bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential expression of survivin splice isoforms in medulloblastomas
Authors: Li X.‐N. , Shu Q. , Su J. M. , Adesina A. M. , Wong K. K. , Perlaky L. , Antalffy B. A. , Blaney S. M. , Lau C. C.
Published: January 2007

Survivin, a member of the inhibitor of apoptosis protein family, is implicated in the dysregulation of apoptosis in human cancers. Survivin and survivin‐deltaEx3, one of its two alternatively spliced isoforms, confer anti‐apoptotic activities in human tumours, while survivin‐2B antagonizes such anti‐apoptotic properties. The current study was undertaken to examine the mRNA expression of survivin isoforms and their correlation with clinical staging and outcome in 20 medulloblastoma (MB) tumours, three MB cell lines and normal brain tissues (a foetal and an adult cerebellum) by densitometry scanning of 32p‐dCTP incorporated reverse transcription polymerase chain reaction (RT‐PCR) products and quantitative real‐time PCR. Our results showed that the normal adult brain only expressed low levels of survivin‐deltaEx3 mRNA, while the foetal brain expressed all three isoforms, with wild‐type survivin as the dominant transcript. All three survivin isoforms were detected in all the MB cell lines and tumours analysed. Immunohistochemical staining also demonstrated survivin protein expressions in all five paraffin‐embedded MBs, with predominant nuclear localization. Although overexpressions of survivin were not associated with the presence of metastatic MB or tumour histological subtypes, elevated expressions of survivin‐deltaEx3 were significantly associated with progressive/recurrent tumours (P‐value = 0.024). Our data demonstrated that overexpression of survivin mRNA is a common feature in MBs, may contribute to their anti‐apoptosis properties and clinical behaviours, and predicts a poor clinical outcome, independent of clinical staging or tumour histology.
Promyelocytic leukaemia‐immunoreactive neuronal intranuclear rodlets in the human brain
Authors: Woulfe J. M. , Prichett‐Pejic W. , Rippstein P. , Munoz D. G.
Published: January 2007

In a previous study, we demonstrated immunoreactivity of a subset of neuronal intranuclear rodlets (INRs) in the human substantia nigra for promyelocytic leukaemia (PML) protein, the signature protein of PML bodies. In the present study, we extend these observations and describe the ultrastructural features, immunohistochemical staining characteristics, and topographical pattern of distribution of PML‐immunoreactive intranuclear rodlets (PML‐INRs). Consistent with a purported role for PML bodies in nuclear proteolysis and/or transcriptional regulation, PML‐INRs are immunoreactive for components of the ubiquitin–proteasome system, the transcriptional regulator CREB‐binding protein, acetylated histone H4, and the eukaryotic translation initiation factor eIF4E. Immunoelectron microscopy reveals that they all possess a filamentous core and, in some, this is surrounded by a granular shell. We further demonstrate that a proportion of INRs in extranigral sites also show partial immunoreactivity for PML. These observations indicate an intimate association between two neuronal nuclear bodies, PML bodies and INRs. Because both of these structures have been implicated in neurodegenerative disease, PML‐INRs may provide a tool with which to study changes in nuclear substructure in disease.
Disruption of Friend of GATA 2 gene (FOG‐2) by a de novo t(8;10) chromosomal translocation is associated with heart defects and gonadal dysgenesis
Authors: Finelli P , Pincelli AI , Russo S , Bonati MT , Recalcati MP , Masciadri M , Giardino D , Cavagnini F , Larizza L
Published: January 2007

FOG‐2 (Friend of GATA 2) is a transcriptional cofactor able to differentially regulate the expression of GATA‐target genes in different promoter contexts. Mouse models evidenced that FOG‐2 plays a role in congenital heart disease and normal testis development. In human, while FOG‐2 mutations have been identified in sporadic cases of tetralogy of Fallot, no mutations are described to be associated with impaired gonadal function. We here describe a young boy with a balanced t(8;10)(q23.1;q21.1) translocation who was born with congenital secundum‐type atrial septal defect and gonadal dysgenesis. Fluorescence in situ hybridization mapped the chromosome 8 translocation breakpoint (bkp) to within the IVS4 of the FOG‐2 gene, whereas the chromosome 10 bkp was found to lie in a desert gene region. Quantitative analysis of FOG‐2 expression revealed the presence of a truncated transcript but there was no detectable change in the expression of the genes flanking the 10q bkp, thus making it possible to assign the observed clinical phenotype to altered FOG‐2 expression. Genetic and clinical analyses provide insights into the signaling pathways by which FOG‐2 affects not only cardiac development but also gonadal function and its preservation.
Differential regulation of immune responses by odontoblasts
Authors: Veerayutthwilai O. , Byers M. R. , Pham T.‐T. T. , Darveau R. P. , Dale B. A.
Published: January 2007

Odontoblasts (OBs) are cells lining the inner surface of the tooth. Their potential role in host defenses within the tooth is suggested by their production of antimicrobial β‐defensins, but their role needs confirmation. The present study sought to define the roles of human OBs in microbial recognition and innate host responses. Toll‐like receptor 2 (TLR2) and TLR4, as well as CCR6, were immunolocalized in human OBs and their dentinal processes in situ. To examine OB function we used organotypic tooth crown cultures to maintain human OBs within their dentin scaffold. Cells in the OB layer of cultured and non‐cultured crown preparations expressed mRNA for several markers of innate immunity including chemokine CCL20, chemokine receptor CCR6, TLR2, TLR4 and the OB marker dentin sialophosphoprotein (DSPP). Expression of human β‐defensin 1 (hBD1), hBD2, hBD3, interleukin‐8 (IL‐8), and CCL20 increased with time in culture. Tooth crown odontoblast (TcOB) cultures were stimulated with agonist that was specific for TLR2 (Pam3CSK4) or TLR4 [Escherichia coli lipopolysaccharide (LPS)]. Nuclear factor‐κB assays confirmed the TLR2 activity of Pam3CSK4 and the TLR4 activity of LPS. LPS up‐regulated IL‐1β, tumor necrosis factor‐α (TNF‐α), CCL20, hBD2, IL‐8, TLR2 and TLR4; however, Pam3CSK4 down‐regulated these mRNAs. IL‐1β, TNF‐α, CCL20 were also up‐regulated from six‐fold to 30‐fold in TcOB preparations from decayed teeth. Our results show for the first time that OBs express microbial pattern recognition receptors in situ, thus allowing differential responses to gram‐positive and gram‐negative bacteria, and suggest that pro‐inflammatory cytokines and innate immune responses in decayed teeth may result from TLR4 signaling.
Salivary nitrate – an ecological factor in reducing oral acidity
Authors: Li H. , Thompson I. , Carter P. , Whiteley A. , Bailey M. , Leifert C. , Killham K.
Published: January 2007

Human oral cavities represent a novel environment with a constant supply of concentrated nitrate. For humans, over 80% of dietary nitrate originates from fruit and vegetables. With a healthy, balanced diet, rich in fruit and vegetables, the concentration of nitrate in saliva can reach up to more than three times the European drinking water standard. The physiological function of the active excretion of salivary nitrate is unknown. Furthermore, little is known of the ecological function of oral nitrate and the effect on the oral environment during its subsequent oral microbial conversions. The objectives of the research were to investigate the effect on salivary pH coupled with oral microbial nitrate and/or nitrite reduction. Human saliva samples were incubated anaerobically in the presence of 111.0 mmol glucose (2%), with and without 1.5 mmol nitrate/nitrite, and pH and nitrate/nitrite consumption were measured during the time‐course of the incubations. We found that anaerobic incubation of saliva containing a mixture of oral bacteria in the presence of nitrate/nitrite substrates and glucose resulted in a higher pH than was found in controls in the absence of nitrate/nitrite. These results suggest that the presence of these electron acceptors repressed acid fermentation, or increased alkali production, or consumed acid produced, thus reducing salivary acidity. This finding identifies salivary nitrate as a possible ecological factor in reducing oral acidity. The possibility that a symbiotic relationship between host nitrate excretion and nitrate‐reducing microorganisms might help to protect against tooth decay should be explored further.
Bacterial reduction and persistence after endodontic treatment procedures
Authors: Sakamoto M. , Siqueira J. F. , Rôças I. N. , Benno Y.
Published: January 2007

Bacteria that persist after endodontic disinfection procedures may lead to treatment failure. Over 50% of the bacteria found in endodontic infections are as‐yet‐uncultivated so investigations of bacteria that endure treatment procedures should include techniques that side‐step cultivation. This culture‐independent study evaluated the bacterial reduction promoted by intracanal disinfection procedures and identified the taxa persisting after treatment. Samples taken from the infected canals of teeth with apical periodontitis before treatment (S1), after instrumentation using NaOCl as irrigant (S2) and after interappointment medication with a calcium hydroxide paste (S3) were subjected to 16S rRNA gene clone library and real‐time polymerase chain reaction analyses. The S2 and S3 samples from five of the 15 canals showed negative results. In the other cases, instrumentation and instrumentation/medication promoted a significant reduction (99.67% and 99.85%, respectively) in the number of bacteria when compared to S1 samples. Forty‐three distinct bacterial taxa were identified, of which 24 (56%) were as‐yet‐uncultivated phylotypes. Nineteen of these 43 taxa (including eight as‐yet‐uncultivated phylotypes) were disclosed in post‐treatment samples, with streptococci being the most prevalent taxa. Findings demonstrated that culture‐independent methods provide a detailed insight into the effects of intracanal disinfection protocols, helping to define more effective strategies to deal with endodontic bacteria, including as‐yet‐uncultivated phylotypes.
Interleukin‐1α stimulation in monocytes by periodontal bacteria: antagonistic effects of Porphyromonas gingivalis
Authors: Bostanci N. , Allaker R. , Johansson U. , Rangarajan M. , Curtis M. A. , Hughes F. J. , McKay I. J.
Published: January 2007

Periodontal pathogenic bacteria are associated with elevated levels of interleukin‐1α (IL‐1α) but it is unclear if all species can induce cytokine production equally. Porphyromonas gingivalis may be able antagonize IL‐1α induced by other species through the activity of its proteases or lipopolysaccharide (LPS). Monomac‐6 cells and primary human monocytes were treated with culture supernatants from Porphyromonas gingivalis, Fusobacterium nucleatum, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedius, Veillonella atypical and Prevotella nigrescens. IL‐1α protein levels were measured after 6 h of incubation. In addition, monocytes were co‐stimulated with supernatants from P. gingivalis and other bacteria. The role of P. gingivalis proteases was tested using Arg‐X and Lys‐X mutant strains. The role of LPS was investigated using purified P. gingivalis LPS and polymixin depletion. All species tested induced significant IL‐1α production, but P. gingivalis was the weakest. Co‐stimulation of monocytes with P. gingivalis antagonized the ability of other bacterial species to induce IL‐1α production. This effect was at its greatest with C. rectus (resulting in a 70% reduction). Gingipain mutant strains and chemical inhibition of protease activity did not reduce antagonistic activity. However, 100 ng/ml of P. gingivalis LPS can reproduce the antagonistic activity of P. gingivalis culture supernatants. Periodontitis‐associated bacterial species stimulate IL‐1α production by monocytes. P. gingivalis can antagonize this effect, and its LPS appears to be the crucial component. This study highlights the importance of mixed infections in the pathogenesis of periodontal disease because reduction of pro‐inflammatory cytokine levels may impair the ability of the host to tackle infection.
Reliability and validity of the Turkish form of the Somatosensory Amplification Scale
Authors: GÜLEÇ HÜSEYIN , SAYAR KEMAL
Published: January 2007

Abstract  In this study, the authors aimed to investigate the reliability and validity of the Somatosensory Amplification Scale (SSAS) that was developed by Barsky et al. in the Turkish population. The study was carried out with 42 patients with Fibromyalgia Syndrome and Asthma Diseases attending to outpatient Physical Therapy and Rehabilitation and Chest Diseases clinics and 86 healthy students from Karadeniz Technical University. SSAS scores were normally distributed, and had acceptable test–retest reliability (r: 0.73) and internal consistency (α, 0.62–0.76). Item to scale correlations varied from 0.10 to 0.72, and most were highly significant. Whereas, one item (item 1) in the control group and one item (item 2) in the patients group had low item–total score correlation (r < 0.15). Criterion related validity of the SSAS was shown with significant correlation between the Symptom Interpretation Questionnaire, the Toronto Alexithymia Scale and the Symptom Check List 90 Revised somatization subscale. The validity analysis of the scale resulted in a very high significant difference (P < 0.01) between the mean SSAS scores of the control and patient’s group. Test–retest, internal reliability, and item–total score correlation, discriminating power for specific groups and criterion related validity of the SSAS show that the scale has acceptable reliability and validity for the Turkish population.
Activation of the prefrontal cortex during memory learning: Near‐infrared spectroscopy study
Authors: MATSUI MIÉ , TANAKA KUNIKO , YONEZAWA MINEO , KURACHI MASAYOSHI
Published: January 2007

Abstract  Near‐infrared spectroscopy (NIRS) is an optical method to determine oxygenated and deoxygenated hemoglobin concentration changes in the human cerebral cortex. The purpose of this study was to examine the hemodynamic response of the prefrontal area during words memory learning using NIRS. A total of 23 healthy subjects participated in the present study. Hemodynamic response in the prefrontal cortex was measured using a NIRS system. The number of words recalled and stimulus category repetition (SCR) were analyzed by the words memory learning task. During the words memory learning task, oxygenated hemoglobin concentrations increased and deoxygenated hemoglobin concentrations decreased. This typical pattern was maintained during each memory stage, but the degree of change of [oxyHb] during encoding from the first condition to the second condition was significantly larger than that during retrieval. This suggests that memory organization is facilitated during encoding of the first condition, and that the retrieval period through two conditions still involves more activation in the prefrontal area than the encoding period. An increase of [oxyHb] was not recognized and activation was inhibited when the strategy was applied. Subjects produced more SCR in the second condition than in the first condition in spite of strategy instruction. This result suggests healthy people can find out implicit category by themselves following learning even without instruction. There were no significant relationships between the behavior indices and the changes in hemoglobin. Further studies are needed to clarify usefulness of NIRS in patients with psychiatric disorder.
Attention and cognition in patients with obsessive–compulsive disorder
Authors: DE GEUS FEMKE , DENYS DAMIAAN A. J. P. , SITSKOORN MARGRIET M. , WESTENBERG HERMAN G. M.
Published: January 2007

Abstract  Although a dysfunctional prefrontal‐striatal system is presupposed in obsessive–compulsive disorder (OCD), this is not sustained by neuropsychological studies. The aim of this study was twofold: (i) to investigate the cognitive deficits in patients with OCD compared to matched healthy controls; and (ii) to relate cognitive performance to clinical characteristics in patients with OCD. In this study, 39 patients with primary OCD according to Diagnostic and Statistical Manual, fourth edition criteria were compared to 26 healthy control subjects on a battery measuring verbal memory and executive functioning. Patients with OCD showed slowed learning on the verbal memory task and made more errors on the Wisconsin Card Sorting Test. Errors were failures to maintain set, which were related to severity of OCD symptomatology. The results show that patients with OCD have cognitive deficits. The authors hypothesize that these deficits may be interpreted by attentional deficits caused by a dysfunctional anterior cingulate cortex.
Perospirone in the treatment of patients with delirium
Authors: TAKEUCHI TAKASHI , FURUTA KO , HIRASAWA TOSHIYUKI , MASAKI HIDEKAZU , YUKIZANE TOMOAKI , ATSUTA HIDENORI , NISHIKAWA TORU
Published: January 2007

Abstract  Perospirone is a recently developed atypical antipsychotic with potent serotonin 5‐HT2 and dopamine D2 antagonist activity. Other atypical antipsychotics including risperidone, quetiapine and olanzapine have been widely used for treatment, not only for schizophrenia symptoms but also for delirium, because of their low potential to induce extrapyramidal disturbances. In the present study the effectiveness and safety of perospirone in patients with delirium are described. Thirty‐eight patients with DSM‐IV delirium were given open‐label perospirone. To evaluate the usefulness of perospirone, scores from 13 severity items of the Delirium Rating Scale‐Revised‐98 were assessed. Data were gathered from October 2003 to September 2004. Perospirone was effective in 86.8% (33/38) of patients, and the effect appeared within several days (5.1 ± 4.9 days). The initial dose was 6.5 ± 3.7 mg/day and maximum dose of perospirone was 10.0 ± 5.3 mg/day. There were no serious adverse effects. However, increased fatigue (15.2%), sleepiness (6.1%), akathisia (3.0%) and a decline in blood pressure (3.0%) were observed. It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients. This is a preliminary open trial, and further randomized double‐blind placebo‐controlled tests are needed.
How many long‐stay schizophrenia patients can be discharged in Japan?
Authors: OSHIMA IWAO , MINO YOSHIO , INOMATA YOSHIMASA
Published: January 2007

Abstract  The mental health‐care system in Japan remains hospital‐based, and has the largest number of psychiatric beds per capita in the world. However, serious discussion about deinstitutionalization has recently begun. This study attempts to determine the proportion of inpatients that would benefit from community‐based programs, as judged by hospital psychiatrists, and to evaluate the need for community resources for their community placement. Inpatients with schizophrenia from 139 hospitals were randomly selected. Data on the psychiatrists’ judgment of discharge and required resources for community placement were obtained for 2758 subjects. Among the subjects, 1097 (39.8%) were judged to have the possibility of being discharged using community resources (possible discharge group; PDG). Provided that the proportion of PDG was 40%, controlling for the hospital background variables, the number of schizophrenia inpatients with a hospital stay of ≥1 year who could be discharged from psychiatric hospitals in Japan was estimated to be 66 000. For the PDG, the required community resources, including accommodation, daytime activity, and daily living support services, were calculated. The numbers of governmental targets for community resources, including community accommodation, daytime activities, and daily living support services may have been underestimated.
Mental health nurses’ experiences of schizophrenia rehabilitation in China and India: A preliminary study
Authors: Higgins Louise , Dey‐Ghatak Priya , Davey Gareth
Published: January 2007

ABSTRACT:  Nursing methods based on Western models may not be culturally relevant to patients from ethnic minority groups or other countries. In order to meet the needs of all patients, more research is needed to understand the cultural and social factors that influence nursing approaches. This paper reports preliminary open‐ended discussions with mental health nurses in China and India in order to gain insights into the cultural and social issues that surround social rehabilitation of patients with schizophrenia. Rehabilitation methods included cognitive behavioural therapy, psychosocial methods, and employment/vocational training. Several cultural and social issues drive the rehabilitation process in both countries, including the use of traditional medicine and healers, emphasis on family involvement, stigma, gender inequality, and lack of resources. Participants in both countries were working hard to tackle some of these issues, but also expressed need for improved resources. The study provides an insight into the cultural and social factors that shape schizophrenia rehabilitation in China and India, and serves as a baseline for further research about nursing across cultures. The study also highlights the marked differences in attitudes, values, and behaviours across cultural groups that need to be considered by nursing professionals to ensure that services are culturally competent.
Self‐reported consequences and needs for support associated with abuse in female users of psychiatric care
Authors: Bengtsson‐Tops Anita , Tops Dolf
Published: January 2007

ABSTRACT: The aims of the study were to investigate the prevalence of adult abuse in female users of psychiatric care, the relationship between abuse and self‐esteem and self‐reported consequences of abuse, and women’s self‐reported needs of support. A total of 1382 women participated in the study. A self‐administrated anonymous questionnaire with both closed‐ended and open‐ended questions was used. Quantitative data were analysed by mainly descriptive statistics and qualitative data were analysed by content analysis. Forty‐six per cent (n = 638) of the women had been exposed to emotional, sexual, and/or physical abuse in adulthood. Twenty‐eight per cent (n = 385) reported experiences of moderate physical abuse, 27% (n = 373) reported threats of injury, and 20% (n = 277) reported threats of being killed. Further, 19% (n = 261) reported experience of sexual violence, and 12% (n = 164) had experiences of serious physical violence. Women who had been abused rated lower self‐esteem than those who were not abused. Self‐reported consequences of abuse included intrapersonal problems such as poor self‐esteem, fears, anxiety, and worries but also problems in social relations especially with regard to close relationships and reliance to others. To a lesser extent, disease‐specific manifestations were reported. The needs of support included interventions directed to the experiences of abuse by professionals trained in the area, family interventions, self‐help groups, medical care, legal support, or practical help to find new housing situations. It is concluded that female users of psychiatric care services constitute a vulnerable group with regard to abuse. To meet the women’s needs, the care system has to adopt a perspective that includes personal, social, and societal factors.
Impaired hippocampal plasticity and errors in cognitive performance in mice with maladaptive AChE splice site selection
Authors: Farchi Noa , Shoham Shai , Hochner Binyamin , Soreq Hermona
Published: January 2007

Neuronal splice site selection events control multiple brain functions. Here, we report their involvement in stress‐modulated hippocampal plasticity and errors of cognitive performance. Under stress, alternative splicing changes priority from synaptic acetylcholinesterase (AChE‐S) to the normally rare, soluble and monomeric AChE‐R variant, which facilitates hippocampal long‐term potentiation (LTP) and intensifies fear‐motivated learning. To explore the adaptive value of changes in AChE splicing, we compared hippocampal plasticity and errors of executive function in TgS and TgR transgenic mice overexpressing AChE‐S or AChE‐R, respectively. Hippocampal slices from TgS and TgR mice presented delayed and facilitated transition to LTP maintenance, respectively, compared with strain‐matched FVB/N controls. TgS slices further showed failed recruitment of both the α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate and N‐methyl‐d‐aspartate components of LTP, refractory response to cholinergic enhancement and suppressed protein kinase C (PKC) levels. Stable LTP could, however, be rescued by phorbol ester priming, attributing the TgS deficits to disrupted signal transduction. In serial maze tests, TgS mice displayed more errors of conflict and executive function than did FVB/N controls, reflecting maladaptive performance under chronic AChE‐S overexpression. In contrast, TgR mice displayed enhanced serial maze performance, suggesting that chronic AChE‐R overexpression facilitates adaptive reactions. Our findings are compatible with the notion that changes in the alternative splicing of AChE pre‐mRNA and consequent alterations in PKC signalling are causally involved in modulating hippocampal plasticity and cognitive performance.
Hibernation model of tau phosphorylation in hamsters: selective vulnerability of cholinergic basal forebrain neurons – implications for Alzheimer's disease
Authors: Härtig Wolfgang , Stieler Jens , Boerema Ate S. , Wolf Jennifer , Schmidt Udo , Weißfuß Jana , Bullmann Torsten , Strijkstra Arjen M. , Arendt Thomas
Published: January 2007

Neurofibrillar tangles made up of ‘paired helical filaments’ (PHFs) consisting of hyperphosphorylated microtubule‐associated protein tau are major hallmarks of Alzheimer's disease (AD). Tangle formation selectively affects certain neuronal types and systematically progresses throughout numerous brain areas, which reflects a hierarchy of neuronal vulnerability and provides the basis for the neuropathological staging of disease severity. Mechanisms underlying this selective neuronal vulnerability are unknown. We showed previously that reversible PHF‐like phosphorylation of tau occurs during obligate hibernation. Here we extend these findings to facultative hibernators such as Syrian hamsters (Mesocricetus auratus) forced into hibernation. In this model, we showed in the basal forebrain projection system that cholinergic neurons are selectively affected by PHF‐like phosphorylated tau, while γ‐aminobutyric acid (GABA)ergic neurons are largely spared, which shows strong parallels to the situation in AD. Formation of PHF‐tau in these neurons apparently does not affect their function as pacemaker for terminating hibernation. We conclude that although formation of PHF‐like phosphorylated tau in the mammalian brain follows a certain hierarchy, affecting some neurons more frequently than others, it is not necessarily associated with impaired neuronal function and viability. This indicates a more general link between PHF‐like phosphorylation of tau and the adaptation of neurons under conditions of a ‘vita minima’.
Optical imaging of temporal integration in human auditory cortex
Authors: Sable Jeffrey J. , Low Kathy A. , Whalen Christopher J. , Maclin Edward L. , Fabiani Monica , Gratton Gabriele
Published: January 2007

Behavioral and physiological studies have indicated the existence of a temporal window of auditory integration (TWI), within which similar sounds are perceptually grouped. The current study exploits the combined temporal and spatial resolution of fast optical imaging (the event‐related optical signal, EROS) to show that brain activity elicited by sounds within and outside the TWI differs in location and latency. In a previous event‐related brain potential (ERP) study [Sable, Gratton, and Fabiani (2003) European Journal of Neuroscience, 17, 2492–2496], we found that the mismatch negativity (MMN; a brain response to acoustic irregularities) elicited by deviations in stimulus onset asynchronies (SOAs) had a unique shape when the deviant SOA was within the TWI. In the present study, we extended these ERP results using EROS. Participants heard trains of five tones. The first four tones had SOAs of 96, 192, 288 or 384 ms. The SOA of the fourth and fifth tones was either the same (standard) or one of the other three (deviant) SOAs. With a deviant SOA of 96 ms, the cortical response was approximately 2 cm anterior to responses to longer SOA deviants, and was followed by a later response that was absent in the other conditions. Similarly to the electrical MMN, the optical mismatch response amplitudes were proportional to the magnitude of interval deviance. These results, in combination with our previous findings, indicate that the temporal integration of sounds is reflected in cortical mismatch responses that differ from the typical response to interval deviance.
L‐type calcium channels and NMDA receptors: a determinant duo for short‐term nociceptive plasticity
Authors: Fossat Pascal , Sibon Igor , Le Masson Gwendal , Landry Marc , Nagy Frédéric
Published: January 2007

In the dorsal horn of the spinal cord, pain‐transmitting neurons exhibit action potential windup, a form of short‐term plasticity, which consists of a progressive increase in neuronal response during repetitive stimulation of nociceptive input fibers. Windup depends on N‐methyl‐d‐aspartate (NMDA) receptor activation, but previous in vitro studies indicated that windup also relies on intrinsic plateau properties of spinal neurons. In the present study, we considered the possible involvement of these properties in windup in vivo. For this purpose, we first studied a nociceptive flexion reflex in the rat. We showed that windup of the reflex is actually suppressed by blockers of L‐type calcium current and Ca2+‐activated non‐specific cationic current (Ican), the two main depolarizing conductances of plateau potentials. We further showed that, during windup, NMDA receptors provide a critical excitatory component in a dynamic balance of excitatory and inhibitory inputs which ultimately activates L‐type calcium channels. The nociceptive reflex involves at least two neuronal groups, which may express intrinsic amplification properties, motor neurons and dorsal horn neurons. By means of extracellular recordings in the dorsal horn, we showed that windup of dorsal horn neuron discharge was sensitive to the modulators of L‐type calcium current. Altogether, our results suggest that, in vivo, windup also depends on the amplification properties of spinal neurons, the triggering of which requires previous activation of NMDA receptors.
Visualization of corticofugal projections during early cortical development in a τ‐GFP‐transgenic mouse
Authors: Jacobs Erin C. , Campagnoni Celia , Kampf Kathy , Reyes Samuel D. , Kalra Vikram , Handley Vance , Xie Yuan‐Yun , Hong‐Hu Yan , Spreur Vilma , Fisher Robin S. , Campagnoni Anthony T.
Published: January 2007

The first postmitotic neurons in the developing neocortex establish the preplate layer. These early‐born neurons have a significant influence on the circuitry of the developing cortex. However, the exact timing and trajectory of their projections, between cortical hemispheres and intra‐ and extra‐cortical regions, remain unresolved. Here, we describe the creation of a transgenic mouse using a 1.3 kb golli promoter element of the myelin basic protein gene to target expression of a τ–green fluorescent protein (GFP) fusion protein in the cell bodies and processes of pioneer cortical neurons. During embryonic and early neonatal development, the timing and patterning of process extension from these neurons was examined. Analysis of τ‐GFP fluorescent fibers revealed that progression of early labeled projections was interrupted unexpectedly by transient pauses at the corticostriatal and telencephalic–diencephalic boundaries before invading the thalamus just prior to birth. After birth the pioneering projections differentially invaded the thalamus, excluding some nuclei, e.g. medial and lateral geniculate, until postnatal days 10–14. Early labeled projections were also found to cross to the contralateral hemisphere as well as to the superior colliculus. These results indicate that early corticothalamic projections appear to pause before invading specific subcortical regions during development, that there is developmental regulation of innervation of individual thalamic nuclei, and that these early‐generated neurons also establish early projections to commissural and subcortical targets.
Auditory processing in a patient with a unilateral lesion of the inferior colliculus
Authors: Champoux F. , Paiement P. , Mercier C. , Lepore F. , Lassonde M. , Gagné J.‐P.
Published: January 2007

The role of the inferior colliculus (IC) in human auditory processing is still poorly understood. We report here the results obtained with a 12‐year‐old boy (FX) who suffered a very circumscribed lesion of the right IC without additional neurological damage. The child underwent an extensive battery of psychophysical hearing tests. Results revealed normal peripheral auditory functioning, bilaterally. Furthermore, masking‐level differences and frequency‐pattern recognition were normal for each ear. When the right ear was stimulated, behavioural tests assessing central auditory processing yielded normal results. However, when the left ear was stimulated, speech recognition in the presence of a competing ipsilateral signal and duration‐pattern recognition were impaired. Similarly, performance on two dichotic speech recognition tests was poor when the target stimulus was presented in the left and the competing signal in the right ear. Finally, sound‐source localization in space was deficient for speakers located on the side contralateral to the lesion. The pattern of results suggests that auditory functions such as recognition of low‐redundancy speech presented monaurally, recognition of tone duration patterns, binaural separation and integration, as well as sound‐source localization in space, depend on the integrity of the bilateral auditory pathways at the IC level.
Regulation of ΔFosB transcriptional activity by Ser27 phosphorylation
Authors: Ulery Paula G. , Nestler Eric J.
Published: January 2007

The transcription factor, ΔFosB, is an important mediator of the long‐term plasticity induced in brain by chronic exposure to drugs of abuse, stress, or several other psychoactive stimuli. We have previously demonstrated that the casein kinase 2 (CK2)‐mediated phosphorylation of a highly conserved N‐terminal serine (Ser27) plays a critical role in regulating ΔFosB's unusual stability, while it does not affect that of the full‐length FosB protein. In the present study, we analysed whether CK2 and Ser27 phosphorylation also play a role in regulating ΔFosB's transcriptional activity. Our findings indicate that CK2 activation increases ΔFosB's transactivation potential, while CK2 inhibition decreases it. Further, we show that preventing Ser27 phosphorylation by mutating the site to Ala results in a significant decrease in ΔFosB transactivation, without affecting ΔFosB's subcellular localization or DNA‐binding affinity. In contrast, Ser27 does not seem to play a role in the transactivation potential of full‐length FosB. These findings constitute the first evidence of a role for phosphorylation in ΔFosB's transcriptional activity.
Enhanced fidelity of diffusive nitric oxide signalling by the spatial segregation of source and target neurones in the memory centre of an insect brain
Authors: Ott Swidbert R. , Philippides Andrew , Elphick Maurice R. , O'Shea Michael
Published: January 2007

The messenger molecule nitric oxide (NO) is a key mediator of memory formation that can diffuse in the brain over tens of micrometres. It would seem therefore that NO derived from many individual neurones may merge into a volume signal that is inevitably ambiguous, relatively unspecific and thus unreliable. Here we report on the neuronal architecture that supports the NO−cyclic GMP signalling pathway in the mushroom body of an insect brain, the key centre for associative learning. We show that, in the locust (Schistocerca gregaria), parallel axons of intrinsic neurones (Kenyon cells) form tubular NO‐producing zones surrounding central cores of NO‐receptive Kenyon cell axons, which do not produce NO. This segregated architecture requires NO to spread at physiological concentrations up to 60 µm from the tube walls into the central NO‐receptive cores. By modelling NO diffusion we show that a segregated architecture, which requires NO to act at a distance, affords significant advantages over a system where the same sources and targets intermingle. Segregation enhances the precision of NO volume signals by reducing noise and ambiguity, achieving a reliable integration of the activity of thousands of NO‐source neurones. In a neural structure that forms NO‐dependent associations, these properties of the segregated architecture may reduce the likelihood of forming spurious memories.
A novel enteropathogenic, strongly haemolytic spirochaete isolated from pig and mallard, provisionally designated ‘Brachyspira suanatina’ sp. nov.
Authors: Råsbäck Thérése , Jansson Désirée S. , Johansson Karl‐Erik , Fellström Claes
Published: January 2007

Atypical, strongly haemolytic porcine isolates of intestinal spirochaetes differing genetically from Brachyspira hyodysenteriae were identified and characterized. The isolates were subjected to culture and biochemical tests, antimicrobial susceptibility testing and molecular analyses. None of four species‐specific polymerase chain reaction systems targeting genes of B. hyodysenteriae gave a positive reaction. All the atypical porcine isolates were identical in their partial 16S rRNA and nox gene sequences with a previously described isolate from a mallard (Anas platyrhynchos), and differed only slightly from another mallard isolate. All these isolates were distinctly different from all currently recognized Brachyspira species. A challenge study was carried out using recently weaned pigs. Clinical signs and macroscopic changes consistent with swine dysentery were seen both in pigs given the atypical porcine isolate and in control pigs given the reference strain of B. hyodysenteriae (B204R). Pigs given the genetically similar isolate from a mallard became colonized and diarrhoea was observed. This is the first study indicating that Brachyspira isolates from mallard can infect pigs and induce diarrhoea. We propose that this atypical spirochaete genotype should be regarded as a new species within the genus Brachyspira, and be provisionally designated ‘Brachyspira suanatina’ sp. nov.
Delineating the anatomy of an entrepreneurial university: the Massachusetts Institute of Technology experience
Authors: O'Shea Rory P. , Allen Thomas J. , Morse Kenneth P. , O'Gorman Colm , Roche Frank
Published: January 2007

In many universities, heads, administrators and faculty seek to increase the propensity to engage in commercialization of research activity through the spinoff of new companies. The highly complex mechanism of spinoff generation is typically considered the result of either the characteristics of individuals, organizational policies and structures, organizational culture, or the external environment. Explanations of spinoff activity have in the main focused on only one of these dimensions at a time. In this paper we integrate these four dimensions of academic entrepreneurship to develop a more systemic understanding of spinoff activity at the university level. Using the case of Massachusetts Institute of Technology (MIT), a top spinoff generator in the United States, a systemic analysis is presented. We identify the inter‐related factors that have contributed to successful academic entrepreneurship in MIT. We argue that MIT's success is based on the science and engineering resource base at MIT; the quality of research faculty; supporting organizational mechanisms and policies such as MIT's Technology Licensing Office; and the culture within MIT faculty that encourages entrepreneurship. However, to understand why MIT has developed these resources and organizational mechanisms, it is necessary to understand the historical context and emergence of MIT, and in particular the historical mission of the university, the role of key individuals and university leaders in supporting this mission, and the impact of past success at commercialization activity. Finally, we suggest that MIT's success needs to be understood in the context of the local regional environment. We argue that university administrators and academics can learn from the case of MIT, but that efforts at transposing or replicating single elements of MIT's model may only have limited success, given the inter‐related nature of the drivers of spinoff activity.
Safe as Houses? Ageing in Place and Vulnerable Older People in the UK
Authors: Means Robin
Published: January 2007

The UK is very similar to many other European, North American and Australasian countries in its emphasis on ‘ageing in place’. This article does not seek to challenge the importance of this for most older people but rather draws out the challenges and issues raised by older people who are vulnerable or in vulnerable housing situations. This is illustrated through drawing upon three separate studies which are on older homelessness, older people in the private rented sector and owner‐occupiers with dementia.
Optimal Additions to and Deletions from Two-Level Orthogonal Arrays
Authors: Butler Neil A. , Ramos Victorino M.
Published: January 2007

Consider the problem of selecting a two-level factorial design. It is well known that two-level orthogonal arrays of strength 4 or more with e extra runs have various optimality properties including generalized Cheng (type 1) optimality when e=1, restricted Cheng (type 1) optimality when e=2 and E-optimality when 3⩽e⩽5. More general Schur optimality results are derived for more general values of e within the more restricted class of augmented two-level orthogonal arrays. Similar results are derived for the class of orthogonal arrays with deletions. Examples are used to illustrate the results and in many cases the designs are confirmed to be optimal across all two-level designs.
Nail changes in connective tissue diseases: do nail changes provide clues for the diagnosis?
Authors: Tunc SE , Ertam I , Pirildar T , Turk T , Ozturk M , Doganavsargil E
Published: January 2007

Objective  To evaluate the frequency and the specificity of nail changes associated with connective tissue diseases (CTD).

Methods  In a case–control study, 190 patients including those with systemic lupus erythematosus (SLE; 56), rheumatoid arthritis (RA, 47), primary Sjögren's syndrome (pSS; 35), systemic sclerosis (SSc; 39), and dermatomyositis/polymyositis (DM/PM; 13) were enrolled in the study. Patients with SLE and other CTDs were compared with two different control groups. Twenty nails were examined. Nail features were noted and classified. Nail samples were collected for mycological cultures.

Results  In patients with SLE, erythema of proximal nailfold (P < 0.01), splinter haemorrhages in fingernails (P < 0.01), capillary loops in proximal nailfold (P < 0.05), periungual erythema (P < 0.05), and thin nail plates (P < 0.05) were more common than those in controls. Only splinter haemorrhages were associated with the disease activity. In patients with SSc and DM/PM, splinter haemorrhages (P < 0.05) and capillary loops in proximal nailfold (P < 0.01) in fingernails were common as well. Increase in longitudinal curvature (P < 0.001), transverse curvature (P < 0.01), and white dull colour in fingernails were other frequent findings in patients with SSc. Increase in transverse curvature was associated with the disease activity in SSc. In patients with RA, splinter haemorrhages (P < 0.05), red lunula (P < 0.05), and white dull colour (P < 0.05) in fingernails were frequent. The sensitivity values of all these changes were very low. However, their specificity values were found to be relatively high.

Conclusion  Proximal nailfold is the most important site of affection in CTDs. These nail changes can be used in combination with highly sensitive diagnostic modalities to establish an accurate diagnosis.
Sun protection in Iranian kidney transplant recipients: knowledge, attitude and practice
Authors: Firooz A , Amin‐Nejad R , Bouzari N , Nafar M , Firoozan A , Mahdavi‐Mazdeh M
Published: January 2007

Background  Kidney transplant recipients (KTR) are at increased risk of developing skin cancer. The purpose of this study was to evaluate the knowledge, attitude, and practices of KTRs regarding skin cancer after transplantation and to identify the role of education in motivating these patients to practice sun‐protective behaviours.

Methods  Two hundred and fifty KTRs in a referral hospital were interviewed using a questionnaire. All patients received a skin cancer information booklet after completion of the questionnaire. Six months later, these patients were invited and interviewed again about their skin cancer‐prevention practices.

Results  The patients consisted of 153 men and 97 women patients with a mean age of 35.9 ± 14.2 years and mean of 49.7 ± 53.1 months after their transplantation. A total of 102 patients (40.8%) mentioned receiving skin care advice after transplantation. Nonetheless, the majority of patients did not have appropriate skin cancer‐prevention practices. Patients who had received advice on skin care after transplantation were significantly more likely to do skin self‐examination (chi‐squared test; P < 0.001) and have less sun exposure daily (Mann–Whitney test; P = 0.019) than those who did not. Half of the patients (125 patients) participated in the second part of the study 6 months after the first interview and providing skin care instruction booklet. Although regular skin self‐examination and sunscreen use was significantly increased (P = 0.006 and P = 0.001, respectively), but daily sun exposure was not changed significantly (P = 0.64).

Conclusions  Post‐transplantation education does not necessarily lead to patients’ awareness about their increased risk of skin cancer, and subsequent motivation to practice effective sun protection. Health professionals and dermatologists in particular need to establish better methods of dissemination of information, repeatedly and at the proper time.