bluuebunny/crossref_metadata_2025 huggingface dataset:
High levels of nucleotide diversity in the European rabbit (Oryctolagus cuniculus) SRY gene
Authors: Geraldes A. , Rogel‐Gaillard C. , Ferrand N.
Published: July 2005

We have sequenced 2388 bp of the European rabbit sex determining region Y (SRY) gene. These data provide a 10‐fold increase in the coverage of the Y chromosome in this species, including the entire open reading frame of the SRY, the polyadenylation signal, and two repetitive sequences in the 5′ ‐region. A survey of 2021 bp of this gene in eight domestic breeds and four wild individuals revealed a total of nine single nucleotide polymorphisms and one indel, defining two deeply divergent lineages. The resulting estimation of nucleotide diversity (π = 1.34 × 10−3) is very high when compared with other species, but no variability was detected among the domestic breeds. This study represents a first step in the characterization of the European rabbit Y chromosome and its variability. These sequences can be used in additional phylogeographical analyses of the European rabbit and other Leporid species, as well as in evolutionary studies of sex determination and the Y chromosome in wild species.
Identification of a mutation in the ovine uroporphyrinogen decarboxylase (UROD) gene associated with a type of porphyria
Authors: Nezamzadeh R. , Seubert A. , Pohlenz J. , Brenig B.
Published: July 2005

Porphyria is a group of at least eight diseases caused by abnormalities in the chemical steps that lead to haeme production. The different types of porphyria show different signs and symptoms and can be strongly influenced by environmental factors. Mutations of the uroporphyrinogen decarboxylase (UROD) gene have been shown to be causative for porphyria cutanea tarda (PCT) in humans. Porphyria is a rare disorder in livestock. Although disorders of haeme biosynthesis have been described in cattle, pigs, sheep and cats, PCT has only been reported in pigs. We observed typical signs of porphyria (photosensitivity and porphyrinuria) in a flock of German Blackface sheep and postulated that the porphyria could be caused by a mutation in the UROD gene. To investigate this, we cloned and sequenced the ovine UROD gene. We identified a single point mutation (C → T) in UROD which leads to an amino acid substitution at Leu131Pro, which is located within the active cleft site of the UROD protein.
Physical mapping of genes in the porcine ovarian transcriptome
Authors: Caetano A. R. , Edeal J. B. , Burns K. , Johnson R. K. , Tuggle C. K. , Pomp D.
Published: July 2005

Reproductive efficiency and associated traits are of major economic importance to the swine industry and have been more difficult to improve genetically than other production traits. Integration of phenotypical data with gene mapping and expression studies provides a powerful approach for dissection of the genetic basis regulating complex traits. We developed a total of 101 polymerase chain reaction‐based markers, representing 91 unique genes, for expressed sequence tags previously reported to be putatively differentially expressed in the porcine ovarian transcriptome of a swine line selected on an index of high ovulation rate and embryonic survival. These were subsequently used in physical mapping experiments with a porcine radiation hybrid and somatic cell hybrid panels. Our results increased the information content of the porcine physical map useful for comparative mapping by c. 10%. Moreover, the mapped genes are likely to be biologically relevant to the molecular mechanisms that control ovulation rate in the pig. A total of 12 differentially expressed genes were mapped to regions previously reported to contain quantitative trait loci affecting swine ovulation rate.
A novel maternal lineage revealed in sheep (Ovis aries)
Authors: Guo J. , Du L.‐X. , Ma Y.‐H. , Guan W.‐J. , Li H.‐B. , Zhao Q.‐J. , Li X. , Rao S.‐Q.
Published: July 2005

It is generally believed that domestic sheep have two maternal lineages (haplotypes A and B), based on mitochondrial DNA analysis. In the present study, we provide evidence that a novel maternal lineage (haplotype C) is exhibited in Chinese native sheep. To verify this finding, 231 samples were collected from six Chinese local breeds, which cover the vast geographical region of sheep inhabitation in China. For comparison, 50 samples were collected from two Western breeds collected in China. Mitochondrial DNA was screened by PCR single‐strand conformational polymorphism (SSCP), leading to the identification of novel band patterns in ND2 and ND4 genes in the Chinese breeds. Interestingly, mutations at the two loci were in strong linkage disequilibrium. Direct sequencing of the DNA fragments revealed a non‐synonymous substitution in ND2. Furthermore, two synonymous mutations were identified by comparisons of the novel type (haplotype C) and the established types (haplotypes A and B). The entire mitochondrial control region for 55 samples was then sequenced to construct a phylogenetic tree and median joining network. Both the tree and network demonstrated a topology of three groups, which is in consistent with the SSCP analysis. Unlike Western breeds, Chinese breeds are composed mainly of haplotypes A and B, but with a small fraction of haplotype C. According to Fu's test and mismatch distribution, haplotype C has not been subject to a recent population expansion. Based on these results, we propose a novel origin for Chinese sheep.
Confirmation of QTL on porcine chromosomes 1 and 8 influencing leukocyte numbers, haematological parameters and leukocyte function
Authors: Wattrang E. , Almqvist M. , Johansson A. , Fossum C. , Wallgren P. , Pielberg G. , Andersson L. , Edfors‐Lilja I.
Published: July 2005

A genome wide search in European Wild Boar × Swedish Yorkshire (W × Y) inter‐cross pigs has earlier identified quantitative trait loci (QTL) for leucocyte number and function on porcine chromosomes 1 and 8 (SSC1 and 8). To verify the involvement of these chromosomal regions in the regulation of haematocrit (Hem) and haemoglobin (Hb) levels, leucocyte numbers andin vitroleukocyte functions (mitogen induced proliferation and IL‐2 production, virus induced interferon‐αproduction and neutrophil phagocytosis), animals of different genetic backgrounds were analysed. The animals comprised a back‐cross sire family (n = 47) of W × Y pigs and six crossbred [Y × Landrace (L)] sire families (n = 191). They were genotyped for 16 genetic markers and an interval analysis was performed. On SSC1, a QTL close toS0082on the q‐arm that influenced numbers of white blood cells in L × Y pigs and numbers of band neutrophils and CD8+cells in W × Y pigs was identified (P ≤ 0.01). An additional SSC1 QTL was identified on the p‐arm close toS0008with influence on numbers of CD2+cells in W × Y pigs (P ≤ 0.05). On SSC8, a QTL influencing Hb (P ≤ 0.01) and Hem (P ≤ 0.05) levels was identified close toKITin the W × Y pigs. For L × Y pigs, a second QTL, distal toKITand close toS0069, on SSC8 influenced the numbers of MHCII+cells and mitogen induced proliferation (P ≤ 0.05), whilst the QTL close toKITinfluenced the number of IgM+cells in these pigs (P ≤ 0.05). The results confirm the involvement of earlier identified regions of SSC1 and SSC8 on porcine immune parameters and some candidate genes were suggested.
How we did it: neopharyngeal stricture management with the nitinol stent in the laryngectomized patient: our disappointing results
Authors: Thornton M.A. , Conlon B.J. , Timon C.
Published: July 2005

Keypoints

• Serial dilatation, the mainstay of benign ‘neopharyngeal’ stricture management, can have inconsistent results.

• Nitinol stents, as a metallic self‐expanding coil, may have a role in such patients.

• Such stents were inserted in four patients but two had to be removed because of intractable pain.

• It is concluded that nitinol stents are unlikely to have a significant role in the management of neopharyngeal stricture management.
How we do it: A series of 114 primary pharyngeal space neoplasms
Authors: Shahab R. , Heliwell T. , Jones A.S.
Published: July 2005

Keypoints

• Primary parapharyngeal space tumours are exceedingly rare.

• We present a series of 114 parapharyngeal space tumours, the second largest in the literature.

• The most frequent benign tumours were pleomorphic adenoma (34) and paraganglioma (33); the commonest malignancies were of salivary gland origin (12).

• The 5‐ and 10‐year survival for benign tumours was 100%.

• The 5‐ and 10‐year survival for malignancies was 93% and 57% respectively.

• The importance of long‐term follow‐up is evidently crucial.
Pharyngeal and laryngeal symptoms and signs related to extraesophageal reflux in patients with heartburn in gastroenterology practice: a prospective study
Authors: Ylitalo R. , Lindestad P. , Hertegård S.
Published: July 2005

Objectives:  To describe pharyngeal and laryngeal symptoms and findings in correlation to extraesophageal reflux (EER) in patients with heartburn.

Design:  A prospective study.

Setting:  Patients referred to Department of Gastroenterology, Karolinska University Hospital Huddinge.

Participants:  Forty‐three patients with chronic heartburn as the primary symptom, subdivided on the basis of oesophageal manometry to have gastro‐oesophageal reflux disease (GORD) (n = 25) or not (n = 18).

Main outcome measures:  Laryngeal video recordings of 43 patients were examined off‐line. The occurrence of symptoms and laryngeal pathology were correlated to the results of 24‐h double‐probe pH monitoring.

Results:  Pharyngeal or laryngeal symptoms occurred often or quite often in 72% (18 of 25) of the GORD patients and 61% (11 of 18) of the patients without GORD. EER occurred in 73% (16 of 22) of the GORD patients with laryngeal symptoms and in 38% (6 of 16) of those without GORD but with laryngeal symptoms (P = 0.047). In the multivariate analysis the odds for hoarseness was 17 times higher if the patient had heartburn more than five times a day, compared with patients with heartburn less than once a day (OR 17.8, CI 1.7–405.9; P = 0.01). Cohen's kappa for intrarater reliability was 0.851 (P = 0.001). Laryngeal pathology was found in 56% of the GORD patients and 44% patients without GORD. There was no significant difference in the occurrence of any specific symptom or finding between the patients with and without GORD, nor with and without EER.

Conclusions:  Although GORD together with laryngeal symptoms seem to be predictive of EER, there are no specific pharyngeal and laryngeal symptoms or findings that would help distinguishing patients with EER from those without. However, the more frequent the heartburn to the more frequent is hoarseness.
A non‐randomized comparison of earwax removal with a ‘Do‐it‐yourself’ ear vacuum kit and a Jobson‐Horne Probe
Authors: Leong A.C. , Aldren C.
Published: July 2005

Objectives:  Do‐it‐yourself ear vacuum kits (ear vacs) have recently been introduced as an effective method of earwax removal. This study assesses the efficacy of ear vacs in comparison with a conventional mechanical method of earwax removal, the Jobson‐Horne probe.

Methods:  Forty healthy relatives who had accompanied family members to orthopaedic and haematology clinics were screened with otoscopy. Sixteen participants with earwax were selected.

Main outcome measures:  (i) Weight of earwax removed, (ii) proportion of tympanic membrane visible before and after each intervention, (iii) participants’ subjective assessment of any improvement in hearing. Suction pressure generated by the ear vac was also compared with that of microsuctioning.

Results:  No earwax was removed with the ear vac but the Jobson‐Horne probe was significantly more effective at removing a greater weight of earwax (P < 0.001, mean weight 92.4 mg). There was no improvement in visibility of the tympanic membrane after the ear vac but the Jobson‐Horne probe restored visibility to 100% (P < 0.001). No participant felt that there was an improvement in their hearing after the ear vac, but the majority (88%) reported an improvement in their hearing after the Jobson‐horne probe.

Conclusion:  A Jobson‐Horne probe is significantly more effective than an ear vac for the removal of earwax.
The reliability and validity of patient self‐rating of their own voice quality
Authors: Lee M. , Drinnan M. , Carding P.
Published: July 2005

Objectives:  To provide preliminary data on the reliability and validity of dysphonic patients rating their own voice quality.

Design:  Prospective reliability/validity assessment of voice ratings in dysphonic patients.

Setting:  The Royal Free Hampstead NHS Primary Care Trust.

Participants:  Thirty‐five adult dysphonia patients recruited from ENT referrals to a speech and language therapy department. Exclusion criteria were (i) a hearing impairment which may affect auditory discrimination and (ii) a diagnosis of cognitive impairment which may affect task comprehension.

Main outcome measures:  Patient intra‐rater reliability was assessed by test–retest ratings, using G (Grade), R (Rough), B (Breathy), A (Asthenic), S (Strained) (GRBAS). Validity was assessed by comparing (i) patient–clinician inter‐rater reliability, (ii) patients’ GRBAS ratings with their Vocal Performance Questionnaire (VPQ) responses.

Result:  (i) Patients had lower intrarater reliability than clinicians (for G of GRBAS, kappa = 0.51 versus 0.74); (ii) patients consistently rated their voices more severely than clinicians (for G of GRBAS, mean rating = 1.4 versus 1.0); (iii) clinician–patient inter‐rater agreement was no better than chance (paired t‐test, all P < 0.05); (iv) patient ratings correlated significantly with vocal performance scores (r > 0.4, P < 0.05).

Conclusions:  Patients appear to have good validity and consistency using GRBAS as a self‐perception tool. However, validity measured in terms of agreement with clinician ratings is poor. Voice patients may rate what they perceive rather than what they hear. Disagreement between patient and clinician ratings has implications for therapy aims, prognosis, patient expectations and outcomes. Where disagreement persists, the clinician may have to determine whether therapy priorities need redesigning to reflect patients’ perceived needs, or to evaluate whether patient perceptions and expectations are unrealistic.
Wound related complications following full thickness skin graft versus split thickness skin graft on patients with bone anchored hearing aids
Authors: Lekakis G.K. , Najuko A. , Gluckman P.G.
Published: July 2005

Objectives:  The aim of this study was to review complications occurring in bone anchored hearing aid (BAHA) patients in relation to wound healing following full thickness skin graft versus split thickness skin graft.

Design:  Retrospective study. The medical notes of 22 patients who underwent insertion of BAHA over 24 months were reviewed.

Setting:  ENT Department at a District General Hospital in the UK.

Participants:  All patients were adults and underwent one stage procedure following the standard Branemark technique. In 11 cases the skin abutment interface was established by use of full thickness skin graft inset around the implant, and in the other 11 by use of split thickness skin graft.

Main outcomes measures:  The incidence of delayed wound healing resulting in an increase of number of visits for change of wound dressings. In addition the degree of soft tissue reactions around the interface was examined.

Results:  There was a clear difference between the split and full thickness skin graft groups in relation to the severity of adverse skin reactions and number of visits required for change of dressings. The split thickness group required from three minimum to 13 maximum (median 4) visits in outpatients during the initial observation period until healing was complete. The full thickness group demonstrated one minimum and three maximum (median 2) visits.

Conclusions:  In our hands the full thickness skin graft is superior to a split thickness graft.
The use of lubrication in flexible fibreoptic nasendoscopy: a randomized controlled trial
Authors: Pothier D.D. , Awad Z. , Whitehouse M. , Porter G.C.
Published: July 2005

Objectives:  To determine how lubrication of the endoscope prior to flexible fibreoptic nasendoscopy affects levels of patient discomfort and pain during endoscopy. To assess the extent to which lubrication affects the ease of nasendoscopy and the quality of the image obtained.

Design:  Single blind, randomized controlled trial.

Setting:  Outpatient clinic of the Department of Otolaryngology at a secondary level referral centre.

Participants:  A total of 150 participants selected sequentially from patients requiring a nasendoscopy where the endoscope would be passed far enough to view the larynx. Patients requiring topical anaesthetic were excluded. All participants who were entered in the study completed the study. Endoscopy was performed by all grades of medical staff.

Main outcomes measures:  Levels of discomfort and pain experienced by the participants were assessed by a visual analogue scale (VAS). Difficulty of passing the scope was indicated by the endoscopist using a VAS, as was the quality of image obtained.

Results:  There was no significant difference between mean scores for pain or discomfort of the lubricated and unlubricated groups (P = 0.46 and P = 0.82 respectively). Scores for difficulty of passing the scope were significantly lower in the lubricant group (P = 0.003) but loss of image was significantly greater (P = 0.008).

Conclusions:  Lubrication of the endoscope prior to nasendoscopy does not reduce levels of discomfort or pain for the patient, but increases ease in insertion for the operator. However, this may be at the expense of reduced image quality.
Choanal atresia – a recurrent feature of foetal carbimazole syndrome
Authors: Myers A.K. , Reardon W.
Published: July 2005

Keypoints

• Choanal atresia is described as a feature of several congenital anomaly phenotypes.

• Most cases of choanal atresia arises as an isolated clinical finding.

• In utero exposure to carbimazole for maternal hyperthyroidism has been reported in five cases of choanal atresia.

• We report another instance of this teratogenic cause of choanal atresia.

• Maternal drug history is an important aspect of assessment in cases of choanal atresia.
Do Uniform Price Auctions Trade‐off Higher Risk for Higher Return?*
Authors: Beierlein Jaclyn , Kato Hideaki Kiyoshi
Published: July 2005

Results of the recent US Treasury experiment comparing uniform and discriminatory price auctions suggest that uniform price auctions achieve lower award concentration and higher average revenues but experience higher variance of revenues from auction to auction relative to discriminatory price auctions. In other words, uniform pricing offers higher risk for higher return. This apparent trade‐off may deter some sellers considering the switch from discriminatory to uniform pricing; thus, it is important to investigate whether these results can be generalized. The Treasury's results are driven by the tendency for bidders in the uniform auctions to submit multiple bids at a wide range of prices, essentially steep bid curves, instead of the flat bids submitted in the discriminatory auctions. However, theory and data from discriminatory auctions in Sweden and Portugal suggest that bidders in discriminatory auctions will submit steeper bids when there is more potential for winner's curse. It is possible that bidders in the US auctions, which are preceded by a when‐issued market, are relatively unconcerned with the winner's curse. We examine the auction formats in an environment much more likely to generate the winner's curse: the initial public offering market. We compare discriminatory price auctions in Japan and uniform price auctions in Israel on the basis of revenue and slope of the demand curves and test a number of divisible good auction theory implications. In contrast with the Treasury's results, we find that revenues are likely to be insignificantly different in the discriminatory and uniform price auctions and that bid curves may be equally steep under both formats in markets with information asymmetry. The winner's curse increases underpricing and steepens demand curves in Japan's discriminatory price auctions but not in Israel's uniform price auctions.
Future Long‐Horizon Performance Measurement Conditional on Past Survival*
Authors: Gray Philip , Whittaker Mark
Published: July 2005

This paper examines the measurement of long‐horizon abnormal performance when stock selection is conditional on an extended period of past survival. Filtering on survival results in a sample driven towards more‐established, frequently traded stocks and this has implications for the choice of benchmark used in performance measurement (especially in the presence of the well‐documented size effect). A simulation study is conducted to document the properties of commonly employed performance measures conditional on past survival. The results suggest that the popular index benchmarks used in long‐horizon event studies are severely biased and yield test statistics that are badly misspecified. In contrast, a matched‐stock benchmark based on size and industry performs consistently well. Also, an eligible‐stock index designed to mitigate the influence of the size effect proves effective.
Dynamic Optimality of Yield Curve Strategies*
Authors: Kobayashi Takao , Takahashi Akihiko , Tokioka Norio
Published: July 2005

This paper formulates and analyzes a dynamic optimization problem of bond portfolios within Markovian Heath–Jarrow–Morton term structure models. In particular, we investigate optimal yield curve strategies analytically and numerically, and provide theoretical justification for a typical strategy which is recommended in practice for an expected change in the shape of the yield curve. In the numerical analysis, we utilize a new technique based on the asymptotic expansion approach in order to increase efficiency in computation.
Measuring Productive Efficiency of Stock Exchanges using Price Adjustment Coefficients
Authors: Marisetty Vijaya B.
Published: July 2005

A stock exchange's efficiency can be measured by its liquidity and price discovery mechanism. An exchange that provides price discovery will have high liquidity. By measuring the speed of stock price adjustment to its intrinsic value with the arrival of new information, we can understand the price discovery process and productive efficiency of a stock exchange. India has 23 stock exchanges, 20 of which have almost become dysfunctional due to negligible trading during the last five years. Measuring productive efficiency of the current active stock exchanges will help to understand the future direction of the Indian stock market. Using the corrected Damodaran (1993) model and a new model proposed in this paper, I found that information adjustment in the Indian market is very slow. Contrary to the developed markets, in the Indian stock market, stock prices overreact before adjusting to their intrinsic values. I also found that market‐wide information adjusts faster than firm‐specific information.
Re‐evaluation of randomized control trials of lithium monotherapy: a cohort effect
Authors: Deshauer D , Fergusson D , Duffy A , Albuquerque J , Grof P
Published: July 2005

Objective:  The reported reduction of lithium's efficacy in the prophylaxis of bipolar illness has been attributed to various factors, including diagnostic changes and heterogeneous study designs. We attempted to quantify the impact of pre‐randomization enrichment designs and diagnostic drift on randomized controlled trials (RCTs) of lithium maintenance therapy.

Methods:  Using the Cochrane RCT search filter, MEDLINE, EMBASE, and PSYCHINFO were searched (1966 to June 2004) for all available randomized studies using the text word ‘lithium’. Studies of 1 year minimum duration in bipolar disorder involving lithium and placebo arms were identified. Superiority trials without a placebo arm, discontinuation and mirror image studies were excluded. Standardized scales were used to assess randomization and allocation concealment.

Results:  Nine RCTs enrolling 1432 bipolar I and II patients, randomizing 341 to lithium and 386 to placebo were identified, with 705 reported pre‐randomization dropouts. The pooled odds of remaining recurrence free in two non‐enriched RCTS using Research Diagnostic Criteria (RDC) or Feighner criteria were 3.2:1 (95% CI 0.65–15.46) trending in favor of lithium over placebo, and 22.0:1 (95% CI 7.0–68.7) for three trials using lithium enrichment and excluding atypical bipolar disorder. The odds of remaining recurrence free using DSM‐IV criteria and lamotrigine enrichment were 1.9:1 (95% CI 1.2–2.8).

Conclusion:  Lithium maintenance RCTs differ in patient selection, design, and outcome. A cohort effect can be associated with the use of pre‐randomization enrichment phases and, to a lesser extent, with diagnostic drift, compromising straightforward comparisons across three decades of lithium monotherapy in bipolar illness.
Five‐year prospective outcome of psychopathology in the adolescent offspring of bipolar parents
Authors: Hillegers Manon HJ , Reichart Catrien G , Wals Marjolein , Verhulst Frank C , Ormel Johan , Nolen Willem A
Published: July 2005

Objective:  For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent.

Method:  At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi‐structured psychiatric interview (K‐SADS‐PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16–26 years).

Results:  Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode.

Conclusion:  At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.
Psychotic features in borderline patients: is there a connection to mood dysregulation?
Authors: A Benvenuti , P Rucci , L Ravani , C Gonnelli , E Frank , M Balestrieri , A Sbrana , L Dell'Osso , GB Cassano
Published: July 2005

Objective:  To investigate the relationship between lifetime mood and psychotic spectrum features in patients with borderline personality disorder (BPD).

Method:  The study sample consisted of BPD patients with (n = 39, BPD‐M) or without (n = 21, BPD‐noM) lifetime mood disorders. The diagnostic assessment was conducted with the Structured Clinical Interview for DSM‐IV Axis I Disorders (SCID‐I). The diagnosis of BPD was made clinically and then confirmed by Gunderson's diagnostic interview for borderlines. Subjects were also administered the Structured Clinical Interview for Psychotic Spectrum (SCI‐PSY) and the Mood Spectrum self‐report questionnaire (MOODS‐SR).

Results:  BPD‐M had significantly higher scores than BPD‐noM on the ‘lifetime’ mood spectrum subdomains ‘depressive mood’ and ‘depressive cognition’. The two groups did not differ on the scores of psychotic spectrum except for higher ‘hypertrophic self‐esteem’ scores in BPD‐noM. In BPD‐noM both the depressive and the manic‐hypomanic component of mood spectrum were significantly correlated with the ‘delusion’ subdomain of the psychotic spectrum. The depressive component was correlated with ‘depersonalization/derealization’ and the manic‐hypomanic component was correlated with ‘hypertrophic self‐esteem’. In BPD‐M, the manic‐hypomanic component of mood spectrum was correlated with different subdomains of the psychotic spectrum: ‘hypertrophic self‐esteem’, ‘self‐reference’, ‘interpretive attitude’, ‘anger/overreactivity, ‘unusual and odd thoughts’, ‘illusions’, ‘delusions’, ‘hallucinations’ and ‘catatonia’. The depressive component of mood spectrum was ‘uncorrelated’ with the subdomains of the psychotic spectrum.

Conclusions:  Our data support the hypothesis that ‘lifetime’ manic‐hypomanic mood dysregulations are correlated with psychotic spectrum features in borderline patients. The assessment of these spectrum features in borderline patients may be useful to inform treatment choices.
Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia
Authors: Cotter David , Hudson Lance , Landau Sabine
Published: July 2005

Background: The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in subjects with major depressive disorder (MDD).

Aims: Stereologically based investigation of caudal orbitofrontal cortex (cOFC), in 60 postmortem brains from four groups of 14 subjects each with bipolar disorder (BPD), schizophrenia and MDD.

Methods: Glial cell and neuronal size and density were examined in all subjects using stereological probes such as the nucleator and the optical disector.

Results: We found statistical evidence for a neuronal size reduction in BPD in layer 1 (21%, p = 0.007) and a trend for a reduction in layer 5 (20%, p = 0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p = 0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p < 0.001). We found no evidence for group differences in glial cell size nor for differences in glial or neuronal density.

Conclusions: These findings provide preliminary evidence that neuronal size reduction in cOFC is a component of the pathology of BPD. Overall, the data implicate this cortical region in affective disorders, but provide no evidence for neuronal or glial pathology in this region in schizophrenia.
Multisensory integration in the dorsal cochlear nucleus: unit responses to acoustic and trigeminal ganglion stimulation
Authors: Shore S. E.
Published: July 2005

A necessary requirement for multisensory integration is the convergence of pathways from different senses. The dorsal cochlear nucleus (DCN) receives auditory input directly via the VIIIth nerve and somatosensory input indirectly from the Vth nerve via granule cells. Multisensory integration may occur in DCN cells that receive both trigeminal and auditory nerve input, such as the fusiform cell. We investigated trigeminal system influences on guinea pig DCN cells by stimulating the trigeminal ganglion while recording spontaneous and sound‐driven activity from DCN neurons. A bipolar stimulating electrode was placed into the trigeminal ganglion of anesthetized guinea pigs using stereotaxic co‐ordinates. Electrical stimuli were applied as bipolar pulses (100 µs per phase) with amplitudes ranging from 10 to 100 µA. Responses from DCN units were obtained using a 16‐channel, four‐shank electrode. Current pulses were presented alone or preceding 100‐ or 200‐ms broadband noise (BBN) bursts. Thirty percent of DCN units showed either excitatory, inhibitory or excitatory–inhibitory responses to trigeminal ganglion stimulation. When paired with BBN stimulation, trigeminal stimulation suppressed or facilitated the firing rate in response to BBN in 78% of units, reflecting multisensory integration. Pulses preceding the acoustic stimuli by as much as 95 ms were able to alter responses to BBN. Bimodal suppression may play a role in attenuating body‐generated sounds, such as vocalization or respiration, whereas bimodal enhancement may serve to direct attention in low signal‐to‐noise environments.
Differential involvement of the cerebellum in biological and coherent motion perception
Authors: Jokisch Daniel , Troje Nikolaus F. , Koch Benno , Schwarz Michael , Daum Irene
Published: July 2005

Perception of biological motion (BM) is a fundamental property of the human visual system. It is as yet unclear which role the cerebellum plays with respect to the perceptual analysis of BM represented as point‐light displays. Imaging studies investigating BM perception revealed inconsistent results concerning cerebellar contribution. The present study aimed to explore the role of the cerebellum in the perception of BM by testing the performance of BM perception in patients suffering from circumscribed cerebellar lesions and comparing their performance with an age‐matched control group. Perceptual performance was investigated in an experimental task testing the threshold to detect BM masked by scrambled motion and a control task testing the detection of motion direction of coherent motion masked by random noise. Results show clear evidence for a differential contribution of the cerebellum to the perceptual analysis of coherent motion compared with BM. Whereas the ability to detect BM masked by scrambled motion was unaffected in the patient group, their ability to discriminate the direction of coherent motion in random noise was substantially affected. We conclude that intact cerebellar function is not a prerequisite for a preserved ability to detect BM. Because the dorsal motion pathway as well as the ventral form pathway contribute to the visual perception of BM, the question of whether cerebellar dysfunction affecting the dorsal pathway is compensated for by the unaffected ventral pathway or whether perceptual analysis of BM is performed completely without cerebellar contribution remains to be determined.
Silencing dopamine D3‐receptors in the nucleus accumbens shell in vivo induces changes in cocaine‐induced hyperlocomotion
Authors: Bahi Amine , Boyer Frederic , Bussard Gaelle , Dreyer Jean‐Luc
Published: July 2005

The dopamine D3 receptor (D3R) is an important pharmacotherapeutic target for its potential role in psychiatric disorders and drug dependence. To further explore its function in rats, a regulatable lentivirus, Lenti‐D3, holding the rat D3R cDNA, has been constructed as well as three nonregulatable lentiviruses, Lenti‐D3‐siRNA1, Lenti‐D3‐siRNA2 and Lenti‐D3‐siRNA3, expressing small hairpin RNAs, aimed at silencing D3R expression and specifically targeted against different regions of the D3R mRNA. In vitro, Lenti‐D3 expressed D3R and could efficiently be blocked with Lenti‐D3‐Sils. These viruses were stereotaxically injected into the shell part of the nucleus accumbens (NAcc) and effects of passive cocaine delivery on locomotor activity were assessed. Manipulations of D3R levels induced changes in the locomotor stimulant effects of cocaine as compared to control treatment. Suppression of dopamine (DA) D3R in the NAcc by means of local knockdown (with Lenti‐D3‐Sils) increased locomotor stimulant effects, whereas its overexpression with Lenti‐D3 drastically reduced them. The latter effects could be reversed when animals were fed doxycycline, which prevented lentiviral‐mediated DA D3R overexpression in the NAcc. Gene expression assessed by quantitative RT‐PCR confirmed very efficient gene knockdown in vivo in animals treated with Lenti‐D3‐Sils (> 93% silencing of D3R gene). Thus D3R expression significantly contributes to behavioural changes associated with chronic cocaine delivery.
Selective dopamine D3 receptor antagonism by SB‐277011A attenuates cocaine reinforcement as assessed by progressive‐ratio and variable‐cost–variable‐payoff fixed‐ratio cocaine self‐administration in rats
Authors: Xi Zheng‐Xiong , Gilbert Jeremy G. , Pak Arlene C. , Ashby Charles R. , Heidbreder Christian A. , Gardner Eliot L.
Published: July 2005

In rats, acute administration of SB‐277011A, a highly selective dopamine (DA) D3 receptor antagonist, blocks cocaine‐enhanced brain stimulation reward, cocaine‐seeking behaviour and reinstatement of cocaine‐seeking behaviour. Here, we investigated whether SB‐277011A attenuates cocaine reinforcement as assessed by cocaine self‐administration under variable‐cost–variable‐payoff fixed‐ratio (FR) and progressive‐ratio (PR) reinforcement schedules. Acute i.p. administration of SB‐277011A (3–24 mg/kg) did not significantly alter cocaine (0.75 mg/kg/infusion) self‐administration reinforced under FR1 (one lever press for one cocaine infusion) conditions. However, acute administration of SB‐277011A (24 mg/kg, i.p.) progressively attenuated cocaine self‐administration when: (a) the unit dose of self‐administered cocaine was lowered from 0.75 to 0.125–0.5 mg/kg, and (b) the work demand for cocaine reinforcement was increased from FR1 to FR10. Under PR (increasing number of lever presses for each successive cocaine infusion) cocaine reinforcement, acute administration of SB‐277011A (6–24 mg/kg i.p.) lowered the PR break point for cocaine self‐administration in a dose‐dependent manner. The reduction in the cocaine (0.25–1.0 mg/kg) dose–response break‐point curve produced by 24 mg/kg SB‐277011A is consistent with a reduction in cocaine's reinforcing efficacy. When substituted for cocaine, SB‐277011A alone did not sustain self‐administration behaviour. In contrast with the mixed DA D2/D3 receptor antagonist haloperidol (1 mg/kg), SB‐277011A (3, 12 or 24 mg/kg) failed to impede locomotor activity, failed to impair rearing behaviour, failed to produce catalepsy and failed to impair rotarod performance. These results show that SB‐277011A significantly inhibits acute cocaine‐induced reinforcement except at high cocaine doses and low work requirement for cocaine. If these results extrapolate to humans, SB‐277011A or similar selective DA D3 receptor antagonists may be useful in the treatment of cocaine addiction.
Dopamine D1‐like receptor modulates layer‐ and frequency‐specific short‐term synaptic plasticity in rat prefrontal cortical neurons
Authors: Young Clint E. , Yang Charles R.
Published: July 2005

The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short‐term working memory (STWM) to guide forthcoming behavior. Short‐term plasticity‐like post‐tetanic potentiation (PTP, < 3 min) and short‐term potentiation (STP, < 10 min) may underlie STWM. Using whole‐cell voltage‐clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 × 50 Hz) induced a homosynaptic PTP (decayed: ∼1 min). The D1‐like antagonist SCH23390 (1 µm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1‐like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting ∼4 min, but only at 2× intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer‐V→V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting ∼6 min), but a long‐term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1‐like receptor to induce STP in layer V→V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III→V synapses that receive higher (0.5 Hz) frequency inputs. This D1‐like modulation of layer‐ and frequency‐specific synaptic responses in the PFC may contribute to STWM processing.
Role of the GLT‐1 subtype of glutamate transporter in glutamate homeostasis: the GLT‐1‐preferring inhibitor WAY‐855 produces marginal neurotoxicity in the rat hippocampus
Authors: Selkirk Julie V. , Nottebaum Lisa M. , Vana Alicia M. , Verge Gail M. , Mackay Kenneth B. , Stiefel Theodore H. , Naeve Greg S. , Pomeroy Jordan E. , Petroski Robert E. , Moyer John , Dunlop John , Foster Alan C.
Published: July 2005

Glutamate is the major excitatory neurotransmitter in the central nervous system and is tightly regulated by cell surface transporters to avoid increases in concentration and associated neurotoxicity. Selective blockers of glutamate transporter subtypes are sparse and so knock‐out animals and antisense techniques have been used to study their specific roles. Here we used WAY‐855, a GLT‐1‐preferring blocker, to assess the role of GLT‐1 in rat hippocampus. GLT‐1 was the most abundant transporter in the hippocampus at the mRNA level. According to [3H]‐l‐glutamate uptake data, GLT‐1 was responsible for approximately 80% of the GLAST‐, GLT‐1‐, and EAAC1‐mediated uptake that occurs within dissociated hippocampal tissue, yet when this transporter was preferentially blocked for 120 h with WAY‐855 (100 µm), no significant neurotoxicity was observed in hippocampal slices. This is in stark contrast to results obtained with TBOA, a broad‐spectrum transport blocker, which, at concentrations that caused a similar inhibition of glutamate uptake (10 and 30 µm), caused substantial neuronal death when exposed to the slices for 24 h or longer. Likewise, WAY‐855, did not significantly exacerbate neurotoxicity associated with simulated ischemia, whereas TBOA did. Finally, intrahippocampal microinjection of WAY‐855 (200 and 300 nmol)in vivoresulted in marginal damage compared with TBOA (20 and 200 nmol), which killed the majority of both CA1–4 pyramidal cells and dentate gyrus granule cells. These results indicate that selective inhibition of GLT‐1 is insufficient to provoke glutamate build‐up, leading to NMDA receptor‐mediated neurotoxic effects, and suggest a prominent role of GLAST and/or EAAC1 in extracellular glutamate maintenance.
UMODL1/Olfactorin is an extracellular membrane‐bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons
Authors: Di Schiavi Elia , Riano Elena , Heye Babett , Bazzicalupo Paolo , Rugarli Elena I.
Published: July 2005

The olfactory system provides a unique model for developmental neurobiology. Precise targeting of axonal projections from sensory neurons located in the olfactory epithelium to specific neurons in the olfactory bulb establishes a highly refined spatial sensory map. Distinctively, this process is not restricted to embryonic stages, but continues during the entire life of mammals. A number of secreted and membrane molecules have been implicated in guidance and targeting of olfactory sensory neurons. Here we describe olfactorin, the protein product of the mouse Umodl1 gene, as a potential new element in this process. Olfactorin is a secreted modular protein containing several domains typically present in extracellular matrix proteins (EMI, WAP, FNIII, Ca2+‐binding EGF‐like, SEA and ZP domains). By in situ hybridization we find that during embryonic development expression of the Umodl1 gene is detectable only in the olfactory epithelium and vomeronasal organ starting at embryonic day 16.5. At this stage, Umodl1 expression within the olfactory epithelium is punctate, and is restricted to only some of the sensory neurons. At birth and postnatally, expression in these organs continues and involves more neurons. Kallmann syndrome is a genetic disease in which olfactory axons fail to connect to target neurons in the bulb. We tested whether olfactorin might be responsible for an autosomal form of this disease and show that this is not the case. However, based on its domain composition and on the expression in olfactory neurons we suggest that olfactorin may play a role in correct olfactory axon navigation to the brain.
Essential roles of Homer‐1a in homeostatic regulation of pyramidal cell excitability: a possible link to clinical benefits of electroconvulsive shock
Authors: Sakagami Yu , Yamamoto Kenji , Sugiura Shigeki , Inokuchi Kaoru , Hayashi Takuji , Kato Nobuo
Published: July 2005

Homer‐1a/Vesl1S, a member of the scaffold protein family Homer/Vesl, is expressed during seizure and serves to reduce seizure susceptibility. Cellular mechanisms for this feedback regulation were studied in neocortex pyramidal cells by injecting Homer‐1a protein intracellularly. The injection reduced membrane excitability as demonstrated in two ways. First, the resting potential was hyperpolarized by 5–10 mV. Second, the mean frequency of spikes evoked by depolarizing current injection was decreased. This reduction of excitability was prevented by applying each of the followings: the calcium chelator BAPTA, the calcium store depletor cyclopiazonic acid (CPA), the insitol‐1,4,5‐trisphosphate receptor (IP3R) blocker heparin, the phospholipase C (PLC) inhibitor U‐73122, the metabotropic glutamate receptor (mGluR) antagonist 2‐methyl‐6‐(phenylethynyl)‐pyridine (MPEP), and the large‐conductance calcium activated potassium channel (BK channel) antagonist charybdotoxin. The small‐conductance calcium activated potassium channel (SK channel) blocker dequalinium was ineffective. These findings suggest that activation of mGluR by Homer‐1a produced IP3, which caused inositol‐induced calcium release and a consequent BK channel opening, thus hyperpolarizing the injected neurons. In slices from rats subjected to electroconvulsive shock (ECS), a comparable reduction of excitability was observed without Homer‐1a injection. The ECS‐induced reduction of excitability was abolished by MPEP, charybdotoxin, heparin or BAPTA. Intracellular injection of anti‐Homer‐1a antibody was suppressive as well, but anti‐Homer‐1b/c antibody was not. We propose that ECS‐induced Homer‐1a stimulated the same pathway as did the injected Homer‐1a, thereby driving a feedback regulation of excitability.
Two‐way active avoidance training‐specific increases in phosphorylated cAMP response element‐binding protein in the dorsal hippocampus, amygdala, and hypothalamus
Authors: Saha Subhash , Datta Subimal
Published: July 2005

Previous studies have demonstrated that the activation of pontine‐wave (P‐wave) generating cells in the brainstem during post‐training rapid eye movement (REM) sleep is critical for the consolidation of memory for two‐way active avoidance (TWAA) learning in the rat. Here, using immunocytochemistry, we investigated the spatio‐temporal distribution of CREB phosphorylation within different parts of the dorsal hippocampus, amygdala, and hypothalamus following a session of TWAA training in the rat. We show that the TWAA training trials increased phosphorylation of CREB (p‐CREB) in the dorsal hippocampus, amygdala, amygdalo‐hippocampal junction (AHi), and hypothalamus. However, the time intervals leading to training‐induced p‐CREB activity were different for different regions of the brain. In the dorsal hippocampus, p‐CREB activity was maximal at 90 min and this activity disappeared by 180 min. In the AHi, activity of the p‐CREB peaked by 180 min and disappeared by 360 min. In the amygdala, the p‐CREB activity peaked at 180 min and still remained higher than the control at the 360 min interval. In the hypothalamus, at 90 min p‐CREB activity was present only in the ventromedial hypothalamus; however, by 180 min this p‐CREB activity was also present in the dorsal hypothalamus, perifornical area, and lateral hypothalamus. By 360 min, p‐CREB activity disappeared from the hypothalamus. This TWAA training trials‐induced spatiotemporal characteristic of CREB phosphorylation, for the first time, suggests that REM sleep P‐wave generator activation‐dependent memory processing involves different parts of the dorsal hippocampus, amygdala, and hypothalamus.