more intensive management. Specialist gastroenterology care appears to be under‐utilized in operated patients yet may reduce future IBD morbidity.
Interobserver and intraobserver variability in evaluating vascular invasion in hepatocellular carcinoma
Authors: Fan Lifang , Mac Mylinh T , Frishberg David P , Fan Xuemo , Dhall Deepti , Balzer Bonnie L , Geller Stephen A , Wang Hanlin L
Published: February 2010

Background and Aim:  Hepatocellular carcinoma (HCC) is unique in that the presence of vascular invasion significantly changes tumor stage. Even though searching for vascular invasion is a common practice in surgical pathology, there appears to be a great variation among pathologists in its recognition. This study was designed to assess whether HCC could be accurately staged using vascular invasion as a staging parameter.

Methods:  The interobserver and intraobserver agreement for vascular invasion was analyzed in 126 liver resections for HCC. Selected slides were circulated twice among six pathologists for independent review using their own criteria. One to three representative images from 26 equivocal cases selected by one of the authors were re‐evaluated by the pathologists. The presence or absence of vascular invasion on each slide or image was recorded as yes or no. The results were analyzed using unweighted kappa statistic analysis for multiple raters.

Results:  The interobserver agreement was moderate on two slide circulations with kappa values of 0.50 (95% confidence interval 0.45–0.55) and 0.43 (0.38–0.47), respectively. The kappa value dropped significantly to 0.19 (0.09–0.29) on selected images photographed from controversial cases. The intraobserver agreement was moderate, with kappa values ranging from 0.23 to 0.56 (mean = 0.45).

Conclusions:  Pathologists can reproducibly recognize vascular invasion in many HCC cases but may have difficulty in equivocal cases, which may lead to either understaging or overstaging of the tumors. This may have a significant impact on prognostic assessment and therapeutic decision making. Our observations indicate the need for improved definition for vascular invasion in HCC.
Hepatocellular carcinoma with persistent hepatitis B virus infection shows unusual downregulation of Ras expression and differential response to Ras mediated signaling
Authors: Bose Sujoy , Sakhuja Puja , Bezawada Lavanaya , Agarwal Anil K , Kazim Seyed N , Khan Luqman A , Sarin Shiv K , Ramakrishna Gayatri
Published: February 2010

Background and Aim:  Persistent infection with hepatitis B virus (HBV) is a major etiological risk factor for hepatocellular carcinoma (HCC). The host cellular components involved in the progression of the carcinoma are still unclear. In the present study we aimed to evaluate Ras mediated signaling in hepatocellular carcinoma with persistent HBV infection.

Methods:  To gain insight into the role of Ras mediated signaling in HBV mediated carcinogenesis we evaluated Ras functionality by mutation analysis, reverse transcription‐polymerase chain reaction, immunohistochemistry (IHC), Ras‐guanosine triphosphate bound functionality assay and Ras‐mediated downstream signaling in a cohort of primary HCC tissues positive for HBV‐DNA.

Results:  Mutation in codon 12 of K‐ras appeared to be an uncommon event in the pathogenesis of HCC. We found unusually low levels of Ras expression in HCC compared with those with normal liver and chronic liver disease (cirrhosis and chronic hepatitis). Considerable heterogeneity was found with respect to Ras‐mediated signaling events (pRaf, pMAPK and pAKT). The hepatoma cell line (Hep3B) with integrated HBV showed upregulation in expression and activation of Ras and its downstream signaling in comparison to HBV a negative cell line (HepG2). The contrasting result between the cell lines and primary tumors is worthy of note.

Conclusions:  The unusual finding on downregulation of Ras expression in primary HCC tumors in the present study together with tumor heterogeneity with respect to Ras‐mediated signaling events prompts a new role of the wild type K‐Ras as a possible growth suppressor and a stochastic model for progression of hepatic cancer.
Effects of branched‐chain amino acid‐enriched nutrient for patients with hepatocellular carcinoma following radiofrequency ablation: A one‐year prospective trial
Authors: Kuroda Hidekatsu , Ushio Akira , Miyamoto Yasuhiro , Sawara Kei , Oikawa Kanta , Kasai Kazuhiro , Endo Ryujin , Takikawa Yasuhiro , Kato Akinobu , Suzuki Kazuyuki
Published: February 2010

Background and Aim:  This prospective control study examined whether supplementation with branched‐chain amino acid (BCAA)‐enriched nutrients can help maintain and improve residual liver function and nutritional status in cirrhotic patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).

Methods:  Subjects were 49 patients with hepatitis C‐related HCC who underwent RFA. Two groups were formed: BCAA group (BCAA‐enriched nutrient, aminoleban EN) and controls (standard diet only). Event‐free survival rate, liver function tests, and Short Form (SF)‐8 scores were evaluated in both groups before and one year after RFA. Energy metabolism using indirect calorimetry was measured before and after 3 months.

Results:  Complete data were obtained from 35 patients (BCAA group, n = 20; controls, n = 15). Six events (death, recurrence of HCC, rupture of esophageal varices and liver failure) occurred during the observation period, but frequencies of these events did not differ between groups. Event‐free survival rate tended to be higher in the BCA group than in controls. Among the parameters of liver function, serum albumin level was only significantly increased over 6 months, and remained at similar values for one year (P < 0.05). SF‐8 scores for general health, physical functioning, and social functioning were significantly elevated in the BCAA group (P < 0.05). Non‐protein respiratory quotient was significantly improved in the BCAA group (P < 0.01).

Conclusion:  Supplementation with BCAA‐enriched nutrients for one year in cirrhotic patients with HCC after RFA therapy can perform safety and improve both nutritional state and quality of life.
Sauna lung: Hypersensitivity pneumonitis due to Exophiala jeanselmei
Authors: HUANG Wei‐Chen , LU Yin‐Hsiu , LIN Zih‐Gong , SU Wen‐Lin
Published: February 2010

A 55‐year‐old man developed progressive cough and dyspnoea after regular attendance at a public steam bath. Hypoxaemia, diffuse pulmonary infiltrates and a predominance of lymphocytes with an increased percentage of CD8+ T cells in his bronchoalveolar lavage fluid suggested hypersensitivity pneumonitis. Microbial cultures from the steam bath room and tank identified Exophiala jeanselmei. Immunoblotting assays from the patient's serum confirmed the major antigenic stimulus. The patient recovered fully after systemic corticosteroid treatment and cessation of further exposure.
Local inflammation occurs before systemic inflammation in patients with COPD
Authors: HE Zhihui , CHEN Yan , CHEN Ping , WU Guobao , CAI Shan
Published: February 2010

Background and objective:  COPD is associated not only with an abnormal inflammatory response in the lung but also with systemic inflammation, including systemic oxidative stress, activation of circulating inflammatory cells and increased circulating levels of inflammatory cytokines. Understanding the nature and course of systemic inflammation in COPD is important given the potential for anti‐inflammatory therapy. This study explored whether local and systemic inflammation occur concurrently in patients with COPD.

Methods:  Forty‐four patients with stable COPD, 10 smoking controls and 10 non‐smoking controls were enrolled in this observational study. Induced sputum and peripheral blood samples were obtained simultaneously for measurement of inflammatory cell numbers and the concentrations of IL‐6 and CRP.

Results:  The total number of cells in the sputum total cell number, percentage of neutrophils and the concentration of IL‐6 were significantly higher in smoking controls and patients with COPD than in non‐smoking controls (P < 0.05 and P < 0.01, respectively). As the disease stage progressed, airway inflammatory cells and IL‐6 levels increased. CRP levels in sputum were significantly higher in stage II, III and IV COPD patients than in smoking and non‐smoking controls (P < 0.01). However, the peripheral WCC and percentage of neutrophils were similar in patients with COPD, smoking and non‐smoking controls. Circulatory concentrations of IL‐6 and CRP in stages III and IV COPD patients were significantly higher than in smoking and non‐smoking controls (P < 0.05 and P < 0.01, respectively). Additionally, there were positive correlations between sputum and blood IL‐6 and CRP levels (r = 0.566, P < 0.01 and r = 0.443, P < 0.01, respectively).

Conclusions:  The increase in the inflammatory cell population and IL‐6 and CRP levels in the airway may occur earlier than in the peripheral blood, and reflect the degree of airflow limitation better than do peripheral blood measurements. Systemic inflammation may be present in patients with severe or very severe COPD.
Role of targeted therapy in the treatment of advanced prostate cancer
Authors: Fizazi Karim , Sternberg Cora N. , Fitzpatrick John M. , Watson R. William , Tabesh Majid
Published: February 2010

Over the past decade, the treatment of advanced prostate cancer has developed significantly, and perhaps the most dramatic shift came in 2004 with the demonstration that docetaxel‐based chemotherapy significantly improved overall survival in patients with castration‐resistant prostate cancer. This led to a significant expansion of the role of chemotherapy in the management of prostate cancer. In addition, there is now considerable progress being made in the development of more effective antiandrogens, cytochrome P17 inhibitors, novel chemotherapy regimens, targeted therapies, and immunotherapies that can complement existing therapies and may soon become integrated into the treatment paradigm. Progress in our understanding of molecular signalling pathways that play an important role in prostate cancer has stimulated the investigation of targeted therapies, including antiangiogenic agents, bone‐targeted agents, and specific inhibitors of key signalling molecules and chaperone proteins. For the most part, targeted agents are being combined with chemotherapy, similar to the approach taken in other solid tumours. Various therapeutic vaccine strategies also appear to have potential in the treatment of advanced prostate cancer. However, the development of new approaches to the treatment of prostate cancer presents many challenges that will demand collaboration and consensus building with respect to biomarkers for patient selection, clinical endpoints, and trial designs.
OPTIMAL COMPETITIVE BALANCE IN A SEASON TICKET LEAGUE
Authors: FORT RODNEY , QUIRK JAMES
Published: February 2010

Theory predicts that a planner maximizing the sum of fan and owner surpluses from a league dominated by season ticket sales may prefer more, less, or the same level of competitive balance produced by a league of profit‐maximizing owners. The optimal level of balance depends on the relationship between marginal impacts of talent rearrangements in larger‐revenue and smaller‐revenue markets. Ultimately, then, judging whether an increase in balance enhances welfare rests on careful and thorough empirical investigation. Our reading of the literature and the policy debate shows that this careful work remains to be done. (JEL D6, L83)
The Value Relevance of Management Forecasts and Their Impact on Analysts' Forecasts: Empirical Evidence From Japan
Authors: OTA KOJI
Published: February 2010

A major financial disclosure feature in Japan is that stock exchanges require firms to provide next year's earnings forecasts. This study investigates the value relevance of Japanese management earnings forecasts and their impact on analysts' earnings forecasts. First, the value relevance of management forecasts is investigated using a valuation framework provided by Ohlson (2001), in which firm value is expressed as a function of book value, current earnings and next year's expected earnings. The analysis yields that of the three accounting variables examined, management forecasts have the highest correlation and incremental explanatory power with stock price.

Next, the impact of management forecasts on analysts' forecasts is examined. The results show that more than 90% of changes in analysts' forecasts are explained by management forecasts alone. Further analysis reveals that the heavy dependence of financial analysts on management forecasts in formulating their own forecasts may partially be attributed to the relatively high accuracy of management forecasts. At the same time, financial analysts also somewhat modify management forecasts when certain financial factors indicate that the credibility of management forecasts is in doubt.

Overall, this study presents empirical evidence that Japanese management forecasts provide useful information for the market and have a significant influence on analysts' forecasts.
Phonological awareness in young Chinese children
Authors: Shu Hua , Peng Hong , McBride‐Chang Catherine
Published: February 2010

Two studies explored the nature of phonological awareness (PA) in Chinese. In Study 1, involving 146 children, awareness of phoneme onset did not differ from chance levels at ages 3–5 years in preschool but increased to 70% correct in first grade, when children first received phonological coding (Pinyin) instruction. Similarly, tone awareness was at better than chance levels from second year kindergarten (age 4), but increased strongly and significantly in first grade to 74% accuracy. In contrast, syllable and rime awareness increased gradually and steadily across ages 3–6 years. Patterns suggest different influences of age and literacy instruction for different PA levels. In Study 2, involving 202 preschoolers, variance in Chinese character recognition was best explained by tasks of syllable awareness, tone awareness, and speeded naming. Findings underscore the unique importance of both tone and syllable for early character acquisition in Chinese children.
Emergence of syntax: commonalities and differences across children
Authors: Vasilyeva Marina , Waterfall Heidi , Huttenlocher Janellen
Published: February 2010

This paper presents the results of a longitudinal examination of syntactic skills, starting at the age of emergence of simple sentences and continuing through the emergence of complex sentences. We ask whether there is systematic variability among children from different socioeconomic backgrounds in the early stages of sentence production. The results suggest a different answer for simple versus complex sentences. We found a striking similarity across SES groups on the measures tapping early mastery of basic syntactic rules of simple sentences. At the same time, there was a significant difference between SES groups in the mastery of complex sentence structures. This difference emerged at the earliest stages of production of multi‐clause sentences and persisted throughout the period of observation. The implications of these findings for the understanding of mechanisms of syntactic development are discussed.
Young Humeans: the role of emotions in children's evaluation of moral reasoning abilities
Authors: Danovitch Judith H. , Keil Frank C.
Published: February 2010

Three experiments investigated whether children in grades K, 2, and 4 (n =144) view emotional comprehension as important in solving moral dilemmas. The experiments asked whether a human or an artificially intelligent machine would be best at solving different types of problems, ranging from moral and emotional to nonmoral and pragmatic. InExperiment 1, children in all age groups indicated that a human would be superior to a computer not only at comprehending emotions, but also at solving moral dilemmas. InExperiment 2, older children also indicated that a human could solve moral dilemmas better than a ‘robot’ with human‐like perceptual and physical abilities.Experiment 3further demonstrated that these effects were not solely due to a bias towards humans. Thus, children as young as age 5 view emotional understanding as an important element for moral, but not for nonmoral, reasoning, suggesting that the basis for Humean intuitions emerges early in life.
Development of using experimenter‐given cues in infant chimpanzees: longitudinal changes in behavior and cognitive development
Authors: Okamoto‐Barth Sanae , Tomonaga Masaki , Tanaka Masayuki , Matsuzawa Tetsuro
Published: February 2010

The use of gaze shifts as social cues has various evolutionary advantages. To investigate the developmental processes of this ability, we conducted an object‐choice task by using longitudinal methods with infant chimpanzees tested from 8 months old until 3 years old. The experimenter used one of six gestures towards a cup concealing food; tapping, touching, whole‐hand pointing, gazing plus close‐pointing, distant‐pointing, close‐gazing, and distant‐gazing. Unlike any other previous study, we analyzed the behavioral changes that occurred before and after choosing the cup. We assumed that pre‐choice behavior indicates the development of an attentional and spatial connection between a pointing cue and an object (e.g. Woodward, 2005); and post‐choice behavior indicates the emergence of object permanence (e.g. Piaget, 1954). Our study demonstrated that infant chimpanzees begin to use experimenter‐given cues with age (after 11 months of age). Moreover, the results from the behavioral analysis showed that the infants gradually developed the spatial link between the pointing as an object‐directed action and the object. Moreover, when they were 11 months old, the infants began to inspect the inside of the cup, suggesting the onset of object permanence. Overall, our results imply that the ability to use the cues is developing and mutually related with other cognitive developments. The present study also suggests what the standard object‐choice task actually measures by breaking the task down into the developmental trajectories of its component parts, and describes for the first time the social‐physical cognitive development during the task with a longitudinal method.
Fearful faces modulate looking duration and attention disengagement in 7‐month‐old infants
Authors: Peltola Mikko J. , Leppänen Jukka M. , Palokangas Tiina , Hietanen Jari K.
Published: February 2010

The present study investigated whether facial expressions modulate visual attention in 7‐month‐old infants. First, infants’ looking duration to individually presented fearful, happy, and novel facial expressions was compared to looking duration to a control stimulus (scrambled face). The face with a novel expression was included to examine the hypothesis that the earlier findings of greater allocation of attention to fearful as compared to happy faces could be due to the novelty of fearful faces in infants’ rearing environment. The infants looked longer at the fearful face than at the control stimulus, whereas no such difference was found between the other expressions and the control stimulus. Second, a gap/overlap paradigm was used to determine whether facial expressions affect the infants’ ability to disengage their fixation from a centrally presented face and shift attention to a peripheral target. It was found that infants disengaged their fixation significantly less frequently from fearful faces than from control stimuli and happy faces. Novel facial expressions did not have a similar effect on attention disengagement. Thus, it seems that adult‐like modulation of the disengagement of attention by threat‐related stimuli can be observed early in life, and that the influence of emotionally salient (fearful) faces on visual attention is not simply attributable to the novelty of these expressions in infants’ rearing environment.
Developmental changes in children's understanding of the similarity between photographs and their referents
Authors: Uttal David H. , Gentner Dedre , Liu Linda L. , Lewis Alison R.
Published: February 2010

In a series of three experiments, we investigated the development of children's understanding of the similarities between photographs and their referents. Based on prior work on the development of analogical understanding (e.g. Gentner & Rattermann, 1991), we suggest that the appreciation of this relation involves multiple levels. Photographs are similar to their referents both in terms of the constituent objects and in terms of the relations among these objects. We predicted that children would appreciate object similarity (whether photographs depict the same objects as in the referent scene) before they would appreciate relational similarity (whether photographs depict the objects in the same spatial positions as in the referent scene). To test this hypothesis, we presented 3‐, 4‐, 5‐, 6‐, and 7‐year‐old children and adults with several candidate photographs of an arrangement of objects. Participants were asked to choose which of the photographs was ‘the same’ as the arrangement. We manipulated the types of information the photographs preserved about the referent objects. One set of photographs did not preserve the object properties of the scene. Another set of photographs preserved the object properties of the scene, but not the relational similarity, such that the original objects were depicted but occupied different spatial positions in the arrangement. As predicted, younger children based their choices of the photographs largely on object similarity, whereas older children and adults also took relational similarity into account. Results are discussed in terms of the development of children's appreciation of different levels of similarity.
Neural substrates for processing task‐irrelevant sad images in adolescents
Authors: Wang Lihong , Huettel Scott , De Bellis Michael D.
Published: February 2010

Neural systems related to cognitive and emotional processing were examined in adolescents using event‐related functional magnetic resonance imaging (fMRI). Ten healthy adolescents performed an emotional oddball task. Subjects detected infrequent circles (targets) within a continual stream of phase‐scrambled images (standards). Sad and neutral images were intermittently presented as task‐irrelevant distracters (novels). As previously shown for adults, when the adolescents responded to the task‐relevant targets, activation increased in the dorsal attention‐executive system including the anterior middle frontal gyrus (aMFG), dorsal anterior cingulate (ACG), posterior cingulate (PCG), insula, and supramarginal gyrus (SMG). Unlike adults, however, the adolescents exhibited strong activation to the emotional distracter images not only in the ventromedial prefrontal cortex (VmPFC), but also in the posterior middle frontal gyrus (pMFG) and in the parietal cortex. Those subjects who had stronger VmPFC activation to emotional distraction also had reduced activation in the aMFG during target detection, suggesting that emotional information may interfere with executive processing in these adolescents. In contrast, pMFG and PCG activation to emotional distracters was positively correlated with aMFG activation to targets, indicating a different role of these regions from the VmPFC. The pattern of activation to task‐irrelevant emotional distraction suggests a possible immaturity of brain function in cognitive control over emotional distraction in adolescents.