bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbohydrate- and Conformation-dependent Cargo Capture for ER-Exit
Authors: Appenzeller-Herzog Christian , Nyfeler Beat , Burkhard Peter , Santamaria Inigo , Lopez-Otin Carlos , Hauri Hans-Peter
Published: January 2005

Some secretory proteins leave the endoplasmic reticulum (ER) by a receptor-mediated cargo capture mechanism, but the signals required for the cargo-receptor interaction are largely unknown. Here, we describe a novel targeting motif that is composed of a high-mannose type oligosaccharide intimately associated with a surface-exposed peptide β-hairpin loop. The motif accounts for lectin ERGIC-53–assisted ER-export of the lyososomal enzyme procathepsin Z. The second oligosaccharide chain of procathepsin Z exhibits no binding activity for ERGIC-53, illustrating the selective lectin properties of ERGIC-53. Our data suggest that the conformation-based motif is only present in fully folded procathepsin Z and that its recognition by ERGIC-53 reflects a quality control mechanism that acts complementary to the primary folding machinery in the ER. A similar oligosaccharide/β-hairpin loop structure is present in cathepsin C, another cargo of ERGIC-53, suggesting the general nature of this ER-exit signal. To our knowledge this is the first documentation of an ER-exit signal in soluble cargo in conjunction with its decoding by a transport receptor.
J-Domain Protein CDJ2 and HSP70B Are a Plastidic Chaperone Pair That Interacts with Vesicle-Inducing Protein in Plastids 1
Authors: Liu Cuimin , Willmund Felix , Whitelegge Julian P. , Hawat Susan , Knapp Bettina , Lodha Mukesh , Schroda Michael
Published: January 2005

J-domain cochaperones confer functional specificity to their heat shock protein (HSP)70 partner by recruiting it to specific substrate proteins. To gain insight into the functions of plastidic HSP70s, we searched in Chlamydomonas databases for expressed sequence tags that potentially encode chloroplast-targeted J-domain cochaperones. Two such cDNAs were found: the encoded J-domain proteins were named chloroplast DnaJ homolog 1 and 2 (CDJ1 and CDJ2). CDJ2 was shown to interact with a ∼28-kDa protein that by mass spectrometry was identified as the vesicle-inducing protein in plastids 1 (VIPP1). In fractionation experiments, CDJ2 was detected almost exclusively in the stroma, whereas VIPP1 was found in low-density membranes, thylakoids, and in the stroma. Coimmunoprecipitation and mass spectrometry analyses identified stromal HSP70B as the major protein interacting with soluble VIPP1, and, as confirmed by cross-linking data, as chaperone partner of CDJ2. In blue native-PAGE of soluble cell extracts, CDJ2 and VIPP1 comigrated in complexes of >>669, ∼150, and perhaps ∼300 kDa. Our data suggest that CDJ2, presumably via coiled-coil interactions, binds to VIPP1 and presents it to HSP70B in the ATP state. Our findings and the previously reported requirement of VIPP1 for the biogenesis of thylakoid membranes point to a role for the HSP70B/CDJ2 chaperone pair in this process.
Syngeneic blood stem cell transplantation for infectious mononucleosis‐related aplastic anaemia
Authors: Anderlini Paolo , Riggs Shirley Ann , Körbling Martin , Champlin Richard
Published: January 2005

A 17‐year‐old girl developed severe aplastic anaemia following an episode of infectious mononucleosis. Her identical twin sister underwent mobilization with filgrastim and subsequent leukapheresis for blood stem cell collection. The cells were freshly infused without prior immunosuppression. The patient became transfusion‐independent and achieved a trilineage complete haematological response. Her engraftment lasted 6 months, but subsequently she relapsed with pancytopenia. The patient then received a second infusion of syngeneic blood stem cells, preceded by conditioning with cyclophosphamide and antithymocyte globulin. This led to durable trilineage haematological recovery still ongoing at 16 months after her second transplant.
The impact of idiopathic childhood‐onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHD
Authors: Lange Martin , Müller Jørn , Svendsen Ole Lander , Kastrup Knud William , Juul Anders , Feldt‐Rasmussen Ulla
Published: January 2005

objective  Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood‐onset (CO) GHD, 18 years after stopping GH treatment.

subjects and methods  Twenty‐six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty‐six healthy subjects acted as age‐, gender‐ and body mass index (BMI)‐matched controls.

results  The patients who did not have persistent GHD had significantly lower IGF‐I values and whole‐body, femoral neck and lumbar spine BMD compared to controls [0·994 ± 0·10 vs. 1·114 ± 0·11 g/cm2 (P = 0·003), 0·842 ± 0·12 vs. 0·962 ± 0·11 g/cm2 (P = 0·006) and 1·026 ± 0·14 vs. 1·127 ± 0·13 g/cm2 (P = 0·004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0·842 ± 0·09 vs. 0·938 ± 0·11, P = 0·04). Significant correlations were observed between all bone variables and IGF‐I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients.

conclusion  In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF‐I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH–IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF‐I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary.
Impaired circulating glucagon‐like peptide‐1 response to oral glucose in women with previous gestational diabetes
Authors: Forbes Shareen , Moonan May , Robinson Stephen , Anyaoku Victor , Patterson Michael , Murphy Kevin G. , Ghatei Mohammed A. , Bloom Stephen R. , Johnston Desmond G.
Published: January 2005

Background and objective  Women with previous gestational diabetes (pGDM) are at risk of developing Type 2 diabetes. Glucagon‐like peptide‐1 (GLP‐1) potentiates the insulin response to oral glucose, and its secretion is diminished in Type 2 diabetes. The aim of the study was to see if decreased GLP‐1 secretion might be an early abnormality in the progression to Type 2 diabetes and would therefore be diminished in women with pGDM.

Patients and methods  Eleven women with pGDM and previously documented normal glucose tolerance and 11 control women underwent a 75 g oral glucose tolerance test (OGTT). Circulating plasma glucose, insulin, nonesterified fatty acids (NEFA) and GLP‐1 concentrations were sampled.

Results  One of the women with pGDM had impaired glucose tolerance and was excluded from the study. All other women had normal glucose tolerance. The women with pGDM had higher fasting glucose concentrations than controls (5·1; 4·9–5·3 vs. 4·8; 4·4–5·1 mmol/l, median; interquartile range, P = 0·04) and greater circulating glucose area under the curve (AUC) following the oral glucose load (930; 818–1015 vs. 668; 584–737 min × mmol/l, P = 0·0007). Fasting insulin concentrations and total insulin AUC were similar. The initial (0–30 min) insulin response was decreased in the pGDM women (AUC 3981; 2783–4795 vs. 6167; 5009–8145 min × pmol/l, P = 0·05). The initial (0–30 min) GLP‐1 response was reduced in the pGDM women (AUC 816; 663–984 vs. 1163; 872–2024 min × pmol/l, P = 0·02).

Conclusion  A reduced initial GLP‐1 response to oral glucose may therefore be an early abnormality in the progression to Type 2 diabetes.
A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients
Authors: Chiang Cherie Y. , Andrewes David G. , Anderson Dianne , Devere Michael , Schweitzer Isaac , Zajac Jeffrey D.
Published: January 2005

Background  There is an increasing number of primary hyperparathyroidism (PHPT) patients with neuropsychological or psychiatric symptoms. Many of these patients do not have osseous or renal complications to satisfy the criteria for parathyroidectomy according to the NIH guidelines.

Objective  To assess whether there is any improvement in neuropsychological and mood symptoms following parathyroidectomy.

Patients and Design  Twenty PHPT patients undergoing parathyroidectomy and 20 orthopaedic controls matched for age, gender and estimated intelligence were subjects to pre and postoperative assessment of cognition and mood with a mean surgery‐retest interval of 3 months.

Results  Using two tests of attentional flexibility [the Stroop test, the Digit symbol test of the Wechsler Adult Intelligence Scale – Revised (WAIS‐R)], and two memory tests for prose and nonverbal material, no significant change was found between the groups when comparing scores before and after surgery. There was no improvement between pre and postoperative measures of verbal (dominant hemisphere) as opposed to visuo‐spatial (nondominant hemisphere) function when compared to controls. There was no relationship between the reduction in serum calcium and the change in the neuropsychological measures postoperatively.

Conclusion  This controlled, prospective study demonstrates no significant improvement in neuropsychological indices using objective, validated psychometric tools in an unselected cohort of PHPT patients. No relationship was found between serum calcium level and the degree of neuropsychological deficit. More studies are needed to assess whether the effect of parathyroidectomy is beneficial and sustainable in PHPT patients with neuropsychological symptoms alone.
A trial of nurse practitioner scope of practice
Authors: Gardner Anne , Gardner Glenn
Published: January 2005

Aims.  The aim of this paper is to report a trial to investigate the feasibility of the nurse practitioner role in local health service delivery and to provide information about the educational and legislative requirements for nurse practitioner practice.

Background.  Nurse practitioners have been shown to offer a beneficial service and fill a gap in health care provision. However, the lack of publications describing, critiquing, or defending the way that existing nurse practitioner roles have been developed may lead to a lack of clarity in comparing the nurse practitioner scope of practice internationally. In Australia, credible exploratory research is needed to realize the potential of nurse practitioners to bridge the divide of inequitable distribution of health services. A trial of nurse practitioner services in the Australian Capital Territory provided an excellent opportunity to investigate these scope and continuity issues.

Methods.  This was an observational analytic study using multiple data sources. Four models of nurse practitioner service were chosen from a competitive field of applications that were evaluated according to efficacy, feasibility, and sustainability across specified selection criteria. Each model in the trial included a clinical support team, with the nurse practitioner candidate ‘working‐into‐the‐role’ and collecting demographic, clinical practice, patient outcome, and health service and consumer survey data over a 10 month period.

Findings.  The trial identified the broad potential of the nurse practitioner role, its breadth and limitations, and its impact on selected health services in the Australian Capital Territory. Data from individual models were compared highlighting generic elements, and formed the basis for the development of the scope of practice for the Australian Capital Territory nurse practitioner models.

Conclusions.  This study has validated a research‐based, iterative process for initial development of nurse practitioner scope of practice for any Australian specialization. Importantly, the study concluded with the scope of practice as a finding, rather than commencing with it a priori. Although general areas of health care need and under‐servicing were identified at the outset, the process tested both the expansion and parameters of the roles.
Evolutionary nursing: the case of infectious diseases
Authors: Purssell Edward
Published: January 2005

Aim. The aim of this paper is to examine the effect of evolution on infectious diseases nursing, and propose a model that may help to increase understanding of how hosts and microorganisms co‐exist and how humans can alter the delicate balance between them.

Background and rationale. Infectious diseases occur as the result of interactions between hosts and microorganisms. There is an increasing acceptance that the evolution of host and parasite is important in the development of infectious diseases. However, such views have made little impact in nursing, and the use of evolutionary interventions remains controversial.

Method. The Medline database was searched from 1966 to present using the terms pathogen$, virulen$, evolution, bacteria, and all combinations of these. Additionally reference lists of text books and papers were hand searched for relevant papers. Papers were selected from a variety of disciplines, including infectious diseases, microbiology, evolutionary biology, and ecology. Recurrent themes from these papers were identified and a model of evolutionary nursing constructed.

Results. Microorganisms are plentiful, ubiquitous, and rapidly evolving by comparison with humans and other animals. As a result of this, attempts to ‘outwit’ them have been, and are, doomed to failure. However, through careful management of public and personal health, a balance encouraging co‐existence may be possible. A number of specific interventions is proposed.

Conclusions. There are a number of key interventions that may reduce the virulence of microorganisms. With an increasing world population, antibiotic resistance and international travel, such an approach may be one way of reducing the morbidity associated with infectious diseases.
Effects of nurse‐initiated telephone follow‐up on self‐efficacy among patients with chronic obstructive pulmonary disease
Authors: Wong Kwan Wai , Wong Frances K.Y. , Chan Moon Fai
Published: January 2005

Aim.  This paper reports a study to determine whether a nurse‐initiated telephone follow‐up programme could increase patients’ self‐efficacy in managing dyspnoea and decrease health care service use.

Background.  Chronic obstructive pulmonary disease is a worldwide health problem and has been labelled a burdensome disease. Because of the fear of activity‐induced dyspnoea, patients with chronic obstructive pulmonary disease lack the confidence to perform daily activities. Studies of cardiac and diabetic patients have shown that telephone follow‐up care is an effective approach to increasing self‐efficacy. However, little such research has been done with patients with chronic obstructive pulmonary disease.

Methods.  This was a randomized controlled study. A total of 60 participants (30 telephone follow‐up, 30 control) with chronic obstructive pulmonary disease were recruited from an acute care hospital in Hong Kong. The Chinese Self‐Efficacy Scale was used to assess self‐efficacy. Measures of health care use were numbers of visits to an accident and emergency department, hospitalizations, and unscheduled visits by physicians.

Findings.  The self‐efficacy scores (U = 272·5, P = 0·009) of patients who were followed up by telephone improved significantly compared with those of patients in the control group. Multiple regression analyses showed that telephone follow‐up (Beta = 0·33, CI: 0·19–0·48, P = 0·001), the pulmonary rehabilitation programme (Beta = 0·44, CI: 0·16–0·72, P = 0·003), smoking (Beta = 0·34, CI: 0·09–0·57, P = 0·009), and health care use (Beta = −0·27, CI: −0·47–(−0·07), P = 0·008) were significant factors in predicting patient self‐efficacy.

Conclusions.  Nurse‐initiated telephone follow‐up care was effective in increasing self‐efficacy in managing dyspnoea. The study needs to be replicated in other setting to strengthen its external validity.
The early development of stereotypy and self‐injury: a review of research methods
Authors: Symons F. J. , Sperry L. A. , Dropik P. L. , Bodfish J. W.
Published: January 2005

Background The origin and developmental course of stereotypic and self‐injurious behaviour among individuals with developmental disabilities such as intellectual disability (ID) or pervasive development disorders such as autism is not well understood.

Method Twelve studies designed to document the prevalence, nature, or development of stereotypic and/or self‐injurious behaviour in children under 5 years of age and identified as at risk for developmental delay or disability were reviewed. Comparisons were made with similar studies with typically developing children.

Results It appears that the onset of naturally occurring rhythmic motor stereotypies is delayed in young at‐risk children, but that the sequencing may be similar. A very small database, differences in samples, measures, and designs limited the degree to which comparisons could be made across studies.

Conclusion Future work is needed based on appropriately designed prospective comparison studies and uniform quantitative measures to provide an empirical basis for new knowledge about the early development of one of the most serious behaviour disorders afflicting children with ID and related problems of development.
Coevolutionary arms races: increased host immune defense promotes specialization by avian fleas
Authors: Møller A. P. , Christe P. , Garamszegi L. Z.
Published: January 2005

We investigated the relationship between host defense and specialization by parasites in comparative analyses of bird fleas and T‐cell mediated immune response of their avian hosts, showing that fleas with few main host species exploited hosts with weak or strong immune defenses, whereas flea species that parasitized a large number of host species only exploited hosts with weak immune responses. Hosts with strong immune responses were exploited by a larger number of flea species than hosts with weak responses. A path analysis model with an effect of T‐cell response on the number of host species, or a model with host coloniality directly affecting host T‐cell response, which in turn affected the number of host species used by fleas, best explained the data. Therefore, parasite specialization may have evolved in response to strong host defenses.
Clinal variation and laboratory adaptation in the rainforest species Drosophila birchii for stress resistance, wing size, wing shape and development time
Authors: Griffiths J. A. , Schiffer M. , Hoffmann A. A.
Published: January 2005

Clinal variation has been described in many invertebrates including drosophilids but usually over broad geographical gradients. Here we describe clinal variation in the rainforest species Drosophila birchii from Queensland, Australia, and potential confounding effects of laboratory adaptation. Clinal variation was detected for starvation and development time, but not for size or resistance to temperature extremes. Starvation resistance was higher at southern locations. Wing shape components were not associated with latitude although they did differ among populations. Time in laboratory culture did not influence wing size or heat knockdown resistance, but increased starvation resistance and decreased recovery time following a cold shock. Laboratory culture also increased development time and altered wing shape. The results indicate that clinal patterns can be detected in Drosophila over a relatively narrow geographical area. Laboratory adaptation is unlikely to have confounded the detection of geographical patterns.
Escape behaviour and ultimate causes of specific induced defences in an anuran tadpole
Authors: Teplitsky C. , Plenet S. , Léna J. ‐P. , Mermet N. , Malet E. , Joly P.
Published: January 2005

Induced defences, such as the predator avoidance morphologies in amphibians, result from spatial or temporal variability in predation risk. One important component of this variability should be the difference in hunting strategies between predators. However, little is known about how specific and effective induced defences are to different types of predators. We analysed the impact of both pursuing (fish, Gasterosteus aculeatus) and sit‐and‐wait (dragonfly, Aeshna cyanea) predators on tadpole (Rana dalmatina) morphology and performance (viz locomotive performance and growth rate). We also investigated the potential benefits of the predator‐induced phenotype in the presence of fish predators. Both predators induced deeper tail fins in tadpoles exposed to threat of predation, and stickleback presence also induced longer tails and deeper tail muscles. Morphological and behavioural differences resulted in better escape ability of stickleback‐induced tadpoles, leading to improved survival in the face of stickleback predation. These results clearly indicate that specific morphological responses to different types of predators have evolved in R. dalmatina. The specific morphologies suggest low correlations between the traits involved in the defence. Independence of traits allows prey species to fine‐tune their response according to current predation risk, so that the benefit of the defence can be maximal.
Possible coevolution of male and female genital form and function in a calopterygid damselfly
Authors: Córdoba‐Aguilar A.
Published: January 2005

In this paper some evolutionary changes of genitalia in the damselfly Calopteryx haemorrhoidalis are investigated by determining their current and past function. Calopteryx haemorrhoidalis males stimulate females by aedeagal frictioning on a set of vaginal sensilla. The aedeagus is considerably variable and positively correlates with volumes of ejected sperm from the spermatheca. Interestingly, females show a significantly reduced sensillum number compared with other family members. Here I explore whether there existed directional selection for aedeagal width at its evolutionary onset; and whether the sensillum reduction evolved to make sperm ejection less effective. Using C. haemorrhoidalis aedeagi in females whose species retained the ancestral conditions (no stimulatory ability and large sensillum numbers), Hetaerina cruentata and C. xanthostoma, my results corroborated these assumptions: variation in aedeagal width inversely correlated with sperm ejection rate while sperm ejection was higher in species with high sensillum numbers. A suggested coevolutionary interpretation of these results in C. haemorrhoidalis is that aedeagal width was favoured which was followed by a sensillum reduction.
Maintenance of genetic differentiation across a transition zone in the sea: discordance between nuclear and cytoplasmic markers
Authors: Lemaire C. , Versini J.‐J. , Bonhomme F.
Published: January 2005

To investigate the origin and maintenance of the genetic discontinuity between Atlantic and Mediterranean populations of the common sea bass (Dicentrarchus labrax) we analysed the genetic variation at a fragment of mitochondrial cytochrome b sequence for 18 population samples. The result were also compared with new or previously published microsatellite data. Seven mitochondrial haplotypes and an average nucleotidic divergence of 0.02 between Atlantic and Mediterranean populations that matches a Pleistocene allopatric isolation were found. The frequency variation at the cytochrome b locus was many times greater between Atlantic and Mediterranean populations ( = 0.67) than at microsatellite loci ( = 0.02). The examination of the different evolutionary forces at play suggests that a sex‐biased hybrid breakdown is a likely explanation for part of the observed discrepancy between mitochondrial and nuclear loci. In addition, an analysis is made of the correlation between microsatellite loci points towards the possible existence of a hybrid zone in samples from the Alboran Sea.
In vivo gene delivery of urokinase‐type plasminogen activator with regulatable lentivirus induces behavioural changes in chronic cocaine administration
Authors: Bahi Amine , Boyer Frederic , Gumy Christèle , Kafri Tal , Dreyer Jean‐Luc
Published: January 2005

Serine proteases play a key function in extracellular processes affecting central nervous system plasticity. Recently, the role of extracellular proteolytic processes in regulating synaptic structure and function has been described. However, to date direct evidence linking extracellular serine protease activity with drug‐related behavioural changes has not been documented. Importantly, in a screening for genes induced after drug treatment we found that urokinase plasminogen‐type activator (uPA) was strongly regulated by cocaine in several protocols of drug administration. Cocaine‐induced up‐regulation could be verified on microarray analysis under several protocols of drug administration, then further fully confirmed by means of qRT‐PCR. As a result, we chose to investigate further uPA function in the mesolimbic dopaminergic pathway, a major target area of cocaine and drugs of misuse. Our approach was based on the characterization of cocaine‐induced behavioural changes following lentiviral vector delivery of a doxycycline‐regulated uPA expression cassette (or of its mutated form), into specific rat brain areas (the hippocampus, the nucleus accumbens and the ventral tegmental area). We show that doxycycline‐dependent over‐expression of uPA in these regions yields a 10‐ to 12.3‐fold increase in locomotor activity after cocaine administration. These behavioural effects were completely abolished when the active site of the protease was point‐mutated and used as a dominant negative. The physiological relevance of these drastic behavioural changes is discussed.
Oxytocin neuron activation in NCAM‐deficient mice: anatomical and functional consequences
Authors: Theodosis D. T. , Schachner M. , Neumann I. D.
Published: January 2005

During stimulated neurosecretion in the rat, oxytocin neurons display a reduced glial coverage and receive an increased number of synapses, changes that are reversed on arrest of stimulation. We identified polysialic acid on the neural cell adhesion molecule (NCAM) as an important mediator of such plasticity. To investigate further the role of this cell surface glycoprotein, we examined the oxytocin system in mice genetically deficient in NCAM. First, ultrastructural analyses revealed that in wild‐type mice, the supraoptic nucleus (SON) underwent the same remodelling as in the rat because oxytocin neurons had a diminished astrocytic coverage and increased synaptic input during lactation or chronic salt loading. Surprisingly, the SON displayed this morphology in NCAM‐deficient mice as well, whether they were nongestating and hydrated, lactating or dehydrated. The oxytocin system in NCAM‐deficient mice was abnormally hyperactive, as illustrated by enhanced plasma and intranuclear concentrations of oxytocin and reduced anxiety‐related behaviour. Plasma oxytocin concentrations were also high in lactating NCAM‐deficient dams but certain parameters of lactation and maternal behaviour were impaired. NCAM‐deficient mice survived ingestion of 2% saline for 7 days and had increased plasma oxytocin but they did not cope with more severe osmotic challenges. Our observations highlight further the remarkable capacity of the adult oxytocin system to undergo neuronal and glial remodelling whenever it is activated. That lack of NCAM did not prevent remodelling indicates that NCAM can be substituted by other molecular mechanisms. Finally, while NCAM deficiency greatly enhanced oxytocin release, it led to impaired oxytocin‐dependent physiological and behavioural responses.
Rapid functional plasticity in the primary somatomotor cortex and perceptual changes after nerve block
Authors: Weiss Thomas , Miltner Wolfgang H. R. , Liepert Joachim , Meissner Winfried , Taub Edward
Published: January 2005

The mature human primary somatosensory cortex displays a striking plastic capacity to reorganize itself in response to changes in sensory input. Following the elimination of afferent return, produced by either amputation, deafferentation by dorsal rhizotomy, or nerve block, there is a well‐known but little‐understood ‘invasion’ of the deafferented region of the brain by the cortical representation zones of still‐intact portions of the brain adjacent to it. We report here that within an hour of abolishing sensation from the radial and medial three‐quarters of the hand by pharmacological blockade of the radial and median nerves, magnetic source imaging showed that the cortical representation of the little finger and the skin beneath the lower lip, whose intact cortical representation zones are adjacent to the deafferented region, had moved closer together, presumably because of their expansion across the deafferented area. A paired‐pulse transcranial magnetic stimulation procedure revealed a motor cortex disinhibition for two muscles supplied by the unaffected ulnar nerve. In addition, two notable perceptual changes were observed: increased two‐point discrimination ability near the lip and mislocalization of touch of the intact ulnar portion of the fourth finger to the neighbouring third finger whose nerve supply was blocked. We suggest that disinhibition within the somatosensory system as a functional correlate for the known enlargement of cortical representation zones might account for not only the ‘invasion’ phenomenon, but also for the observed behavioural correlates of the nerve block.
Gene expression profiling of the rat superior olivary complex using serial analysis of gene expression
Authors: Koehl Alexander , Schmidt Nicole , Rieger Anne , Pilgram Sara M. , Letunic Ivica , Bork Peer , Soto Florentina , Friauf Eckhard , Nothwang Hans Gerd
Published: January 2005

The superior olivary complex (SOC) is an auditory brainstem region that represents a favourable system to study rapid neurotransmission and the maturation of neuronal circuits. Here we performed serial analysis of gene expression (SAGE) on the SOC in 60‐day‐old Sprague–Dawley rats to identify genes specifically important for its function and to create a transcriptome reference for the subsequent identification of age‐related or disease‐related changes. Sequencing of 31 035 tags identified 10 473 different transcripts. Fifty‐seven per cent of the unique tags with a count greater than four were statistically more highly represented in the SOC than in the hippocampus. Among them were genes encoding proteins involved in energy supply, the glutamate/glutamine shuttle, and myelination. Approximately 80 plasma membrane transporters, receptors, channels, and vesicular transporters were identified, and 25% of them displayed a significantly higher expression level in the SOC than in the hippocampus. Some of the plasma membrane proteins were not previously characterized in the SOC, e.g. the purinergic receptor subunit P2X6and the metabotropic GABA receptor Gpr51. Differential gene expression between SOC and hippocampus was confirmed using RNAin situhybridization or immunohistochemistry. The extensive gene inventory presented here will alleviate the dissection of the molecular mechanisms underlying specific SOC functions and the comparison with other SAGE libraries from brain will ease the identification of promoters to generate region‐specific transgenic animals. The analysis will be part of the publicly available database ID‐GRAB.
Dissociable roles of the human somatosensory and superior temporal cortices for processing social face signals
Authors: Pourtois Gilles , Sander David , Andres Michael , Grandjean Didier , Reveret Lionel , Olivier Etienne , Vuilleumier Patrik
Published: January 2005

Faces are multi‐dimensional stimuli bearing important social signals, such as gaze direction and emotion expression. To test whether perception of these two facial attributes recruits distinct cortical areas within the right hemisphere, we used single‐pulse transcranial magnetic stimulation (TMS) in healthy volunteers while they performed two different tasks on the same face stimuli. In each task, two successive faces were presented with varying eye‐gaze directions and emotional expressions, separated by a short interval of random duration. TMS was applied over either the right somatosensory cortex or the right superior lateral temporal cortex, 100 or 200 ms after presentation of the second face stimulus. Participants performed a speeded matching task on the second face during one of two possible conditions, requiring judgements about either gaze direction or emotion expression (same/different as the first face). Our results reveal a significant task–stimulation site interaction, indicating a selective TMS‐related interference following stimulations of somatosensory cortex during the emotional expression task. Conversely, TMS of the superior lateral temporal cortex selectively interfered with the gaze direction task. We also found that the interference effect was specific to the stimulus content in each condition, affecting judgements of gaze shifts (not static eye positions) with TMS over the right superior temporal cortex, and judgements of fearful expressions (not happy expressions) with TMS over the right somatosensory cortex. These results provide for the first time a double dissociation in normal subjects during social face recognition, due to transient disruption of non‐overlapping brain regions. The present study supports a critical role of the somatosensory and superior lateral temporal regions in the perception of fear expression and gaze shift in seen faces, respectively.
Synaptic distribution of the NR1, NR2A and NR2B subunits of the N‐methyl‐d‐aspartate receptor in the rat lumbar spinal cord revealed with an antigen‐unmasking technique
Authors: Nagy Gergely G. , Watanabe Masahiko , Fukaya Masahiro , Todd Andrew J.
Published: January 2005

Glutamate is the main excitatory neurotransmitter in the spinal cord and acts on several types of receptor, including N‐methyl‐d‐aspartate (NMDA) receptors, which play an important role in synaptic plasticity and chronic pain. Three families of NMDA receptor subunit have been identified: NR1, NR2 (A–D) and NR3 (A and B). NMDA receptors are heteromeric channels that contain NR1 with at least one NR2 subunit. There is extensive evidence that NMDA receptors are present in spinal cord but little is known about their synaptic distribution. We have used an antigen‐unmasking method involving pepsin treatment to reveal NR1, NR2A and NR2B subunits and have compared their distribution with that of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptor GluR2 subunit, which is thought to be present at most glutamatergic synapses throughout the spinal cord. After pepsin treatment, punctate labelling was seen with antibodies against each of these subunits. Although NR1 puncta were present throughout the grey matter, NR2A was concentrated in laminae III–IV and NR2B in laminae I–II. The majority of puncta labelled with each NMDA receptor antibody were GluR2‐immunoreactive, which suggests that they were present at synapses, and this was confirmed with electron microscopy for the NR1 and NR2A antibodies. However, many GluR2‐immunoreactive puncta did not show NMDA receptor immunoreactivity. In laminae I–II, most NR2B puncta were also NR1‐immunoreactive and a similar arrangement was found for NR2A/NR1 in laminae III–IV. These results suggest that many, but not all, glutamatergic synapses in the spinal cord possess NMDA receptors and that subunit composition varies in different regions.
Inhibition of tumour necrosis factor‐α by antisense targeting produces immunophenotypical and morphological changes in injury‐activated microglia and macrophages
Authors: Pearse Damien D. , Pereira Francisco C. , Stolyarova Anna , Barakat David J. , Bunge Mary Bartlett
Published: January 2005

Microglia respond in a stereotypical pattern to a diverse array of pathological states. These changes are coupled to morphological and immunophenotypical alterations and the release of a variety of reactive species, trophic factors and cytokines that modify both microglia and their cellular environment. We examined whether a microglial‐produced cytokine, tumour necrosis factor‐α (TNF‐α), was involved in the maintenance of microglial activation after spinal cord injury by selective inhibition using TNF‐α antisense deoxyoligonucleotides (ASOs). Microglia and macrophages harvested from 3 d post‐contused rat spinal cord were large and rounded (86.3 ± 9.6%). They were GSA‐IB4‐positive (GSA‐IB4+) (Griffonia simplicifolia lectin, microglia specific; 94.8 ± 5.1%), strongly OX‐42 positive (raised against a type 3 complement/integrin receptor, CD11b; 78.9 ± 9.1%), ED‐1 positive (a lysosomal marker shown to correlate well with immune cell activation; 97.2 ± 2.6%) and IIA positive (antibody recognizes major histocompatibility complex II; 57.2 ± 5.6%), indicative of fully activated cells, for up to 48 h after plating. These cells also secreted significant amounts of TNF‐α (up to 436 pg/µg total protein, 16 h). Fluoroscein isothiocyanate‐labelled TNF‐α ASOs (5, 50 and 200 nm) added to the culture medium were taken up very efficiently into the cells (> 90% cells) and significantly reduced TNF‐α production by up to 92% (26.5 pg/µg total protein, 16 h, 200 nm TNF‐α ASOs). Furthermore, few of the treated cells at this time were round (5.4 ± 2.7%), having become predominantly spindle shaped (74.9 ± 6.3%) or stellate (21.4 ± 2.7%); immunophenotypically, although all of them remained GSA‐IB4 positive (91.6 ± 6.2%), many were weakly OX‐42 positive and few expressed either ED‐1 (12.9 ± 2.5%) or IIA (19.8 ± 7.4%). Thus, the secretion of TNF‐α early in spinal cord injury may be involved in autoactivating microglia/macrophages. However, at the peak of microglial activation after injury, the activation state of microglia/macrophages is not stable and this process may still be reversible by blocking TNF‐α.
Reconsolidation of fresh, remote, and extinguished fear memory in medaka: old fears don't die
Authors: Eisenberg Mark , Dudai Yadin
Published: January 2005

Long‐term fear memory in the medaka fish (Oryzias latipes) regains transient sensitivity to a consolidation blocker immediately after memory reactivation in retrieval (‘reconsolidation’). Here we show that reconsolidation occurs in fresh long‐term memories but not in remote memories, and that the apparent amnesia induced by blockade of reconsolidation can be reinstated by an unpaired reinforcer, a procedure that has no effect on amnesia induced by blockade of consolidation. Extinction memory also undergoes post‐reactivation reconsolidation, the blockade of which exposes the previously acquired fear. Hence in medaka, the process manifested in reconsolidation seems itself to consolidate; moreover, even when the post‐reactivation application of the consolidation blocker is still able to disrupt the memory, the conditioned fear does not seem to go away permanently.
Inhibition of superior colliculus neurons by a GABAergic input from the pretectal nuclear complex in the rat
Authors: Born Gesche , Schmidt Matthias
Published: January 2005

The mammalian pretectal nuclear complex (PNC) is a visual and visuomotor control structure which is strongly connected to other subcortical visual structures. This indicates that the PNC also controls subcortical visual information flow during the execution of various oculomotor programs. A prominent, presumably GABAergic, projection from the PNC targets the superficial grey layer of the superior colliculus (SC), which itself is a central structure for visual information processing necessary for the generation of saccadic eye movements. In order to characterize the pretecto‐tectal projection in vitro, we performed whole‐cell patch‐clamp recordings from SC and PNC neurons in slices obtained from 3–6‐week‐old pigmented rats. Focal glutamate injections into the PNC and electrical PNC stimulation were used to induce postsynaptic responses in SC neurons. Electrical stimulation of the SC allowed electrophysiological identification of PNC neurons that provide the inhibitory pretecto‐tectal input. Only inhibitory postsynaptic currents could be elicited in SC neurons both by pharmacological and by electrical activation of the ipsilateral PNC. Concomitantly, a small number of PNC neurons could be antidromically activated from the ipsilateral SC. Most SC cells postsynaptic to the prectectal input showed the dendritic morphology of wide‐field and narrow‐field cells and are therefore regarded as projection neurons. All inhibitory currents evoked by PNC activation could be completely blocked by bath application of the selective GABAA receptor antagonist bicuculline. Together these results indicate that SC projection neurons receive a direct inhibitory input from the ipsilateral PNC and that this input is mediated by GABAA receptors.
Environmental enrichment enhances auditory takeover of the occipital cortex in anophthalmic mice
Authors: Piché Mathieu , Robert Stéphane , Miceli Dom , Bronchti Gilles
Published: January 2005

Enrichment of the environment is an effective means of enhancing neuronal development and plasticity but its effect on the cross‐modal compensation resulting from sensory deprivation has never been investigated. The present study used c‐Fos immunohistochemistry and dextran–biotin neuronal tracing to examine the reorganization of sensory modalities in the brain of anophthalmic mutant mice (ZRDCT/An) raised in either enriched or standard environments. Auditory stimulation was found to elicit strong neuronal activation in thalamic and cortical structures that are normally visual. An important finding was that the latter auditory‐evoked cortical activity was considerably enhanced in blind mice raised in the enriched environment. The axonal tracing study demonstrated auditory inputs from the inferior colliculus to the visual thalamus. This animal model will be useful for understanding neuronal mechanisms underlying some cross‐modal sensory phenomena observed in blind or deaf humans.
Olfactory transduction in ciliated receptor neurons of the Cabinza grunt, Isacia conceptionis (teleostei: haemulidae)
Authors: Schmachtenberg Oliver , Bacigalupo Juan
Published: January 2005

The ciliated receptor neurons of fish olfactory organs are thought to transduce amino acids through a cAMP‐dependent transduction pathway, but direct physiological evidence for this hypothesis remains scarce and is confined to catfish and trout. We investigated olfactory transduction in a marine fish, the Cabinza grunt Isacia conceptionis (Perciformes, Teleostei). The olfactory epithelium was characterized using light and electron microscopy, and isolated ciliated receptor neurons were recorded with the perforated patch‐clamp technique. Cells were stimulated with puffer pipettes containing amino acid odourants, IBMX plus forskolin or 8bromo‐cAMP. All three stimuli triggered transient inward currents at a holding potential of −70 mV and responses with outward‐rectifying current–voltage relationships. The characteristics of the transduction currents induced by each stimulus were similar across cells and indistinguishable within the same cell, supporting the hypothesis of a cAMP pathway mediating transduction of amino acids in ciliated olfactory receptor neurons.
Difference Equations for the Higher Order Moments and Cumulants of the INAR(p) Model
Authors: Silva Maria Eduarda , Oliveira Vera Lúcia
Published: January 2005

Abstract.  Here we obtain difference equations for the higher order moments and cumulants of a time series {Xt} satisfying an INAR(p) model. These equations are similar to the difference equations for the higher order moments and cumulants of the bilinear time series model. We obtain the spectral and bispectral density functions for the INAR(p) process in state–space form, thus characterizing it in the frequency domain. We consider a frequency domain method – the Whittle criterion – to estimate the parameters of the INAR(p) model and illustrate it with the series of the number of epilepsy seizures of a patient.
Testing Non‐Correlation and Non‐Causality between Multivariate ARMA Time Series
Authors: Hallin Marc , Saidi Abdessamad
Published: January 2005

Abstract.  Haugh [Journal of the American Statistical Association (1976) Vol. 71, pp. 378–85] developed an approach to the problem of testing non‐correlation (at all leads and lags) between two univariate time series. Haugh's tests however have low power against two series which are related over a long distributed lag when individual lag coefficients are relatively small. As a remedy, Koch and Yang [Journal of the American Statistical Association (1986) Vol. 8, pp. 533–44] proposed an alternative method that performs better than Haugh's under such dependencies. A multivariate extension of Haugh's procedure was proposed by El Himdi and Roy [The Canadian Journal of Statistics (1997) Vol. 25, pp. 233–56], but suffers the same weaknesses as the original univariate method. We develop here an asymptotic test generalizing Koch and Yang's method to the multivariate case. Our method includes El Himdi and Roy's as a special case. Based on the same idea, we also suggest a generalization of the El Himdi and Roy procedure for testing causality in the sense of Granger [Econometrica (1969) Vol. 37, pp. 424–38] between two multivariate series. A Monte Carlo study is conducted, which indicates that our approach performs better than El Himdi and Roy's for a wide range of models. Both procedures are applied to the problem of testing the absence of correlation between Canadian and US economic indicators, and to a brief study of causality between money and income in Canada.
Peripheral ameloblastoma of the gingiva: the importance of diagnosis
Authors: López‐Jornet Pía , Bermejo‐Fenoll Ambrosio
Published: January 2005

Background: Peripheral ameloblastoma is an extremely rare epithelial odontogenic tumor, limited to the soft tissues of the gums or oral mucosa. Although the lesion is benign, it may be locally aggressive.

Methods: The present study describes the case of a 31‐year‐old male presenting a firm, symptomless tumor mass of irregular appearance and measuring approximately 12 mm in diameter, located in the distal zone of 4.7.

Results: An excision biopsy was performed. The lesion was covered with hyperplastic squamous epithelium, with islets of epithelial cells located at subepithelial level. The cells in the peripheral zone adopted a palisade distribution, and presented the appearance of a lax reticulum at central level. A fibroblastic stroma was observed between the islets. The diagnosis was peripheral ameloblastoma.

Conclusions: Although the origin of the lesion remains unclear, it is able to recur and undergo malignant transformation. Consequently, peripheral ameloblastoma should not be viewed as a harmless mass.