bluuebunny/crossref_metadata_2025 huggingface dataset:
Electromagnetic source imaging: Backus–Gilbert resolution spread function‐constrained and functional MRI‐guided spatial filtering
Authors: Wan Xiaohong , Sekiguchi Atsushi , Yokoyama Satoru , Riera Jorge , Kawashima Ryuta
Published: June 2007

Electromagnetic source imaging techniques are usually limited by their low spatial resolution, even though these techniques have high temporal resolution. Our heuristic analysis shows that the spatial ambiguity of electromagnetic source localization arises from interference from other sources. In this paper, we suggest a new inverse solution based on the principle of spatial filtering to effectively suppress the interference from other sources, especially from the far sources. By means of this approach, functional MRI information can also be effectively integrated into the inverse solution to further improve spatial accuracy of source localization. Most importantly, the results of source localization by this approach are not significantly biased by incompatible fMRI information. Our simulations and experimental results using electroencephalography based on a realistic head model show that the Backus–Gilbert resolution spread function‐constrained and functional MRI‐guided spatial filtering suggested in this paper provide high spatial accuracy and resolution of source localization, even in the presence of multiple simultaneously active sources. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
A meta‐analytic study of changes in brain activation in depression
Authors: Fitzgerald Paul B. , Laird Angela R. , Maller Jerome , Daskalakis Zafiris J.
Published: June 2007

Objective: A large number of studies with considerably variable methods have been performed to investigate brain regions involved in the pathophysiology of major depressive disorder. The aim of this study was to use a quantitative meta‐analytic technique to synthesise the results of much of this research. Methods: Three separate quantitative meta‐analytical studies were conducted using the Activation Likelihood Estimation technique. Analysis was performed on three types of studies: (1) those conducted at rest comparing brain activation in patients with depression and controls; (2) those involving brain changes following antidepressant treatment; and (3) those comparing brain activation patterns induced by the induction of positive or negative emotion in patients with depression compared with controls. Results: There appears to be a complex series of areas of the brain implicated in the pathophysiology of depression although limited overlap was found across imaging paradigms. This included a network of regions including frontal and temporal cortex as well as the insula and cerebellum that are hypoactive in depressed subjects and in which there is increase in activity with treatment. There was a corresponding set of subcortical and limbic regions in which opposite changes were found. Conclusions: There is limited overlap between the brain regions identified using differing imaging methods. The most consistently identified regions include areas of the anterior cingulate, dorsolateral, medial and inferior prefrontal cortex, insula, superior temporal gyrus, basal ganglia and cerebellum. Further research is required to identify if different imaging methods are identifying complementary networks that are equally involved in the disorder. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
fMRI reveals that non‐local processing in ventral retinotopic cortex underlies perceptual grouping by temporal synchrony
Authors: Caplovitz Gideon P. , Barroso Diego J. , Hsieh Po‐Jang , Tse Peter U.
Published: June 2007

When spatially separated objects appear and disappear in a synchronous manner, they perceptually group into a single global object that itself appears and disappears. We employed functional magnetic resonance imaging (fMRI) to identify brain regions involved in this type of perceptual grouping. Subjects viewed four chromatically‐defined disks (one per visual quadrant) that flashed on and off. We contrasted %BOLD signal changes between blocks of synchronously flashing disks (Grouping) with blocks of asynchronously flashing disks (no‐Grouping). Results: A region of interest analysis revealed %BOLD signal change in the Grouping condition was significantly greater than in the no‐Grouping condition within retinotopic areas V2, V3, and V4v. Within a single quadrant of the visual field, the spatio‐temporal information present in the image was identical across the two stimulus conditions. As such, the two conditions could not be distinguished from each other on the basis of the rate or pattern of flashing within a single visual quadrant. The observed results must therefore arise through nonlocal interactions between or within these retinotopic areas, or arise from outside these retinotopic areas. Furthermore, when V2 and V3 were split into ventral and dorsal sub‐ROIs, ventral retinotopic areas V2v and V3v preferentially differentiated between the two conditions whereas the corresponding dorsal areas V2d and V3d did not. In contrast, within hMT+, %BOLD signal was significantly greater in the no‐Grouping condition. Conclusion: Nonlocal processing within, between, or to ventral retinotopic cortex at least as early as V2v, and including V3v, and V4v, underlies perceptual grouping via temporal synchrony. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Ranking and averaging independent component analysis by reproducibility (RAICAR)
Authors: Yang Zhi , LaConte Stephen , Weng Xuchu , Hu Xiaoping
Published: June 2007

Independent component analysis (ICA) is a data‐driven approach that has exhibited great utility for functional magnetic resonance imaging (fMRI). Standard ICA implementations, however, do not provide the number and relative importance of the resulting components. In addition, ICA algorithms utilizing gradient‐based optimization give decompositions that are dependent on initialization values, which can lead to dramatically different results. In this work, a new method, RAICAR (Ranking and Averaging Independent Component Analysis by Reproducibility), is introduced to address these issues for spatial ICA applied to fMRI. RAICAR utilizes repeated ICA realizations and relies on the reproducibility between them to rank and select components. Different realizations are aligned based on correlations, leading to aligned components. Each component is ranked and thresholded based on between‐realization correlations. Furthermore, different realizations of each aligned component are selectively averaged to generate the final estimate of the given component. Reliability and accuracy of this method are demonstrated with both simulated and experimental fMRI data. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.
Targeted inhibition of HBV gene expression by single-chain antibody mediated small interfering RNA delivery
Authors: Wen Wei-Hong , Liu Jia-Yun , Qin Wei-Jun , Zhao Jing , Wang Tao , Jia Lin-Tao , Meng Yan-Ling , Gao Hui , Xue Cai-Fang , Jin Bo-Quan , Yao Li-Bo , Chen Si-Yi , Yang An-Gang
Published: June 2007

RNA interference is highly effective at inhibiting HBV gene expression and replication. However, before small interfering RNA (siRNA) can be used in the clinic, it is essential to develop a system to target their delivery. Antibody-mediated delivery is a novel approach for targeting siRNA to appropriate cells. In this report, we asked whether this siRNA delivery strategy would be effective against HBV. Of 5 candidates, a specific siRNA that effectively inhibited HBV gene expression and replication was determined. Two fusion proteins, s-tP and sCκ-tP, were constructed to contain a single chain of the human variable fragment, scFv, against hepatitis B surface antigen (HBsAg), a truncated protamine (tP), and in the case of sCκ-tP, a constant region of the κ chain (Cκ). S-tP and sCκ-tP were developed to provide targeted delivery of the siRNA, siRNA expressing cassettes (SEC), and siRNA-producing plasmids. Fluorescein isothiocyanate-siRNA, fluorescein isothiocyanate-SEC, and plasmid DNA were specifically delivered into HBsAg-positive cells using the sCκ-tP fusion protein, and effectively inhibited HBV gene expression and replication. HBV gene expression was also inhibited by siRNA or siRNA-producing plasmids in HBV transgenic mice.

Conclusion:

Our results describe a potential method for the targeted delivery of siRNA or siRNA-producing plasmids against HBV, using anti-HBsAg fusion proteins. (HEPATOLOGY 2007;46:84–94.)
A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes
Authors: Fraser Abigail , Ebrahim Shah , Davey Smith George , Lawlor Debbie A.
Published: June 2007

Associations between biomarkers of nonalcoholic fatty liver disease (NAFLD) alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), with 3 separate measures of glucose homeostasis: fasting glucose, fasting insulin and glycated hemoglobin (HbA1c) were studied and compared between women with and without diabetes in order to gain insight into the documented associations between NAFLD, insulin resistance and diabetes. Data from the British Women's Health and Heart Study, a random sample of British women aged 60-79 years (N = 3394; 3086 without diabetes and 308 with diabetes) was used. Associations of ALT and GGT with fasting glucose and HbA1c and of ALT with fasting insulin (and homeostasis model assessment of insulin resistance [HOMA]) are stronger in women with diabetes compared to women without diabetes (

P

for interaction < 0.001). GGT is associated with fasting insulin (and HOMA) to the same extent in all women, irrespective of diabetes status. Results excluding hyperinsulinemic women, i.e., in the highest fourth of the fasting insulin distribution, were similar to those obtained for all non-diabetic women as were results excluding women in the highest quartile of the alcohol consumption distribution and for women with ALT and GGT levels within the normal range. Associations did not differ substantially between obese and non-obese non-diabetic women.

Conclusion:

elevation of liver enzymes and hepatic insulin resistance as reflected by fasting insulin occur in the early stages of insulin resistance and highlight the central role of the liver in insulin resistance in the general population. (HEPATOLOGY 2007;46:158–165.)
Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver
Authors: Patel Rushang D. , Hollingshead Brett D. , Omiecinski Curtis J. , Perdew Gary H.
Published: June 2007

The aryl-hydrocarbon receptor (AhR) is a basic helix-loop-helix/Per-Arnt-Sim transcription factor that can be activated by exogenous as well as endogenous ligands. AhR is traditionally associated with xenobiotic metabolism. In an attempt to identify novel target genes, C57BL/6J mice were treated with β-naphthoflavone (BNF), a known AhR ligand, and genome-wide expression analysis studies were performed using high-density microarrays. Constitutive androstane receptor (CAR) was found to be one of the differentially regulated genes. Real-time quantitative polymerase chain reaction (qPCR) verified the increase in CAR messenger RNA (mRNA) level. BNF treatment did not increase CAR mRNA in AhR-null mice. Time-course studies in mice revealed that the regulation of CAR mRNA mimicked that of

Cyp1A1

, a known AhR target gene. To demonstrate that the increase in CAR mRNA translates to an increase in functional CAR protein, mice were sequentially treated with BNF (6 hours) followed by the selective CAR agonist, TCPOBOP (3 hours). qPCR revealed an increase in the mRNA level of

Cyp2b10

, previously known to be regulated by CAR. This also suggests that CAR protein is present in limiting amounts with respect to its transactivation ability. Finally, CAR was also up-regulated in primary human hepatocytes in response to AhR activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo[a]pyrene.

Conclusion:

This study identifies a mode of up-regulating CAR and potentially expands the role of AhR in drug metabolism. This study also demonstrates

in vivo

up-regulation of CAR through chemical exposure. (HEPATOLOGY 2007;46:209–218.)
Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor β signaling, promoting cirrhosis and hepatocellular carcinoma
Authors: Matsuzaki Koichi , Murata Miki , Yoshida Katsunori , Sekimoto Go , Uemura Yoshiko , Sakaida Noriko , Kaibori Masaki , Kamiyama Yasuo , Nishizawa Mikio , Fujisawa Junichi , Okazaki Kazuichi , Seki Toshihito
Published: June 2007

Many patients with chronic hepatitis caused by hepatitis C virus (HCV) infection develop liver fibrosis with high risk for hepatocellular carcinoma (HCC), but the mechanism underling this process is unclear. Conversely, transforming growth factor beta (TGF-β) activates not only TGF-β type I receptor (TβRI) but also c-Jun N-terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). Whereas the TβRI/pSmad3C pathway suppresses epithelial cell growth by upregulating p21WAF1 transcription, JNK/pSmad3L-mediated signaling promotes extracellular matrix deposition, partly, by upregulating plasminogen activator inhibitor 1 (PAI-1). We studied the domain-specific Smad3 phosphorylation in biopsy specimens representing chronic hepatitis, cirrhosis, or HCC from 100 patients chronically infected with HCV, and correlated Smad3 phosphorylation with clinical course. As HCV-infected livers progressed from chronic hepatitis through cirrhosis to HCC, hepatocytic pSmad3L/PAI-1 increased with fibrotic stage and necroinflammatory grade, and pSmad3C/p21WAF1 decreased. Of 14 patients with chronic hepatitis C with strong hepatocytic pSmad3L positivity, 8 developed HCC within 12 years; only 1 of 12 showing little pSmad3L positivity developed HCC. We further sought molecular mechanisms

in vitro

. JNK activation by the pro-inflammatory cytokine interleukin-1β stimulated the pSmad3L/PAI-1 pathway in facilitating hepatocytic invasion, in the meantime reducing TGF-β-dependent tumor-suppressive activity by the pSmad3C/p21WAF1 pathway.

Conclusion:

These results indicate that chronic inflammation associated with HCV infection shifts hepatocytic TGF-β signaling from tumor-suppression to fibrogenesis, accelerating liver fibrosis and increasing risk for HCC. (HEPATOLOGY 2007;46:48–57.)
Telangiectatic adenoma
Authors: Paradis Valérie , Champault Axelle , Ronot Maxime , Deschamps Lydia , Valla Dominique-Charles , Vidaud Dominique , Vilgrain Valérie , Belghiti Jacques , Bedossa Pierre
Published: June 2007

What were previously called telangiectatic focal nodular hyperplasias are in fact true adenomas with telangiectatic features (TAs) without overt characterized genetic abnormalities. The aim of our study was to review a surgical series of TAs in order to describe clinical, biological, and radiological findings of these lesions and to evaluate their outcomes. From January 1996 to November 2005, 284 patients with benign hepatocellular nodules underwent surgical resection at Beaujon Hospital. Among them, 32 TAs from 27 patients were diagnosed. Ninety-two percent of the patients were women. Mean age was 38 years (range 17–63). Mean body mass index was 28 (range 18–49), with 16 patients being overweight. Symptoms revealed lesions in 10 patients. In 13 patients, TA was associated with another benign liver lesion. Mean size of the TAs was 5 cm (range 1–17 cm). Histological analysis showed cellular atypias in 6 cases (19%), steatosis in 17 cases (53%), vascular changes in 19 cases (59%), and significant inflammatory infiltrate in 29 cases (91%). In 1 case, the TA had foci of well-differentiated hepatocellular carcinoma. In 18 of the 26 cases (69%), adjacent liver showed significant steatosis. Serum biomarkers of inflammation were increased in 90% of patients (19 of 22). After surgical resection, inflammatory marker levels returned to normal values in all patients tested.

Conclusion:

This study has shown that TAs occur in a characteristic background of overweight patients and are often associated with a biological inflammatory syndrome. Moreover, a TA may progress to malignancy. (HEPATOLOGY 2007;46:140–146.)
Development and validation of a disease-targeted quality of life instrument in chronic hepatitis B
Authors: Spiegel Brennan M. R. , Bolus Roger , Han Steven , Tong Myron , Esrailian Eric , Talley Jennifer , Tran Tram , Smith Jason , Karsan Hetal A. , Durazo Francisco , Bacon Bruce , Martin Paul , Younossi Zobair , Hwa-Ong Siew , Kanwal Fasiha
Published: June 2007

Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test–retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test–retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health.

Conclusion

: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials. (HEPATOLOGY 2007;46:113–121.)
Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines
Authors: Cua Ian Homer Y. , Hui Jason M. , Bandara Priyanka , Kench James G. , Farrell Geoffrey C. , McCaughan Geoffrey W. , George Jacob
Published: June 2007

The role of tumor necrosis factor α, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCV-infected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63,

P

= 0.01), TNFα (1.28 versus 0.60 pg/ml,

P

< 0.001) and IL6 (2.42 versus 1.15 pg/ml,

P

= 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. By multiple linear regression, independent predictors of HOMA-IR included the body mass index, and the serum levels of leptin (positive correlation) and adiponectin (negative correlation), but not that of TNFα and IL6. Only TNFα levels were correlated with the extent of histological injury (portal/periportal inflammation,

P

= 0.02).

Conclusion:

Whereas leptin and adiponectin contribute to IR, none of the adipocytokines accounted for the

elevated

IR in HCV-infected subjects. The adipocytokines were not associated with histological features of chronic HCV infection except for TNFα which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity. (HEPATOLOGY 2007;46:66–73.)
On the TRAIL to therapeutic intervention in liver disease
Authors: Herr Ingrid , Schemmer Peter , Büchler Markus W.
Published: June 2007

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. The fact that HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. HCCs are phenotypically and genetically heterogeneous tumors that commonly emerge on a background of chronic liver diseases, most of which culminate in cirrhosis, such as alcoholic cirrhosis and chronic hepatitis B and C infections. This review outlines recent findings on the progression of liver disease, including our knowledge of the role of apoptotic processes, with an emphasis on the tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). The proapoptotic and antiapoptotic properties of TRAIL, its involvement in liver injury, and its potential as a therapeutic agent in fibrosis and HCC are discussed. Several contradictory and confusing data have not yet been resolved or placed into perspective, such as the influence of factors that determine the TRAIL sensitivity of target cells, including the tumor microenvironment or cirrhotic tissue. Therefore, we assess these data from the perspectives of gastroenterologists (P.S. and M.W.B.) and a molecular oncologist (I.H.) with research interests in liver injury, apoptosis, and experimental therapeutics. (HEPATOLOGY 2007;46:266–274.)
Hypoxia modulates cholinergic but not opioid activation of G proteins in rat hippocampus
Authors: Hambrecht V.S. , Vlisides P.E. , Row B.W. , Gozal D. , Baghdoyan H.A. , Lydic R.
Published: June 2007

Intermittent hypoxia, such as that associated with obstructive sleep apnea, can cause neuronal death and neurobehavioral dysfunction. The cellular and molecular mechanisms through which hypoxia alter hippocampal function are incompletely understood. This study used in vitro [35S]guanylyl‐5′‐O‐(γ‐thio)‐triphosphate ([35S]GTPγS) autoradiography to test the hypothesis that carbachol and DAMGO activate hippocampal G proteins. In addition, this study tested the hypothesis that in vivo exposure to different oxygen (O2) concentrations causes a differential activation of G proteins in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus. G protein activation was quantified as nCi/g tissue in CA1, CA3, and DG from rats housed for 14 days under one of three different oxygen conditions: normoxic (21% O2) room air, or hypoxia (10% O2) that was intermittent or sustained. Across all regions of the hippocampus, activation of G proteins by the cholinergic agonist carbachol and the mu opioid agonist [D‐Ala2, N‐Met‐Phe4, Gly5] enkephalin (DAMGO) was ordered by the degree of hypoxia such that sustained hypoxia > intermittent hypoxia > room air. Carbachol increased G protein activation during sustained hypoxia (38%), intermittent hypoxia (29%), and room air (27%). DAMGO also activated G proteins during sustained hypoxia (52%), intermittent hypoxia (48%), and room air (43%). Region‐specific comparisons of G protein activation revealed that the DG showed significantly less activation by carbachol following intermittent hypoxia and sustained hypoxia than the CA1. Considered together, the results suggest the potential for hypoxia to alter hippocampal function by blunting the cholinergic activation of G proteins within the DG. © 2007 Wiley‐Liss, Inc.
Integrating associative learning signals across the brain
Authors: Suzuki Wendy A.
Published: June 2007

Associative learning is defined as the ability to link arbitrary stimuli or actions together in memory. The neural correlates of this fundamental form of plasticity were first described in the hippocampus during delay eye blink conditioning and have since been examined using a variety of tasks in both rats and monkeys. In monkeys, the neural correlates of associative learning have been studied using conditional motor learning tasks where animals learn to associate particular visual stimuli with particular motor responses (i.e., touch left or touch right). Similar tasks have also been used to examine learning‐related plasticity in motor‐related areas throughout the frontal lobe and striatum. Here, we review the patterns of learning‐related activity seen in these diverse brain areas during conditional motor learning. While each of these areas exhibits strong associative learning signals, the differential patterns and time courses of these signals provides insight into the unique contribution of each area to associative learning. © 2007 Wiley‐Liss, Inc.
Structural learning and the hippocampus
Authors: Aggleton John P. , Sanderson David J. , Pearce John M.
Published: June 2007

It is argued that while the hippocampus is not vital for all classes of configural learning, it is vital for a specific subclass of configural tasks called “structural learning.” The defining feature of structural learning is that in addition to binding stimulus elements to make unique arrays (as in all configural learning), the relationship of these elements to each other, be it spatial or temporal, is specified. Direct evidence supporting the proposal that the hippocampus is required for structural learning comes from recent lesion studies with rats. While rats with hippocampal lesions were impaired at relearning a set of spatial structural problems, they showed no impairment when relearning two configural tasks (transverse patterning and the biconditional discrimination), neither of which required structural learning. Other support comes from surveys of spatial and temporal learning by amnesic patients with hippocampal damage, and from imaging studies of both humans and rats. While these studies offer consistent support for the structural hypothesis, very few provide a rigorous test as the tasks can often be solved by other strategies. For this reason, the present review details the design features of future stringent tests of the structural hypothesis. © 2007 Wiley‐Liss, Inc.
Which computational mechanisms operate in the hippocampus during novelty detection?
Authors: Kumaran Dharshan , Maguire Eleanor A.
Published: June 2007

A fundamental property of adaptive behavior is the ability to rapidly distinguish what is novel from what is familiar in our environment. Empirical evidence and computational work have provided biologically plausible models of the neural substrate and mechanisms underlying the coding of stimulus novelty in the perirhinal cortex. In this article, we highlight the importance of a different category of novelty, namely associative novelty, which has received relatively little attention, despite its clear ecological importance. While previous studies in both animals and humans have documented hippocampal responses in relation to associative novelty, a key issue concerning the computations underlying these novelty signals has not been previously addressed. We argue that this question has importance not only for our understanding of novelty processing, but also for advancing our knowledge of the fundamental computational operations performed by the hippocampus. We suggest a different approach to this problem, and discuss recent evidence supporting the hypothesis that the hippocampus operates as a comparator during the processing of associative novelty, generating mismatch/novelty signals when prior predictions are violated by sensory reality. We also draw on conceptual similarities between associative novelty and contextual novelty to suggest that empirical findings from these two seemingly distant research fields accord with the operation of a comparator mechanism during novelty detection more generally. We therefore conclude that a comparator mechanism may underlie the role of the hippocampus not only in detecting occurrences that are unexpected given specific associatively retrieved predictions, but also events that violate more abstract properties of the experimental context. © 2007 Wiley‐Liss, Inc.
Contribution of Na+/Ca2+exchange to excessive Ca2+loading in dendrites and somata of CA1 neurons in acute slice
Authors: Dietz Robert M. , Kiedrowski Lech , Shuttleworth C. William
Published: June 2007

Multiple Ca2+entry routes have been implicated in excitotoxic Ca2+loading in neurons and reverse‐operation of sodium–calcium exchangers (NCX) has been shown to contribute under conditions where intracellular Na+levels are enhanced. We have investigated effects of KB‐R7943, an inhibitor of reverse‐operation NCX activity, on Ca2+elevations in single CA1 neurons in acute hippocampal slices. KB‐R7943 had no significant effect on input resistance, action potential waveform, or action potential frequency adaptation, but reduced L‐type Ca2+entry in somata. Nimodipine was therefore included in subsequent experiments to prevent complication from effects of L‐type influx on evaluation of NCX activity. NMDA produced transient primary Ca2+increases, followed by propagating secondary Ca2+increases that initiated in apical dendrites. KB‐R7943 had no significant effect on primary or secondary Ca2+increases generated by NMDA. The Na+/K+ATPase inhibitor ouabain (30 μM) produced degenerative Ca2+overload that was initiated in basal dendrites. KB‐R7943 significantly reduced initial Ca2+increases and delayed the propagation of degenerative Ca2+loads triggered by ouabain, raising the possibility that excessive intracellular Na+loading can trigger reverse‐operation NCX activity. A combination of NMDA and ouabain produced more rapid Ca2+overload, that was contributed to by NCX activity. These results suggest that degenerative Ca2+signaling can be triggered by NMDA in dendrites, before intracellular Na+levels become sufficient to reverse NCX activity. However, since Na+/K+ATPase inhibition does appear to produce significant reverse‐operation NCX activity, this additional Ca2+influx pathway may operate in ATP‐deprived CA1 neurons and play a role in ischemic neurodegeneration. © 2007 Wiley‐Liss, Inc.
Long‐term administration of the low‐dose risperidone in schizotaxia subjects
Authors: Rybakowski Janusz K. , Drozdz Wiktor , Borkowska Alina
Published: June 2007

The term schizotaxia is currently defined as a syndrome of neuropsychological deficits and negative symptoms found in relatives of schizophrenic patients. The aim of this study was to assess the effect of long‐term treatment with the low‐dose risperidone on cognitive and social functioning in seven schizotaxia patients. There were four males and three females, aged between 17 and 44 years, first‐degree (four patients) or second‐degree (three patients) relatives of schizophrenic patients. Schizotaxia was recognized in them on account of neuropsychological and social function impairment. They all consented to risperidone administration, 1–2 mg/day. Duration of risperidone treatment has ranged between 3–7 years. In all subjects, the continuous treatment with risperidone brought about a marked improvement in their cognitive, social, and vocational functioning. Neuropsychological testing after 6–24 months showed significant improvement on such tests as Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), and Stroop Test. Discontinuation of treatment after 3–4 years did not cause deterioration of functioning. Copyright © 2007 John Wiley & Sons, Ltd.
Reduction of discharge hydrograph and flood stage resulted from upstream detention ponds
Authors: Chen Ching‐Nuo , Tsai Chih‐Heng , Tsai Chang‐Tai
Published: June 2007

The models of physiographic inundation and flood routing for channel network were used in this study to analyse the influence of the Tainan Scientific Base Industrial Park (TSBIP) and Feng‐Hua detention ponds on the inundated potential, inundated volume, flood damage, and flood stage of peak flow along the Yen‐Shui creek in 2‐day flood for the 2‐, 10‐ and 50‐year return periods, respectively. The computed results show that the TSBIP detention ponds are able to reduce the inundated area and flood damage. However, the decrease in inundated area is not obvious for the 50‐year return‐period flood. Construction of the Feng‐Hua detention pond resulted in a significant decrease in the flood stage along the Yen‐Shui creek in the downstream reach. Moreover, the decrease in peak flow and lag of time‐to‐peak become increasingly evident in the downstream direction for the 2‐ and 10‐year return‐period events. For the 50‐year return period, the lag of time‐to‐peak is not apparent, but the decrease in peak flow is still noticeable. In respect to the performance of detention ponds, the slopes of hydrographs in the rising and recession segments are smoother than those without detention ponds. Meanwhile, the shapes of peak become flatter if the detention ponds are installed. Copyright © 2007 John Wiley & Sons, Ltd.
Electrochemical treatment of olive mill wastewater
Authors: Giannis Apostolos , Kalaitzakis Michael , Diamadopoulos Evan
Published: June 2007

Background Olive mill wastewater (OMW) constitutes a very strong agro‐industrial wastewater posing severe environmental threats in olive oil producing countries. The main objective of this study was to treat olive mill wastewater by electrochemical oxidation. The variables studied included the type and concentration of electrolyte solutions, voltage and time applied.

Results: The electrolyte type and concentration significantly affected the degradation efficiency of the electrochemical oxidation. Optimal conditions for NaCl concentration were 3% (w/v) and 16 V. At these conditions chemical oxygen demand (COD) removal reached 70.8% after 8 h of electrochemical treatment, while color and turbidity were completely removed after short periods of treatment. However, bio‐assays indicated that the ecotoxicity of the treated wastewater remained unchanged, possibly due to the formation of chlorinated by‐products. Na2SO4 did not demonstrate sufficient efficiency. The simultaneous use of FeCl3 and NaCl contributed to electro‐coagulation of OMW. After settlement, two separate phases were formed: the supernatant phase and the settled solids. Under optimal conditions (2% Na2SO4 + 1% FeCl3; 24 V), the removal efficiency of COD reached 85.5% at the supernatant phase.

Conclusion: NaCl was an effective electrolyte for OMW treatment. The electro‐coagulation process was also a successful process, but as in the case of NaCl the remaining acute toxicity of treated OMW was high. Copyright © 2007 Society of Chemical Industry
Determining the source of nosocomial transmission in hemodialysis units in Tunisia by sequencing NS5B and E2 sequences of HCV
Authors: Hmaïed Fatma , Mamou Myriam Ben , Dubois Martine , Pasquier Christophe , Sandres‐Saune Karine , Rostaing Lionel , Slim Amine , Arrouji Zakia , Redjeb Saïda Ben , Izopet Jacques
Published: June 2007

Hepatitis C virus infection is a significant problem in hemodialysis units. HCV is very variable genetically with six genotypes. Clinical and epidemiological investigation of a new infection requires the determination of both the genotype and the strain of the HCV involved. A prospective, epidemiologic study of 395 dialysis patients in Tunisia was conducted from November 2001 to November 2003 to identify the source of nosocomial transmission using phylogenetic analysis of NS5b and E2 sequences. Hepatitis C infection was diagnosed by screening for anti‐HCV antibodies and HCV RNA in sera using third generation ELISA and a qualitative RT‐PCR assay. HCV strains were genotyped by sequencing the NS5b region. The genetic relatedness of the HCV strains was studied by sequencing the NS5b and the HVR‐1 regions of the HCV genome. Two de novo cases of HCV infection were detected during the follow‐up. One of them has been described previously. The case described in this study occurred in a center in which 12 patients were already infected with HCV strains belonging to genotypes 1b (n = 8) and 1a (n = 4). Phylogenetic analysis of the NS5b region from the HCV strains circulating in this center disclosed four clusters, confirmed by analysis of the HVR‐1 region, providing strong evidence for nosocomial infection. Epidemiological data showed that these patients were dialyzed during the same shift and in the same area. Phylogenetic analysis of NS5b sequences is useful for determining the HCV genotype and providing evidence of nosocomial transmission. J. Med. Virol. 79: 1089–1094, 2007. © 2007 Wiley‐Liss, Inc.
Latent membrane protein 1 encoded by Epstein–Barr virus induces telomerase activity via p16INK4A/Rb/E2F1 and JNK signaling pathways
Authors: Ding Lin , Li Lili , Yang Jing , Zhou Shanghui , Li Wei , Tang Min , Shi Ying , Yi Wei , Cao Ya
Published: June 2007

Elevated telomerase activity is observed in about 90% of human cancers. This activity correlates strictly with human telomerase reverse transcriptase (hTERT). Previously, it was shown that the Epstein–Barr virus‐encoded latent membrane protein 1 (LMP1) induced telomerase activity in nasopharyngeal carcinoma cells. In this study, it was indicated that LMP1 inhibited p16INK4A expression, promoted phosphorylation of p105 Rb and upregulated E2F1 expression as well as transactivation, and overexpression of E2F1 alone was sufficient to upregulate telomerase activity. The JNK kinase cascade could also promote telomerase activity modulated by LMP1, that inhibition of JNK by JIP and TAM 67 dominant negative mutant abrogated telomerase activity. The data show that p16INK4A/Rb/E2F1 and JNK signaling pathways are involved in the regulation of telomerase activity via LMP1. The present study provides new perspectives on carcinogenesis of nasopharyngeal carcinoma that may be exploited for novel therapeutic strategies. J. Med. Virol. 79: 1153–1163, 2007. © 2007 Wiley‐Liss, Inc.
Humoral immune responses against norovirus infections of children
Authors: Iritani Nobuhiro , Seto Toshiyuki , Hattori Hideji , Natori Katsurou , Takeda Naokazu , Kubo Hideyuki , Yamano Tsunekazu , Ayata Minoru , Ogura Hisashi , Seto Yoshiyuki
Published: June 2007

In 2 infants with gastroenteritis associated with Norovirus (NoV), serum immunoglobulin (Ig) G, IgM, IgA, and fecal IgA antibody responses against NoV were examined by enzyme‐linked immunosorbent assay using 11 different antigenic and genetic types of NoV virus‐like particles expressed in insect cells. These two cases were putative primary single NoV infections, because antibodies against NoVs were not detected in acute‐phase serums. In one of two cases, long‐term excretion of virus RNA for 33 days was observed. Serum IgG responses demonstrated strong seroresponse to the homologous type, and weak seroresponse to the heterologous types within the genogroup. After more than 2 years, the IgG antibody titer remained high to the homologous type and low to the heterologous type within the genogroup. IgM and IgA were specific to the homologous type. IgM was short lived and the serum IgA antibody titer remained low to the homologous type for a long period. These results improve our understanding of the humoral immune response to NoV infection. J. Med. Virol. 79: 1187–1193, 2007. © 2007 Wiley‐Liss, Inc.
Human cytomegalovirus glycoprotein B genotypes in Brazilian mothers and their congenitally infected infants
Authors: Yamamoto Aparecida Yulie , Mussi‐Pinhata Marisa Marcia , de Deus Wagatsuma Virginia Mara , Marin Lauro Juliano , Duarte Geraldo , Figueiredo Luis Tadeu Moraes
Published: June 2007

A case‐control study design was used in order to compare the distribution of human cytomegalovirus (HCMV) glycoprotein B (gB) genotypes in 48 mothers of 49 congenitally infected infants with that observed in 144 mothers of 146 uninfected infants to study genetic variation of HCMV strains and maternal‐fetal transmission. Congenital infection with HCMV was characterized by DNA detection and virus isolation from two urine or saliva samples collected prior to the third week of life. Genotyping of HCMV was carried out by a polymerase chain reaction‐restriction fragment length polymorphism analysis of the variable region of the gB gene, testing for four genotypes. Genotype frequency was similar among the 28 non‐transmitting mothers who were shedding virus (gB1: 25%; gB2: 28.6%; gB3: 42.8%; gB4: 0%), the 37 transmitting mothers (gB1: 21.6%; gB2: 46%; gB3: 27%; gB4: 0%), and the 49 infected infants (gB1: 39%; gB2: 37%; gB3: 24%; gB4: 0%). The same genotype was detected at different body sites (urine, saliva, and blood) of each infected newborn and in the respective mother (breast milk, urine, and saliva). Co‐infection with multiple genotypes was observed in the immediate postpartum period in two mothers of infected infants (5.4%) and one non‐transmitting mother (3.6%). The gB genotype was not correlated with intrauterine HCMV transmission. The genotype distribution found reflects the overall frequency of wild strains circulating in this geographic region. A single genotype is responsible for congenital HCMV infection. Co‐infection with more than one strain, as characterized by gB genotype, was infrequent in women who were presumably immunocompetent. J. Med. Virol. 79: 1164–1168, 2007. © 2007 Wiley‐Liss, Inc.
Identification of genotype 4 hepatitis E virus strains from a patient with acute hepatitis E and farm pigs in Bali, Indonesia
Authors: Wibawa I. Dewa Nyoman , Suryadarma I.G.A. , Mulyanto  , Tsuda Fumio , Matsumoto Yasunobu , Ninomiya Masashi , Takahashi Masaharu , Okamoto Hiroaki
Published: June 2007

A previous study revealed that antibodies to hepatitis E virus (HEV) (anti‐HEV) are highly prevalent among healthy individuals and farm pigs in Bali, Indonesia, and suggested that HEV infection may occur via zoonosis among Balinese people. However, there were no reports of acute hepatitis E in Bali. To elucidate whether Balinese HEV strains recovered from infected humans and pigs have significant sequence similarity, serum samples obtained from 57 patients (age, mean ± standard deviation, 31.1 ± 11.9 years) with sporadic acute hepatitis and from one hundred and one 2‐ or 3‐month‐old farm pigs in Bali were tested for anti‐HEV and HEV RNA. Among the 57 patients, 2 (3.5%) had high‐titer IgM/IgA class anti‐HEV antibodies and one of them had detectable HEV RNA (BaliE03‐46). Overall, 58 pigs (57.4%) tested positive for anti‐HEV, while 5 pigs (5.0%) had detectable HEV RNA. Based on the 412‐nucleotide sequence within open reading frame 2, the BaliE03‐46 isolate and the 5 swine HEV isolates recovered from the viremic pigs were phylogenetically classified in genotype 4, but were only 77.3–90.8% identical to the genotype 4 HEV isolates reported thus far in China, India, Japan, Taiwan, and Vietnam. The BaliE03‐46 isolate of human origin shared high identities of 97.3–98.3% with 4 of the 5 Balinese swine isolates, but differed by 16.1% from the remaining swine isolate. These results suggest that indigenous HEV strains of genotype 4 with marked heterogeneity are circulating in Bali, Indonesia, and that pigs are reservoirs of HEV for Balinese people who have a habit of ingesting uncooked pigs. J. Med. Virol. 79: 1138–1146, 2007. © 2007 Wiley‐Liss, Inc.
Analysis of the full‐length genome of hepatitis E virus isolates obtained from farm pigs in Mongolia
Authors: Lorenzo Felipe R. , Tsatsralt‐Od Bira , Ganbat Sanjaa , Takahashi Masaharu , Okamoto Hiroaki
Published: June 2007

Although no outbreaks of hepatitis E have been reported in Mongolia, a significant proportion of the general population had antibodies to hepatitis E virus (HEV). To investigate whether pigs are possible reservoirs of HEV in Mongolia, serum samples obtained from 243 2‐ or 3‐month‐old pigs on four swine farms surrounding Ulaanbaatar, the capital city of Mongolia, were tested for the presence of anti‐HEV antibodies and HEV RNA. Overall, 223 pigs (91.8%) tested positive for anti‐HEV, while 89 pigs (36.6%) had detectable HEV RNA. The 89 HEV isolates obtained from the viremic pigs were 78.7–100% identical to each other, and 80.9–85.9% similar to the prototype genotype 3 HEV isolate (US1) in the 412‐nucleotide (nt) sequence within open reading frame 2. They were classified into two novel phylogenetic groups within genotype 3, differing by 16.4–21.3%. The swMN06‐A1288 and swMN06‐C1056 isolates, representing each of the two clusters within genotype 3, had a genomic length of nucleotides (nt) 7,222 nt and 7,223 nt, respectively, excluding the poly(A) tail, and shared only 81.6% over the entire genome. Upon comparison with the 25‐reported genotype 3 HEV isolates over the entire genome, swMN06‐A1288 had identities of merely up to 84.9%, while swMN06‐C1056 of only up to 85.9%. Phylogenetic analysis confirmed the remote relatedness of the Mongolian swine isolates to the genotype 3 HEV isolates reported thus far. These results indicate that farm pigs in Mongolia are frequently infected with presumably indigenous HEV strains of genotype 3 and could be a source of HEV infections in humans in Mongolia. J. Med. Virol. 79: 1128–1137, 2007. © 2007 Wiley‐Liss, Inc.
Molecular epidemiology characterization of the urinary excretion of polyomavirus in healthy individuals from portugal—a Southern European population
Authors: Rodrigues Carla , Pinto Daniela , Medeiros Rui
Published: June 2007

The human polyomaviruses—BKV and JCV—are members of Polyomaviridae family and after primary infections they persist as latent infection especially in the kidneys. BKV reactivation is mainly related to urinary tract diseases and JCV reactivation can induce the disease progressive multifocal leukoencephalopathy. The aim of our study was to characterize the excretion of polyomaviruses in urine samples of healthy individuals from a Portuguese population. We analyzed 498 DNA samples using PCR‐RFLP, the sequence amplified consisted in 176 or 173 bp within the antigen T region. Our results indicate that 23.9% of the samples were positive for JCV, 1.8% positive for BKV and 74.3% of the individuals were negative for both viruses. We observed an increased prevalence of JCV shedding in male individuals in comparison to female (P = 0.026). Furthermore, the shedding of both polyomaviruses was influenced by the age of individuals with a significant increase in individuals with more than 56 years old (P = 0.005). Our results show that the shedding of polyomavirus in urine of healthy individuals is highly variable between genders, is influenced by age and differs from region to region. Further studies are needed to evaluate the prevalence of polyomaviruses in healthy individuals, in order to understand the biological behaviour of these viruses. J. Med. Virol. 79: 1194–1198, 2007. © 2007 Wiley‐Liss, Inc.