bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of power Doppler sonography with 3D reconstruction in preoperative diagnostics of extraprostatic tumor extension in clinically localized prostate cancer
Authors: Zalesky Miroslav , Urban Michael , Smerhovský Zdenek , Zachoval Roman , Lukes Martin , Heracek Jiri 
Published: November 2007

Aim:  The aim of the study is to investigate the value of preoperative power Doppler sonography with 3D reconstruction (3D‐PDS) for diagnostics of extraprostatic extension of prostate cancer.Patients and Methods:  In the prospective study we examined 146 patients with clinically localized prostate cancer who underwent radical prostatectomy. Prior to surgery, each patient underwent 3D‐PDS, transrectal ultrasound (TRUS), and digital rectal examination (DRE). Furthermore, we determined the prostate volume, prostate specific antigen (PSA) level, PSA density (PSAD), and Gleason score. The risk of locally advanced cancer was assessed using Partin tables. We determined the sensitivity, specificity, and predictive values of these diagnostic procedures. We plotted the receiver operating characteristic (ROC) curves and calculated the areas under the curves (AUC). Multivariate logistic regression was used to identify the significant predictors of extraprostatic tumor extension. Based on this we developed diagnostic nomograms maximizing the probability of accurate diagnosis.Results:  The significant differences between patients with organ confined and locally advanced tumor (based on the postoperative assessment) were observed in the PSA levels (P < 0.014), PSAD (P < 0.004), DRE (P < 0.037), TRUS (P < 0.003), and 3D‐PDS (P < 0.000). The highest AUC value of 0.776 (P < 0.000) was found for 3D‐PDS. The observed AUC value for TRUS was 0.670 (P < 0.000) and for PSAD 0.639 (P < 0.004). In multivariate regression analysis, the PSAD, preoperative Gleason score, and 3D‐PDS finding were identified as significant preoperative predictors of extraprostatic tumor extension.Conclusion:  Our data suggest that the 3D‐PDS is a valuable preoperative diagnostic examination to identify locally advanced prostate cancer. Therefore, it can be used to maximize the probability of the accurate diagnosis of extraprostatic tumor extension.
Recovery of skilled reaching following motor cortex stroke: do residual corticofugal fibers mediate compensatory recovery?
Authors: Gharbawie Omar A. , Karl Jenni M. , Whishaw Ian Q. 
Published: November 2007

AbstractMotor cortex (MC) injury impairs skilled reaching in rats, but success scores are eventually restored to approximate preoperative levels. The improvement is attributed to compensatory strategies, such as substituting trunk rotations for the chronically lost rotatory movement of the forelimb, that occur during transport and withdrawal. The present study examined the contributions of the rostral motor cortex (RMC) and the caudal motor cortex (CMC) to skilled reaching performance. The study also examined the role of the ipsilateral and the contralateral hemispheres in supporting the spontaneous recovery. Rats were trained to reach for single food pellets, and their recovery from partial or complete MC injury was documented with quantitative scores and movement element measures in three experiments: (1) devascularization of the CMC, or the RMC, or both, in the hemisphere contralateral to the reaching paw; (2) additional lesions to the CMC and RMC injuries such that the conjoint damage amounted to an MC lesion; and (3) MC lesion followed by damage in the neocortex lateral to the injury or in the opposite MC. The results showed that the CMC made the main contribution to skilled reaching performance, and that there was a lesser contribution by the RMC. MC damage was exacerbated by additional damage to the ipsilateral neocortex as compared to the contralateral neocortex. The results are discussed in relation to the idea that the involvement of the neocortical areas in skilled reaching performance and its recovery is proportional to the region from which corticospinal projections originate.
Phenotype of V2‐derived interneurons and their relationship to the axon guidance molecule EphA4 in the developing mouse spinal cord
Authors: Lundfald Line , Restrepo C. Ernesto , Butt Simon J. B. , Peng Chian‐Yu , Droho Steven , Endo Toshiaki , Zeilhofer Hanns Ulrich , Sharma Kamal , Kiehn Ole 
Published: November 2007

AbstractThe ventral spinal cord consists of interneuron groups arising from distinct, genetically defined, progenitor domains along the dorsoventral axis. Many of these interneuron groups settle in the ventral spinal cord which, in mammals, contains the central pattern generator for locomotion. In order to better understand the locomotor networks, we have used different transgenic mice for anatomical characterization of one of these interneuron groups, called V2 interneurons. Neurons in this group are either V2a interneurons marked by the postmitotic expression of the transcription factor Chx10, or V2b interneurons which express the transcription factors Gata2 and Gata3. We found that all V2a and most V2b interneurons were ipsilaterally projecting in embryos as well as in newborns. V2a interneurons were for the most part glutamatergic while V2b interneurons were mainly GABAergic or glycinergic. Furthermore, we demonstrated that a large proportion of V2 interneurons expressed the axon guidance molecule EphA4, a molecule previously shown to be important for correct organization of locomotor networks. We also showed that V2 interneurons and motor neurons alone did not account for all EphA4‐expressing neurons in the spinal cord. Together, these findings enable a better interpretation of neural networks underlying locomotion, and open up the search for as yet unknown components of the mammalian central pattern generator.
Heterogeneity of V2‐derived interneurons in the adult mouse spinal cord
Authors: Al‐Mosawie A. , Wilson J. M. , Brownstone R. M. 
Published: November 2007

AbstractSpinal neurons and networks that generate rhythmic locomotor activity remain incompletely defined, prompting the use of molecular biological strategies to label populations of neurons in the postnatal mouse. During spinal cord development, expression of Lhx3 in the absence of Isl1 specifies a V2 interneuronal fate. In this study, postnatal V2‐derived interneurons were identified by yellow fluorescent protein (YFP) expression in the double‐transgenic offspring of Lhx3Cre/+ × thy1‐loxP‐stop‐loxP‐YFP mice. While some motoneurons were labelled, several populations of interneurons predominantly located in lamina VII could also be distinguished. Small interneurons were located throughout the spinal cord whereas larger interneurons were concentrated in the lumbar enlargement. Some V2‐derived interneurons were propriospinal, with axons that bifurcated in the lateral funiculus. V2‐derived interneurons gave rise to populations of both excitatory and inhibitory interneurons in approximately equal proportions, as demonstrated by in situ hybridization with VGLUT2 mRNA. Immunohistochemical studies revealed YFP+ boutons throughout the spinal cord. Both glutamatergic and glycinergic YFP+ boutons were observed in lamina IX where many apposed motoneuron somata. GABAergic YFP+ boutons were also observed in lamina IX, and they did not form P‐boutons. At P0, more than half of the YFP+ interneurons expressed Chx10 and thus were derived from the V2a subclass. In adult mice, there was an increase in Fos expression in V2‐derived interneurons following locomotion, indicating that these neurons are active during this behaviour. The heterogeneity of V2‐derived interneurons in adult mice indicates that physiologically distinct subpopulations, including last‐order interneurons, arise from these embryonically defined neurons.
The prokineticin receptor agonist Bv8 increases GABA release in the periaqueductal grey and modifies RVM cell activities and thermoceptive reflexes in the rat
Authors: De Novellis Vito , Negri Lucia , Lattanzi Roberta , Rossi Francesca , Palazzo Enza , Marabese Ida , Giannini Elisa , Vita Daniela , Melchiorri Pietro , Maione Sabatino 
Published: November 2007

AbstractThe prokineticin Bv8, a small protein secreted by the skin of the Bombina variegata frog, is a potent agonist of both the identified prokineticin receptors, the G‐protein‐coupled PK‐R1 and PK‐R2. We found in this study that intraperiaqueductal grey (PAG) Bv8, 100 and 200 pmol per rat, exerted a pronociceptive action and caused opposite effects on the ongoing rostral ventromedial medulla (RVM) On‐ and Off‐cell activities in rats. Bv8 increased and decreased the ongoing activity of RVM On and Off cells, respectively. Bv8 decreased tail flick latency and increased the pause and shortened the onset of the Off‐cell pause. Bv8 did not change either the tail flick‐induced On‐cell burst of activity or the onset of On‐cell peak firing. Microdialysis analysis, applied in combination with the plantar test, showed that intra‐PAG perfusion with Bv8 (0.25 and 0.5 pm) increased GABA, but not glutamate, extracellular levels, and decreased thermoceptive thresholds. These findings show that stimulation of PAG PK‐Rs might worsen pain perception and this effect is consistent with both RVM On‐ and Off‐cell ongoing and tail flick‐related activities, as well as with the increase induced by Bv8 in PAG GABA levels.
Disruption of dopamine homeostasis underlies selective neurodegeneration mediated by α‐synuclein
Authors: Park Soon S. , Schulz Emily M. , Lee Daewoo 
Published: November 2007

AbstractA key challenge in Parkinson's disease research is to understand mechanisms underlying selective degeneration of dopaminergic neurons mediated by genetic factors such as α‐synuclein (α‐Syn). The present study examined whether dopamine (DA)‐dependent oxidative stress underlies α‐Syn‐mediated neurodegeneration using Drosophila primary neuronal cultures. Green fluorescent protein (GFP) was used to identify live dopaminergic neurons in primary cultures prepared on a marked photoetched coverslip, which allowed us to repeatedly access preidentified dopaminergic neurons at different time points in a non‐invasive manner. This live tracking of GFP‐marked dopaminergic neurons revealed age‐dependent neurodegeneration mediated by a mutant human α‐Syn (A30P). Degeneration was rescued when α‐Syn neuronal cultures were incubated with 1 mm glutathione from Day 3 after culturing. Furthermore, depletion of cytoplasmic DA by 100 µmα‐methyl‐p‐tyrosine completely rescued the early stage of α‐Syn‐mediated dopaminergic cell loss, demonstrating that DA plays a major role in oxidative stress‐dependent neurodegeneration mediated by α‐Syn. In contrast, overexpression of a Drosophila tyrosine hydroxylase gene (dTH1) alone caused DA neurodegeneration by enhanced DA synthesis in the cytoplasm. Age‐dependent dopaminergic cell loss was comparable in α‐Syn vs dTH1‐overexpressed neuronal cultures, indicating that increased DA levels in the cytoplasm is a critical change downstream of mutant α‐Syn function. Finally, overexpression of a Drosophila vesicular monoamine transporter rescued α‐Syn‐mediated neurodegeneration through enhanced sequestration of cytoplasmic DA into synaptic vesicles, further indicating that a main cause of selective neurodegeneration is α‐Syn‐induced disruption of DA homeostasis. All of these results demonstrate that elevated cytoplasmic DA is a main factor underlying the early stage of α‐Syn‐mediated neurodegeneration.
Aggregate formation of mutant protein kinase C gamma found in spinocerebellar ataxia type 14 impairs ubiquitin‐proteasome system and induces endoplasmic reticulum stress
Authors: Seki Takahiro , Takahashi Hideyuki , Adachi Naoko , Abe Nana , Shimahara Takayuki , Saito Naoaki , Sakai Norio 
Published: November 2007

AbstractSeveral causal missense mutations in protein kinase Cγ (γPKC) gene have been found in spinocerebellar ataxia type 14 (SCA14), an autosomal dominant neurodegenerative disease. We previously demonstrated that mutant γPKC found in SCA14 is susceptible to two types of aggregation, cytoplasmic dot‐like and perinuclear massive aggregation, and causes cell death in Chinese hamster ovary cells. Long‐term time‐lapse imaging revealed that firstly accumulated dot‐like aggregation of mutant γPKC‐green fluorescent protein (GFP) gradually formed perinuclear massive aggregations, followed by cell death. However, it remains unclear how aggregate formation of mutant γPKC causes cell death. In the present study, we examined whether these mutant aggregations affect the ubiquitin‐proteasome system (UPS) and endoplasmic reticular (ER) stress. Two mutant γPKC‐GFPs (S119P and G128D) were strongly ubiquitinated, and dot‐like aggregations of these mutants were ubiquitin‐positive and colocalized with proteasome 20S. Furthermore, proteasome activity in cells with aggregates, especially massive ones, was significantly decreased. Aggregate formation of mutant γPKC‐GFP induced phosphorylation of PERK (PKR‐like ER kinase) and nuclear expression of CHOP (C/EBP homologous protein), hallmarks of ER stress and subsequently activated caspase‐3. These results indicate that aggregate formation of mutant γPKC found in SCA14 impairs UPS and induces ER stress, leading to apoptotic cell death.
Activation of protease‐activated receptors in astrocytes evokes a novel neuroprotective pathway through release of chemokines of the growth‐regulated oncogene/cytokine‐induced neutrophil chemoattractant family
Authors: Wang Yingfei , Luo Weibo , Reiser Georg 
Published: November 2007

AbstractActivation of protease‐activated receptors (PARs) is known to exert neuroprotection when low concentrations of the agonist protease thrombin are applied. However, the mechanism of protection is still unclear. Here, we showed that activation of multiple PARs, including PAR‐1, PAR‐2 and PAR‐4, was able to elevate the release of the chemokine cytokine‐induced neutrophil chemoattractant (CINC)‐3 from rat astrocytes, in addition to evoking CINC‐1 secretion. Different molecular mechanisms were identified as being involved in the secretion of CINC‐1 and CINC‐3, upon activation of different PARs. Importantly, we found that both CINC‐1 and CINC‐3 could signal to rat cortical neurons. Both chemokines acted via CXCR2 to prevent C2‐ceramide‐induced cytochrome c release from mitochondria. Consequently CINC‐1 and CINC‐3 protected neurons from apoptosis. We further revealed that conditioned media obtained from PAR‐activated astrocytes similarly protected cortical neurons against C2‐ceramide‐induced cell death. The neuroprotection was considerably suppressed by a CXCR2 antagonist. CXCR2 is the cognate receptor for CINC. Therefore, our findings demonstrate that PAR‐activated astrocytes are able to protect neurons against neurodegeneration and cell death via regulation of the secretion of chemokines CINC‐1 and CINC‐3. These data indicate a previously unknown mechanism for astrocyte‐mediated neuroprotection achieved by PAR activation.
Enhanced markers of oxidative stress, altered antioxidants and NADPH‐oxidase activation in brains from Fragile X mental retardation 1‐deficient mice, a pathological model for Fragile X syndrome
Authors: El Bekay Rajaa , Romero‐Zerbo Yanina , Decara Juan , Sanchez‐Salido Lourdes , Del Arco‐Herrera Ignacio , Rodríguez‐de Fonseca Fernando , De Diego‐Otero Yolanda 
Published: November 2007

AbstractFragile X syndrome is the most common form of inherited mental retardation in humans. It originates from the loss of expression of the Fragile X mental retardation 1 (FMR1) gene, which results in the absence of the Fragile X mental retardation protein. However, the biochemical mechanisms involved in the pathological phenotype are mostly unknown. The availability of the FMR1‐knockout mouse model offers an excellent model system in which to study the biochemical alterations related to brain abnormalities in the syndrome. We show for the first time that brains from Fmr1‐knockout mice, a validated model for the syndrome, display higher levels of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH)‐oxidase activation, lipid peroxidation and protein oxidation than brains from wild‐type mice. Furthermore, the antioxidant system is deficient in Fmr1‐knockout mice, as shown by altered levels of components of the glutathione system. FMR1‐knockout mice lacking Fragile X mental retardation protein were compared with congenic FVB129 wild‐type controls. Our results support the hypothesis that the lack of Fragile X mental retardation protein function leads to a moderate increase of the oxidative stress status in the brain that may contribute to the pathophysiology of the Fragile X syndrome.
A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo
Authors: Hampton David W. , Asher Richard A. , Kondo Toru , Steeves John D. , Ramer Matt S. , Fawcett James W. 
Published: November 2007

AbstractBone morphogenetic proteins (BMPs) and their endogenous inhibitors, including noggin, chordin and follistatin, have roles in pattern formation and fate specification of neuronal and glial cells during nervous system development. We have examined their influence on glial reactions in the injured central nervous system (CNS). We show that penetrating injuries to the brain and spinal cord resulted in the upregulation of BMP‐2/4, BMP‐7, and noggin, with the latter being expressed almost exclusively by reactive astrocytes at the injury site, and we show that astrocytes in vitro produce noggin. As BMPs have been shown to drive cultured NG2‐positive oligodendrocyte precursors (OPCs) towards a multipotential phenotype (type II astrocytes), we investigated the effects of inhibiting noggin with a function‐blocking antibody (noggin‐FbAb). In vitro, BMP‐driven conversion of OPCs to type 2 astrocytes was inhibited by noggin, an effect that was reversed by noggin‐FbAb. Noggin‐FbAb also increased the number of type 2 astrocytes generated from cultured OPCs exposed to an astrocyte feeder layer, consistent with astrocytes producing both BMPs and noggin. In knife cut injuries in vivo, noggin‐FbAb treatment resulted in an increase in the number of NG2‐positive cells and small GFAP‐positive cells in the injury site, and the appearance of glial cells with the morphological and antigenic characteristics of type 2 astrocytes (as generated in vitro), with coexpression of both GFAP and NG2. This potential conversion of inhibitory OPCs to type 2 astrocyte‐like cells in vivo suggests that endogenous BMPs, unmasked by noggin antagonism, might be exploited to manipulate cell fate following CNS trauma.
An experimentally induced duplication of retinotopic mapping within the hamster primary visual cortex
Authors: Trevelyan Andrew J. , Upton A. L. , Cordery Patricia M. , Thompson Ian D. 
Published: November 2007

AbstractPrimary cortical areas normally have a single mapping of the receptor array arising from a ‘point‐to‐point’ projection from the thalamus. We show that, for the visual cortex, this simple mapping rule breaks down when retinal input to the thalamus is altered. We utilize the monocular enucleation paradigm, which alters subcortical mappings ipsilateral to the remaining eye. We show that this manipulation produces an altered visuotopic map in area 17 with two separated, mirror‐imaged representations of the central visual field. Furthermore, thalamic point‐to‐point connectivity is dramatically changed. There are now two overlapping geniculocortical projections: the predominant projection maps with apparently normal topography, and a second projection maps with the opposite polarity. The plane of symmetry of the duplicated anatomical projection coincides precisely with the functional map reversal and, notably, geniculocortical magnification factors are identical in the two projections. We suggest that the duplicated, abnormal geniculocortical projection is retinotopically matched to the normal projection. We speculate that aberrant geniculocortical terminals are stabilized because they have coherent activity patterns with topographically normal terminals.
Cannabinoid regulation in identified synapse of terrestrial snail
Authors: Lemak M.S. , Bravarenko N.I. , Bobrov M.Yu. , Bezuglov V.V. , Ierusalimsky V.N. , Storozhuk M.V. , Malyshev A.Y. , Balaban P.M. 
Published: November 2007

AbstractIn the terrestrial snail a direct monosynaptic glutamatergic connection between the primary sensory neuron and a premotor interneuron involved in withdrawal behaviour can be functionally identified using electrophysiological techniques. We investigated the involvement of cannabinoids in regulation of this synaptic contact. The results demonstrate that the specific binding sites for agonists to mammalian type 1 cannabinoid receptors (CB1Rs) exist in the snail's nervous system. Application of a synthetic cannabinoid agonist anandamide selectively changed the efficacy of synaptic contacts between the identified neurons. A decrease in the long‐term synaptic facilitation of the synaptic contact elicited by high‐frequency nerve tetanization in the presence of cannabinoid agonist anandamide was observed, suggesting a possible role of endocannabinoids in regulation of plasticity at this synaptic site. The selective antagonist of CB1Rs [N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide] AM251 bath application was changing the efficacy of the synaptic contact only when the postsynaptic neuron had been intracellularly activated before its application. This observation implies an involvement of endocannabinoids in plasticity phenomena induced by activity in the postsynaptic target. Additional support of endocannabinoid involvement in synaptic function at this site was given by experiments in which AM251 blocked the short‐term suppression of synaptic excitation evoked by low‐frequency nerve tetanization, a phenomenon qualitatively similar to cannabinoid‐dependent synaptically evoked suppression of excitation demonstrated in the mammalian nervous system. The results of the present study suggest an involvement of cannabinoids in the regulation of synaptic efficacy. Further, anandamide could be a candidate for an endogenous neuromessenger involved in plasticity processes.
Multiple nutrients limit litterfall and decomposition in a tropical forest
Authors: Kaspari Michael , Garcia Milton N. , Harms Kyle E. , Santana Mirna , Wright S. Joseph , Yavitt Joseph B. 
Published: November 2007

AbstractTo explore the importance of 12 elements in litter production and decomposition, we fertilized 36 1600 m2‐plots with combinations of N, P, K, or micronutrients (i.e. B, Ca, Cu, Fe, Mg, Mn, Mo, S, Zn) for 6 years in a lowland Panamanian forest. The 90% of litter falling as leaves and twigs failed to increase with fertilization, but reproductive litter (fruits and flowers) increased by 43% with N. K enhanced cellulose decomposition; one or more micronutrients enhanced leaf‐litter decomposition; P enhanced both. Our results suggest tropical forests are a non‐Liebig world of multiple nutrient limitations, with at least four elements shaping rates of litterfall and decomposition. Multiple metallomic enzymes and cofactors likely create gradients in the break down of leaf litter. Selection favours individuals that make more propagules, and even in an N‐rich forest, N is a non‐substitutable resource for reproduction.