bluuebunny/crossref_metadata_2025_split huggingface dataset:
BMP4 induction of sensory neurons from human embryonic stem cells and reinnervation of sensory epithelium
Authors: Shi Fuxin , Corrales Carleton Eduardo , Liberman M. Charles , Edge Albert S. B. 
Published: November 2007

AbstractIn mammals, hair cells and auditory neurons lack the capacity to regenerate, and damage to either cell type can result in hearing loss. Replacement cells for regeneration could potentially be made by directed differentiation of human embryonic stem (hES) cells. To generate sensory neurons from hES cells, neural progenitors were first made by suspension culture of hES cells in a defined medium. The cells were positive for nestin, a neural progenitor marker, and Pax2, a marker for cranial placodes, and were negative for α‐fetoprotein, an endoderm marker. The precursor cells could be expanded in vitro in fibroblast growth factor (FGF)‐2. Neurons and glial cells were found after differentiation of the neural progenitors by removal of FGF‐2, but evaluation of neuronal markers indicated insignificant production of sensory neurons. Addition of bone morphogenetic protein 4 (BMP4) to neural progenitors upon removal of FGF‐2, however, induced significant numbers of neurons that were positive for markers associated with cranial placodes and neural crest, the sources of sensory neurons in the embryo. Neuronal processes from hES cell‐derived neurons made contacts with hair cells in denervated ex vivo sensory epithelia and expressed synaptic markers, suggesting the formation of synapses. In a gerbil model with a denervated cochlea, the ES cell‐derived neurons engrafted in the auditory nerve trunk and sent out neurites that grew toward the auditory sensory epithelium. These data indicate that hES cells can be induced to form sensory neurons that have the potential to treat neural degeneration associated with sensorineural hearing loss.
Sigma 1 receptor‐mediated increase in hippocampal extracellular dopamine contributes to the mechanism of the anticonvulsant action of neuropeptide Y
Authors: Meurs Alfred , Clinckers Ralph , Ebinger Guy , Michotte Yvette , Smolders Ilse 
Published: November 2007

AbstractThe potent anticonvulsant properties of neuropeptide Y (NPY) are generally attributed to a Y2receptor‐mediated inhibition of glutamatergic synaptic transmission. Independent studies have shown that NPY increases brain dopamine content, possibly via interaction with sigma 1 receptors. Recently, we showed that increased extracellular hippocampal dopamine attenuates pilocarpine‐induced limbic seizures via activation of hippocampal D2receptors. Our aim in this study was to elucidate the role of increased hippocampal dopamine in the mechanism of the anticonvulsant action of NPY and to investigate the involvement of Y2and sigma 1 receptors in this process. Limbic seizures were evoked in freely moving rats by intrahippocampal administration of pilocarpine via a microdialysis probe. NPY was administered intracerebroventricularly, intrahippocampally via the microdialysis probe, or coadministered intrahippocampally with the D2receptor antagonist remoxipride, the Y2receptor antagonist BIIE0246 or the sigma 1 receptor antagonist BD1047. Changes in hippocampal extracellular dopamine were monitored, and behavioural changes indicative of seizure activity were scored. Intracerebroventricular (10 nmol/3 µL) and intrahippocampal (20–50 µm) NPY administration increased hippocampal dopamine and attenuated pilocarpine‐induced seizures. Hippocampal D2receptor blockade (4 µmremoxipride) reversed the anticonvulsant effect of NPY. Y2receptor blockade (1 µmBIIE0246) reversed the anticonvulsant effect of NPY but did not prevent NPY‐induced increases in hippocampal dopamine. Sigma 1 receptor blockade (10 µmBD1047) abolished NPY‐induced increases in hippocampal dopamine and reversed the anticonvulsant effect of NPY. Our results indicate that NPY‐induced increases in hippocampal dopamine are mediated via sigma 1 receptors and contribute to the anticonvulsant effect of NPY via increased activation of hippocampal D2receptors. This novel mechanism of anticonvulsant action of NPY is separate from, and may be complementary to, the well established Y2receptor‐mediated inhibition of hippocampal excitability.
Evidence for a major role of endogenous fibroblast growth factor‐2 in apoptotic cortex‐induced subventricular zone cell proliferation
Authors: Agasse F. , Nicoleau C. , Petit J. , Jaber M. , Roger M. , Benzakour O. , Coronas V. 
Published: November 2007

AbstractIn the adult mammalian brain, neural stem cells persist in the subventricular zone (SVZ) of lateral ventricles. It is well established that cortical damage leads to SVZ cell proliferation and neuronal differentiation. We have previously demonstrated in rat that, when treated with the apoptosis‐inducing agent staurosporine, cortex explants release heat‐labile factors that promote SVZ cell culture proliferation. In the present report, we investigated in vitro mechanisms involved in cortex injury‐triggered neurogenesis in the rat. We demonstrated, using immunoblotting analysis and fibroblast growth factor (FGF)‐2 enzyme‐linked sandwich immunosorbent assay, that treatment of cortex explants with apoptosis‐inducing agents increases the release of FGF‐2. We next determined the effects of apoptotic cortex‐released factors in regulating SVZ cell proliferation and neuronal differentiation by using bromodeoxyuridine incorporation and microtubule‐associated protein 2 immunostaining assays, respectively. We found that conditioned media derived from staurosporine‐treated cortex explants enhanced SVZ cell culture proliferation and differentiation by over 50 and 80%, respectively. Finally, we showed that immunodepletion of FGF‐2 or pharmacological blockade of FGF‐2 receptor by SU5402 completely abolished staurosporine‐treated cortex mitogenic activity on SVZ cultures but did not alter its activity on neuronal cell differentiation. Altogether, the present report establishes that the release of endogenous FGF‐2 by apoptotic cortex explants plays a major role in the induction of SVZ cell proliferation but not neuronal differentiation, which probably depends on the release of other as yet unidentified cortical factors.
Effector‐dependent activity in the left dorsal premotor cortex in motor imagery
Authors: Szameitat André J. , Shen Shan , Sterr Annette 
Published: November 2007

AbstractAlthough right‐ and left‐hand motor imagery (MI) typically results in lateralized cortical activation patterns in various areas, such an effect has never been observed in the left premotor cortex (PMC). Using functional magnetic resonance imaging we tested whether the left PMC, which is supposed to be effector independent, i.e. it is activated irrespective of the hand used for MI, shows differential activation during right‐ and left‐hand MI of ecologically valid everyday actions. Results showed that the left dorsal PMC was activated more strongly during right‐ than left‐hand MI, and that the co‐varying quality of imagination could not explain the observed effects. We conclude that the left dorsal PMC incorporates effector‐dependent functionality and therefore is not fully generic for MI, as has been suggested before. Implications for clinical research are discussed.
MDMA self‐administration in rats: acquisition, progressive ratio responding and serotonin transporter binding
Authors: Schenk Susan , Hely Lincoln , Lake Barbara , Daniela Evangelene , Gittings David , Mash Deborah C. 
Published: November 2007

Abstract3,4‐Methylenedioxymethamphetamine (MDMA) self‐administration has been shown in animals with extensive drug histories, but only a small number of studies have examined high rates of responding maintained by MDMA in previously drug‐naïve animals. In the present study, influence of dose (0.25 or 1.0 mg/kg/infusion) on the acquisition of MDMA self‐administration was measured during daily 6‐h sessions. Dose–effect data were obtained for MDMA (0.25–1.0 mg/kg/infusion) self‐administration under a progressive ratio (PR) schedule of reinforcement. The effect of experimenter‐ or self‐administered MDMA on [3H] paroxetine binding in several brain regions was measured. Acquisition of MDMA self‐administration was highly variable and not different for 0.25 or 1.0 mg/kg/infusion progressed with approximately 60% of the rats acquiring reliable self‐administration during the 15‐day test period. The percentage of rats that acquired MDMA self‐administration was lower than the percentage of rats that acquired cocaine (0.5 mg/kg/infusion) self‐administration, and cocaine self‐administration was acquired with a shorter latency. Responding maintained by MDMA was dose dependent, and breakpoints under a PR schedule increased with dose. Radioligand binding and autoradiography demonstrated lower densities of serotonin transporter sites (SERT) in MDMA self‐administering rats as compared with controls across brain regions. The reduction in SERT densities was comparable in magnitude to rats treated with experimenter‐administered doses of MDMA. These data support the idea that MDMA is a drug with high abuse liability, and long‐term self‐administration may lead to long‐lasting deficits in serotonin neurotransmission.
General and outcome‐specific forms of Pavlovian‐instrumental transfer: the effect of shifts in motivational state and inactivation of the ventral tegmental area
Authors: Corbit Laura H. , Janak Patricia H. , Balleine Bernard W. 
Published: November 2007

AbstractThis study compared the contribution of the general activating and specific cueing properties of Pavlovian stimuli to Pavlovian‐instrumental transfer (PIT) and the role of the ventral tegmental area (VTA) in mediating these effects. In Experiment 1, hungry rats initially received Pavlovian training, in which three distinct auditory stimuli predicted the delivery of three different food outcomes. Next, the rats were trained to perform two instrumental actions, each earning a unique outcome selected from the three used in Pavlovian conditioning. Finally, the effects of the three stimuli on performance of the two actions were assessed in extinction. Presentation of a stimulus that had been paired with the same outcome as an action increased its performance relative to the other action, demonstrating that PIT effects can be outcome selective. In contrast, presentation of the stimulus that predicted the outcome that was not earned during instrumental training facilitated the performance of both actions indiscriminately. This effect, but not the outcome‐selective effect, was abolished by a shift from a hungry to a relatively sated state. Experiment 2 examined the effects of inactivation of the VTA on these two forms of PIT. VTA inactivation was found to attenuate PIT but, unlike satiety, did not appear to differentially affect the general or the outcome‐selective forms of PIT. The VTA appears therefore to play an important but general role in the initiation of instrumental actions, enabling cues to influence performance whether they enhance responding by changes in arousal or by retrieving particular actions based on their consequences.
Overexpression of Septin 4, the Drosophila homologue of human CDCrel‐1, is toxic for dopaminergic neurons
Authors: Muñoz‐Soriano Verónica , Paricio Nuria 
Published: November 2007

Abstract parkin loss‐of‐function mutations are linked to autosomal recessive juvenile parkinsonism. Parkin is an E3 ubiquitin ligase that promotes degradation of specific target proteins by the proteasome. It has been proposed that loss of Parkin activity will result in accumulation of its substrates, thus leading to dopaminergic (DA) neuron death. In Drosophila, parkin mutations cause degeneration of a subset of DA neurons in the brain but no Parkin substrates have yet been described. Here we characterized the septin 4 gene, which encodes the Drosophila orthologue of human CDCrel‐1, a Parkin substrate. We showed that Septin 4 overexpression causes age‐dependent disruption of DA neuron integrity in the dorsomedial cluster, which is suppressed by coexpression of Parkin and enhanced by reducing parkin function. Furthermore, other phenotypes caused by Septin 4 overexpression are also enhanced in a heterozygous parkin mutant background. This indicates that Septin 4 accumulation is toxic for DA neurons and suggests that Septin 4 could be a genuine substrate of Drosophila Parkin. Regarding this, we also showed that both proteins are able to interact physically with each other in vitro, thus supporting this hypothesis.
Species diversity in neutral metacommunities: a network approach
Authors: Economo Evan P. , Keitt Timothy H. 
Published: November 2007

AbstractBiologists seek an understanding of the processes underlying spatial biodiversity patterns. Neutral theory links those patterns to dispersal, speciation and community drift. Here, we advance the spatially explicit neutral model by representing the metacommunity as a network of smaller communities. Analytic theory is presented for a set of equilibrium diversity patterns in networks of communities, facilitating the exploration of parameter space not accessible by simulation. We use this theory to evaluate how the basic properties of a metacommunity – connectivity, size, and speciation rate – determine overall metacommunityγ‐diversity, and how that is partitioned intoα‐ andβ‐components. We find spatial structure can increaseγ‐diversity relative to a well‐mixed model, even whenθis held constant. The magnitude of deviations from the well‐mixed model and the partitioning intoα‐ andβ‐diversity is related to the ratio of migration and speciation rates.γ‐diversity scales linearly with metacommunity size even asα‐ andβ‐diversity scale nonlinearly with size.
Epigenetics for ecologists
Authors: Bossdorf Oliver , Richards Christina L. , Pigliucci Massimo 
Published: November 2007

AbstractThere is now mounting evidence that heritable variation in ecologically relevant traits can be generated through a suite of epigenetic mechanisms, even in the absence of genetic variation. Moreover, recent studies indicate that epigenetic variation in natural populations can be independent from genetic variation, and that in some cases environmentally induced epigenetic changes may be inherited by future generations. These novel findings are potentially highly relevant to ecologists because they could significantly improve our understanding of the mechanisms underlying natural phenotypic variation and the responses of organisms to environmental change. To understand the full significance of epigenetic processes, however, it is imperative to study them in an ecological context. Ecologists should therefore start using a combination of experimental approaches borrowed from ecological genetics, novel techniques to analyse and manipulate epigenetic variation, and genomic tools, to investigate the extent and structure of epigenetic variation within and among natural populations, as well as the interrelations between epigenetic variation, phenotypic variation and ecological interactions.
Leading indicators of trophic cascades
Authors: Carpenter S. R. , Brock W. A. , Cole J. J. , Kitchell J. F. , Pace M. L. 
Published: November 2007

AbstractRegime shifts are large, long‐lasting changes in ecosystems. They are often hard to predict but may have leading indicators which are detectable in advance. Potential leading indicators include wider swings in dynamics of key ecosystem variables, slower return rates after perturbation and shift of variance towards lower frequencies. We evaluated these indicators using a food web model calibrated to long‐term whole‐lake experiments. We investigated whether impending regime shifts driven by gradual increase in exploitation of the top predator can create signals that cascade through food webs and be discerned in phytoplankton. Substantial changes in standard deviations, return rates and spectra occurred near the switch point, even two trophic levels removed from the regime shift in fishes. Signals of regime shift can be detected well in advance, if the driver of the regime shift changes much more slowly than the dynamics of key ecosystem variables which can be sampled frequently enough to measure the indicators. However, the regime shift may occur long after the driver has passed the critical point, because of very slow transient dynamics near the critical point. Thus, the ecosystem can be poised for regime shift by the time the signal is discernible. Field tests are needed to evaluate these indicators.
Surgically treated perforations of the gastrointestinal tract caused by ingested foreign bodies
Authors: Rodríguez‐Hermosa J. I. , Codina‐Cazador A. , Sirvent J. M. , Martín A. , Gironès J. , Garsot E. 
Published: November 2007

AbstractObjective  Intestinal perforation due to foreign body (FB) ingestion is rare (1%). We describe our experience in treating these lesions surgically.Method  From 1995 to 2006, data were collected prospectively in 33 patients (18 women and 15 men; mean age 64 years) operated on for intestinal perforation due to an ingested FB. The type of object, preoperative diagnosis, perforation site, treatment, morbidity and mortality were reviewed.Results  Foreign body ingestion was predominantly involuntary (88%). The mean time from ingestion to perforation was 10.4 days. The most frequently ingested objects were dietary FB (n = 21) and toothpicks (n = 6). The most frequent predisposing factors were dentures or an orthodontic appliance (73%). The most common preoperative diagnoses were acute abdomen of uncertain origin (n = 7), acute appendicitis (n = 7) and acute diverticulitis (n = 5). Pneumoperitoneum was observed in 10 cases. The diagnosis was reached during laparotomy in 30 (91%) cases. The most frequent perforation site was the colorectal region (n = 18, 54.5%), followed by the terminal ileum (n = 7, 21.2%); intraperitoneal perforation was the most common (n = 30, 91%). All cases had abdominal contamination and 22 (66.7%) had diffuse peritonitis. Treatment was always by surgery and antibiotics. Thirteen patients required a colostomy. Morbidity was 57.6% (n = 19) and mortality 6.1% (n = 2).Conclusion  Intestinal perforation by a foreign body is rare and normally affects the sigmoid colon, rectum or distal ileum. Dentures are a common risk factor. Patients are rarely aware of foreign body ingestion. Dietary FB and toothpicks are the most commonly ingested objects. Treatment consists of surgery and antibiotics. Appendicitis and acute diverticulitis should be considered in the differential diagnosis.
Enteral vs parenteral nutrition in reconstructive anal surgery – a prospective‐randomized trial
Authors: Joos A. K. , Palma P. , Jonescheit J. O. , Hasenberg T. , Herold A. 
Published: November 2007

AbstractObjective  Early defecation after reconstructive anal surgery may influence the outcome negatively. Different methods are used to avoid bowel movements in the early postoperative period.We questioned whether stool behaviour is influenced by total parenteral nutrition as opposed to enteral nutrition with resorbable sip feeds. Furthermore, satisfaction of patients with each nutrition regime, cost differences and influence of the postoperative outcome were evaluated.Method  Between January and October 2004, 32 patients were evaluated in a prospective randomized, surgeon‐blinded trial. The parenteral group (PG, n = 16) received 1250 ml Nutriflex lipid basal™ (B. Braun Comp., Melsungen, Germany) intravenously. The enteral group (EG, n = 16) was offered a total amount of three cups of Clinutren fruit™ (Nestle Nutrition GmbH, Frankfurt, Germany), two boxes of OPD (oligopeptid diet) Elemental 028 extra™ (SHS, Liverpool, UK) and two cups of OPD Peptamen™ (Nestle Nutrition GmbH). Both groups received 1000 ml of isotonic cristalloid solution and were allowed to drink up to 1000 ml of tea or water per 24 h.Results  The satisfaction of patients was significantly higher in the EG. In regard to stool behaviour both groups showed no differences, in the number of bowel movements or in the time to the first postoperative defecation. Enteral feeding resulted in a minimum saving of €220. Postoperative results in the case of plastic fistula closure did not differ between both groups.Conclusions  Sufficient bowel confinement during the early postoperative period after anal reconstructive surgery may be achieved by using resorbable sip feeds rather than parenteral nutrition.
The relationship between tumour proliferative activity, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer
Authors: Canna K. , Hilmy M. , McMillan D. C. , Smith G. W. , McKee R. F. , McArdle C. S. , McNicol A.‐M. 
Published: November 2007

AbstractBackground The aim of the present study was to examine the relationship between Ki‐67, C‐reactive protein and cancer‐specific survival in patients undergoing resection for colorectal cancer.Method One hundred and forty‐seven patients undergoing potentially curative resection for colorectal cancer had preoperative C‐reactive protein concentrations and tumour Ki‐67 labelling index measured.Results On univariate analysis, age (P < 0.001), Dukes stage (P < 0.001), C‐reactive protein (P < 0.001) and expression of Ki‐67 (< 0.01) were associated with poorer cancer‐specific survival. Ki‐67 labelling index and C‐reactive protein were correlated (rs = 0.172, P = 0.037). On multivariate analysis, age (HR 1.96, 95% CI 1.26–3.04, P = 0.003), Dukes stage (HR 4.38, 95% CI 2.11–9.09, P < 0.001) and C‐reactive protein (HR 4.09, 95% CI 2.04–8.24, P < 0.001) retained significance.Conclusion Increased tumour proliferation is associated with a systemic inflammatory response and poor cancer‐specific survival in patients undergoing potentially curative surgery for colorectal cancer.
Surgical strategies for faecal incontinence – a decision analysis between dynamic graciloplasty, artificial bowel sphincter and end stoma
Authors: Tan E. K. , Vaizey C. , Cornish J. , Darzi A. , Tekkis P. P. 
Published: November 2007

AbstractBackground Artificial bowel sphincter (ABS) and dynamic graciloplasty (DG) are surgical treatments for faecal incontinence (FI). FI may affect quality of life (QOL) so severely that patients are often willing to consider a permanent end stoma (ES). It is unclear which is the more cost‐effective strategy.Method Probability estimates for patients with FI were obtained from published data (ABS, n = 319; DG, n = 301), supplemented by expert opinion. The primary outcome was quality‐adjusted life years (QALYs) gained from each strategy. Factors considered were the risk of failure of the primary and redo operation and the consequent risk of permanent stoma. Results were assessed as incremental cost‐effectiveness ratio (ICER).Results Over the 5‐year time horizon, ES gave a QALY gain of 3.45 for £16 280, giving an ICER of £4719/QALY. ABS produced a gain of 4.38 QALYs for £23 569, giving an ICER of £5387/QALY. DG produced a gain of 4.00 QALYs for £25 035, giving an ICER of £6257/QALY. With the willingness‐to‐pay threshold set at £30 000/QALY, ES was the most cost‐effective intervention. The ABS was most cost‐effective after 10 years.Conclusion All three procedures were found to be cost‐effective. The ES was most cost‐effective over 5 years, while the ABS was most cost‐effective in excess of 10. DG maybe considered as an alternative in specialist centres.