bluuebunny/crossref_metadata_2025_split huggingface dataset:
Flies lacking all synapsins are unexpectedly healthy but are impaired in complex behaviour
Authors: Godenschwege Tanja A. , Reisch Dietmar , Diegelmann Sören , Eberle Kai , Funk Natalja , Heisenberg Martin , Hoppe Viviane , Hoppe Jürgen , Klagges Bert R. E. , Martin Jean‐René , Nikitina Ekaterina A. , Putz Gabi , Reifegerste Rita , Reisch Natascha , Rister Jens , Schaupp Michael , Scholz Henrike , Schwärzel Martin , Werner Ursula , Zars Troy D. , Buchner Sigrid , Buchner Erich 
Published: July 2004

AbstractVertebrate synapsins are abundant synaptic vesicle phosphoproteins that have been proposed to fine‐regulate neurotransmitter release by phosphorylation‐dependent control of synaptic vesicle motility. However, the consequences of a total lack of all synapsin isoforms due to a knock‐out of all three mouse synapsin genes have not yet been investigated. In Drosophila a single synapsin gene encodes several isoforms and is expressed in most synaptic terminals. Thus the targeted deletion of the synapsin gene of Drosophila eliminates the possibility of functional knock‐out complementation by other isoforms. Unexpectedly, synapsin null mutant flies show no obvious defects in brain morphology, and no striking qualitative changes in behaviour are observed. Ultrastructural analysis of an identified ‘model’ synapse of the larval nerve muscle preparation revealed no difference between wild‐type and mutant, and spontaneous or evoked excitatory junction potentials at this synapse were normal up to a stimulus frequency of 5 Hz. However, when several behavioural responses were analysed quantitatively, specific differences between mutant and wild‐type flies are noted. Adult locomotor activity, optomotor responses at high pattern velocities, wing beat frequency, and visual pattern preference are modified. Synapsin mutant flies show faster habituation of an olfactory jump response, enhanced ethanol tolerance, and significant defects in learning and memory as measured using three different paradigms. Larval behavioural defects are described in a separate paper. We conclude that Drosophila synapsins play a significant role in nervous system function, which is subtle at the cellular level but manifests itself in complex behaviour.
Axonal injury‐dependent induction of the peripheral benzodiazepine receptor in small‐diameter adult rat primary sensory neurons
Authors: Karchewski Laurie A. , Bloechlinger Stefan , Woolf Clifford J. 
Published: July 2004

AbstractThe peripheral benzodiazepine receptor (PBR), a benzodiazepine but not γ‐aminobutyric acid‐binding mitochondrial membrane protein, has roles in steroid production, energy metabolism, cell survival and growth. PBR expression in the nervous system has been reported in non‐neuronal glial and immune cells. We now show expression of both PBR mRNA and protein, and the appearance of binding of a synthetic ligand, [3H]PK11195, in dorsal root ganglion (DRG) neurons following injury to the sciatic nerve. In naïve animals, PBR mRNA, protein expression and ligand binding are undetectable in the DRG. Three days after sciatic nerve transection, however, PBR mRNA begins to be expressed in injured neurons, and 4 weeks after the injury, expression and ligand binding are present in 35% of L4 DRG neurons. PBR ligand binding also appears after injury in the superficial dorsal horn of the spinal cord. The PBR expression in the DRG is restricted to small and medium‐sized neurons and returns to naïve levels if the injured peripheral axons are allowed to regrow and reinnervate targets. No non‐neuronal PBR expression is detected, unlike its putative endogenous ligand the diazepam binding inhibitor (DBI), which is expressed only in non‐neuronal cells, including the satellite cells that surround DRG neurons. DBI expression does not change with sciatic nerve transection. PBR acting on small‐calibre neurons could play a role in the adaptive survival and growth responses of these cells to injury of their axons.
Latent inhibition of cued fear conditioning: an NMDA receptor‐dependent process that can be established in the presence of anisomycin
Authors: Lewis Michael C. , Gould Thomas J. 
Published: July 2004

AbstractMuch of the research examining the biological basis for long‐term memories has focused on mechanisms that support the formation of conditioned associations. Less information is available on biological mechanisms which underlie processes that modify the strength of conditioned associations. Latent inhibition is a phenomenon by which pre‐exposure to a to‐be‐conditioned stimulus (CS) weakens subsequent conditioning of that CS to an unconditioned stimulus (US). Here we report that latent inhibition of cued fear conditioning is dependent on NMDA receptor activation. MK‐801 (1 mg/kg), an NMDA receptor antagonist, abolished latent inhibition of cued fear conditioning. This dose of MK‐801 administered before training did not disrupt cued fear conditioning. Conversely, anisomycin (150 mg/kg), a protein synthesis inhibitor, had no effect on latent inhibition of cued fear conditioning when administered 20 min before, immediately after, or 2, 4, 6, or 8 h after CS pre‐exposure. Furthermore, continuous anisomycin administration (50 mg/kg, administered every 2 h for 6 h starting 20 min prior to pre‐exposure) did not disrupt latent inhibition of cued fear conditioning. In addition, anisomycin had no effect on a long‐lasting version of latent inhibition of cued fear conditioning that was maintained over a 7‐day interval. Anisomycin administered before training, however, disrupted learning of the CS–US association. These findings suggest that latent inhibition of cued fear conditioning is a long‐lasting NMDA receptor‐dependent process that can develop during the inhibition of protein synthesis.
Functional topology of the mossy fibre–granule cell– Purkinje cell system revealed by imaging of intrinsic fluorescence in mouse cerebellum
Authors: Coutinho V. , Mutoh H. , Knöpfel T. 
Published: July 2004

AbstractWe report an activity‐induced green fluorescence signal observed when mouse cerebellar slices were illuminated with blue light and parallel fibre–Purkinje cell synapses were activated. The optical signal consisted of an initial increase in fluorescence that peaked within 1–2 s after the onset of stimulation, followed by a long lasting (40 s) transient decrease in fluorescence. Single or tetanic electrical stimuli applied to the molecular layer elicited ‘beam‐shaped’ fluorescence changes along the trajectory of parallel fibres. These signals reported activation of Purkinje cells as they were depressed by antagonists of ionotropic and metabotropic glutamate receptors at Purkinje cells and correlated with Purkinje cell spiking activity. Optical responses induced by direct pharmacological activation of glutamate receptors were reduced by a calcium‐free extracellular medium, consistent with the hypothesis that they reflect metabolic activity due to an increased intracellular calcium load associated with neuronal activation. We used these intrinsic fluorescence signals to address the question of whether granule cells excite Purkinje cells only locally via the ascending branches of their axons, or more widespread along the parallel fibre trajectory. White matter stimulation of the mossy fibres also elicited a beam‐like fluorescence change along the trajectory of parallel fibres. Simultaneous imaging and extracellular recording demonstrated the association between the beam‐like fluorescence signal and Purkinje cell spiking. This non‐invasive imaging technique supports the notion that parallel fibre activity, evoked either locally or through the mossy fibre–granule cell pathway, can activate postsynaptic Purkinje cells along more than 3 mm of the parallel fibre trajectory.
Restricted diffusion in the brain of transgenic mice with cerebral amyloidosis
Authors: Mueggler Thomas , Meyer‐Luehmann Melanie , Rausch Martin , Staufenbiel Matthias , Jucker Mathias , Rudin Markus 
Published: July 2004

AbstractA prominent hallmark of Alzheimer's disease pathology is cerebral amyloidosis. However, it is not clear how extracellular amyloid‐β peptide (Aβ) deposition and amyloid formation compromise brain function and lead to dementia. It has been argued that extracellular amyloid deposition is neurotoxic and/or that soluble Aβ oligomers impair synaptic function. Amyloid deposits, by contrast, may affect diffusion properties of the brain interstitium with implications for the transport of endogenous signalling molecules during synaptic and/or extrasynaptic transmission. We have used diffusion‐weighted magnetic resonance imaging to study diffusion properties in brains of young (6‐month‐old) and aged (25‐month‐old) APP23 transgenic mice and control littermates. Our results demonstrate that fibrillar amyloid deposits and associated gliosis in brains of aged APP23 transgenic mice are accompanied by a reduction in the apparent diffusion coefficient. This decrease was most pronounced in neocortical areas with a high percentage of congophilic amyloid and was not significant in the caudate putamen, an area with only modest and diffuse amyloid deposition. These findings suggest that extracellular deposition of fibrillar amyloid and/or associated glial proliferation and hypertrophy cause restrictions to interstitial fluid diffusion. Reduced diffusivity within the interstitial space may alter volume transmission and therefore contribute to the cognitive impairment in Alzheimer's disease.
Time‐dependent changes in the expression of the MEF2 transcription factor family during topographic map reorganization in mammalian visual cortex
Authors: Leysen Inge , Van der Gucht Estel , Eysel Ulf T. , Huybrechts Roger , Vandesande Frans , Arckens Lutgarde 
Published: July 2004

AbstractRemoval of retinal input from a restricted region of adult mammalian visual cortex leads to a substantial reorganization of the retinotopy within the lesion projection zone (LPZ) of primary visual cortex (area 17). Little is known about the molecular mechanisms underlying such cortical plasticity. We investigated whether small but homonymous central retinal lesions induced differences in gene expression patterns between central area 17, the LPZ, vs. peripheral area 17 of the adult cat. Systematic differential mRNA display screening revealed higher levels for the mRNA encoding the transcription factor MEF2A in the LPZ. Semi‐quantitative PCR confirmed this dependency of mef2A mRNA expression on visual eccentricity in area 17 of animals with retinal lesions in contrast to normal animals. Western blotting experiments extended these data to the protein level and to two other members of the MEF2 transcription factor family, i.e. MEF2C and MEF2D. Quantitative analysis of the Western blotting experiments further revealed a post‐lesion survival time‐dependent change in expression for all three MEF2 family members. The lesion effect was maximal at 3 days and 1 month post‐lesion, but only minor at 2 weeks post‐lesion. Interestingly, complete removal of retinal input from area 17 by surgery did not significantly alter the expression of the MEF2 transcription factors, excluding a definite correlation between neuronal activity and MEF2A expression levels. MEF2A immunocytochemistry confirmed both qualitatively and quantitatively the Western blotting observations in all animal models. Together, our findings identified a brain plasticity‐related expression pattern for the MEF2 transcription factor family in adult mammalian neocortex.
Transfer of adaptation from visually guided saccades to averaging saccades elicited by double visual targets
Authors: Alahyane Nadia , Koene Ansgar , Pélisson Denis 
Published: July 2004

AbstractThe adaptive mechanisms that control the amplitude of visually guided saccades (VGS) are only partially elucidated. In this study, we investigated, in six human subjects, the transfer of VGS adaptation to averaging saccades elicited by the simultaneous presentation of two visual targets. The generation of averaging saccades requires the transformation of two representations encoding the desired eye displacement toward each of the two targets into a single representation encoding the averaging saccade (averaging programming site). We aimed to evaluate whether VGS adaptation acts upstream (hypothesis 1) or at/below (hypothesis 2) the level of averaging saccades programming. Using the double‐step target paradigm, we simultaneously induced a backward adaptation of 17.5° horizontal VGS and a forward adaptation of 17.5° oblique VGS performed along the ± 40° directions relative to the azimuth. We measured the effects of this dual adaptation protocol on averaging saccades triggered by two simultaneous targets located at 17.5° along the ± 40° directions. To increase the yield of averaging saccades, we instructed the subjects to move their eyes as fast as possible to an intermediate position between the two targets. We found that the amplitude of averaging saccades was smaller after VGS adaptation than before and differed significantly from that predicted by hypothesis 1, but not by hypothesis 2, with an adaptation transfer of 50%. These findings indicate that VGS adaptation largely occurs at/below the averaging saccade programming site. Based on current knowledge of the neural substrate of averaging saccades, we suggest that VGS adaptation mainly acts at the level of the superior colliculus or downstream.
Resistance to extinction is associated with impaired immediate early gene induction in medial prefrontal cortex and amygdala
Authors: Herry Cyril , Mons Nicole 
Published: July 2004

AbstractExtinction of classical fear conditioning is thought to involve activity‐dependent potentiation of synaptic transmission in the medial prefrontal cortex (mPFC), resulting in the inhibition of amygdala‐dependent fear responses. While many studies have addressed the mechanisms underlying extinction learning, it is unclear what determines whether extinction memory is consolidated or whether spontaneous recovery of the fear response occurs. Here we show, using a combined electrophysiological and immunocytochemical approach, that spontaneous recovery of conditioned fear in mice is associated with a prolonged expression of long‐term depression of synaptic transmission in the mPFC and the failure of induction of the immediate–early genesc‐Fos and zif268 in the mPFC and the basolateral nucleus of the amygdala. This suggests that coordinated activity‐dependent changes in gene expression in the mPFC and the amygdala may underlie the formation of long‐term fear extinction memory.
Familial risk of prostate cancer in Iceland
Authors: Eldon B.J. , Jonsson E. , Tomasson J. , Tryggvadottir L. , Tulinius H. 
Published: July 2004

OBJECTIVETo estimate the risk of prostate and other types of cancer among relatives of Icelandic men diagnosed with prostate cancer over a 5‐year period.PATIENTS AND METHODSThe risk ratio (RR) was used to estimate the risk among relatives of 371 patients with prostate cancer, all of whom lived in Iceland and were diagnosed when alive over a 5‐year interval (1983–7). Information on cancer incidence was obtained from the population‐based Icelandic Cancer Registry, and information on families from a comprehensive genealogical database covering the population of Iceland.RESULTSFirst‐degree male relatives were at a 1.7‐fold greater age‐adjusted risk of prostate cancer (1832 men; 95% confidence interval, CI, 1.28–2.34). The risk was independent of proband's age at diagnosis. First‐degree male relatives of patients who died from prostate cancer were at a statistically significantly greater risk of the disease (784 men; RR 2.17; 95% CI 1.34–3.53) and relatives of patients with incidental disease (T1a) were at a greater risk but not statistically significant so (261; RR 1.86; 95% CI 0.75–4.58). Female first‐degree relatives were not at greater risk of breast cancer. The risk of kidney cancer was higher in first‐ and second‐degree female relatives, with an RR (n, CI) of 2.50 (1780, 1.10–5.66) and 2.67 (5534, 1.04–6.81), respectively. The risk of kidney cancer was not statistically significantly greater in male relatives.CONCLUSIONFamily history is a risk factor for prostate cancer in Icelandic men. The risk is potentially higher for relatives of patients who die from the disease. Female relatives are not at greater risk of breast cancer but they may be at greater risk of kidney cancer.
Comparison of ultrasound and magnetic resonance imaging in 100 singleton pregnancies with suspected brain abnormalities
Authors: Whitby E.H. , Paley M.N.J. , Sprigg A. , Rutter S. , Davies N.P. , Wilkinson I.D. , Griffiths P.D. 
Published: July 2004

Objective  To compare the diagnostic accuracy of the current reference standard‐ultrasound with in utero magnetic resonance imaging, in a selected group of patients.Design  Prospective study.Setting  Five fetal maternal tertiary referral centres and an academic radiology unit.Sample  One hundred cases of fetuses with central nervous system abnormalities where there has been diagnostic difficulties on ultrasound. In 48 cases the women were less than 24 weeks of gestation and in 52 cases later in pregnancy.Methods  All women were imaged on a 1.5 T clinical system using a single shot fast spin echo technique. The results of antenatal ultrasound and in utero magnetic rosenance were compared.Main outcome measures  The definitive diagnosis was made either at autopsy or by postmortem magnetic resonance imaging, in cases that went to termination of pregnancy, or a combination of postnatal imaging and clinical follow up in the others.Results  In 52 of cases, ultrasound and magnetic resonance gave identical results and in a further 12, magnetic resonance provided extra information that was judged not to have had direct effects on management. In 35 of cases, magnetic resonance either changed the diagnosis (29) or gave extra information that could have altered management (6). In 11 of the 30 cases where magnetic resonance changed the diagnosis, the brain was described as normal on magnetic resonance.Conclusions  In utero magnetic resonance imaging is a powerful tool in investigating fetal brain abnormalities. Our results suggest that in selected cases of brain abnormalitites, detected by ultrasound, antenatal magnetic resonance may provide additional, clinically useful information that may alter management.
Home‐based care after a shortened hospital stay versus hospital‐based care postpartum: an economic evaluation
Authors: Petrou Stavros , Boulvain Michel , Simon Judit , Maricot Patrice , Borst François , Perneger Thomas , Irion Olivier 
Published: July 2004

Objectives  To compare the cost effectiveness of early postnatal discharge and home midwifery support with a traditional postnatal hospital stay.Design  Cost minimisation analysis within a pragmatic randomised controlled trial.Setting  The University Hospital of Geneva and its catchment area.Population  Four hundred and fifty‐nine deliveries of a single infant at term following an uncomplicated pregnancy.Methods  Prospective economic evaluation alongside a randomised controlled trial in which women were allocated to either early postnatal discharge combined with home midwifery support (n= 228) or a traditional postnatal hospital stay (n= 231).Main outcome measures  Costs (Swiss francs, 2000 prices) to the health service, social services, patients, carers and society accrued between delivery and 28 days postpartum.Results  Clinical and psychosocial outcomes were similar in the two trial arms. Early postnatal discharge combined with home midwifery support resulted in a significant reduction in postnatal hospital care costs (bootstrap mean difference 1524 francs, 95% confidence interval [CI] 675 to 2403) and a significant increase in community care costs (bootstrap mean difference 295 francs, 95% CI 245 to 343). There were no significant differences in average hospital readmission, hospital outpatient care, direct non‐medical and indirect costs between the two trial groups. Overall, early postnatal discharge combined with home midwifery support resulted in a significant cost saving of 1221 francs per mother–infant dyad (bootstrap mean difference 1209 francs, 95% CI 202 to 2155). This finding remained relatively robust following variations in the values of key economic parameters performed as part of a comprehensive sensitivity analysis.Conclusions  A policy of early postnatal discharge combined with home midwifery support exhibits weak economic dominance over traditional postnatal care, that is, it significantly reduces costs without compromising the health and wellbeing of the mother and infant.
Women and health care professionals' preferences for Down's Syndrome screening tests: a conjoint analysis study
Authors: Bishop Amanda J. , Marteau Theresa M. , Armstrong David , Chitty Lyn S. , Longworth Louise , Buxton Martin J. , Berlin Cheryl 
Published: July 2004

Objective  To describe and compare women and health care professionals' preferences for Down's Syndrome screening tests with different test characteristics.Design  Cross sectional questionnaire based conjoint analysis study.Setting  London teaching hospital.Sample  291/383 women in their first or second trimester of pregnancy and 98/122 health care professionals (41 obstetricians, senior house officers and above and 57 qualified midwives) providing care at the same hospital.Methods  Women completed a questionnaire while attending a clinic visit for a dating scan or a routine 20‐week anomaly scan. Health care professionals completed a postal questionnaire.Main outcome measures  The relative values participants attach to Down's Syndrome screening test attributes: time of test, detection rate and risk of miscarriage of a baby unaffected by Down's Syndrome as a result of subsequent diagnostic tests.Results  Pregnant women and health care professionals shared broadly similar relative values regarding the importance of safe tests, conducted early and with high detection rates. When asked to choose between different Down's Syndrome screening tests, health care professionals valued earlier tests more highly than did women.Conclusions  While pregnant women and health care professionals share similar relative values regarding optimal prenatal tests, health care professionals place a higher value on earlier tests. This may result in screening policies that overweight timing in the selection of a test to the relative neglect of tests associated with lower miscarriage rates and higher detection rates but conducted later in pregnancy.
A case‐controlled study comparing clinical course and outcomes of pregnant and non‐pregnant women with severe acute respiratory syndrome
Authors: Lam Chui Miu , Wong Shell Fean , Leung Tse Ngong , Chow Kam Ming , Yu Wai Cho , Wong Tin Yau , Lai Sik To , Ho Lau Cheung 
Published: July 2004

Objective  To compare the clinical courses and outcomes of pregnant severe acute respiratory syndrome (SARS) patients and non‐pregnant SARS patients.Design  A case–control study.Setting  Tertiary Hospital for Infectious Disease.Sample  Ten pregnant and 40 non‐pregnant female patients infected with SARS.Methods  Clinical course and outcomes of pregnant SARS patients were compared with a group of non‐pregnant SARS patient. Cases and controls were matched with respect to sex, age, timing of contracting SARS, health care workers status and underlying illness.Main outcome measures  The incidence of intensive care unit admission, intubation, medical complications and death rate.Results  Pregnancy had no discernible impact on clinical symptoms and presentation delay. Four out of the 10 pregnant patients, nevertheless, required endotracheal intubation and six were admitted to the intensive care unit (ICU), as compared with 12.5% intubation rate (P= 0.065) and 17.5% ICU admission rate (P= 0.012) in the non‐pregnant group. More pregnant SARS patients developed renal failure (P= 0.006) and disseminated intravascular coagulopathy (P= 0.006), as compared with non‐pregnant SARS group. There were three deaths in the pregnant group, whereas there was no death in the non‐pregnant control group (P= 0.006).Conclusion  Pregnant women with SARS experience a worse clinical course and poorer outcomes compared with non‐pregnant women.