bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Why Left Events are the Right Ones: Neural Mechanisms Underlying the Left-hemifield Advantage in Rapid Serial Visual Presentation
Authors: Verleger Rolf , Sprenger Andreas , Gebauer Sina , Fritzmannova Michaela , Friedrich Monique , Kraft Stefanie , Jaśkowski Piotr 
Published: June 2008

AbstractWhen simultaneous series of stimuli are rapidly presented left and right, containing two target stimuli T1 and T2, T2 is much better identified when presented in the left than in the right hemifield. Here, this effect was replicated, even when shifts of gaze were controlled, and was only partially compensated when T1 side provided the cue where to expect T2. Electrophysiological measurement revealed earlier latencies of T1- and T2-evoked N2pc peaks at the right than at the left visual cortex, and larger right-hemisphere T2-evoked N2pc amplitudes when T2 closely followed T1. These findings suggest that the right hemisphere was better able to single out the targets in time. Further, sustained contralateral slow shifts remained active after T1 for longer time at the right than at the left visual cortex, and developed more consistently at the right visual cortex when expecting T2 on the contralateral side. These findings might reflect better capacity of right-hemisphere visual working memory. These findings about the neurophysiological underpinnings of the large right-hemisphere advantage in this complex visual task might help elucidating the mechanisms responsible for the severe disturbance of hemineglect following damage to the right hemisphere.
Kynurenine pathway in psychosis: evidence of increased tryptophan degradation
Authors: Barry S , Clarke G , Scully P , Dinan TG 
Published: June 2008

AbstractThe kynurenine pathway of tryptophan degradation may serve to integrate disparate abnormalities heretofore identified in research aiming to elucidate the complex aetiopathogenesis of psychotic disorders. Post-mortem brain tissue studies have reported elevated kynurenine and kynurenic acid in the frontal cortex and upregulation of the first step of the pathway in the anterior cingulate cortex of individuals with schizophrenia. In this study, we examined kynurenine pathway activity by measuring tryptophan breakdown, a number of pathway metabolites and interferon gamma (IFN-γ), which is the preferential activator of the first-step enzyme, indoleamine dioxygenase (IDO), in the plasma of patients with major psychotic disorder. Plasma tryptophan, kynurenine pathway metabolites were measured using high-performance liquid chromatography (HPLC) in 34 patients with a diagnosis on the psychotic spectrum (schizophrenia or schizoaffective disorder) and in 36 healthy control subjects. IFN-γ was measured using enzyme-linked immunosorbent assay (ELISA). The mean tryptophan breakdown index (kynurenine/tryptophan) was significantly higher in the patient group compared with controls ( P < 0.05). IFN-γ measures did not differ between groups ( P = 0.23). No relationship was found between measures of psychopathology, symptom severity and activity in the first step in the pathway. A modest correlation was established between the tryptophan breakdown index and illness duration. These results provide evidence for kynurenine pathway upregulation, specifically involving the first enzymatic step, in patients with major psychotic disorder. Increased tryptophan degradation in psychoses may have potential consequences for the treatment of these disorders by informing the development of novel therapeutic compounds.
Efficacy and tolerability of ziprasidone versus risperidone as augmentation in patients partially responsive to clozapine: a randomised controlled clinical trial
Authors: Zink M , Kuwilsky A , Krumm B , Dressing H 
Published: June 2008

Abstract Patients suffering from schizophrenic psychoses sometimes insufficiently respond to antipsychotic monotherapy and then combination approaches are preferred. We aimed in validating the add-on of ziprasidone and risperidone to clozapine, and we performed a randomised head-to-head trial. Patients with partial response to clozapine were randomly attributed to augmentation with ziprasidone ( n = 12) or risperidone ( n = 12). Efficacy assessments included the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Negative Symptoms (SANS), the Hamilton Depression Scale (HAMD), the Clinical Global Impression (CGI) and the Global Assessment of Functioning (GAF). Furthermore, several safety and tolerability measures were obtained. After six weeks, both groups showed significant reductions of positive and negative symptoms. In addition, affective state, psychosocial functioning and clozapine side effects improved without significant differences between the groups. Both approaches were well tolerated. However, the ziprasidone group experienced a small elongation of the QTc interval and a reduction of extrapyramidal symptoms. Patients under clozapine–risperidone therapy developed a rise of serum prolactin levels. The clozapine augmentation with ziprasidone or risperidone resulted in significant psychopathological improvements. The side effects differed between the treatment groups. Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary.
Anhedonia and activity deficits in rats: impact of post-stroke depression
Authors: Wang SH , Zhang ZJ , Guo YJ , Zhou H , Teng GJ , Chen BA 
Published: June 2008

Abstract Animal models may allow investigation into the aetiology and treatment of various human disorders. In the present study, a rat model for post-stroke depression (PSD) has been developed using middle cerebral artery occlusion (MCAO), followed by an 18-day chronic mild stress (CMS) paradigm in conjuncture with isolation rearing. The open-field test (OFT) and the sucrose consumption test were used to assess depression-like behaviour and the effects of the antidepressant citalopram. CMS induced behavioural changes in the ischemic animals, including decreased locomotor and rearing activity and reduced sucrose preference (compared with baseline, control and stroke groups respectively), all these behaviours were reversed by chronic administration of citalopram. During the recovery period for the PSD models, the open-field activity and preference for sweet sucrose solution decreased continually, opposed to rats subjected to stress only. Decreased locomotor and rearing represents activity deficits, whereas reduced sucrose preference may indicate desensitisation of the brain reward mechanism (anhedonia). Our findings suggest that anhedonia, one of the core symptoms in patients with PSD, and activity deficits can be found in the MCAO+CMS group of animals. Furthermore, citalopram can ameliorate the behavioural abnormalities observed in these animals. With high validity, good operability and repeatability, our findings suggest that the ischemic rat CMS model is an appropriate model for further PSD research.
Effect of antidepressants on melatonin metabolite in depressed patients
Authors: Carvalho LA , Gorenstein C , Moreno R , Pariante C , Markus RP 
Published: June 2008

Abstract Antidepressants increase melatonin levels, but it is still unclear whether this effect is related to the improvement of depressive symptoms or to unrelated pharmacological action of antidepressants. To answer this question, the effect of antidepressants on 6-sulphatoxymelatonin (aMT6s), the main melatonin urinary metabolite, was examined in drug-free depressed patients – most of them antidepressant-naive. aMT6s was evaluated in 34 depressed patients, before and after 8 weeks of placebo ( n = 12) or antidepressant ( n = 22; fluoxetine, duloxetine or Hypericum perforatum). Both groups showed an improvement of depressive symptoms after treatment compared to baseline (Hamilton Depression scores): 17.0 ± 1.4 vs. 9.0 ± 2.8, P = 0.007 for placebo, and 18.6 ± 1.1 vs. 11.8 ± 1.6, P < 0.001 for antidepressants). After treatment, aMT6s levels increased after antidepressants ( P < 0.01), but not after placebo ( P > 0.05). As depressive symptoms improved both in patients taking antidepressant and in those taking placebo, but an effect of antidepressants could only be seen in those taking antidepressants, we suggest that melatonin changes after antidepressants are more likely due to a pharmacological action of these drugs on melatonin secretion.
Efficacy, tolerability and side-effect profile of fluvoxamine for major depression: meta-analysis
Authors: Omori IM , Watanabe N , Nakagawa A , Akechi T , Cipriani A , Barbui C , McGuire H , Churchill R , Furukawa TA 
Published: June 2008

Abstract Fluvoxamine, one of the oldest selective serotonin reuptaking inhibitors, is commonly prescribed to patients with major depression. Several studies have reviewed the efficacy and tolerability of fluvoxamine for the treatment of major depression. However, these reviews are outdated, have not been systematic and/or suffered from several methodological weaknesses. We conducted a systematic review to synthesize the best available evidence on the efficacy of fluvoxamine for adult patients suffering from major depression in comparison with other active antidepressive agents. Relevant randomized controlled trials were identified through a comprehensive search. The primary outcome was a relative risk of response, and the secondary outcome was a relative risk of remission. Tolerability and side-effect profile were also examined. Fifty-three trials were included. There were no large differences between fluvoxamine and any other antidepressants in terms of efficacy and tolerability. There is evidence of differing side effect profiles, especially when comparing gastrointestinal side effects between fluvoxamine and tricyclics. Clinicians should focus on practically or clinically relevant differences including those in side-effect profiles.
Hyperprolactinemia and possibly related development of prolactinoma during amisulpride treatment; three cases
Authors: Akkaya C , Kaya B , Kotan Z , Sarandol A , Ersoy C , Kirli S 
Published: June 2008

Abstract Schizophrenia is a chronic and debilitating psychotic mental disorder that affects about 1% of the world's population. Antipsychotic drugs are the mainstay of treatment in schizophrenia. Hyperprolactinemia, which is a common side effect of typical antipsychotics, is also associated with the use of some of the newer atypical agents. Antipsychotics may enhance prolactinoma growth as manifested by an increase in serum prolactin concentration. Prolactin-secreting pituitary adenomas possibly related with antipsychotics have been described in the literature. To our knowledge, this is the first series of cases showing a possible relation between pituitary adenomas and amisulpride treatment in patients with schizophrenia.
The addiction Stroop task: examining the fast and slow effects of smoking and marijuana-related cues
Authors: Cane JE , Sharma D , Albery IP 
Published: June 2008

Abstract Research has shown that attentional bias toward smoking-related stimuli is related to the maintenance of smoking behaviour and the chance of a relapse during a quit attempt. Effects of smoking attentional bias can occur both during smoking stimulus presentation (fast effect) and on stimuli that immediately follow smoking stimuli (slow effect). The current research builds on these findings by closely examining the temporal aspects of these fast and slow effects across groups of different smoking status. In Experiment 1 ( n = 64), smokers, smokers attempting to quit (SATQ) and non-smokers completed an addiction Stroop task using smoking related, negative emotion and neutral stimuli. In Experiment 2 ( n = 32), marijuana smokers and non-marijuana smokers completed an addiction Stroop task using marijuana and neutral stimuli. Results showed fast effects across all smoking groups (except non-smokers) and slow effects in SATQ and marijuana smokers. Furthermore, marijuana smokers showed slow effects over extended periods of time. Results also show a relationship between anxiety, nicotine dependence and attentional bias in SATQ. The implications of these findings are discussed.
Restless legs syndrome and periodic limb movements during sleep probably associated with olanzapine
Authors: Kang Seung-Gul , Lee Heon-Jeong , Kim Leen 
Published: June 2008

Abstract We report five cases of restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) that were probably associated with olanzapine. The first patient showed a good response to olanzapine, but the RLS symptoms associated with olanzapine resulted in poor long-term compliance, eventually leading to frequent relapse of psychotic symptoms. The second patient exhibited sudden PLMS following olanzapine injection. The third patient had been suffering from serious akathisia while on risperidone, and was cured after switching to olanzapine, but thereafter the patient suffered from RLS at nighttime. The fourth patient showed RLS symptoms that were initially caused by a 20-mg daily olanzapine dosage and were later mitigated when olanzapine was reduced and ropinirole was administered. The fifth patient exhibited paraesthesia and agitation caused by olanzapine that was misdiagnosed as psychotic agitation. Increasing the olanzapine dosage severely aggravated the symptoms of RLS. Antipsychotic-induced RLS and PLMS are not well-recognized side effects of antipsychotics, with the symptoms often misdiagnosed as psychotic agitation. These cases also suggest that the occurrence of RLS can cause noncompliance with antipsychotics in psychiatric patients, and thus aggravate their psychotic symptoms.
An experimental study of aggressive and neutral interpretative bias in opiate-dependent and opiate-abstinent men
Authors: Clair J , Martin L , Bond AJ , O’Ryan D , Davis P , Curran HV 
Published: June 2008

Abstract There is a paucity of research on the relationship between opiate use and aggression, and no previous study has examined this from a cognitive theoretical perspective, which views an individual’s interpretation of information as a central mediator of their response to it. This study aimed to determine whether opiate users and ex-users differed from opiate-naïve controls on a task which involved processing ambiguous sentences. In an independent group design, the interpretative bias task was administered to 64 participants: 21 opiate-dependent receiving methadone maintenance treatment, 21 opiate-abstinent in rehabilitation, and 22 healthy unemployed controls. We found that both opiate-dependent and opiate-abstinent groups interpreted ambiguous sentences in a neutral rather than an aggressive way, whereas controls showed no bias in either direction. In the opiate-dependent group, neutral interpretative bias correlated both with their current dose of methadone and years of methadone use. These findings indicate that current and ex-opiate users in treatment have a bias towards neutral interpretations of ambiguous information. The fact that neutral interpretative bias in opiate-dependent individuals correlated with current dose and years of methadone use suggests that methadone treatment is associated with a neutral cognitive bias. Decreased testosterone levels associated with chronic opiate use may underpin this neutral bias.
Disease-modifying agents in the Sonya Slifka Longitudinal Multiple Sclerosis Study
Authors: Minden S , Hoaglin D , Jureidini S , Hadden L , Frankel D , Komatsuzaki Y , Outley J 
Published: June 2008

Background Although experts recommend that people with multiple sclerosis (MS) should begin treatment with disease-modifying agents (DMAs) as soon as possible after diagnosis and continue indefinitely, many do not use these agents or discontinue them prematurely. Since DMAs reduce relapse rates and slow disease progression, and since even benign relapses and course can lead to axonal damage and permanent neurologic impairment, it is important that all appropriate candidates have access to treatment. We used a population-based sample of people with MS to determine rates, predictors, and reasons for use, non-use, and discontinuation of DMAs. Methods We collected data from 2156 people with MS on their use of and experience with DMAs. We used chi-squared tests to compare current, past, and never users of any DMA and ever users of individual DMAs, and logistic regression to identify predictors of use. Results One-half of the participants were using a DMA at the time of the interview; 12.2% had used previously, but stopped. Reasons for never using and reasons for stopping were at odds with expert recommendations. Characterization of users, and of their experiences by type of DMA, was consistent with current knowledge of these agents. Seeing a neurologist for usual MS care was an important factor in starting and persisting with DMA therapy. Conclusions Dissemination of expert opinion about, and management strategies for, use of DMAs to non-neurologic professionals and patients and their families might help more people who are appropriate candidates for DMA therapy to start and continue treatment.
Molecular basis of bortezomib resistance: proteasome subunit β5 (PSMB5) gene mutation and overexpression of PSMB5 protein
Authors: Oerlemans Ruud , Franke Niels E. , Assaraf Yehuda G. , Cloos Jacqueline , van Zantwijk Ina , Berkers Celia R. , Scheffer George L. , Debipersad Kabir , Vojtekova Katharina , Lemos Clara , van der Heijden Joost W. , Ylstra Bauke , Peters Godefridus J. , Kaspers Gertjan L. , Dijkmans Ben A. C. , Scheper Rik J. , Jansen Gerrit 
Published: June 2008

AbstractThe proteasome inhibitor bortezomib is a novel anticancer drug that has shown promise in the treatment of refractory multiple myeloma. However, its clinical efficacy has been hampered by the emergence of drug-resistance phenomena, the molecular basis of which remains elusive. Toward this end, we here developed high levels (45- to 129-fold) of acquired resistance to bortezomib in human myelomonocytic THP1 cells by exposure to stepwise increasing (2.5-200 nM) concentrations of bortezomib. Study of the molecular mechanism of bortezomib resistance in these cells revealed (1) an Ala49Thr mutation residing in a highly conserved bortezomib-binding pocket in the proteasome β5-subunit (PSMB5) protein, (2) a dramatic overexpression (up to 60-fold) of PSMB5 protein but not of other proteasome subunits including PSMB6, PSMB7, and PSMA7, (3) high levels of cross-resistance to β5 subunit-targeted cytotoxic peptides 4A6, MG132, MG262, and ALLN, but not to a broad spectrum of chemotherapeutic drugs, (4) no marked changes in chymotrypsin-like proteasome activity, and (5) restoration of bortezomib sensitivity in bortezomib-resistant cells by siRNA-mediated silencing of PSMB5 gene expression. Collectively, these findings establish a novel mechanism of bortezomib resistance associated with the selective overexpression of a mutant PSMB5 protein.
Molecular evolution of B6 enzymes: Binding of pyridoxal-5'-phosphate and Lys41Arg substitution turn ribonuclease A into a model B6 protoenzyme
Authors: Vacca Rosa A , Giannattasio Sergio , Capitani Guido , Marra Ersilia , Christen Philipp 
Published: June 2008

Abstract

Background
The pyridoxal-5'-phosphate (PLP)-dependent or vitamin B6-dependent enzymes that catalyze manifold reactions in the metabolism of amino acids belong to no fewer than four evolutionarily independent protein families. The multiple evolutionary origin and the essential mechanistic role of PLP in these enzymes argue for the cofactor having arrived on the evolutionary scene before the emergence of the respective apoenzymes and having played a dominant role in the molecular evolution of the B6 enzyme families. Here we report on an attempt to re-enact the emergence of a PLP-dependent protoenzyme. The starting protein was pancreatic ribonuclease A (RNase), in which active-site Lys41 or Lys7 readily form a covalent adduct with PLP.

Results
We screened the PLP adduct of wild-type RNase and two variant RNases (K7R and K41R) for catalytic effects toward L- and D-amino acids. RNase(K41R)-PLP, in which the cofactor is bound through an imine linkage to Lys7, qualifies for a model proto-B6 enzyme by the following criteria: (1) covalent linkage of PLP (internal aldimine); (2) catalytic activity toward amino acids that depends on formation of an imine linkage with the substrate (external aldimine); (3) adjoining binding sites for the cofactor and amino acid moiety that facilitate the transimination reaction of the internal to the external aldimine and stabilize the resulting noncovalent complex of the coenzyme-substrate adduct with the protein; (4) reaction specificity, the only detectable reactions being racemization of diverse amino acids and β-decarboxylation of L-aspartate; (5) acceleration factors for racemization and β-decarboxylation of >103 over and above that of PLP alone; (6) ribonuclease activity that is 103-fold lower than that of wild-type RNase, attenuation of a pre-existing biological activity being indispensable for the further evolution as a PLP-dependent protoenzyme.

Conclusion
A single amino acid substitution (Lys41Arg) and covalent binding of PLP to active-site Lys7 suffice to turn pancreatic ribonuclease A into a protein catalyst that complies with all plausible criteria for a proto-B6 enzyme. The study thus retraces in a model system what may be considered the committed step in the molecular evolution of a potential ancestor of a B6 enzyme family.
In silico identification of genes involved in selenium metabolism: evidence for a third selenium utilization trait
Authors: Zhang Yan , Turanov Anton A , Hatfield Dolph L , Gladyshev Vadim N 
Published: June 2008

Abstract

Background
Selenium (Se) is a trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine (SeU). Selenophosphate synthetase (SelD) is required for both utilization traits. However, previous research also revealed SelDs in two organisms lacking Sec and SeU, suggesting a possible additional use of Se that is dependent on SelD.

Results
In this study, we conducted comparative genomics and phylogenetic analyses to characterize genes involved in Se utilization. Candidate genes identified included SelA/SelB and YbbB that define Sec and SeU pathways, respectively, and NADH oxidoreductase that is predicted to generate a SelD substrate. In addition, among 227 organisms containing SelD, 10 prokaryotes were identified that lacked SelA/SelB and YbbB. Investigation of selD neighboring genes in these organisms revealed a SirA-like protein and two hypothetical proteins HP1 and HP2 that were strongly linked to a novel Se utilization. With these new signature proteins, 32 bacteria and archaea were found that utilized these proteins, likely as part of the new Se utilization trait. Metabolic labeling of one organism containing an orphan SelD, Enterococcus faecalis, with 75Se revealed a protein containing labile Se species that could be released by treatment with reducing agents, suggesting non-Sec utilization of Se in this organism.

Conclusion
These studies suggest the occurrence of a third Se utilization trait in bacteria and archaea.