bluuebunny/crossref_metadata_2025 huggingface dataset:
NADPH Oxidase Plays a Central Role in Blood-Brain Barrier Damage in Experimental Stroke
Authors: Kahles Timo , Luedike Peter , Endres Matthias , Galla Hans-Joachim , Steinmetz Helmuth , Busse Rudi , Neumann-Haefelin Tobias , Brandes Ralf P.
Published: October 2007

Background and Purpose—

Cerebral ischemia/reperfusion is associated with reactive oxygen species (ROS) generation, and NADPH oxidases are important sources of ROS. We hypothesized that NADPH oxidases mediate blood-brain barrier (BBB) disruption and contribute to tissue damage in ischemia/reperfusion.

Methods—

Ischemia was induced by filament occlusion of the middle cerebral artery in mice for 2 hours followed by reperfusion. BBB permeability was measured by Evans blue extravasation. Monolayer permeability was determined from transendothelial electrical resistance of cultured porcine brain capillary endothelial cells.

Results—

BBB permeability was increased in the ischemic hemisphere 1 hour after reperfusion. In NADPH oxidase–knockout (gp91phox
−/−
) mice, middle cerebral artery occlusion–induced BBB disruption and lesion volume were largely attenuated compared with those in wild-type mice. Inhibition of NADPH oxidase by apocynin prevented BBB damage. In porcine brain capillary endothelial cells, hypoxia/reoxygenation induced translocation of the NADPH oxidase activator Rac-1 to the membrane. In vivo inhibition of Rac-1 by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin or
Clostridium difficile
lethal toxin B also prevented the ischemia/reperfusion–induced BBB disruption. Stimulation of porcine brain capillary endothelial cells with H
2
O
2
increased permeability, an effect attenuated by inhibition of phosphatidyl inositol 3-kinase or
c
-Jun
N
-terminal kinase but not blockade of extracellular signal–regulated kinase-1/2 or p38 mitogen-activated protein kinase. Inhibition of Rho kinase completely prevented the ROS-induced increase in permeability and the ROS-induced polymerization of the actin cytoskeleton.

Conclusions—

Activation of Rac and subsequently of the gp91phox containing NADPH oxidase promotes cerebral ROS formation, which then leads to Rho kinase–mediated endothelial cell contraction and disruption of the BBB. Inhibition of NAPDH oxidase is a promising approach to reduce brain injury after stroke.
Interleukin-6 −174G/C Polymorphism and Ischemic Stroke
Authors: Tso Amy R. , Merino José G. , Warach Steven
Published: October 2007

Background and Purpose—

Interleukin-6 (IL-6) is associated with atherosclerotic disease and is also a key mediator in the inflammatory response to cerebral ischemia. Although the IL-6 −174G/C promoter polymorphism has been associated with carotid artery atherosclerosis and coronary heart disease, its relation to ischemic stroke is unclear. This review summarizes the current literature and discusses methodological considerations for future studies.

Methods—

Electronic searches were conducted in the PubMed MEDLINE, Scopus, and ISI Web of Science databases. Two investigators independently reviewed all abstracts to identify studies examining the association between the IL-6 −174G/C polymorphism and ischemic cerebrovascular events.

Results—

Twelve relevant publications were identified. Three reported on a subset of patients from a later publication, leaving 9 independent studies. Two studies found an association between ischemic stroke and the G allele or
GG
genotype, whereas 4 found an association with the C allele or
CC
genotype. One study found the
CC
genotype to be significantly less frequent in retinal artery occlusion patients. Two studies found no association between the −174G/C polymorphism and stroke.

Conclusions—

Studies investigating stroke and the −174G/C polymorphism report conflicting results, which may reflect the complex physiology of IL-6 and true differences between stroke subtypes and populations. However, interpretation of published results is hindered by methodological limitations, and greater rigor and consistency in future studies will help unravel the relationship between the −174G/C polymorphism and stroke.
Interactive Processing of Timbre Dimensions: An Exploration with Event-related Potentials
Authors: Caclin Anne , McAdams Stephen , Smith Bennett K. , Giard Marie-Hélène
Published: October 2007

Timbre characterizes the identity of a sound source. On psychoacoustic grounds, it has been described as a multidimensional perceptual attribute of complex sounds. Using Garner's interference paradigm, we found in a previous behavioral study that three timbral dimensions exhibited interactive processing. These timbral dimensions acoustically corresponded to attack time, spectral centroid, and spectrum fine structure. Here, using event-related potentials (ERPs), we sought neurophysiological correlates of the interactive processing of these dimensions of timbre. ERPs allowed us to dissociate several levels of interaction, at both early perceptual and late stimulus identification stages of processing. The cost of filtering out an irrelevant timbral dimension was accompanied by a late negative-going activity, whereas congruency effects between timbre dimensions were associated with interactions in both early sensory and late processing stages. ERPs also helped to determine the similarities and differences in the interactions displayed by the different pairs of timbre dimensions, revealing in particular variations in the latencies at which temporal and spectral timbre dimensions can interfere with the processing of another spectral timbre dimension.
To Ignore or Explore: Top–Down Modulation of Novelty Processing
Authors: Chong Hyemi , Riis Jenna L. , McGinnis Scott M. , Williams Danielle M. , Holcomb Phillip J. , Daffner Kirk R.
Published: October 2007

Attending to novelty is a critical element of human behavior and learning. Novel events can serve as task-irrelevant distracters or as potential sources of engagement by interesting or important aspects of one's environment. An optimally functioning brain should have the capacity to respond differentially to novel events depending on the circumstances in which they occur. In the present study, a subject-controlled variant of the visual novelty oddball paradigm was employed under two different conditions in which novel stimuli were characterized either as distracters from a main task or as potentially meaningful “invitations” to explore the environment. Differences in context, derived from varying the emphasis of task instructions, strongly modulated both the behavioral and electrophysiological response to novelty. This modulation was not observed for processing earlier than the P3 component. Subjects who encountered novel events that served as distracters limited the amount of attention and processing resources they appropriated. Remarkably, under this condition, there were no differences in overall P3 amplitude, late positive slow-wave activity, or viewing duration between rare novel and frequent standard events. In contrast, subjects who encountered novel events as potential opportunities to explore augmented the attention and processing resources directed toward these events (as reflected by a larger P3 amplitude, late positive slow-wave activity, and longer viewing durations). Our results suggest that the processing of novelty within the visual modality involves several stages, including: (1) the relatively automatic detection of unfamiliar, novel stimuli (indexed by the N2); (2) the voluntary allocation of resources determined by the broader context in which a novel event occurs (indexed by the P3); and (3) the sustained processing of novelty (indexed by late positive slow-wave activity). This study provides evidence of the brain's ability to generate differential responses to novel events according to the circumstances under which they are encountered. It also points to a greater degree of top–down modulation of the processing of novelty than has been previously emphasized. We suggest that less commonly studied variables, such as subject control, may provide additional insight into the different ways in which novelty is processed.
Lexical Plasticity in Early Bilinguals Does Not Alter Phoneme Categories: I. Neurodynamical Modeling
Authors: Larsson J.P. , Constán Fátima Vera , Sebastián-Gallés Núria , Deco Gustavo
Published: October 2007

Sebastián-Gallés et al. [The influence of initial exposure on lexical representation: Comparing early and simultaneous bilinguals. Journal of Memory and Language, 52, 240–255, 2005] contrasted highly proficient early Spanish-Catalan and Catalan-Spanish bilinguals, using Catalan materials in a lexical decision task (LDT). They constructed two types of experimental pseudowords, substituting Catalan phoneme /e/ for Catalan /ɛ/, or vice versa. Catalan-dominant bilinguals showed a performance asymmetry across experimental conditions, making more mistakes for /ɛ/→/e/ changes, than for /e/→/ɛ/ ones. This was considered evidence of a developed acceptance of mispronounced Catalan /ɛ/-words, caused by exposure to a bilingual environment where mispronunciations by Spanish-dominant bilinguals using their /e/-category abound. Although this indicated modified or added lexical representations, an open issue is whether such lexical information also modifies phoneme categories. We address this using a biophysically realistic neurodynamic model, describing neural activity at the synaptic and spiking levels. We construct a network of pools of neurons, representing phonemic and lexical processing. Carefully analyzing the dependency of network dynamics on connection strengths, by first exploring parameter space under steady-state assumptions (mean-field scans), then running spiking simulations, we investigate the neural substrate role in a representative LDT. We also simulate a phoneme discrimination task to address whether lexical changes affect the phonemic level. We find that the same network configuration which displays asymmetry in the LDT shows equal performance discriminating the two modeled phonemes. Thus, we predicted that the Catalan-dominant bilinguals do not alter their phoneme categories, although showing signs of having stored a new word variation in the lexicon. To explore this prediction, a syllable discrimination task involving the /e/-/ɛ/ contrast was set up, using Catalan-dominants displaying performance asymmetry in a repetition of the original LDT. Discrimination task results support the prediction, showing that these subjects discriminate both categories equally well. We conclude that subjects often exposed to dialectal word variations can store these in their lexicons, without altering their phoneme representations.
The Role of the Right Cerebral Hemisphere in Processing Novel Metaphoric Expressions: A Transcranial Magnetic Stimulation Study
Authors: Pobric Gorana , Mashal Nira , Faust Miriam , Lavidor Michal
Published: October 2007

Previous research suggests that the right hemisphere (RH) may contribute uniquely to the processing of metaphoric language. However, causal relationships between local brain activity in the RH and metaphors comprehension were never established. In addition, most studies have focused on familiar metaphoric expressions which might be processed similarly to any conventional word combination. The present study was designed to overcome these two problems by employing repetitive transcranial magnetic stimulation (rTMS) to examine the role of the RH in processing novel metaphoric expressions taken from poetry. Right-handed participants were presented with four types of word pairs, literal, conventional metaphoric and novel metaphoric expressions, and unrelated word pairs, and were asked to perform a semantic judgment task. rTMS of the right posterior superior temporal sulcus disrupted processing of novel but not conventional metaphors, whereas rTMS over the left inferior frontal gyrus selectively impaired processing of literal word pairs and conventional but not novel metaphors (Experiment 1). In a further experiment, we showed that these effects were due to right-left asymmetries rather than posterior-anterior differences (Experiment 2). This is the first demonstration of TMS-induced impairment in processing novel metaphoric expressions, and as such, confirms the specialization of the RH in the activation of a broader range of related meanings than the left hemisphere, including novel, nonsalient meanings. The findings thus suggest that the RH may be critically involved in at least one important component of novel metaphor comprehension, the integration of the individual meanings of two seemingly unrelated concepts into a meaningful metaphoric expression.
Neural and Behavioral Evidence for Affective Priming from Unconsciously Perceived Emotional Facial Expressions and the Influence of Trait Anxiety
Authors: Li Wen , Zinbarg Richard E. , Boehm Stephan G. , Paller Ken A.
Published: October 2007

Affective judgments can often be influenced by emotional information people unconsciously perceive, but the neural mechanisms responsible for these effects and how they are modulated by individual differences in sensitivity to threat are unclear. Here we studied subliminal affective priming by recording brain potentials to surprise faces preceded by 30-msec happy or fearful prime faces. Participants showed valence-consistent changes in affective ratings of surprise faces, although they reported no knowledge of prime-face expressions, nor could they discriminate between prime-face expressions in a forced-choice test. In conjunction with the priming effect on affective evaluation, larger occipital P1 potentials at 145–175 msec were found with fearful than with happy primes, and source analyses implicated the bilateral extrastriate cortex in this effect. Later brain potentials at 300–400 msec were enhanced with happy versus fearful primes, which may reflect differential attentional orienting. Personality testing for sensitivity to threat, especially social threat, was also used to evaluate individual differences potentially relevant to subliminal affective priming. Indeed, participants with high trait anxiety demonstrated stronger affective priming and greater P1 differences than did those with low trait anxiety, and these effects were driven by fearful primes. Results thus suggest that unconsciously perceived affective information influences social judgments by altering very early perceptual analyses, and that this influence is accentuated to the extent that people are oversensitive to threat. In this way, perception may be subject to a variety of influences that govern social preferences in the absence of concomitant awareness of such influences.
Effects of Varying the Experimental Design of a Cognitive Control Paradigm on Behavioral and Functional Imaging Outcome Measures
Authors: Goghari Vina M. , MacDonald Angus W.
Published: October 2007

A number of experimental techniques are commonly used within the field of functional neuroimaging to measure successive cognitive processes within a single trial. This study evaluated three experimental techniques to assess the comparability of behavioral and functional outcome measures in a task involving higher-level cognitive processing while controlling for the task duration. Twelve participants completed a cognitive control paradigm using the three techniques. Each trial of the task consisted of a green or red cue followed by a “Left” or “Right” probe. Green cues indicated that participants should respond in the direction of the probe. Red cues indicated participants should overcome their automatic tendency and respond in the direction opposite to the probe. The “slow” technique involved a sufficiently long trial allowing the blood oxygenation level-dependent response to rise and return to baseline before the next trial. The “jitter” technique involved varying the interstimulus and intertrial intervals. The “catch” technique involved presenting some cue-only trials in the midst of cue-probe trials. Predicted brain regions were activated by all the experimental techniques combined including the middle frontal, anterior cingulate, and inferior parietal cortices. Although there were more commonalties than differences between the three experimental techniques, generally, it appeared that the slow technique was effective at detecting posterior activity; the jitter technique was effective at detecting probe-related activity; and the catch technique was effective at detecting cue-related activity, especially in prefrontal regions. Thus, experiments measuring successive cognitive processes may have differential detection power for every event in a trial.
Dissociable Roles of the Superior Temporal Sulcus and the Intraparietal Sulcus in Joint Attention: A Functional Magnetic Resonance Imaging Study
Authors: Materna Simone , Dicke Peter W. , Thier Peter
Published: October 2007

Previous imaging work has shown that the superior temporal sulcus (STS) region and the intraparietal sulcus (IPS) are specifically activated during the passive observation of shifts in eye gaze [Pelphrey, K. A., Singerman, J. D., Allison, T., & McCarthy, G. Brain activation evoked by perception of gaze shifts: The influence of context. Neuropsychologia, 41, 156–170, 2003; Hoffman, E. A., & Haxby, J. V. Distinct representations of eye gaze and identity in the distributed human neural system for face perception. Nature Neuroscience, 3, 80–84, 2000; Puce, A., Allison, T., Bentin, S., Gore, J. C., & McCarthy, G. Temporal cortex activation in humans viewing eye and mouth movements. Journal of Neuroscience, 18, 2188–2199, 1998; Wicker, B., Michel, F., Henaff, M. A., & Decety, J. Brain regions involved in the perception of gaze: A PET study. Neuroimage, 8, 221–227, 1998]. Are the same brain regions also involved in extracting gaze direction in order to establish joint attention? In an event-related functional magnetic resonance imaging experiment, healthy human subjects actively followed the directional cue provided by the eyes of another person toward an object in space or, in the control condition, used a nondirectional symbolic cue to make an eye movement toward an object in space. Our results show that the posterior part of the STS region and the cuneus are specifically involved in extracting and using detailed directional information from the eyes of another person to redirect one's own gaze and establish joint attention. The IPS, on the other hand, seems to be involved in encoding spatial direction and mediating shifts of spatial attention independent of the type of cue that triggers this process.
Inhibition of Return Arises from Inhibition of Response Processes: An Analysis of Oscillatory Beta Activity
Authors: Pastötter Bernhard , Hanslmayr Simon , Bäuml Karl-Heinz
Published: October 2007

In the orienting of attention paradigm, inhibition of return (IOR) refers to slowed responses to targets presented at the same location as a preceding stimulus. No consensus has yet been reached regarding the stages of information processing underlying the inhibition. We report the results of an electro-encephalogram experiment designed to examine the involvement of response inhibition in IOR. Using a cue-target design and a target-target design, we addressed the role of response inhibition in a location discrimination task. Event-related changes in beta power were measured because oscillatory beta activity has been shown to be related to motor activity. Bilaterally located sources in the primary motor cortex showed event-related beta desynchronization (ERD) both at cue and target presentation and a rebound to event-related beta synchronization (ERS) after movement execution. In both designs, IOR arose from an enhancement of beta synchrony. IOR was related to an increase of beta ERS in the target-target design and to a decrease of beta ERD in the cue-target design. These results suggest an important role of response inhibition in IOR.
Bilingual and Monolingual Brains Compared: A Functional Magnetic Resonance Imaging Investigation of Syntactic Processing and a Possible “Neural Signature” of Bilingualism
Authors: Kovelman Ioulia , Baker Stephanie A. , Petitto Laura-Ann
Published: October 2007

Does the brain of a bilingual process language differently from that of a monolingual? We compared how bilinguals and monolinguals recruit classic language brain areas in response to a language task and asked whether there is a “neural signature” of bilingualism. Highly proficient and early-exposed adult Spanish-English bilinguals and English monolinguals participated. During functional magnetic resonance imaging (fMRI), participants completed a syntactic “sentence judgment task” [Caplan, D., Alpert, N., & Waters, G. Effects of syntactic structure and propositional number on patterns of regional cerebral blood flow. Journal of Cognitive Neuroscience, 10, 541–552, 1998]. The sentences exploited differences between Spanish and English linguistic properties, allowing us to explore similarities and differences in behavioral and neural responses between bilinguals and monolinguals, and between a bilingual's two languages. If bilinguals' neural processing differs across their two languages, then differential behavioral and neural patterns should be observed in Spanish and English. Results show that behaviorally, in English, bilinguals and monolinguals had the same speed and accuracy, yet, as predicted from the Spanish-English structural differences, bilinguals had a different pattern of performance in Spanish. fMRI analyses revealed that both monolinguals (in one language) and bilinguals (in each language) showed predicted increases in activation in classic language areas (e.g., left inferior frontal cortex, LIFC), with any neural differences between the bilingual's two languages being principled and predictable based on the morphosyntactic differences between Spanish and English. However, an important difference was that bilinguals had a significantly greater increase in the blood oxygenation level-dependent signal in the LIFC (BA 45) when processing English than the English monolinguals. The results provide insight into the decades-old question about the degree of separation of bilinguals' dual-language representation. The differential activation for bilinguals and monolinguals opens the question as to whether there may possibly be a “neural signature” of bilingualism. Differential activation may further provide a fascinating window into the language processing potential not recruited in monolingual brains and reveal the biological extent of the neural architecture underlying all human language.
The Meta-Analysis of Clinical Judgment Project
Authors: Spengler Paul M. , White Michael J. , Ægisdóttir Stefanía , Maugherman Alan S. , Anderson Linda A. , Cook Robert S. , Nichols Cassandra N. , Lampropoulos Georgios K. , Walker Blain S. , Cohen Genna R. , Rush Jeffrey D.
Published: October 2007

Clinical and educational experience is one of the most commonly studied variables in clinical judgment research. Contrary to clinicians' perceptions, clinical judgment researchers have generally concluded that accuracy does not improve with increased education, training, or clinical experience. In this meta-analysis, the authors synthesized results from 75 clinical judgment studies where the experience of 4,607 clinicians was assessed in relation to the accuracy of their judgments about mental health (e.g., diagnosis, prognosis, treatment) and psychological issues (e.g., vocational, personality). The authors found a small but reliable effect, d = .12, showing that experience, whether educational or clinical, is positively associated with judgment accuracy. This small effect was robust across several tested moderator models, indicating experienced counselors and clinicians acquire, in general, almost a 13% increase in their decision-making accuracy, regardless of other factors. Results are discussed in light of their implications for clinical judgment research and for counseling psychology training and practice.
Predicting Adolescent and Adult Antisocial Behavior Among Adjudicated Delinquent Females
Authors: Cernkovich Stephen A. , Lanctôt Nadine , Giordano Peggy C.
Published: October 2007

Studies identifying the mechanisms underlying the causes and consequences of antisocial behavior among female delinquents as they transit to adulthood are scarce and have important limitations: Most are based on official statistics, they typically are restricted to normative samples, and rarely do they gather prospective data from samples of high-risk females. By contrast, this research is based on a longitudinal sample of females who were interviewed initially in 1982 ( n = 127) when they were institutionalized adolescent offenders, and subsequently as young adults in 1995 ( n = 109). Our analyses, focusing on the impact of a variety of family factors derived from social control and strain theory, show that physical and sexual abuse during childhood and adolescence are potent predictors of adult criminality, though not of adolescent delinquency. The implications of the long-term negative impact of childhood and adolescent abuse are discussed, and concrete policy recommendations offered.
Understanding the Black Box of Gang Organization
Authors: Decker Scott H. , Katz Charles M. , Webb Vincent J.
Published: October 2007

This article examines the influence of gang organization on several behavioral measures. Using interview data from juvenile detention facilities in three Arizona sites, this article examines the relationship between gang organizational structure and involvement in violent crime, drug sales, victimization, and arrest. The gang literature suggests that gangs are not very well organized. However, the findings from the current research suggest that even low levels of gang organization are important for their influence on behavior. Indeed, even incremental increases in gang organization are related to increased involvement in offending and victimization.
Reconciling the Differences Between the “Gender-Responsive” and the “What Works” Literatures to Improve Services for Girls
Authors: Hubbard Dana Jones , Matthews Betsy
Published: October 2007

Recent increases in the delinquency and incarceration of girls have prompted juvenile justice professionals to search for effective, gender-specific prevention and treatment strategies. Given the dearth of research on girls' programming, these professionals are often left to sort out discrepancies between two major bodies of literature that address the needs of delinquent girls—the “what works” literature and the “gender-responsive” literature. This article culls the best of what is available within both these bodies of literature and suggests programmatic elements deemed essential for working effectively with girls.
General Strain Theory and Delinquency
Authors: Moon Byongook , Blurton David , McCluskey John D.
Published: October 2007

The study examines the effects of recent, older, and chronic strains and of perceived injustice of strain on delinquency, sampling 777 Korean youth. Seven key strains most likely leading to delinquency, some of which were often overlooked in previous research, were included, and these are family conflict, parental punishment, teachers' punishment, financial strain, examination-related strain, being bullied, and criminal victimization. Overall, the findings provide some support for general strain theory's prediction that some recent strains and perceived injustice have significant effects on delinquency. The results show that recent and older teachers' physical and emotional punishment and victimization are positively related to general delinquency. However, chronic parental punishment and chronic bullying are negatively related to general delinquency, inconsistent with Agnew's prediction. The findings also indicate the critical importance of including types of strain that are unique to certain cultures into tests of the theory.
Removing a Nail From the Boot Camp Coffin
Authors: Duwe Grant , Kerschner Deborah
Published: October 2007

Using a retrospective, quasiexperimental design, this study evaluates Minnesota's Challenge Incarceration Program (CIP), examining whether it has lowered recidivism and saved money. In addition to utilizing a lengthy follow-up period and multiple measures of recidivism and participation, a multistage sampling design was employed to create a control group that was not significantly different from the CIP group with respect to control variables. The results reveal that although CIP significantly reduced the time to reoffense, it did not have a significant effect when recidivism was measured as any return to prison. CIP reduced costs through a recidivism reduction, however, because when CIP offenders returned to prison, they stayed 40 fewer days than control group offenders because they were less likely to return for a new crime. Overall, the analyses show that CIP has saved Minnesota at least $6.2 million by providing early release to program graduates and reducing the time they later spend in prison.
Research Note: Assessing the Perceived Seriousness of White-Collar and Street Crimes
Authors: Leeper Piquero Nicole , Carmichael Stephanie , Piquero Alex R.
Published: October 2007

Controversy surrounds the ranking of crime seriousness of white-collar crimes relative to street crimes, with early research suggesting the general public is indifferent to crimes of the elite, whereas more recent research indicates that the public thinks certain types of white-collar crime are serious. Building on prior research limitations and using data from a national random probability sample, this study compares the seriousness ratings of a number of white-collar and street crimes and examines the factors that distinguish seriousness ratings across the crime types. The analyses indicate that certain types of white-collar crimes are ranked as more serious than street crimes and that a limited set of demographic correlates distinguish seriousness ratings across the two crime types. Future research directions are outlined.
Short-Term Changes in and Predictors of Participation of Older Adults After Stroke Following Acute Care or Rehabilitation
Authors: Desrosiers Johanne , Demers Louise , Robichaud Line , Vincent Claude , Belleville Sylvie , Ska Bernadette
Published: October 2007

Background. Stroke can lead to restrictions in participation in daily activities and social roles. Although considered an important rehabilitation outcome, little is known about participation after stroke and its predictors, and about the differences associated with the types of services provided following stroke. Objective . The aims of this study were 1) to follow and compare changes in participation of older adults discharged home after stroke from acute care or postacute rehabilitation, and 2) to identify the best predictors of participation after stroke from physical, cognitive, perceptual, and psychological ability measures taken shortly after discharge. Methods. Level of participation in daily activities and social roles of 197 older adults who had a stroke was evaluated at 2 to 3 weeks (T1), 3 months (T2), and 6 months (T3) after being discharged home from acute care (n = 86) or rehabilitation (n = 111). Physical, cognitive, perceptual, and psychological abilities were assessed at T1. Results. A significant increase in participation was found over time for both groups, mainly in the first 3 months. The best predictors of participation differed between the groups and between the daily activities and social roles domains. Walking and acceptance of the stroke or fewer depressive symptoms were the best predictors of the level of participation after stroke. Conclusions . Participation was not optimal at discharge because it continued to increase after the return home. The importance of psychological factors in participation after stroke is undeniable. Many predictors are amenable to interventions.
Neural Correlates of Proprioceptive Integration in the Contralesional Hemisphere of Very Impaired Patients Shortly After a Subcortical Stroke: An fMRI Study
Authors: Dechaumont-Palacin S. , Marque P. , De Boissezon X. , Castel-Lacanal E. , Carel C. , Berry I. , Pastor J. , Albucher J.F. , Chollet F. , Loubinoux I.
Published: October 2007

Background. The effects of physiotherapy are difficult to assess in very impaired early stroke patients. Objective. The aim of the study was to characterize the impact of 4 weeks of passive proprioceptive training of the wrist on brain sensorimotor activation after stroke. Methods. Patients with a subcortical ischemic lesion of the pyramidal tract were randomly assigned to a control or a wrist-training group. All patients had a single pure motor hemiplegia with severe motor deficit. The control group (6 patients) underwent standard Bobath rehabilitation. The second, “trained,” group (7 patients) received Bobath rehabilitation plus 4 weeks of proprioceptive training with daily passive calibrated wrist extension. Before and after the training period, patients were examined with validated clinical scales and functional MRI (fMRI) while executing a passive movement versus rest. The effect of standard rehabilitation on sensorimotor activation was assessed in the control group on the wrist, and the effect of standard rehabilitation plus proprioceptive training was assessed in the trained group. The effect of 4-week proprioceptive training alone was statistically evaluated by difference between groups. Results. Standard rehabilitation along with natural recovery mainly led to increases in ipsilesional activation and decreases in contralesional activation. On the contrary, standard rehabilitation and paretic wrist proprioceptive training increased contralesional activation. Proprioceptive training produced change in the supplementary motor area (SMA), prefrontal cortex, and a contralesional network including inferior parietal cortex (lower part of BA 40), secondary sensory cortex, and ventral premotor cortex (PMv). Conclusion. We have demonstrated that purely passive proprioceptive training applied for 4 weeks is able to modify brain sensorimotor activity after a stroke. This training revealed fMRI change in the ventral premotor and parietal cortices of the contralesional hemisphere, which are secondary sensorimotor areas. Recent studies have demonstrated the crucial role of these areas in severely impaired patients. We propose that increased contralesional activity in secondary sensorimotor areas likely facilitates control of recovered motor function by simple proprioceptive integration in those patients with poor recovery.
The factor VIII C1 domain contributes to platelet binding
Authors: Hsu Ting-Chang , Pratt Kathleen P. , Thompson Arthur R.
Published: October 2007

Activated factor VIII (FVIIIa) forms a procoagulant complex with factor IXa on negatively charged membranes, including activated platelet surfaces. Membrane attachment involves the FVIII C2 domain; involvement of the adjacent C1 domain has not been established. Binding of recombinant FVIII C1C2 and C2 proteins to platelets was detected by flow cytometry using (1) anti-C2 monoclonal antibody ESH8 followed by a phycoerythrin-labeled secondary antibody; (2) biotinylated C1C2 detected by phycoerythrin-labeled streptavidin, and (3) C1C2 and C2 site-specifically labeled with fluorescein. Highest binding and lowest background were obtained using fluorescein-conjugated proteins. More than 90% of activated platelets bound C1C2, compared with approximately 50% for equimolar C2. Estimates using fluorescent microbeads indicated approximately 7000 C1C2-binding sites per platelet, approximately 1400 for C2, and approximately 3000 for fluorescein-labeled FVIIIa. Unlike C2 or FVIII(a), C1C2 bound to approximately 700 sites/platelet before activation. C1C2 binding to activated platelets appeared independent of von Willebrand factor and was competed effectively by FVIII(a), but only partially by excess C2. Fluorescein-labeled FVIIIa was competed much more effectively by C1C2 than C2 for binding to activated platelets. Two monoclonal antibodies that inhibit C2 binding to membranes competed platelet binding of C2 more effectively than C1C2. Thus, the C1 domain of FVIII contributes to platelet-binding affinity.
Small-molecule XIAP antagonist restores caspase-9–mediated apoptosis in XIAP-positive diffuse large B-cell lymphoma cells
Authors: Cillessen Saskia A. G. M. , Reed John C. , Welsh Kate , Pinilla Clemencia , Houghten Richard , Hooijberg Erik , Deurhof José , Castricum Kitty C. M. , Kortman Pim , Hess Corine J. , Ossenkoppele Gert J. , Meijer Chris J. L. M. , Oudejans Joost J.
Published: October 2007

Clinical outcome in patients with primary nodal diffuse large B-cell lymphomas (DLBCLs) is correlated with expression of inhibitors of the intrinsic apoptosis pathway, including X-linked inhibitor of apoptosis protein (XIAP). XIAP suppresses apoptosis through inhibiting active caspase-3, caspase-7, and caspase-9. In this study, we investigated to see if the small-molecule XIAP antagonist 1396-12 induces cell death in cultured lymphoma cells of patients with DLBCL. Treatment with this XIAP antagonist resulted in relief of caspase-3 inhibition and in induction of apoptosis in 16 of 20 tested DLBCL samples. Sensitivity to the XIAP antagonist was observed in both chemotherapy-refractory and -responsive DLBCL, but did not affect peripheral blood mononuclear cells and tonsil germinal-center B cells from healthy donors. XIAP antagonist-sensitive samples were characterized by high expression levels of XIAP, relatively low expression levels of Bcl-2, and by constitutive caspase-9 activation. These data indicate that the small-molecule XIAP antagonist can induce apoptosis in cultured DLBCL cells and therefore should be considered for possible development as a therapy for these patients. In vitro sensitivity to the XIAP antagonist can be predicted based on biological markers, suggesting the possibility of predefining patients most likely to benefit from XIAP antagonist therapy.
Activator-specific requirement of properdin in the initiation and amplification of the alternative pathway complement
Authors: Kimura Yuko , Miwa Takashi , Zhou Lin , Song Wen-Chao
Published: October 2007

Properdin is a positive regulator of alternative pathway (AP) complement. The current understanding of properdin function is that it facilitates AP complement activation by stabilizing the C3 convertase C3bBb. Properdin-deficient patients are susceptible to lethal meningococcal infection, but the mechanism of this selective predisposition is not fully understood. By gene targeting in the mouse, we show here that properdin is essential for AP complement activation induced by bacterial lipopolysacharride (LPS) and lipooligosacharride (LOS) and other, but not all, AP complement activators. LPS- and LOS-induced AP complement activation was abolished in properdin−/− mouse serum, and properdin−/− mice were unable to clear Crry-deficient erythrocytes, which are known to be susceptible to AP complement–mediated extravascular hemolysis. In contrast, zymosan- and cobra venom factor–induced AP complement activation, and classical pathwaytriggered AP complement amplification were only partially or minimally affected in properdin−/− mice. We further show that the ability of human properdin to restore LPS-dependent AP complement activity in properdin−/− mouse serum correlated with the human properdin-binding affinity of the LPS. These results reveal a novel role of properdin in AP complement initiation and have implications for understanding the selective predisposition of properdin-deficient patients to meningococcal infection.
Imaging in staging of malignant lymphoma: a systematic review
Authors: Kwee Thomas C. , Kwee Robert M. , Nievelstein Rutger A. J.
Published: October 2007

Computed tomography (CT) is currently the most commonly used means for staging malignant lymphoma. 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), FDG-PET/CT fusion, and whole-body magnetic resonance imaging (WB-MRI) are potential alternatives. The purpose of this study was to systematically review published data on the diagnostic performance of CT, FDG-PET, FDG-PET/CT fusion, and WB-MRI in staging of malignant lymphoma. In addition, technical aspects, procedures, advantages, and drawbacks of each imaging modality are outlined. Three CT studies, 17 FDG-PET studies, and 4 FDG-PET/CT fusion studies were included in this systematic review. The studies were of moderate methodological quality and used different scoring systems to stage malignant lymphoma. CT remains the standard imaging modality for initial staging of malignant lymphoma, while FDG-PET has an essential role in restaging after treatment. Early results suggest that FDG-PET/CT fusion outperforms both CT alone and FDG-PET alone. Data on the diagnostic performance of WB-MRI are lacking. Future well-designed studies, expressing their results according to the Ann Arbor staging system, are needed to determine which imaging modality is most accurate and cost-effective in staging malignant lymphoma.
The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation
Authors: Nguyen Vu H. , Shashidhar Sumana , Chang Daisy S. , Ho Lena , Kambham Neeraja , Bachmann Michael , Brown Janice M. , Negrin Robert S.
Published: October 2007

Regulatory T cells (Tregs) prevent graft-versus-host disease (GvHD) by inhibiting the proliferation and function of conventional T cells (Tcons). However, the impact of Tregs on T-cell development and immunity following hematopoietic cell transplantation (HCT) is unknown. Using a murine GvHD model induced by Tcons, we demonstrate that adoptive transfer of Tregs leads to (1) abrogration of GvHD, (2) preservation of thymic and peripheral lymph node architecture, and (3) an accelerated donor lymphoid reconstitution of a diverse TCR-Vβ repertoire. The resultant enhanced lymphoid reconstitution in Treg recipients protects them from lethal cytomegalovirus (MCMV) infection. By contrast, mice that receive Tcons alone have disrupted lymphoid organs from GvHD and remain lymphopenic with a restricted TCR-Vβ repertoire and rapid death on MCMV challenge. Lymphocytes from previously infected Treg recipients generate secondary response specific to MCMV, indicating long-term protective immunity with transferred Tregs. Thymectomy significantly reduces survival after MCMV challenge in Treg recipients compared with euthymic controls. Our results indicate that Tregs enhance immune reconstitution by preventing GvHD-induced damage of the thymic and secondary lymphoid microenvironment. These findings provide new insights into the role of Tregs in affording protection to lymphoid stromal elements important for T-cell immunity.
LPS induces IL-10 production by human alveolar macrophages via MAPKinases- and Sp1-dependent mechanisms
Authors: Chanteux Hugues , Guisset Amélie C , Pilette Charles , Sibille Yves
Published: October 2007

Background

IL-10 is a cytokine mainly produced by macrophages that plays key roles in tolerance to inhaled antigens and in lung homeostasis. Its regulation in alveolar macrophages (HAM), the resident lung phagocytes, remains however unknown.

Methods

The present study investigated the role of intracellular signalling and transcription factors controlling the production of IL-10 in LPS-activated HAM from normal nonsmoking volunteers.

Results

LPS (1–1000 pg/ml) inducedin vitroIL-10 production by HAM, both at mRNA and protein levels. LPS also activated the phosphorylation of ERK, p38 and JNK MAPkinases (immunoblots) and Sp-1 nuclear activity (EMSA). Selective inhibitors of MAPKinases (respectively PD98059, SB203580 and SP600125) and of Sp-1 signaling (mithramycin) decreased IL-10 expression in HAM. In addition, whilst not affecting IL-10 mRNA degradation, the three MAPKinase inhibitors completely abolished Sp-1 activation by LPS in HAM.

Conclusion

These results demonstrate for the first time that expression of IL-10 in lung macrophages stimulated by LPS depends on the concomitant activation of ERK, p38 and JNK MAPKinases, which control downstream signalling to Sp-1 transcription factor. This study further points to Sp-1 as a key signalling pathway for IL-10 expression in the lung.
Genes2Networks: connecting lists of gene symbols using mammalian protein interactions databases
Authors: Berger Seth I , Posner Jeremy M , Ma'ayan Avi
Published: October 2007

Background

In recent years, mammalian protein-protein interaction network databases have been developed. The interactions in these databases are either extracted manually from low-throughput experimental biomedical research literature, extracted automatically from literature using techniques such as natural language processing (NLP), generated experimentally using high-throughput methods such as yeast-2-hybrid screens, or interactions are predicted using an assortment of computational approaches. Genes or proteins identified as significantly changing in proteomic experiments, or identified as susceptibility disease genes in genomic studies, can be placed in the context of protein interaction networks in order to assign these genes and proteins to pathways and protein complexes.

Results

Genes2Networks is a software system that integrates the content of ten mammalian interaction network datasets. Filtering techniques to prune low-confidence interactions were implemented. Genes2Networks is delivered as a web-based service using AJAX. The system can be used to extract relevant subnetworks created from "seed" lists of human Entrez gene symbols. The output includes a dynamic linkable three color web-based network map, with a statistical analysis report that identifies significant intermediate nodes used to connect the seed list.

Conclusion

Genes2Networks is powerful web-based software that can help experimental biologists to interpret lists of genes and proteins such as those commonly produced through genomic and proteomic experiments, as well as lists of genes and proteins associated with disease processes. This system can be used to find relationships between genes and proteins from seed lists, and predict additional genes or proteins that may play key roles in common pathways or protein complexes.
Statistical power of phylo-HMM for evolutionarily conserved element detection
Authors: Fan Xiaodan , Zhu Jun , Schadt Eric E , Liu Jun S
Published: October 2007

Background

An important goal of comparative genomics is the identification of functional elements through conservation analysis. Phylo-HMM was recently introduced to detect conserved elements based on multiple genome alignments, but the method has not been rigorously evaluated.

Results

We report here a simulation study to investigate the power of phylo-HMM. We show that the power of the phylo-HMM approach depends on many factors, the most important being the number of species-specific genomes used and evolutionary distances between pairs of species. This finding is consistent with results reported by other groups for simpler comparative genomics models. In addition, the conservation ratio of conserved elements and the expected length of the conserved elements are also major factors. In contrast, the influence of the topology and the nucleotide substitution model are relatively minor factors.

Conclusion

Our results provide for general guidelines on how to select the number of genomes and their evolutionary distance in comparative genomics studies, as well as the level of power we can expect under different parameter settings.