bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Pou3f3/Brn‐1 and its genomic methylation in developing auditory epithelium
Authors: Mutai Hideki , Nagashima Reiko , Sugitani Yoshinobu , Noda Tetsuo , Fujii Masato , Matsunaga Tatsuo
Published: September 2009

In the mammalian cochlea, both the sensory cells—called hair cells (HCs)—and nonsensory cells such as supporting cells (SCs) and mesenchymal cells participate in proper auditory function through the expression of various functional molecules. During development, expression of certain genes is repressed through genomic methylation, one of the major epigenetic regulatory mechanisms. We explored the genomic regions that were differentially methylated in rat auditory epithelium at postnatal day 1 (P1) and P14 using amplification of intermethylated sites (AIMS). An AIMS fragment was mapped to the 3′‐flanking region of Pou3f3/Brn‐1. Bisulfite‐converted PCR and quantitative methylation‐specific PCR showed that the methylation frequency of the AIMS region and the adjacent CpG island was increased at P14, when the expression of Pou3f3 and the noncoding RNAs nearby decreased. Expression of de novo DNA methyltransferases 3a and 3b also suggests a role of epigenetic regulation during postnatal inner ear development. Immunohistochemical analysis showed that Pou3f3 was expressed specifically in the SCs and mesenchymal cells in the cochlea and established that Pou3f3 is a new cell‐type marker for studying inner ear development. Mice deficient in Pou3f3 or Pou3f2 plus Pou3f3 did not exhibit any abnormality in the embryonic cochlea. Absence of Pou3f3 affected neither the proliferation nor the differentiation activities of HC progenitor cells. Pou3f3 may, however, be important for the maintenance or functional development of the postnatal cochlea. This is the first report to study involvement of an epigenetic regulatory mechanism in the developing mammalian auditory epithelium. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009
Ethnocultural identification and naturally occurring interethnic social interactions: Muslim minorities in Europe
Authors: Schaafsma Juliette , Nezlek John B. , Krejtz Izabela , Safron Magdalena
Published: September 2009

This study examined relationships between ethnic identification and ethnic minority members' interactions with majority group members. Members of Muslim minority groups, ethnic Turks and Moroccans in the Netherlands and Chechens in Poland, described the social interactions they had for two weeks using a variant of the Rochester Interaction Record (RIR). They also completed measures of ethnocultural identification that distinguished involvement with and attachment to their ethnic minority culture and to the majority culture. Relationships between ethnic identification and contact with the majority group varied as a function of the dimension and source of identification and the aspect of interaction (quantity or quality) being considered. Across the samples, involvement with the ethnic minority culture was negatively related to the quantity of contact with majority group members, whereas emotional attachment to the majority culture was positively related to the quality of interactions with majority group members. Attachment to the ethnic minority culture was not related to either the quantity of interaction with majority group members or to the quality of these interactions. These results suggest that when studying interethnic contact, it is important to distinguish different dimensions and sources of ethnic identification and different aspects of interethnic contact. Copyright © 2009 John Wiley & Sons, Ltd.
Social sharing of emotion, post‐traumatic growth, and emotional climate: Follow‐up of Spanish citizen's response to the collective trauma of March 11th terrorist attacks in Madrid
Authors: Rimé Bernard , Páez Darío , Basabe Nekane , Martínez Francisco
Published: September 2009

A questionnaire measuring social sharing of emotion, coping, intensity of emotions and rumination related to March 11th (2004) terrorist attacks in Madrid, emotional climate, social integration, and post‐traumatic growth was completed by 644 students and their relatives (38%) in 5 Spanish regions and 8 universities 1 week, 3 weeks, and 8 weeks after the terrorist act. Results supported a two‐sided model of the effects of social sharing of emotion derived from Durkheim's classic model of the social functional effects of collective remembering. Higher levels of sharing initially predicted (1) higher event‐related emotional arousal and mental rumination and (2) superior social integration and well‐being assessed in later weeks. Structural equation modeling showed that higher levels of initial sharing and coping by search for social support predicted directly or indirectly (1) higher social integration (2) higher perceived post‐traumatic growth, and (3) higher perceived contentment, hope, solidarity, and confidence in the emotional climate. Copyright © 2009 John Wiley & Sons, Ltd.
Watching over your own: How surveillance moderates the impact of shared identity on perceptions of leaders and follower behaviour
Authors: O'Donnell Aisling T. , Jetten Jolanda , Ryan Michelle K.
Published: September 2009

In two studies we investigate how level of surveillance moderates followers' responses to leaders with whom they either do or do not share identity. Study 1 (N = 80) demonstrated that imposing high surveillance where identity is shared with a leader undermined perceptions of the leader as a team member, reducing levels to that of leaders without a shared identity. Study 2 (N = 84) replicated this finding, also demonstrating that willingness to work for the group declined when leaders with shared identity used high surveillance (compared to a low surveillance condition). This process was partially explained by perceptions that surveillance was an invasion of privacy. Together, these studies illustrate that the benefits of shared identity are easily undermined when a leader uses surveillance in a context where it is unnecessary. Copyright © 2009 John Wiley & Sons, Ltd.
I think I like you: Spontaneous and deliberate evaluations of potential romantic partners in an online dating context
Authors: Sritharan Rajees , Heilpern Kimberly , Wilbur Christopher J. , Gawronski Bertram
Published: September 2009

The present research examined processes of impression formation within an online dating context. Across two studies, female participants formed impressions of a potential partner based on an online dating profile containing information about the target's facial attractiveness and self‐described ambition. Afterwards, deliberate evaluations of the target were assessed with a self‐report measure and spontaneous evaluations were measured with an affective priming task. The results showed that deliberate evaluations varied as a function of both self‐described ambition and facial attractiveness. In contrast, spontaneous evaluations varied only as a function of facial attractiveness. Experiment 2 further showed that these effects were independent of the order in which the two types of information had been encoded. The results are discussed in terms of associative and propositional processes, and the conditions under which these processes can lead to conflicting evaluations of the same potential romantic partner. Copyright © 2009 John Wiley & Sons, Ltd.
Network traffic routing using effective bandwidth theory
Authors: Kozakiewicz Adam , Malinowski Krzysztof
Published: September 2009

Optimal routing in a packet network is a difficult task—the amount of connections makes per‐connection routing impractical and even using aggregated connections global optimisation in the network is infeasible. The currently used algorithms are therefore suboptimal heuristics, using shortest path computation instead of e.g. throughput optimisation. The quality of obtained results depends on the selected link weights, but optimisation of those is again a difficult mixed integer‐programming problem. In this paper we discuss some proposed heuristics using the results of large deviation analysis (effective bandwidths) for throughput optimisation. The more advanced approach to traffic modelling uses more of the available information and potentially allows for finding better solutions. The presented algorithms are tested through simulation and discussion of the results is included. Copyright © 2009 John Wiley & Sons, Ltd.
Serum Proteomics and Biomarker Discovery Across the Spectrum of Nonalcoholic Fatty Liver Disease
Authors: Bell Lauren N. , Theodorakis Janice L. , Vuppalanchi Raj , Saxena Romil , Bemis Kerry G. , Wang Mu , Chalasani Naga
Published: September 2009

Nonalcoholic fatty liver disease (NAFLD), ranging from relatively benign simple steatosis to progressive nonalcoholic steatohepatitis (NASH) and fibrosis, is an increasingly common chronic liver disease. Liver biopsy is currently the only reliable tool for staging the subtypes of NAFLD; therefore, noninvasive serum biomarkers for evaluation of liver disease and fibrosis are urgently needed. We performed this study to describe changes in the serum proteome and identify biomarker candidates in serum samples from 69 patients with varying stages of NAFLD (simple steatosis, NASH, and NASH with advanced bridging [F3/F4] fibrosis) and 16 obese controls. Using a label-free mass spectrometry-based approach we identified over 1,700 serum proteins with a peptide identification (ID) confidence level of >75%, 605 of which changed significantly between any two patient groups (false discovery rate <5%). Importantly, expression levels of 55 and 15 proteins changed significantly between the simple steatosis and NASH F3/F4 group and the NASH and NASH F3/F4 group, respectively. Classification of proteins with significant changes showed involvement in immune system regulation and inflammation, coagulation, cellular and extracellular matrix structure and function, and roles as carrier proteins in the blood. Further, many of these proteins are synthesized exclusively by the liver and could potentially serve as diagnostic biomarkers for identifying and staging NAFLD.

Conclusion

: This proteomic analysis reveals important information regarding the pathogenesis/progression of NAFLD and NASH and demonstrates key changes in serum protein expression levels between control subjects and patients with different stages of fatty liver. Future validation of these potential biomarkers is needed such that these proteins may be used in place of liver biopsy to facilitate diagnosis and treatment of patients with NAFLD. (Hepatology 2009.)
Protective Effect of Human Leukocyte Antigen B27 in Hepatitis C Virus Infection Requires the Presence of A Genotype-Specific Immunodominant Cd8+ T-Cell Epitope
Authors: Neumann-Haefelin Christoph , Timm Jörg , Schmidt Julia , Kersting Nadine , Fitzmaurice Karen , Oniangue-Ndza Cesar , Kemper Michael N. , Humphreys Isla , McKiernan Susan , Kelleher Dermot , Lohmann Volker , Bowness Paul , Huzly Daniela , Rosen Hugo R. , Kim Arthur Y. , Lauer Georg M. , Allen Todd M. , Barnes Eleanor , Roggendorf Michael , Blum Hubert E. , Thimme Robert
Published: September 2009

Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role has been described, with the corresponding region in genotype 3 that differs in its sequence by three amino acid residues. The genotype 3a peptide was not recognized by CD8+ T cells specific for the genotype 1 peptide. Furthermore, patients with acute or chronic infection with HCV genotype 3a did not mount T-cell responses to this epitope region, and their autologous viral sequences showed no evidence of T-cell pressure. Finally, we found a significantly higher frequency of HLA-B27 positivity in patients with chronic HCV genotype 3a infection compared to genotype 1 infection, indicating that there is no protection by HLA-B27 in HCV genotype 3 infection.

Conclusion:

Our data indicate that the protective effect of HLA-B27 is limited to HCV genotype 1 infection and does not expand to other genotypes such as genotype 3a. This can most likely be explained by intergenotype sequence diversity leading to the loss of the immunodominant HLA-B27 epitope in viral strains other than genotype 1. Our results underline the central role of a single HLA-B27-restricted epitope-specific CD8+ T-cell response in mediating protection in HCV genotype 1 infection. (Hepatology 2010;51:54–62.)
Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic, and Clinical Implications
Authors: Fabbrini Elisa , Sullivan Shelby , Klein Samuel
Published: September 2009

Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and

de novo

fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low-density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity. (Hepatology 2009.)
Down-Regulation of Connective Tissue Growth Factor by Inhibition of Transforming Growth Factor β Blocks the Tumor–Stroma Cross-Talk and Tumor Progression in Hepatocellular Carcinoma
Authors: Mazzocca Antonio , Fransvea Emilia , Dituri Francesco , Lupo Luigi , Antonaci Salvatore , Giannelli Gianluigi
Published: September 2009

Tumor–stroma interactions in hepatocellular carcinoma (HCC) are of key importance to tumor progression. In this study, we show that HCC invasive cells produce high levels of connective tissue growth factor (CTGF) and generate tumors with a high stromal component in a xenograft model. A transforming growth factor β (TGF-β) receptor inhibitor, LY2109761, inhibited the synthesis and release of CTGF, as well as reducing the stromal component of the tumors. In addition, the TGF-β–dependent down-regulation of CTGF diminished tumor growth, intravasation, and metastatic dissemination of HCC cells by inhibiting cancer-associated fibroblast proliferation. By contrast, noninvasive HCC cells were found to produce low levels of CTGF. Upon TGF-β1 stimulation, noninvasive HCC cells form tumors with a high stromal content and CTGF expression, which is inhibited by treatment with LY2109761. In addition, the acquired intravasation and metastatic spread of noninvasive HCC cells after TGF-β1 stimulation was blocked by LY2109761. LY2109761 interrupts the cross-talk between cancer cells and cancer-associated fibroblasts, leading to a significant reduction of HCC growth and dissemination. Interestingly, patients with high CTGF expression had poor prognosis, suggesting that treatment aimed at reducing TGF-β–dependent CTGF expression may offer clinical benefits.

Conclusion:

Taken together, our preclinical results indicate that LY2109761 targets the cross-talk between HCC and the stroma and provide a rationale for future clinical trials. (Hepatology 2009.)
Systematic Review of Randomized Trials on Vasoconstrictor Drugs for Hepatorenal Syndrome
Authors: Gluud Lise L. , Christensen Kurt , Christensen Erik , Krag Aleksander
Published: September 2009

Vasoconstrictor drugs may improve renal function in hepatorenal syndrome (HRS), but the effect on mortality has not been established. We therefore performed a systematic review of randomized trials on vasoconstrictor drugs for type 1 or type 2 HRS. Mortality was the primary outcome measure. Eligible trials were identified through electronic and manual searches. Intention-to-treat random effects meta-analyses were performed. Ten randomized trials on terlipressin alone or with albumin, octreotide plus albumin, and noradrenalin plus albumin were included. The total number of patients was 376. Overall, vasoconstrictor drugs used alone or with albumin reduced mortality compared with no intervention or albumin (relative risk [RR], 0.82; 95% confidence interval [CI], 0.70–0.96). In subgroup analyses, the effect on mortality was seen at 15 days (RR, 0.60; 95% CI, 0.37–0.97) but not at 30 days (RR, 0.74; 95% CI, 0.40–1.39), 90 days (RR, 0.89; 95% CI, 0.66–1.22), or 180 days (RR, 0.83; 95% CI, 0.65–1.05). Subgroup analyses stratified by the treatments assessed showed that terlipressin plus albumin reduced mortality compared with albumin (RR, 0.81; 95% CI, 0.68–0.97). The effect was seen in subgroup analyses of type 1 but not type 2 HRS. The remaining trials were small and found no beneficial or harmful effects of the treatments assessed.

Conclusion:

Terlipressin plus albumin may prolong short-term survival in type 1 HRS. The duration of the response should be considered when making treatment decisions and in the timing of potential liver transplantations. Considering the small number of patients included, the evidence does not allow for treatment recommendations regarding type 2 HRS or any of the remaining treatment comparisons assessed. (Hepatology 2009.)
Mechanisms for Increased Expression of Cholesterol 7α-Hydroxylase (Cyp7a1) in Lactating Rats
Authors: Wooton-Kee Clavia Ruth , Coy Donna J. , Athippozhy Antony T. , Zhao Tianyong , Jones Brett R. , Vore Mary
Published: September 2009

Cholesterol 7α-hydroxylase (Cyp7a1) and the bile acid pool size are increased 2 to 3-fold in lactating postpartum rats. We investigated the interaction of nuclear receptors with the

Cyp7a1

proximal promoter and the expression of regulatory signaling pathways in postpartum rats at day 10 (PPd10) versus female controls to identify the mechanisms of increased expression of Cyp7a1, which is maximal at 16 hours. Liver X receptor (LXRα) and RNA polymerase II (RNA Pol II) recruitment to Cyp7a1 chromatin were increased 1.5- and 2.5-fold, respectively, at 16 hours on PPd10. Expression of nuclear receptors farnesoid X receptor (FXR), LXRα, liver receptor homolog (LRH-1), hepatocyte nuclear factor 4α (HNF4α), and short heterodimer partner (SHP) messenger RNA (mRNA) and coactivator peroxisome proliferators-activated receptor γ coactivator-1α (PGC-1α) mRNA was unchanged in PPd10 versus controls at 16 hours, whereas chicken ovalbumin upstream transcription factor II (COUP-TFII) was decreased 40% at 16 hours. Investigation of a repressive signaling pathway, the c-Jun-N-terminal kinase (JNK) signaling pathway in PPd10 versus controls, showed decreased mRNA expression of hepatocyte growth factor (HGF; decreased 60% at 16 hours) and tyrosine kinase receptor c-Met (decreased 44%–50% at 16 hours), but these were not accompanied by decreased expression of phosphorylated c-Jun. Importantly, expression of fibroblast growth factor 15 (FGF15) mRNA in the ileum was decreased 70% in PPd10 versus controls, whereas phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Erk1/2) protein expression in liver was decreased 88% at 16 hours.

Conclusion

: The increased recruitment of LXRα, a Cyp7a1 stimulatory pathway, and decreased expression of FGF15 and phosphorylated Erk1/2, a Cyp7a1 repressive pathway, combined to increase Cyp7a1 expression during lactation. (Hepatology 2009.)
Kupffer Cell and Interleukin-12–Dependent Loss of Natural Killer T Cells in Hepatosteatosis
Authors: Kremer Michael , Thomas Emmanuel , Milton Richard J. , Perry Ashley W. , van Rooijen Nico , Wheeler Michael D. , Zacks Steven , Fried Michael , Rippe Richard A. , Hines Ian N.
Published: September 2009

Hepatosteatosis is associated with increased expression of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-12, major T helper (Th) 1 cytokines, and reduced hepatic natural killer T (NKT) cell numbers. The relationship between lipid accumulation, cytokine expression, and hepatic NKT cells is not known. This study was conducted to assess the role of IL-12 in the development of hepatic steatosis and its potential impact on liver NKT cells. Male C57Bl/6 wildtype (WT) and IL-12-deficient (IL-12−/−) mice were fed a choline-deficient diet (CDD) for 0, 10, or 20 weeks. CDD led to marked hepatosteatosis, reduced hepatic but not splenic NKT cell numbers and function, and increased hepatic expression of the Th1-type cytokines IL-12, interferon gamma (IFN-γ), and TNF-α in WT mice. The absence of IL-12 resulted in similar CDD-induced hepatosteatosis, but preserved hepatic NKT cells and significantly reduced hepatic IFN-γ and TNF-α expression. Treatment of CDD-fed mice with lipopolysaccharide led to a significant increase in hepatic IL-12 expression, and Kupffer cell (KC) depletion reduced liver IL-12 expression and restored NKT cells in CDD-induced fatty liver. Interestingly, KCs from CDD-fed mice failed to produce increased quantities of IL-12 upon activation

in vitro

when compared to similarly treated KCs from control fed mice, suggesting that secondary factors

in vivo

promote heightened IL-12 production. Finally, human livers with severe steatosis showed a substantial decrease in NKT cells.

Conclusion:

Hepatosteatosis reduces the numbers of hepatic NKT cells in a KC-and IL-12-dependent manner. Our results suggest a pivotal and multifunctional role of KC-derived IL-12 in the altered immune response in steatotic liver, a process that is likely active within human nonalcoholic fatty liver disease. (Hepatology 2010;51:130–141.)
Cost-Effectiveness of Nationwide Hepatitis B Catch-Up Vaccination Among Children and Adolescents in China
Authors: Hutton David W. , So Samuel K. , Brandeau Margaret L.
Published: September 2009

Liver disease and liver cancer associated with childhood-acquired chronic hepatitis B are leading causes of death among adults in China. Despite expanded newborn hepatitis B vaccination programs, approximately 20% of children under age 5 years and 40% of children aged 5 to 19 years remain unprotected from hepatitis B. Although immunizing them will be beneficial, no studies have examined the cost-effectiveness of hepatitis B catch-up vaccination in an endemic country like China. We examined the cost-effectiveness of a hypothetical nationwide free hepatitis B catch-up vaccination program in China for unvaccinated children and adolescents aged 1 to 19 years. We used a Markov model for disease progression and infections. Cost variables were based on data published by the Chinese Ministry of Health, peer-reviewed Chinese and English publications, and the GAVI Alliance. We measured costs (2008 U.S. dollars and Chinese renminbi), quality-adjusted life years, and incremental cost-effectiveness from a societal perspective. Our results show that hepatitis B catch-up vaccination for children and adolescents in China is cost-saving across a range of parameters, even for adolescents aged 15 to 19 years old. We estimate that if all 150 million susceptible children under 19 were vaccinated, more than 8 million infections and 65,000 deaths due to hepatitis B would be prevented.

Conclusion

: The adoption of a nationwide free catch-up hepatitis B vaccination program for unvaccinated children and adolescents in China, in addition to ongoing efforts to improve birth dose and newborn vaccination coverage, will be cost-saving and can generate significant population-wide health benefits. The success of such a program in China could serve as a model for other endemic countries. (Hepatology 2009.)
Expression and Functional Significance of Twist1 in Hepatocellular Carcinoma: Its Role in Vasculogenic Mimicry
Authors: Sun Tao , Zhao Nan , Zhao Xiu-lan , Gu Qiang , Zhang Shi-wu , Che Na , Wang Xing-hui , Du Jing , Liu Yi-xin , Sun Bao-cun
Published: September 2009

The up-regulation and nuclear relocation of epithelial-mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM-positive HCCs (13/18 [72%]). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)-cadherin promoter and enhances its activity in a transactivation assay.

Conclusion:

The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E-cadherin expression and the induction of VE-cadherin up-regulation than through the VM pattern

in vivo

and in a three-dimensional

in vitro

system. Our findings also demonstrate a novel cogitation in cancer stem-like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis. (Hepatology 2009.)
Adjunctive use of lithium carbonate for the management of neutropenia in clozapine‐treated children
Authors: Mattai Anand , Fung Lawrence , Bakalar Jennifer , Overman Gerald , Tossell Julia , Miller Rachel , Rapoport Judith , Gogtay Nitin
Published: September 2009

Objective

Clozapine, a dibenzodiazepine antipsychotic, is the most effective medication for treatment‐resistant schizophrenia. However, its use has been limited by the high risk of neutropenia. In children, the rate of neutropenia is higher when compared to adults. We decided to explore the use of lithium to manage neutropenia in childhood‐onset schizophrenia (COS) through a systematic audit of COS cases.

Methods

Medical records were reviewed for patients with COS who had been treated with the combination of clozapine and lithium carbonate.

Results

Seven patients were found to have been treated with both clozapine and lithium. After initiation of lithium, ANC increased significantly in six out of seven subjects by 29 to 106% with a mean of 66%. In addition, six out of seven subjects continued using both clozapine and lithium for over 2 years (range: 2.0–7.2 years) and do not have immediate plans for discontinuation of either medications.

Conclusions

Our study bolsters support for the use of lithium in the management of neutropenia in children treated with clozapine. Although the coadministration of lithium and clozapine appears effective in the management of neutropenia, it is not without its risks and clinicians must be diligent in their joint use of these medications. Published in 2009 by John Wiley & Sons, Ltd.
Long‐term exposure to bis(2‐ethylhexyl)phthalate (DEHP) inhibits growth of guppy fish (Poecilia reticulata)
Authors: Zanotelli Vito R.T. , Neuhauss Stephan C.F. , Ehrengruber Markus U.
Published: September 2009

Bis(2‐ethylhexyl)phthalate (DEHP) is a widely used plasticizer that is a commonly found contaminant of aquatic environments. However, little is known about the long‐term effects of DEHP on fish development, as previous studies yielded conflicting results and mostly investigated the effects of concentrations higher than those found in natural habitats. We thus aimed to investigate the effects of DHEP (i) at concentrations present in the environment, and (ii) under conditions that might accentuate any deleterious consequences (larvae rather than adult fish, use of higher temperature). Different concentrations of DEHP (0.1–10 µg l−1rpar; applied continuously for 91 days were tested on guppy fish that were less than one week old at the beginning of the treatment. As early as 14 days after the start of exposure, guppies treated with 10 µg l−1 DEHP showed significantly reduced body length as compared with control fish. The inhibitory effect of DEHP was concentration‐dependent and increased with time, leading to a maximal reduction in body length of 15 and 40% at 1 and 10 µg l−1 DEHP, respectively. The effect was even more pronounced for body weight, which was diminished by up to 40 and 70% at 1 and 10 µg l−1 DEHP, respectively. The reduction in growth was still significant at 91 days of DEHP treatment, whereas the Fulton's condition factor was unaffected. While DEHP significantly blocked growth in both male and female guppies, no shift in the sexual development was observed. These data show that DEHP, at concentrations present in aquatic environments, can profoundly affect development in fish. Copyright © 2009 John Wiley & Sons, Ltd.
Fluoride‐induced changes in haem biosynthesis pathway, neurological variables and tissue histopathology of rats
Authors: Chouhan Swapnila , Lomash Vinay , Flora S.J.S.
Published: September 2009

This study intended to determine the effects of various concentrations of fluoride (1, 10, 50 and 100 ppm) in drinking water for a period of 12 weeks on changes in haem biosynthesis pathway, oxidative stress and neurological variables supported by histopathological observations and fluoride in rats. The data indicates significant alterations in the parameters related to haeme synthesis pathway like inhibition of blood δ‐aminolevulinic acid dehydratase, δ‐aminolevulinic acid synthetase, oxidative stress like depletion of glutathione (GSH) and increase in oxidized glutathione (GSSG) and thiobarbituric acid reactive substances. These changes were accompanied by depletion in GSH:GSSG ratio, whole brain biogenic amine levels and a dose‐dependent increase in fluoride concentration. Interestingly and most significantly, these changes were more pronounced at lower concentrations of fluoride compared with higher fluoride dose. Biochemical changes were supported by the histological observations, which also revealed that at high concentrations of fluoride, toxic effects and damages to organs were more pronounced. These changes support our earlier findings regarding the role of decreased ionic mobility of fluoride ion at higher concentrations, leading to less pronounced toxicity. Copyright © 2009 John Wiley & Sons, Ltd.
Evaluation of aging influence on renal toxicity caused by segment‐specific nephrotoxicants of the proximal tubule in rat†
Authors: Zanetti Edoardo , Chiusolo Arianna , Defazio Rossella , Casartelli Alessandro , Cappelletti Eleonora , Bocchini Nicola , Chiara Federica , Cristofori Patrizia , Trevisan Andrea
Published: September 2009

Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age‐dependent response of the kidney to hexachloro‐1 : 3‐butadiene (HCBD) or potassium dichromate (chromate) was investigated. Rats were treated at different ages with a single dose of segment‐specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S3 and for S1–S2 segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S3 segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. In contrast, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S1–S2 segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirmed a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD‐induced damage and evidence differential age‐related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed. Copyright © 2009 John Wiley & Sons, Ltd.
In vivo fiber‐based multicolor photoacoustic detection and photothermal purging of metastasis in sentinel lymph nodes targeted by nanoparticles
Authors: Galanzha Ekaterina I. , Kokoska Mimi S. , Shashkov Evgeny V. , Kim Jin‐Woo , Tuchin Valery V. , Zharov Vladimir P.
Published: September 2009

This report introduces a novel diagnostic and therapeutic platform for in vivo non‐invasive detection and treatment of metastases in sentinel lymph nodes (SLNs) at single cell level using an integrated system of multicolor photoacoustic (PA) lymph flow cytometry, PA lymphography, absorption image cytometry, and photothermal (PT) therapy. A melanoma‐bearing mouse model was used to demonstrate the capability of this platform for real‐time lymphatic mapping, counting of disseminated tumor cells (DTCs) in prenodal lymphatics, and detecting metastasis in SLNs and its purging. The detection and ablation of non‐pigmented breast cancer cells in SLNs was achieved by labeling them with nanoparticles. The association between DTC count and SLN metastasis progression supports lymphatic DTCs as a novel prognostic marker of metastasis. The fiber‐based portable PA device may replace the conventional SLN(s) excision and histology‐based staging. The earliest detection of DTCs in the lymphatic vessels before the establishment of nodal metastasis may prevent metastasis by well‐timed ablation of DTCs. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Doppler OCT imaging of cytoplasm shuttle flow in Physarum polycephalum
Authors: Bykov Alexander V. , Priezzhev Alexander V. , Lauri Janne , Myllylä Risto
Published: September 2009

The Doppler optical coherence tomography technique was applied to image the oscillatory dynamics of protoplasm in the strands of the plasmodium of slime mould Physarum polycephalum. Radial contractions of the gel‐like walls of the strands and the velocity distributions in the sol‐like endoplasm streaming along the plasmodial strands are imaged. The motility inhibitor effect of carbon dioxide on the cytoplasm shuttle flow and strand‐wall contraction is shown. The optical attenuation coefficient of cytoplasm is estimated. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Porous tantalum and poly‐ε‐caprolactone biocomposites for osteochondral defect repair: Preliminary studies in rabbits
Authors: Mrosek Eike H. , Schagemann Jan C. , Chung Hsi‐Wei , Fitzsimmons James S. , Yaszemski Michael J. , Mardones Rodrigo M. , O'Driscoll Shawn W. , Reinholz Gregory G.
Published: September 2009

Currently, various techniques are in use for the repair of osteochondral defects, none of them being truly satisfactory and they are often two step procedures. Comorbidity due to cancellous bone harvest from the iliac crest further complicates the procedure. Our previous in vitro studies suggest that porous tantalum (TM) or poly‐ε‐caprolactone scaffolds (PCL) in combination with periosteal grafts could be used for osteochondral defect repair. In this in vivo study, cylindrical osteochondral defects were created on the medial and lateral condyles of 10 rabbits and filled with TM/periosteum or PCL/periosteum biosynthetic composites (n = 8 each). The regenerated osteochondral tissue was then analyzed histologically, and evaluated in an independent and blinded manner by five different observers using a 30‐point histological score. The overall histological score for PCL/periosteum was significantly better than for TM/periosteum. However, most of the regenerates were well integrated with the surrounding bone (PCL/periosteum, n = 6.4; TM/periosteum, n = 7) along with partial restoration of the tidemark (PCL/periosteum, n = 4.4; TM/periosteum, n = 5.6). A cover of hyaline‐like morphology was found after PCL/periosteum treatment (n = 4.8), yet the cartilage yields were inconsistent. In conclusion, the applied TM and PCL scaffolds promoted excellent subchondral bone regeneration. Neo‐cartilage formation from periosteum supported by a scaffold was inconsistent. This is the first study to show in vivo results of both PCL and TM scaffolds for a novel approach to osteochondral defect repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:141–148, 2010
Micro‐Raman spectroscopy identification of urinary stone composition from ureteroscopic lithotripsy urine powder
Authors: Chiu Yi‐Chun , Yang Hao‐Yu , Lu Shing‐Hwa , Chiang Huihua Kenny
Published: September 2009

Urolithiasis is a prevalent, disturbing, and highly recurrent disease. Knowing the composition of a urinary stone is important for prevention purposes. Traditional urinary stone analysis methods need large stone fragments for analysis. However, the advancement of ureteroscopic lithotripsy (URSL) has resulted in micro‐stone fragments and unapparently expelled urinary stone powder. In this study, we developed a micro‐Raman spectroscopy (MRS) based diagnosis method for detecting micro‐stones or stone powders in urine after URSL. In our experiment, urine samples of 10 ml each were collected from 12 patients over the fragmented stone site in the ureter after the URSL procedure. The post‐URSL urine sediments extracted from urine were analyzed by MRS. The small urinary stones caught by grasping forceps were analyzed by both MRS and Fourier‐transform infrared (FTIR) spectroscopy. We have identified common urinary stone compositions: calcium oxalate monohydrate (COM), calcium oxalate dihydrate (COD), dicalcium phosphate dihydrate (DCPD), calcium phosphate hydroxide (hydroxyl apatite or HAP), and uric acid, by using a 632.8 nm He‐Ne laser for excitation, a 100× microscope objective lens for irradiation and collection, and a short photobleaching time for fluorescent background reduction. Thus, we developed an MRS‐based method for analyzing the composition of urinary stone powders directly from the urine samples after the URSL procedure. This approach provides a quick and convenient method for urinary stone analysis. Copyright © 2009 John Wiley & Sons, Ltd.
Manifestation of conical intersections in resonance Raman intensities
Authors: Chowdary Praveen D. , Umapathy Siva
Published: September 2009

This paper deals with the manifestations of conical intersections (CIs), unequivocal spectroscopic signatures of which are still elusive, in the resonance Raman intensities. In particular, the results of our calculations on the ‘two state‐two vibrational mode’ and the ‘two state‐three vibrational mode’ models are presented. The models comprise two excited states of different spatial symmetry, one bright and one dark, which are coupled by a nontotally symmetric mode while the energy gap between them is tuned by one/two totally symmetric modes. Time dependent theory for vibronically coupled states is employed for the calculation and analysis of Raman excitation profiles (REPs). The manifestation of intersections in REPs is studied by extensive model calculations and the results of two specific models are presented. The feasibility of using REPs to probe the role of CIs in polyatomic systems is ascertained by multimode calculations on two polyatomic systems viz., pyrazine and trans‐azobenzene. The study also notes the importance of the pump excitation wavelength dependence in a femtosecond time‐resolved experiment probing the intersection‐induced nonadiabatic dynamics. Copyright © 2009 John Wiley & Sons, Ltd.
Decalepis hamiltonii roots boost antioxidant status of rat liver and brain
Authors: Srivastava Anup , Shivanandappa Thimmappa
Published: September 2009

BACKGROUND: Roots of Decalepis hamiltonii are traditionally consumed as pickles and juice for their health benefits. We have earlier demonstrated the antioxidant property of the root extract and identified the constituent antioxidant molecules.

RESULTS: This paper reports the effect of multiple‐dose (7, 15, and 30 days) treatment of Decalepis hamiltonii aqueous root extract (DHA) (50 and 100 mg kg−1 body weight) on the antioxidant profile of rat liver and brain. Activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione‐S‐transferase (GST) were increased and glutathione content was elevated in both liver and brain, apart from reduction in the basal level of lipid peroxidation. DHA induced stronger antioxidant boost in brain by increasing the activities of SOD, CAT, and GPx compared to liver.

CONCLUSION: As failure to grapple with oxidative stress is an important factor in the etiology of several diseases, DHA's effects on improvement of antioxidant status could provide a scientific justification for the health‐promoting properties attributed to it. Copyright © 2009 Society of Chemical Industry
Gene‐environment interaction in posttraumatic stress disorder: An update
Authors: Koenen Karestan C. , Amstadter Ananda B. , Nugent Nicole R.
Published: September 2009

The authors provide a detailed review of the extant gene–environment interaction (GxE) research in the etiology of posttraumatic stress disorder (PTSD). They begin with a discussion of why PTSD is uniquely fitting for the innovative framework of GxE methodology, followed by a review of the heritability and main effect molecular genetics studies of PTSD. Next, they discuss the six GxE investigations to date on PTSD. They end with a discussion of future directions and significance of this research, with an emphasis on the expansion of psychosocial factors that may be fitting environmental variables for inclusion in this new research area. The authors posit that GxE research is vital to elucidating risk and resilience following exposure to a potentially traumatic event.
Parteien zur Wahl
Authors: Bündnis 90/Die Grünen  , Die Linke  , FDP  , SPD  , CDU
Published: September 2009

”Angenommen, Ihre Partei stellt nach der Wahl die Regierung oder ist an der Regierung beteiligt ...“ Unter diesem Motto haben CDU, SPD, FDP , Bündnis 90/Die Grünen und Die Linke dreizehn Fragen beantwortet. Gefragt haben die Nachrichten aus der Chemie, das Physik Journal und der Verband Biologie, Biowissenschaften und Biomedizin in Deutschland.
Frankfurt — in letzter Minute
Authors: Arnold Claudia , Altenburg Horst , Steinbeck Christoph , Brock Thomas , König Burkhard , Barbara Pohl Darmstadt , Kaskel Stefan , Krossing Ingo , Bader Hans‐Joachim , Küchenthal Christian , Herrmann Hartmut , Bräuninger Sigmar , Pütter Hermann
Published: September 2009

Unter dem Motto ”Mit Chemie sicher leben“ präsentiert sich die Chemie in der nächsten Woche auf dem GDCh‐Wissenschaftsforum in Frankfurt. Einen Eindruck vom Programm mit mehr als 250 Vorträgen, Symposien, Podiumsdiskussionen und etwa 300 Postern geben die GDCh‐Fach‐ und ‐Regionalstrukturen.
Nicht unschuldig: chinoide Liganden
Authors: Schweinfurth David , Weisser Fritz , Sarkar Biprajit
Published: September 2009

Liganden mit chinoider Struktur sind aufgrund ihrer Redoxchemie sehr nützlich für die Koordinationschemie. Sowohl einzelne Komplexe als auch Koordinationspolymere solcher Liganden zeigen außergewöhnliche Eigenschaften — etwa in ihren Elektronenübergängen und bei Phänomenen wie Valenztautomerie sowie Spin‐Crossover.
Aziridine in der stereoselektiven Synthese
Authors: Graening Timm
Published: September 2009

Das Potenzial von Aziridinen zur stereoselektiven Synthese von 1,2‐difunktionalisierten Verbindungen und als umgepolte Synthesebausteine ist bei weitem nicht so ausgereift wie das der Epoxide. In jüngster Zeit gab es aber Fortschritte bei asymmetrischen Aza‐Darzens‐Reaktionen, der stereoselektiven Lithiierung des Ringsystems, asymmetrischen Ringöffnungsreaktionen und der Anwendung als Baustein für 1,3‐Diamine und N‐Heterocyclen.
Frictional granular mechanics: A variational approach
Authors: Holtzman R. , Silin D. B. , Patzek T. W.
Published: September 2009

The mechanical properties of a cohesionless granular material are evaluated from grain‐scale simulations. Intergranular interactions, including friction and sliding, are modeled by a set of contact rules based on the theories of Hertz, Mindlin, and Deresiewicz. A computer‐generated, three‐dimensional, irregular pack of spherical grains is loaded by incremental displacement of its boundaries. Deformation is described by a sequence of static equilibrium configurations of the pack. A variational approach is employed to find the equilibrium configurations by minimizing the total work against the intergranular loads. Effective elastic moduli are evaluated from the intergranular forces and the deformation of the pack. Good agreement between the computed and measured moduli, achieved with no adjustment of material parameters, establishes the physical soundness of the proposed model. Copyright © 2009 John Wiley & Sons, Ltd.
Corporate social responsibility in the European Union: a new trade barrier?
Authors: Breitbarth Tim , Harris Phil , Aitken Rob
Published: September 2009

This paper contributes to the discussion about Corporate social responsibility (CSR), competitiveness and trade policies, and how trade barriers emerge between countries already committed to CSR and those for whom CSR is still gaining ground. The authors describe the development of CSR within Europe and explain its role in shaping trade relationships. Gaining access to the European market, and obtaining the ‘licence to operate’ in light of strengthening commitment to CSR, is an issue for many companies. For countries outside the EU it is important to understand what CSR means in the European context and to recognize its implications for conducting business in the region. Further, through its economic power and resources, the EU sets standards and influences international trade norms. The authors conclude that the EU establishes CSR as a trade barrier for non‐complying companies in the terms of organizational culture, communication, capabilities and compliance.

Copyright © 2009 John Wiley & Sons, Ltd.
Caricatures, cartoons, spoofs and satires: political brands as butts
Authors: Bal Anjali Suniti , Pitt Leyland , Berthon Pierre , DesAutels Philip
Published: September 2009

A theory of caricature is used to analyse and explain the nature of—and reactions to—a controversial political cartoon depicting Jacob Zuma, the highly publicized president of South Africa, and how the cartoon both played on and affected his political image and brand. Jacob Zuma has crafted his image as a person who has overcome insurmountable injustices to lead his nation. The cartoon directly questioned Zuma's claims of discrimination by the justice system. The cartoonist (Zapiro) was able to use the cartoon to further solidify Zuma's image as an embattled yet contentious and divisive leader. The framework that follows depicts the spoofing of a political brand, in a marketing environment in which parody and spoofing of more conventional products and services are increasingly common.

Copyright © 2009 John Wiley & Sons, Ltd.